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Levy C, Buchanan-Peart KA, MacEwan JP, Levine A, Nair R, Wheeler D, Bessonova L, Goel A, Gish RG, Bonder A. A nationwide study of primary biliary cholangitis prevalence, geographic distribution, and health care providers. Hepatol Commun 2025; 9:e0677. [PMID: 40227093 PMCID: PMC11999412 DOI: 10.1097/hc9.0000000000000677] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Accepted: 01/08/2025] [Indexed: 04/15/2025] Open
Abstract
BACKGROUND Prevalence estimates of primary biliary cholangitis (PBC) in the United States have evolved with the introduction of newer real-world data capture approaches. Little is known about the geographic distribution of PBC in the United States and the health care provider (HCP) landscape for patients with PBC. This real-world study aimed to estimate the prevalence of PBC in the United States, assess regional variability in its prevalence, and describe HCPs for patients with PBC. METHODS Patients with PBC were identified using Komodo's Healthcare Map, a large national administrative claims database. PBC prevalence per 100,000 adults was adjusted by age and gender at the 3-digit ZIP Code tabulation area level. Patients' PBC-related medical or pharmacy claims were used to determine HCP specialties and affiliations (academic vs. nonacademic); the latest claim and all claims were examined. RESULTS The adjusted 2021 PBC prevalence was 40.9 per 100,000 adults. The highest absolute number of patients with PBC in the United States was in heavily populated urban areas, but prevalence adjusted for population size was highest in some rural areas. Among all claims, most (83.2%) patients received care from a specialist (gastroenterologist/hepatologist) at one time. However, only approximately half (53.5%) of patients with PBC, irrespective of therapy use, were most recently treated for PBC by a specialist. CONCLUSIONS This is the most comprehensive and contemporary estimation of PBC prevalence in the United States to date. The pockets of high prevalence of PBC located in some rural areas highlight the need to better evaluate PBC risk factors and potential barriers in access to specialist care once patients are diagnosed. Greater awareness of PBC and its management are needed.
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Affiliation(s)
- Cynthia Levy
- Schiff Center for Liver Diseases, University of Miami, Miami, Florida, USA
- Division of Digestive Health and Liver Diseases, University of Miami, Miami, Florida, USA
| | | | | | - Alina Levine
- Genesis Research Group, Hoboken, New Jersey, USA
| | - Radhika Nair
- Intercept Pharmaceuticals, Inc., Morristown, New Jersey, USA
| | - Darren Wheeler
- Intercept Pharmaceuticals, Inc., Morristown, New Jersey, USA
- At the time of study
| | - Leona Bessonova
- Intercept Pharmaceuticals, Inc., Morristown, New Jersey, USA
| | - Aparna Goel
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Stanford, California, USA
| | - Robert G. Gish
- Robert G. Gish Consultants, LLC, San Diego, California, USA
| | - Alan Bonder
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
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2
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Wu J, Yin Y, Han X, Di H, Han Y, Shen M, Zhang Y, Zeng X. Clinical characteristics of primary biliary cirrhosis - idiopathic inflammatory myopathy overlap syndrome: A single center study. Am J Med Sci 2025; 369:166-175. [PMID: 39127420 DOI: 10.1016/j.amjms.2024.08.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Revised: 07/28/2024] [Accepted: 08/06/2024] [Indexed: 08/12/2024]
Abstract
PURPOSE Primary biliary cirrhosis-idiopathic inflammatory myopathy (PBC-IIM) overlap syndrome (OS) is a rare condition in which cardiac involvement is observed. We aimed to characterize the clinical features and associated factors of PBC-IIM OS patients with cardiac involvement. METHODS Patients with PBC-IIM OS that visited our hospital from January 1983 to December 2021 were enrolled. Clinical presentations and laboratory and imaging data were recorded. The clinical data of patients with and without cardiac involvement were compared. According to the first instance of a disease flare, prognostic factors were also studied. RESULTS Thirty-four patients with PBC-IIM OS were enrolled. A total of 58.8% of patients presented with muscle weakness at disease onset, which primarily involved skeletal muscle (85.3%). Slight liver dysfunction was discovered in this OS cohort. In patients with cardiac involvement, palpitation (63.6%) and dyspnea (36.4%) were the most common onset symptoms. Arrhythmia was a vital manifestation in OS patients, in which half of OS patients had nonsustained ventricular tachycardia (50.0%, 11/22). Compared with noncardiac involvement, myalgia (4.5%, P = 0.004) and fever (0.0%, P = 0.011) were reported relatively rarely at disease onset in the group with cardiac involvement. The prognosis analysis showed that positivity for anti-Ro52 (HR=0.00, P = 0.034) negatively correlated with relapse in OS patients. CONCLUSION PBC-IIM OS has unique features. Typical clinical manifestations and early worsening cardiac indicators can be used to identify cardiac involvement and predict prognosis. Anti-Ro52 may have prognostic value for PBC-IIM OS.
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Affiliation(s)
- Juan Wu
- Department of family medicine & Division of General Internal Medicine, Department of medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, State Key Laboratory of Complex Severe and Rare Diseases (Peking Union Medical College Hospital), Beijing, China
| | - Yue Yin
- Department of family medicine & Division of General Internal Medicine, Department of medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, State Key Laboratory of Complex Severe and Rare Diseases (Peking Union Medical College Hospital), Beijing, China
| | - Xinxin Han
- Department of family medicine & Division of General Internal Medicine, Department of medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, State Key Laboratory of Complex Severe and Rare Diseases (Peking Union Medical College Hospital), Beijing, China
| | - Hong Di
- Department of family medicine & Division of General Internal Medicine, Department of medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, State Key Laboratory of Complex Severe and Rare Diseases (Peking Union Medical College Hospital), Beijing, China
| | - Yingdong Han
- Department of family medicine & Division of General Internal Medicine, Department of medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, State Key Laboratory of Complex Severe and Rare Diseases (Peking Union Medical College Hospital), Beijing, China
| | - Min Shen
- Department of Rheumatology, Department of medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, State Key Laboratory of Complex Severe and Rare Diseases (Peking Union Medical College Hospital), Beijing, China
| | - Yun Zhang
- Department of family medicine & Division of General Internal Medicine, Department of medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, State Key Laboratory of Complex Severe and Rare Diseases (Peking Union Medical College Hospital), Beijing, China.
| | - Xuejun Zeng
- Department of family medicine & Division of General Internal Medicine, Department of medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, State Key Laboratory of Complex Severe and Rare Diseases (Peking Union Medical College Hospital), Beijing, China.
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Marenco-Flores A, Rojas Amaris N, Kahan T, Sierra L, Barba Bernal R, Medina-Morales E, Goyes D, Patwardhan V, Bonder A. The External Validation of GLOBE and UK-PBC Risk Scores for Predicting Ursodeoxycholic Acid Treatment Response in a Large U.S. Cohort of Primary Biliary Cholangitis Patients. J Clin Med 2024; 13:4497. [PMID: 39124763 PMCID: PMC11312962 DOI: 10.3390/jcm13154497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 07/29/2024] [Accepted: 07/30/2024] [Indexed: 08/12/2024] Open
Abstract
Background: The cornerstone treatment for primary biliary cholangitis (PBC) is ursodeoxycholic acid (UDCA), but many patients exhibit an incomplete response, leading to disease progression. Risk prediction models like the GLOBE and UK-PBC scores hold promise for patient stratification and management. We aimed to independently assess the predictive accuracy of these risk scores for UDCA response in a prospective U.S. cohort. Methods: We conducted a prospective cohort study at a U.S. liver center, monitoring UDCA-treated PBC patients over a one-year follow-up. We evaluated the predictive efficacy of the GLOBE and UK-PBC scores for UDCA treatment response, comparing them to the Paris II criteria. Efficacy was assessed using univariate and multivariate analyses, followed by prognostic performance evaluation via receiver operating characteristic (ROC) curve analysis. Results: We evaluated 136 PBC patients undergoing UDCA therapy. Based on the Paris II criteria, patients were categorized into UDCA full-response and non-response groups. The GLOBE score identified a non-responder rate of 18% (p = 0.205), compared to 20% (p = 0.014) with the Paris II criteria. Multivariate analysis, adjusted for age and biochemical markers, showed that both the GLOBE and UK-PBC scores were strongly associated with treatment response (p < 0.001). The area under the ROC curve was 0.87 (95% CI 0.83-0.95) for the GLOBE score and 0.94 (95% CI 0.86-0.99) for the UK-PBC risk score. Conclusions: Our study demonstrates that GLOBE and UK-PBC scores effectively predict UDCA treatment response in PBC patients. The early identification of patients at risk of an incomplete response could improve treatment strategies and identify patients who may need second-line therapies.
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Affiliation(s)
- Ana Marenco-Flores
- Division of Gastroenterology, Hepatology, and Nutrition, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; (A.M.-F.); (N.R.A.); (V.P.)
| | - Natalia Rojas Amaris
- Division of Gastroenterology, Hepatology, and Nutrition, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; (A.M.-F.); (N.R.A.); (V.P.)
| | - Tamara Kahan
- Division of Gastroenterology, Hepatology, and Nutrition, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; (A.M.-F.); (N.R.A.); (V.P.)
| | - Leandro Sierra
- Division of Gastroenterology, Hepatology, and Nutrition, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; (A.M.-F.); (N.R.A.); (V.P.)
| | - Romelia Barba Bernal
- Department of Internal Medicine, Texas Tech University System, Lubbock, TX 79430, USA
| | - Esli Medina-Morales
- Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USA
| | - Daniela Goyes
- Division of Digestive Diseases, Yale School of Medicine, New Haven, CT 06520, USA
| | - Vilas Patwardhan
- Division of Gastroenterology, Hepatology, and Nutrition, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; (A.M.-F.); (N.R.A.); (V.P.)
| | - Alan Bonder
- Division of Gastroenterology, Hepatology, and Nutrition, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; (A.M.-F.); (N.R.A.); (V.P.)
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Koop PH, Schwenzer C, Clusmann J, Vell MS, Jaeger J, Gui W, Trautwein C, Koch A, Bruns T, Schneider CV, Schneider KM. Comorbidities, mortality and metabolic profile in individuals with primary biliary cholangitis-A Phenome-Wide-Association-Study. Liver Int 2024; 44:2038-2053. [PMID: 38661318 DOI: 10.1111/liv.15945] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 03/05/2024] [Accepted: 04/08/2024] [Indexed: 04/26/2024]
Abstract
BACKGROUND AND AIMS Primary biliary cholangitis (PBC) is a chronic, immune-mediated liver disease that can lead to fibrosis and cirrhosis. In this cohort study, we aimed to investigate morbidity and mortality in conjunction with metabolomic changes of PBC in a UK population-based cohort. METHODS 454 participants with PBC and 908 propensity score (age, sex, BMI, ethnicity) matched controls without liver disease were included in the study. A subset of participants with PBC and controls were analysed for their metabolomic profile. Further, PBC-associated comorbidities were investigated by PheWAS analysis. Lastly, we assessed causes of death in individuals with PBC using a Fine and Grey competing-risks regression model. RESULTS Compared to the control group, various pathways associated with the metabolism of amino acids, lipids, and liver biochemistry were significantly enriched in individuals with PBC. We found reduced levels of S-HDL-cholesterol and Glycoprotein Acetyls in individuals with PBC as well as an association with diseases of the circulatory system. Notably, PBC individuals had a higher prevalence of digestive diseases, autoimmune diseases, cardiovascular diseases, anaemias, mental disorders, and urinary tract infections compared to the control group. Strikingly, the overall mortality was almost three times higher in the PBC group compared to the control group, with diseases of the digestive system accounting for a significant elevation of the death rate. A subsequent analysis, enhanced by propensity score matching that included the APRI score, demonstrated that the observed morbidity could not be exclusively attributed to advanced hepatic disease. CONCLUSIONS Our study provides a detailed perspective on the morbidity of individuals with PBC. The exploration of potential effects of disease state on morbidity suggest that early detection and early treatment of PBC could enhance patient prognosis and prevent the onset of comorbid diseases. Finally, the metabolomic alterations could represent a link between the pathophysiological processes underlying PBC development, progression, and associated morbidity.
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Affiliation(s)
- Paul-Henry Koop
- Department of Internal Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
| | - Constanze Schwenzer
- Department of Internal Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
| | - Jan Clusmann
- Department of Internal Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
| | - Mara S Vell
- Department of Internal Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
| | - Julius Jaeger
- Department of Internal Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
| | - Wenfang Gui
- Department of Internal Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
| | - Christian Trautwein
- Department of Internal Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
| | - Alexander Koch
- Department of Internal Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
| | - Tony Bruns
- Department of Internal Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
| | - Carolin V Schneider
- Department of Internal Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
- The Institute for Translational Medicine and Therapeutics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Kai Markus Schneider
- Department of Internal Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
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5
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Chang ML, Cheng JS, Le PH, Chen WT, Ku HP, Chien RN. Evolutionary relationship between antimitochondrial antibody positivity and primary biliary cholangitis in Taiwan: a 16-year hospital cohort study. Therap Adv Gastroenterol 2024; 17:17562848241241227. [PMID: 38560427 PMCID: PMC10981211 DOI: 10.1177/17562848241241227] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2023] [Accepted: 03/06/2024] [Indexed: 04/04/2024] Open
Abstract
Background How antimitochondrial antibody (AMA)-positive patients evolve to have primary biliary cholangitis (PBC) in viral hepatitis-endemic areas is unknown. Objectives We aimed to investigate this evolution in Taiwan. Design/methods A 16-year medical center-based cohort study of 2,095,628 subjects was conducted in Taiwan, an Asian country endemic to viral hepatitis. AMA-positive subjects were those with positive AMA with alkaline phosphatase (ALP) ⩽1.5 times the upper limit of normal (ULN), and PBC was defined as positive AMA with ALP >1.5 × ULN. Results AMA-positive subjects had a lower average age- and sex-adjusted prevalence than PBC patients (4.68/105 versus 11.61/105, p = 0.0002), but their incidence was comparable (0.99/105 versus 1.12/105, p = 0.36). The former group had a borderline significantly lower mean age (56.59 years versus 58.10 years, p = 0.06) and a lower female-to-male ratio (2.85:1 versus 5.44:1, p < 0.0001). Both AMA-positive subjects (prevalence change: 20.0%, p < 0.01; incidence change: -9.2%, p < 0.01) and PBC patients (prevalence change: 14.6%, p < 0.01; incidence change: -4.7%, p < 0.01) prevalence rate increased but the incidence rate decreased. Among the 423 AMA-positive subjects, 77 (18.2%) developed PBC, for a mean duration of 1.757 years. Compared with AMA-positive subjects, PBC patients had similar concurrent chronic hepatitis B (CHB) rates (2.7% versus 4.3%, p = 0.197) but lower chronic hepatitis C (CHC) rates (3.69% versus 15.60%, p < 0.01). Conclusion PBC was more prevalent than AMA-positive subjects, and PBC patients had a higher female-to-male ratio than AMA-positive subjects, of whom 18.2% developed PBC (mean lag: 1.757 years). Upward trends in prevalence rates and downward trends in incidence rates were noted for both AMA-positive subjects and PBC. CHB was rare, CHC was more prevalent among PBC patients than the general population, and CHC was less prevalent among PBC than among AMA-positive subjects.
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Affiliation(s)
- Ming-Ling Chang
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, No. 5, Fu Hsing Street, Kuei Shan, Taoyuan 333423, Taiwan
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Jur-Shan Cheng
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou, Taiwan
- Clinical Informatics and Medical Statistics Research Center, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Puo-Hsien Le
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou, Taiwan
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Wei-Ting Chen
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou, Taiwan
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Hsin-Ping Ku
- Clinical Informatics and Medical Statistics Research Center, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Rong-Nan Chien
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou, Taiwan
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
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Faisal MS, Gonzalez HC, Gordon SC. Primary Biliary Cholangitis: Epidemiology, Diagnosis, and Presentation. Clin Liver Dis 2024; 28:63-77. [PMID: 37945163 DOI: 10.1016/j.cld.2023.06.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2023]
Abstract
Using ursodeoxycholic acid as a standard treatment and for its ability to test for antimitochondrial antibody to accelerate diagnosis, survival of primary biliary cholangitis patients has approached that of the general population, leading to a change in nomenclature from primary biliary cirrhosis to primary biliary cholangitis to more accurately describe the disease.
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Affiliation(s)
- Muhammad Salman Faisal
- Department of Gastroenterology and Hepatology, Henry Ford Health, 2799 West Grand Boulevard, Detroit, MI 48202, USA
| | - Humberto C Gonzalez
- Department of Gastroenterology and Hepatology, Henry Ford Health, 2799 West Grand Boulevard, Detroit, MI 48202, USA; Wayne State University School of Medicine, 540 East Canfield Street, Detroit, MI 48201, USA
| | - Stuart C Gordon
- Department of Gastroenterology and Hepatology, Henry Ford Health, 2799 West Grand Boulevard, Detroit, MI 48202, USA; Wayne State University School of Medicine, 540 East Canfield Street, Detroit, MI 48201, USA.
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Cheng JS, Chen WT, Ku HP, Chien RN, Chang ML. Characteristic geoepidemiology of primary biliary cholangitis in Taiwan: A nationwide population-based study. Hepatol Res 2023; 53:866-877. [PMID: 37060573 DOI: 10.1111/hepr.13910] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 03/25/2023] [Accepted: 04/06/2023] [Indexed: 04/16/2023]
Abstract
AIM Data on the geoepidemiology and outcomes of primary biliary cholangitis (PBC) in Asia are limited; thus, we aimed to collect and assess this information for Taiwan. METHODS A nationwide population-based cohort study was undertaken using data from the Taiwan National Health Insurance Research Database. Primary biliary cholangitis was defined by the International Classification of Diseases, Ninth Revision, Clinical Modification code 571.6 based on alkaline phosphatase and antimitochondrial antibody measurements and ursodeoxycholic acid treatment. RESULTS During 2002-2015, 2737 patients (2137 female patients; mean age, 57.78 years) had PBC. The average annual age- and sex-adjusted prevalence and incidence rates of PBC were 8.092/105 and 1.148/105 , respectively. Prevalent cases peaked in patients aged 50-59 years; the female-to-male ratio was 4.21. Annual prevalence rates increased with time (average percentage change, 12.03%; p < 0.0001). The annual incidence rates decreased with time (-7.39%; p = 0.000011) in female patients (-8.94%; p = 0.000003) but remained steady in male patients. Female-to-male and northern-to-southern relative risks of PBC incidence rates ranged from 2.2675 to 4.3318 and from 1.5707 to 3.1725, respectively. The 14-year hepatocellular carcinoma (HCC) cumulative incidence was 9.11%, and the mortality rate was 32.44%; the cumulative incidences of dyslipidemia, thyroid disease, and extrahepatic cancers were 65.13%, 24.40%, and 12.79%, respectively. Higher cumulative incidences of HCC (p = 0.0064) and mortality (p < 0.0001) were noted in male than female PBC patients; southern Taiwan PBC patients had higher cumulative incidences of mortality (p < 0.0001) than their northern counterparts. CONCLUSION In Taiwan, decreasing trends in incidence rates and the female-to-male ratio of PBC patients and specific sex and geographic impacts on the incidence rates and outcomes of PBC demand further investigation.
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Affiliation(s)
- Jur-Shan Cheng
- Clinical Informatics and Medical Statistics Research Center, College of Medicine, Chang Gung University, Keelung, Taiwan
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Wei-Ting Chen
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Hsin-Ping Ku
- Clinical Informatics and Medical Statistics Research Center, College of Medicine, Chang Gung University, Keelung, Taiwan
| | - Rong-Nan Chien
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Ming-Ling Chang
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
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8
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Zhao Y, Wei S, Chen L, Zhou X, Ma X. Primary biliary cholangitis: molecular pathogenesis perspectives and therapeutic potential of natural products. Front Immunol 2023; 14:1164202. [PMID: 37457696 PMCID: PMC10349375 DOI: 10.3389/fimmu.2023.1164202] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2023] [Accepted: 06/05/2023] [Indexed: 07/18/2023] Open
Abstract
Primary biliary cirrhosis (PBC) is a chronic cholestatic immune liver disease characterized by persistent cholestasis, interlobular bile duct damage, portal inflammation, liver fibrosis, eventual cirrhosis, and death. Existing clinical and animal studies have made a good progress in bile acid metabolism, intestinal flora disorder inflammatory response, bile duct cell damage, and autoimmune response mechanisms. However, the pathogenesis of PBC has not been clearly elucidated. We focus on the pathological mechanism and new drug research and development of PBC in clinical and laboratory in the recent 20 years, to discuss the latest understanding of the pathological mechanism, treatment options, and drug discovery of PBC. Current clinical treatment mode and symptomatic drug support obviously cannot meet the urgent demand of patients with PBC, especially for the patients who do not respond to the current treatment drugs. New treatment methods are urgently needed. Drug candidates targeting reported targets or signals of PBC are emerging, albeit with some success and some failure. Single-target drugs cannot achieve ideal clinical efficacy. Multitarget drugs are the trend of future research and development of PBC drugs.
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Affiliation(s)
- Yanling Zhao
- Department of Pharmacy, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Shizhang Wei
- Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University, Beijing, China
| | - Lisheng Chen
- Department of Pharmacy, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xuelin Zhou
- Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
| | - Xiao Ma
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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You H, Duan W, Li S, Lv T, Chen S, Lu L, Ma X, Han Y, Nan Y, Xu X, Duan Z, Wei L, Jia J, Zhuang H. Guidelines on the Diagnosis and Management of Primary Biliary Cholangitis (2021). J Clin Transl Hepatol 2023; 11:736-746. [PMID: 36969891 PMCID: PMC10037524 DOI: 10.14218/jcth.2022.00347] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Revised: 11/02/2022] [Accepted: 11/20/2022] [Indexed: 03/29/2023] Open
Abstract
In 2015, the Chinese Society of Hepatology and the Chinese Society of Gastroenterology published a consensus on primary biliary cholangitis (PBC). In the past years, numerous clinical studies have been published in the field of PBC. To guide the clinical diagnosis and management of PBC patients, the Chinese Society of Hepatology invited a panel of experts to assess the new clinical evidence and formulate the current guidelines.
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Affiliation(s)
- Hong You
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University & National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Weijia Duan
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University & National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Shuxiang Li
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University & National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Tingting Lv
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University & National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Sha Chen
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University & National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Lungen Lu
- Department of Gastroenterology, First People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiong Ma
- Department of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Ying Han
- Department of Gastroenterology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China
| | - Yuemin Nan
- Department of Traditional and Western Medical Hepatology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Xiaoyuan Xu
- Department of Infectious Diseases and Center for Liver Diseases, Peking University First Hospital, Beijing, China
- Correspondence to: Jidong Jia, Liver Research Center, Beijing Friendship Hospital, Capital Medical University, 95 Yong-an Road, Beijing 100050, China. ORCID: https://orcid.org/0000-0002-4673-8890. Tel: +86-10-63139816, Fax: +86-10-63139246, E-mail: ; Xiaoyuan Xu, Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, China. ORCID: https://orcid.org/0000-0002-1759-4330. Tel/Fax: +86-10-83575787, E-mail:
| | - Zhongping Duan
- Artificial Liver Center, Beijing You-An Hospital, Capital Medical University, Beijing, China
| | - Lai Wei
- Hepatobiliary Pancreatic Center, Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University & National Clinical Research Center for Digestive Diseases, Beijing, China
- Correspondence to: Jidong Jia, Liver Research Center, Beijing Friendship Hospital, Capital Medical University, 95 Yong-an Road, Beijing 100050, China. ORCID: https://orcid.org/0000-0002-4673-8890. Tel: +86-10-63139816, Fax: +86-10-63139246, E-mail: ; Xiaoyuan Xu, Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, China. ORCID: https://orcid.org/0000-0002-1759-4330. Tel/Fax: +86-10-83575787, E-mail:
| | - Hui Zhuang
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
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10
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Lleo A. Geoepidemiology and the key role of sex chromosomes on autoimmune diseases. PRINCIPLES OF GENDER-SPECIFIC MEDICINE 2023:331-346. [DOI: 10.1016/b978-0-323-88534-8.00051-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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11
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Colapietro F, Bertazzoni A, Lleo A. Contemporary Epidemiology of Primary Biliary Cholangitis. Clin Liver Dis 2022; 26:555-570. [PMID: 36270716 DOI: 10.1016/j.cld.2022.06.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Primary biliary cholangitis (PBC) is a cholestatic liver disease with potential evolution to liver cirrhosis when left untreated. Despite being rare, PBC has a substantial impact on the quality of life and survival of affected patients. Women are the most diagnosed worldwide; however, male subjects seem to have more aggressive disease and worse prognosis. Changing epidemiologic trends are emerging in PBC, with increasing global prevalence and slight smoothing of sex differences. In this review we present available data on incidence rates and prevalence of PBC worldwide, highlighting geographic differences and factors impacting clinical outcomes.
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Affiliation(s)
- Francesca Colapietro
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Via A. Manzoni 56, Rozzano 20089, Italy; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Arianna Bertazzoni
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Via A. Manzoni 56, Rozzano 20089, Italy; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Ana Lleo
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Via A. Manzoni 56, Rozzano 20089, Italy; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.
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12
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Montano-Loza AJ, Allegretti JR, Cheung A, Ebadi M, Jones D, Kerkar N, Levy C, Rizvi S, Vierling JM, Alvarez F, Bai W, Gilmour S, Gulamhusein A, Guttman O, Hansen BE, MacParland S, Mason A, Onofrio F, Santamaria P, Stueck A, Swain M, Vincent C, Ricciuto A, Hirschfield G. Single Topic Conference on Autoimmune Liver Disease from the Canadian Association for the Study of the Liver. CANADIAN LIVER JOURNAL 2021; 4:401-425. [PMID: 35989897 PMCID: PMC9235119 DOI: 10.3138/canlivj-2021-0006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Accepted: 02/09/2021] [Indexed: 11/20/2022]
Abstract
Autoimmune liver disease (AILD) spans a spectrum of chronic disorders affecting the liver parenchyma and biliary system. Three main categories of AILD are autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC). This review condenses the presentation and discussions of the Single Topic Conference (STC) on AILD that was held in Ottawa, Ontario, in November 2019. We cover generalities regarding disease presentation and clinical diagnosis; mechanistic themes; treatment paradigms; clinical trials, including approaches and challenges to new therapies; and looking beyond traditional disease boundaries. Although these diseases are considered autoimmune, the etiology and role of environmental triggers are poorly understood. AILDs are progressive and chronic conditions that affect survival and quality of life. Advances have been made in PBC treatment because second-line treatments are now available (obeticholic acid, bezafibrate); however, a significant proportion still present suboptimal response. AIH treatment has remained unchanged for several decades, and data suggest that fewer than 50% of patients achieve a complete response and as many as 80% develop treatment-related side effects. B-cell depletion therapy to treat AIH is in an early stage of development and has shown promising results. An effective treatment for PSC is urgently needed. Liver transplant remains the best option for patients who develop decompensated cirrhosis or hepatocellular carcinoma within specific criteria, but recurrent AILD might occur. Continued efforts are warranted to develop networks for AILD aimed at assessing geo-epidemiological, clinical, and biochemical differences to capture the new treatment era in Canada.
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Affiliation(s)
- Aldo J Montano-Loza
- Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Alberta, Canada
| | - Jessica R Allegretti
- Division of Gastroenterology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Angela Cheung
- Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA
| | - Maryam Ebadi
- Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Alberta, Canada
| | - David Jones
- Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom
| | - Nanda Kerkar
- Division of Gastroenterology, Hepatology and Nutrition, Golisano Children’s Hospital at Strong, University of Rochester Medical Center, New York, USA
| | - Cynthia Levy
- Schiff Center for Liver Diseases, University of Miami, Miami, Florida, USA
| | - Sumera Rizvi
- Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA
| | | | - Fernando Alvarez
- Department of Pediatrics, Hôpital Sainte-Justine, University of Montreal, Montreal, Quebec, Canada
| | - Wayne Bai
- Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Alberta, Canada
| | - Susan Gilmour
- Stollery Children’s Hospital, University of Alberta, Edmonton, Alberta, Canada
| | - Aliya Gulamhusein
- Ajmera Family Transplant Centre, Toronto General Research Institute, Departments of Laboratory Medicine and Pathobiology and Immunology, University of Toronto, Toronto, Ontario, Canada
| | - Orlee Guttman
- Division of Gastroenterology, Hepatology and Nutrition, British Columbia Children’s Hospital, Vancouver, British Columbia, Canada
| | - Bettina E Hansen
- Ajmera Family Transplant Centre, Toronto General Research Institute, Departments of Laboratory Medicine and Pathobiology and Immunology, University of Toronto, Toronto, Ontario, Canada
| | - Sonya MacParland
- Ajmera Family Transplant Centre, Toronto General Research Institute, Departments of Laboratory Medicine and Pathobiology and Immunology, University of Toronto, Toronto, Ontario, Canada
| | - Andrew Mason
- Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Alberta, Canada
| | - Fernanda Onofrio
- Ajmera Family Transplant Centre, Toronto General Research Institute, Departments of Laboratory Medicine and Pathobiology and Immunology, University of Toronto, Toronto, Ontario, Canada
| | - Pere Santamaria
- Department of Microbiology, Immunology & Infectious Diseases, University of Calgary, Calgary, Alberta, Canada
| | - Ashley Stueck
- Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Mark Swain
- Calgary Liver Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada
| | - Catherine Vincent
- Department of Medicine, University of Montreal, Montreal, Quebec, Canada
| | - Amanda Ricciuto
- Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, Toronto, Ontario, Canada
| | - Gideon Hirschfield
- Toronto Centre for Liver Disease, University Health Network & Institute of Health Policy Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
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13
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Paillet J, Plantureux C, Lévesque S, Le Naour J, Stoll G, Sauvat A, Caudana P, Tosello Boari J, Bloy N, Lachkar S, Martins I, Opolon P, Checcoli A, Delaune A, Robil N, de la Grange P, Hamroune J, Letourneur F, Autret G, Leung PS, Gershwin ME, Zhu JS, Kurth MJ, Lekbaby B, Augustin J, Kim Y, Gujar S, Coulouarn C, Fouassier L, Zitvogel L, Piaggio E, Housset C, Soussan P, Maiuri MC, Kroemer G, Pol JG. Autoimmunity affecting the biliary tract fuels the immunosurveillance of cholangiocarcinoma. J Exp Med 2021; 218:e20200853. [PMID: 34495298 PMCID: PMC8429038 DOI: 10.1084/jem.20200853] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 06/17/2021] [Accepted: 08/09/2021] [Indexed: 12/12/2022] Open
Abstract
Cholangiocarcinoma (CCA) results from the malignant transformation of cholangiocytes. Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are chronic diseases in which cholangiocytes are primarily damaged. Although PSC is an inflammatory condition predisposing to CCA, CCA is almost never found in the autoimmune context of PBC. Here, we hypothesized that PBC might favor CCA immunosurveillance. In preclinical murine models of cholangitis challenged with syngeneic CCA, PBC (but not PSC) reduced the frequency of CCA development and delayed tumor growth kinetics. This PBC-related effect appeared specific to CCA as it was not observed against other cancers, including hepatocellular carcinoma. The protective effect of PBC was relying on type 1 and type 2 T cell responses and, to a lesser extent, on B cells. Single-cell TCR/RNA sequencing revealed the existence of TCR clonotypes shared between the liver and CCA tumor of a PBC host. Altogether, these results evidence a mechanistic overlapping between autoimmunity and cancer immunosurveillance in the biliary tract.
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Affiliation(s)
- Juliette Paillet
- Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Institut National de la Santé et de la Recherche Médicale U1138, Université de Paris, Sorbonne Université, Paris, France
- Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France
- Université Paris-Saclay, Faculté de Médecine, Kremlin-Bicêtre, France
| | - Céleste Plantureux
- Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Institut National de la Santé et de la Recherche Médicale U1138, Université de Paris, Sorbonne Université, Paris, France
- Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France
- Université Paris-Saclay, Faculté de Médecine, Kremlin-Bicêtre, France
| | - Sarah Lévesque
- Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Institut National de la Santé et de la Recherche Médicale U1138, Université de Paris, Sorbonne Université, Paris, France
- Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France
- Université Paris-Saclay, Faculté de Médecine, Kremlin-Bicêtre, France
| | - Julie Le Naour
- Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Institut National de la Santé et de la Recherche Médicale U1138, Université de Paris, Sorbonne Université, Paris, France
- Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France
- Université Paris-Saclay, Faculté de Médecine, Kremlin-Bicêtre, France
| | - Gautier Stoll
- Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Institut National de la Santé et de la Recherche Médicale U1138, Université de Paris, Sorbonne Université, Paris, France
- Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France
| | - Allan Sauvat
- Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Institut National de la Santé et de la Recherche Médicale U1138, Université de Paris, Sorbonne Université, Paris, France
- Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France
| | - Pamela Caudana
- Institut Curie, Paris Sciences et Lettres Research University, Institut National de la Santé et de la Recherche Médicale U932, Paris, France
| | - Jimena Tosello Boari
- Institut Curie, Paris Sciences et Lettres Research University, Institut National de la Santé et de la Recherche Médicale U932, Paris, France
| | - Norma Bloy
- Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Institut National de la Santé et de la Recherche Médicale U1138, Université de Paris, Sorbonne Université, Paris, France
- Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France
- Université Paris-Saclay, Faculté de Médecine, Kremlin-Bicêtre, France
| | - Sylvie Lachkar
- Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Institut National de la Santé et de la Recherche Médicale U1138, Université de Paris, Sorbonne Université, Paris, France
- Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France
| | - Isabelle Martins
- Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Institut National de la Santé et de la Recherche Médicale U1138, Université de Paris, Sorbonne Université, Paris, France
- Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France
| | | | - Andrea Checcoli
- Institut Curie, Paris Sciences et Lettres Research University, Paris, France
- Institut National de la Santé et de la Recherche Médicale U900, Paris, France
| | | | | | | | - Juliette Hamroune
- Institut National de la Santé et de la Recherche Médicale U1016, Institut Cochin, Paris, France
| | - Franck Letourneur
- Institut National de la Santé et de la Recherche Médicale U1016, Institut Cochin, Paris, France
| | - Gwennhael Autret
- Université de Paris, Paris Cardiovascular Research Centre, Institut National de la Santé et de la Recherche Médicale U970, Paris, France
| | - Patrick S.C. Leung
- Division of Rheumatology/Allergy and Clinical Immunology, University of California, Davis School of Medicine, Davis, CA
| | - M. Eric Gershwin
- Division of Rheumatology/Allergy and Clinical Immunology, University of California, Davis School of Medicine, Davis, CA
| | - Jie S. Zhu
- Department of Chemistry, University of California, Davis, Davis, CA
| | - Mark J. Kurth
- Department of Chemistry, University of California, Davis, Davis, CA
| | - Bouchra Lekbaby
- Institut National de la Santé et de la Recherche Médicale U938, Centre de Recherche Saint-Antoine, Sorbonne Université, Paris, France
| | - Jérémy Augustin
- Institut National de la Santé et de la Recherche Médicale U938, Centre de Recherche Saint-Antoine, Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Hôpital Henri-Mondor, Département de Pathologie, Paris, France
| | - Youra Kim
- Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Shashi Gujar
- Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada
- Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada
- Beatrice Hunter Cancer Research Institute, Halifax, Nova Scotia, Canada
- Department of Biology, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Cédric Coulouarn
- Institut National de la Santé et de la Recherche Médicale, Université de Rennes 1, Chemistry, Oncogenesis Stress Signaling, UMR_S 1242, Centre de Lutte contre le Cancer Eugène Marquis, Rennes, France
| | - Laura Fouassier
- Institut National de la Santé et de la Recherche Médicale U938, Centre de Recherche Saint-Antoine, Sorbonne Université, Paris, France
| | - Laurence Zitvogel
- Institut National de la Santé et de la Recherche Médicale U1015, Université Paris-Saclay, Gustave Roussy Cancer Campus, Villejuif, France
| | - Eliane Piaggio
- Centre d'Investigation Clinique Biothérapie 1428, Institut Curie, Paris, France
| | - Chantal Housset
- Institut National de la Santé et de la Recherche Médicale U938, Centre de Recherche Saint-Antoine, Sorbonne Université, Paris, France
- Assistance Publique-Hôpitaux de Paris, Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, Department of Hepatology, Saint-Antoine Hospital, Paris, France
| | - Patrick Soussan
- Institut National de la Santé et de la Recherche Médicale U938, Centre de Recherche Saint-Antoine, Sorbonne Université, Paris, France
| | - Maria Chiara Maiuri
- Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Institut National de la Santé et de la Recherche Médicale U1138, Université de Paris, Sorbonne Université, Paris, France
- Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France
| | - Guido Kroemer
- Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Institut National de la Santé et de la Recherche Médicale U1138, Université de Paris, Sorbonne Université, Paris, France
- Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France
- Institut Universitaire de France, Paris, France
- Pôle de Biologie, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France
- Suzhou Institute for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, China
- Karolinska Institute, Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden
| | - Jonathan G. Pol
- Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Institut National de la Santé et de la Recherche Médicale U1138, Université de Paris, Sorbonne Université, Paris, France
- Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France
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14
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Liu ZY, Xu L, Liu B. Detection of anti-kelch-like 12 and anti-hexokinase 1 antibodies in primary biliary cholangitis patients in China. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2021; 113:585-590. [PMID: 33307711 DOI: 10.17235/reed.2020.7483/2020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
OBJECTIVES primary biliary cholangitis (PBC) is a chronic cholestatic disease, characterized by positive anti-mitochondrial autoantibodies (AMA) in 90-95 % patients. Anti-kelch-like 12 (anti-KLHL12) and anti-hexokinase1 (anti-HK1) antibodies have been identified as the two new serum markers in recent years, which are used in the diagnosis of AMA-negative PBC patients. The objective of the study was to examine the performance of these two new biomarkers in China. METHODS a total of 192 patients were enrolled and screened for anti-KLHL12 and anti-HK1 antibodies and AMA by ELISA. Receiver operating characteristic (ROC curve) analysis was applied to examine the diagnostic importance of AMA, anti-KLHL12 and anti-HK1 antibodies. Furthermore, correlation analysis between some important biochemical indexes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP], bilirubin, gamma-glutamil transferasa [γ-GT]), staging of pathological changes of the liver and the expression of novel antibodies in PBC patients were also examined. RESULTS the positivity of the anti-HK1 antibody in AMA-positive PBC patients and AMA-negative patients was 44.7 % and 33.3 %, respectively. The specificity, proportion of positive patients (PPV) and proportion of negative patients (NPV) were 93 %, 89 % and 53 %, respectively. In contrast, the positivity to the anti-KLHL12 antibody in AMA-positive and negative PBC patients was 41.2 % and 22.2 %, respectively. Specificity, PPV and NPV were 98 %, 95 % and 52 %, respectively. The area under the curve (AUC) with anti-HK1 and anti-KLHL12 antibodies were 0.720 and 0.703. With the combination with anti-HK1 and anti-KLHL12 antibodies, the AUC of AMA increased from 0.889 to 0.891, increasing the sensitivity from 0.764 to 0.836. Anti-KLHL12 and anti-HK1-positive patients had higher serum levels of ALP, γ-GT and bilirubin, with statistically significant differences (p < 0.01) compared with anti-KLHL12 or anti-HK1-negative patients. Notably, correlation analysis showed a significant positive correlation between antibody expression and ALP, γ-GT and bilirubin serum levels (r = 0.735, 0.491, 0.466; p < 0.01). CONCLUSIONS anti-HK1 and anti-KLHL12 antibodies have been identified as two significant biomarkers in PBC patients. Furthermore, the presence of these antibodies is likely to correlate with the severity of PBC.
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Affiliation(s)
- Zhao Yang Liu
- Rheumatology, Affiliated Hospital of Qingdao University
| | - Lishan Xu
- Rheumatology, Affiliated Hospital of Qingdao University
| | - Bin Liu
- Rheumatology, Affiliated hospital of Qingdao University, China
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15
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Cortez-Pinto H, Liberal R, Lopes S, Machado MV, Carvalho J, Dias T, Santos A, Agostinho C, Figueiredo P, Loureiro R, Martins A, Alexandrino G, Cotrim I, Leal C, Presa J, Mesquita M, Nunes J, Gouveia C, Vale AHE, Alves AL, Coelho M, Maia L, Pedroto I, Banhudo A, Pinto JS, Gomes MV, Oliveira J, Andreozzi V, Calinas F. Predictors for incomplete response to ursodeoxycholic acid in primary biliary cholangitis. Data from a national registry of liver disease. United European Gastroenterol J 2021; 9:699-706. [PMID: 34102008 PMCID: PMC8280809 DOI: 10.1002/ueg2.12095] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Accepted: 03/28/2021] [Indexed: 12/11/2022] Open
Abstract
Background The current standard of treatment in primary biliary cholangitis (PBC) is ursodeoxycholic acid (UDCA), although a considerable proportion of patients show incomplete response resulting in disease progression. Objective This study aimed to assess the prevalence of incomplete response to UDCA and determine associated patients' characteristics. Methods Patients with PBC as main diagnosis were included from a national multicentric patient registry—Liver.pt. Main endpoints included incomplete response to UDCA treatment according to Barcelona, Paris I and Paris II criteria, Globe and UK PBC scores and the association between baseline characteristics and incomplete response according to Paris II criteria. Results A total of 434 PBC patients were identified, with a mean age of 55 years and 89.2% females. Nearly half of patients were asymptomatic at diagnosis and 93.2% had positive anti‐mitochondrial antibodies. Almost all patients (95.6%) had been prescribed at least one drug for PBC treatment. At the last follow‐up visit, 93.3% were under treatment of which 99.8% received UDCA. Incomplete response to UDCA was observed in 30.7%, 35.3%, 53.7% and 36.4% of patients according to Barcelona, Paris I, Paris II criteria and Globe score, respectively. After adjusting for age and sex, and accordingly to Paris II criteria, the risk for incomplete biochemical response was 25% higher for patients with cirrhosis at diagnosis (odds ratio [OR] = 1.25; 95% confidence interval [95%CI]: 1.02–1.54; p = 0.033) and 35% (95%CI:1.06–1.72; p = 0.016) and 5% (OR = 1.05; 95%CI:1.01–1.10; p = 0.013) for those with elevated gamma‐glutamyl transferase (GGT) and alkaline phosphatase (ALP). Conclusion A considerable proportion of patients showed incomplete biochemical response to UDCA treatment according to Paris II criteria. Cirrhosis, elevated GGT and ALP at diagnosis were identified as associated risk factors for incomplete response. Early identification of patients at risk of incomplete response could improve treatment care and guide clinical decision to a more careful patient monitorization.
Summarise the established knowledge on this subject
Primary biliary cholangitis is a liver disease that can progress to end‐stage liver disease, with premature death or need for liver transplantation. Treatment with ursodeoxycholic acid (UDCA) significantly increases liver transplant‐free survival. However, incomplete response to UDCA reduces this beneficial effect.
What are the significant and/or new findings of this study?
By evaluating prevalence and risk factors for UDCA incomplete response through a large multicentric national registry it was found that 53.7% of patients were incomplete responders, according to Paris II criteria, with cirrhosis, elevated gamma‐glutamyl transferase and alkaline phosphatase at diagnosis as the main risk factors. These findings suggest that patients diagnosed at an advanced stage should be closely monitored and might benefit from novel therapies to improve outcomes if incomplete response is present.
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Affiliation(s)
- Helena Cortez-Pinto
- Clínica Universitária de Gastrenterologia, Departamento de Gastrenterologia, Faculdade de Medicina, Universidade de Lisboa, Centro Hospitalar Lisboa Norte, Lisboa, Portugal
| | - Rodrigo Liberal
- Gastroenterology Department, Centro Hospitalar e Universitário São João, Porto, Portugal.,Gastroenterology Department, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Susana Lopes
- Gastroenterology Department, Centro Hospitalar e Universitário São João, Porto, Portugal.,Gastroenterology Department, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Mariana V Machado
- Clínica Universitária de Gastrenterologia, Departamento de Gastrenterologia, Faculdade de Medicina, Universidade de Lisboa, Centro Hospitalar Lisboa Norte, Lisboa, Portugal.,Gastroenterology Department, Hospital Vila Franca de Xira, Vila Franca de Xira, Portugal
| | - Joana Carvalho
- Clínica Universitária de Gastrenterologia, Departamento de Gastrenterologia, Faculdade de Medicina, Universidade de Lisboa, Centro Hospitalar Lisboa Norte, Lisboa, Portugal
| | - Teresa Dias
- Department of Internal Medicine, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| | - Arsénio Santos
- Department of Internal Medicine, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| | - Cláudia Agostinho
- Gastroenterology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| | - Pedro Figueiredo
- Gastroenterology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| | - Rafaela Loureiro
- Gastroenterology Department, Central Lisbon Hospital Centre, Lisboa, Portugal
| | - Alexandra Martins
- Gastroenterology Department, Hospital Prof. Doutor Fernando da Fonseca, Lisboa, Portugal
| | - Gonçalo Alexandrino
- Gastroenterology Department, Hospital Prof. Doutor Fernando da Fonseca, Lisboa, Portugal
| | - Isabel Cotrim
- Gastroenterology Department, Centro Hospitalar de Leiria, Leiria, Portugal
| | - Carina Leal
- Gastroenterology Department, Centro Hospitalar de Leiria, Leiria, Portugal
| | - José Presa
- Internal Medicine Department, Liver Unit, Centro Hospitalar de Trás-os-Montes e Alto Douro, Vila Real, Portugal
| | - Mónica Mesquita
- Internal Medicine Department, Liver Unit, Centro Hospitalar de Trás-os-Montes e Alto Douro, Vila Real, Portugal
| | - Joana Nunes
- Gastroenterology Department, Hospital Beatriz Ângelo, Lisboa, Portugal
| | - Catarina Gouveia
- Gastroenterology Department, Hospital Beatriz Ângelo, Lisboa, Portugal
| | | | - Ana Luísa Alves
- Gastroenterology Department, Centro Hospitalar de Setúbal, Setúbal, Portugal
| | - Mariana Coelho
- Gastroenterology Department, Centro Hospitalar de Setúbal, Setúbal, Portugal
| | - Luís Maia
- Gastroenterology Department, Centro Hospitalar Universitário do Porto, Porto, Portugal
| | - Isabel Pedroto
- Gastroenterology Department, Centro Hospitalar Universitário do Porto, Porto, Portugal
| | - António Banhudo
- Gastroenterology Department, Unidade Local de Saúde Castelo Branco, Castelo Branco, Portugal
| | - João Sebastião Pinto
- Gastroenterology Department, Unidade Local de Saúde Castelo Branco, Castelo Branco, Portugal
| | | | | | | | - Filipe Calinas
- Gastroenterology Department, Central Lisbon Hospital Centre, Lisboa, Portugal
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16
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Lv T, Chen S, Li M, Zhang D, Kong Y, Jia J. Regional variation and temporal trend of primary biliary cholangitis epidemiology: A systematic review and meta-analysis. J Gastroenterol Hepatol 2021; 36:1423-1434. [PMID: 33141955 DOI: 10.1111/jgh.15329] [Citation(s) in RCA: 62] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Revised: 10/12/2020] [Accepted: 10/24/2020] [Indexed: 01/27/2023]
Abstract
BACKGROUND AND AIM We aimed to estimate the worldwide incidence and prevalence, with focus on the geographical differences and temporal trends. METHODS Studies on epidemiology of primary biliary cholangitis (PBC) in PubMed, Embase, and Cochrane Library were systematically retrieved from inception to October 2, 2020. Random-effect model was applied to estimate the pooled PBC incidence and prevalence rates. Subgroup analysis, meta-regression, and sensitivity analysis were conducted to find out the cause for heterogeneity. RESULTS Out of 3974 records identified through database searching, 47 population-based studies were finally included. The pooled global incidence and prevalence of PBC were 1.76 and 14.60 per 100 000 persons, respectively. Both the PBC incidence and prevalence were lower in the Asia-Pacific region (0.84, 9.82 per 100 000 persons) than that in North America (2.75, 21.81 per 100 000 persons) and Europe (1.86, 14.59 per 100 000 persons) (P < 0.05). The incidence and prevalence showed an increasing tendency in all three regions, with the fastest growth of prevalence in North America (P < 0.05). We found a similar incidence and a lower prevalence of PBC in Northern Europe than that in Southern Europe. A higher incidence and prevalence were observed in female individuals and in the elderly (60-79). CONCLUSION The PBC incidence and prevalence varied widely across regions, with North America being the highest, followed by Europe, and the lowest in the Asia-Pacific region. Both the incidence and prevalence showed an increasing tendency worldwide, especially in North America.
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Affiliation(s)
- Tingting Lv
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University; Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis; National Clinical Research Center for Digestive Disease, Beijing, China
| | - Sha Chen
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University; Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis; National Clinical Research Center for Digestive Disease, Beijing, China
| | - Min Li
- Clinical Epidemiology and EBM Unit, National Clinical Research Center for Digestive Disease, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Dong Zhang
- Experimental and Translational Research Center, Beijing Friendship Hospital, Capital Medical University; Beijing Clinical Research Institute; Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation, Beijing, China
| | - Yuanyuan Kong
- Clinical Epidemiology and EBM Unit, National Clinical Research Center for Digestive Disease, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University; Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis; National Clinical Research Center for Digestive Disease, Beijing, China
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Chen CJ, Cheng JS, Wang HE, Huang CW, Hu JH, Chen WT, Chang MY, Ku HP, Lin CY, Chien RN, Chang ML. Identification of the Representative Primary Biliary Cholangitis Cohort in Taiwan: A Comparison of Four Nationwide Cohorts. J Clin Med 2021; 10:jcm10112226. [PMID: 34063859 PMCID: PMC8196594 DOI: 10.3390/jcm10112226] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2021] [Revised: 05/12/2021] [Accepted: 05/19/2021] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND/PURPOSE The rates and outcomes of primary biliary cholangitis (PBC) in Taiwan remain unclear. METHODS A nationwide population-based cohort study (Taiwan National Health Insurance Research Database, 2002-2015) was conducted. Data from four PBC cohorts with various definitions were compared (cohort 1 (C1): ICD-9-CM (571.6); C2: alkaline phosphatase (Alk-P) and antimitochondrial antibody (AMA) measurements; C3: Alk-p and AMA measurements and ursodeoxycholic acid (UDCA) treatment; C4: ICD-9-CM (571.6), Alk-p and AMA measurements and UDCA treatment). RESULTS The average prevalence rate ranged from 9.419/105 (C4) to 307.658/105 (C2), and the female-to-male ratio ranged from 1.192 (C1) to 3.66 (C4). Prevalence rates increased over time in all cohorts. The average incidence rates ranged from 1.456/105 (C4) to 66.386/105 (C2). Incidence rates decreased over time in C1 (-9.09%, p < 0.0001) and C4 (-6.68%, p < 0.0001) and remained steady in the others. C4 had the lowest prevalence and incidence rates and highest female-to-male ratio. Cirrhosis rates ranged from 7.21% (C2) to 39.34% (C4), hepatoma rates ranged from 2.77%(C2) to 6.66%(C1), liver transplantation (LT) rates ranged from 1.07% (C2) to 6.77% (C4), and mortality rates ranged from 18.24% (C2) to 47.36% (C1). C4 had the highest LT (6.77%), osteoporosis (13.87%) and dyslipidemia rates (17.21%). CONCLUSIONS Based on the reported ranges of reasonable rates, female predominance and characteristic outcomes, C4 was the most representative Taiwanese PBC cohort, with average prevalence and incidence rates of 9.419/105 and 1.456/105, respectively, and a female-to-male ratio of 3.66. In a 14-year period, cirrhosis, hepatoma, LT, and mortality were noted in 39.34%, 5.52%, 6.77%, and 34.22% of C4 patients, respectively.
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Affiliation(s)
- Cheng-Jen Chen
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan; (C.-J.C.); (H.-E.W.); (C.-W.H.); (W.-T.C.); (H.-P.K.); (C.-Y.L.); (R.-N.C.)
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan
| | - Jur-Shan Cheng
- Clinical Informatics and Medical Statistics Research Center, College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan;
- Department of Emergency Medicine, Chang Gung Memorial Hospital, Keelung 204, Taiwan
| | - Haw-En Wang
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan; (C.-J.C.); (H.-E.W.); (C.-W.H.); (W.-T.C.); (H.-P.K.); (C.-Y.L.); (R.-N.C.)
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan
| | - Chun-Wen Huang
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan; (C.-J.C.); (H.-E.W.); (C.-W.H.); (W.-T.C.); (H.-P.K.); (C.-Y.L.); (R.-N.C.)
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan
| | - Jing-Hong Hu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Yunlin 638, Taiwan;
| | - Wei-Ting Chen
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan; (C.-J.C.); (H.-E.W.); (C.-W.H.); (W.-T.C.); (H.-P.K.); (C.-Y.L.); (R.-N.C.)
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan
| | - Ming-Yu Chang
- Division of Pediatric Neurologic Medicine, Chang Gung Children’s Hospital, Taoyuan 333423, Taiwan;
- Division of Pediatrics, Chang Gung Memorial Hospital, Keelung 20401, Taiwan
| | - Hsin-Ping Ku
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan; (C.-J.C.); (H.-E.W.); (C.-W.H.); (W.-T.C.); (H.-P.K.); (C.-Y.L.); (R.-N.C.)
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan
| | - Cheng-Yu Lin
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan; (C.-J.C.); (H.-E.W.); (C.-W.H.); (W.-T.C.); (H.-P.K.); (C.-Y.L.); (R.-N.C.)
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan
| | - Rong-Nan Chien
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan; (C.-J.C.); (H.-E.W.); (C.-W.H.); (W.-T.C.); (H.-P.K.); (C.-Y.L.); (R.-N.C.)
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan
| | - Ming-Ling Chang
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan; (C.-J.C.); (H.-E.W.); (C.-W.H.); (W.-T.C.); (H.-P.K.); (C.-Y.L.); (R.-N.C.)
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan
- Liver Research Unit, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, No. 5, Fu Hsing Street, Kuei Shan, Taoyuan 333423, Taiwan
- Correspondence: ; Tel.: +886-3-328-1200-8107; Fax: +886-3-327-2236
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French J, Simpson-Yap S, van der Mei I, Ng J, Angus P, Gow PJ. Identification of a Latitude Gradient in the Prevalence of Primary Biliary Cholangitis. Clin Transl Gastroenterol 2021; 12:e00357. [PMID: 34003806 PMCID: PMC8345914 DOI: 10.14309/ctg.0000000000000357] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Accepted: 04/05/2021] [Indexed: 12/03/2022] Open
Abstract
INTRODUCTION The prevalence of primary biliary cholangitis (PBC) reported in different countries varies significantly and seems to have a latitudinal gradient with the highest prevalence reported in higher latitudes, as has been observed with other autoimmune diseases. This study aimed to determine whether there is a latitudinal gradient of PBC prevalence in Australia using 2 methods of case ascertainment. METHODS We investigated the latitudinal variation of PBC prevalence across the states and territories of Australia (latitudinal range 18.0°-42.7°S) using pathology-based (private pathology antimitochondrial antibody results and PBC-specific prescription databases (prescriptions for ursodeoxycholic acid, the only publicly subsidized treatment for this disease). RESULTS PBC prevalence was significantly positively associated with latitude, and the postcodes in the highest quintile of latitude (encompassing the south coastal areas of the Australian mainland and Tasmania; latitude range -37.75° to -42.72°) had a prevalence estimate that was 1.78 times higher using the pathology-based prevalence estimation than those in the lowest quintile (encompassing tropical and southern Queensland; latitude range -18.02° to -27.59°). Comparing prevalence estimates between states/territories, the result was 2.53 and 2.21 times higher in Tasmania compared with Queensland when using the pathology-based and prescription-based methods, respectively. DISCUSSION Using 2 different case-ascertainment methods, we have demonstrated that prevalence estimates of PBC vary significantly with latitude in Australia. Further studies are needed to determine whether factors such as variations in ultraviolet radiation exposure and/or vitamin D levels are responsible for this observation and to investigate the latitudinal prevalence of PBC in other populations.
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Affiliation(s)
- Janine French
- Department of Gastroenterology, Austin Hospital, Heidelberg, Australia
| | - Steve Simpson-Yap
- Department of Biostatistics and Epidemiology, Melbourne School of Population and Global Health, University of Melbourne, Carlton, Australia
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia
| | - Ingrid van der Mei
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia
| | - Justin Ng
- Department of Gastroenterology, Austin Hospital, Heidelberg, Australia
| | - Peter Angus
- Department of Gastroenterology, Austin Hospital, Heidelberg, Australia
| | - Paul J. Gow
- Department of Gastroenterology, Austin Hospital, Heidelberg, Australia
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Adejumo AC, Akhtar DH, Dennis BB, Cholankeril G, Alayo Q, Ogundipe OA, Kim D, Ahmed A. Gender and Racial Differences in Hospitalizations for Primary Biliary Cholangitis in the USA. Dig Dis Sci 2021; 66:1461-1476. [PMID: 32535779 DOI: 10.1007/s10620-020-06402-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2019] [Accepted: 06/05/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND/AIM The prevalence, characteristics, burden and trends of primary biliary cholangitis (PBC) hospitalizations in the USA remain unclear. METHOD We identified primary PBC hospitalizations from the National Inpatient Sample (NIS) 2007 through 2014 using ICD-9-CM codes. We calculated the rates and trends of hospitalization for PBC per 100,000 US population among each gender (males and females) and racial categories (Whites, Blacks, Hispanics and other racial minorities), and measured the predictors of hospitalization, and of mortality, charges and length of stay (LOS) among PBC hospitalizations. RESULT There were 8460 (weighted: 41,191) PBC hospitalizations between 2007 and 2014. The mean national PBC hospitalization rate was 2.2 cases per 100,000 population (2.2/100,000), increasing from 1.7/100,000 (2007) to 2.5/100,000 (2014). From 2007 to 2014, the in-hospital mortality and LOS were unchanged while the charges increased from $65,993 to $73,093 ($225 million to $447 million overall expenses). Compared to Whites, the PBC hospitalization rate was 12% higher among Hispanics (RR: 1.12 [1.09-1.16]), 53% lower in Blacks (RR: 0.47 [0.45-0.49]) and 5% lower among other racial minorities (0.95 [0.91-0.99]). The rate was higher among females (RR:4.02 [3.93-4.12]) compared to males. On multivariate analysis, Blacks and other racial minorities, respectively, had higher odds of mortality (AOR: 1.47 [1.03-2.10] and 1.33 [0.96-1.84]), while other racial minorities had longer LOS (7.0 vs. 5.6 days) and higher hospital charges ($48,984 vs. $41,495) when compared to Whites. CONCLUSION The hospitalization rate and burden of PBC in the USA have increased disproportionately among females and Hispanics with higher mortality in Blacks.
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Affiliation(s)
- Adeyinka Charles Adejumo
- Department of Medicine, North Shore Medical Center, 81 Highland Ave., Salem, MA, 01970, USA. .,Department of Medicine, Tufts University School of Medicine, Boston, MA, USA.
| | - Daud H Akhtar
- Department of Medicine, University of British Columbia Faculty of Medicine, Vancouver General Hospital, Vancouver, Canada
| | - Brittany B Dennis
- Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Canada
| | | | - Quazim Alayo
- Applied Clinical Research Program, St. Cloud State University, Plymouth, MN, USA
| | - Olumuyiwa A Ogundipe
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Donghee Kim
- Department of Medicine, St. Luke's Hospital, St. Louis, MO, USA
| | - Aijaz Ahmed
- Department of Medicine, St. Luke's Hospital, St. Louis, MO, USA
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20
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Trends in Incidence of Autoimmune Liver Diseases and Increasing Incidence of Autoimmune Hepatitis. Clin Gastroenterol Hepatol 2021; 19:573-579.e1. [PMID: 32526342 DOI: 10.1016/j.cgh.2020.05.061] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2019] [Revised: 05/19/2020] [Accepted: 05/29/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) are autoimmune liver diseases of unknown etiology. We studied trends in incidences of AIH, PBC, and PSC in a population-based prospective study Canterbury, New Zealand. METHODS We collected data on patients with AIH (n = 99), PBC (n = 26), or PSC (n = 47) from public hospitals and private practices in Canterbury from 2008 through 2016. Diagnoses were made based on international standardized criteria. We calculated incidence rates for the time periods of 2008-2010, 2011-2013, and 2014-2016 and compared them using 2-tailed mid-P exact tests. RESULTS Overall incidence rates were 1.93 per 100,000 for AIH (95% CI, 1.58-2.34), 0.51 per 100,000 for PBC (95% CI, 0.33-0.73), and 0.92 per 100,000 for PSC (95% CI, 0.68-1.21). The incidence of AIH was significantly higher during the period of 2014-2016 (2.39 per 100,000; 95% CI, 1.76-3.23) than during the period of 2008-2010 (1.37 per 100,000; 95% CI, 0.91- 2.06) (P < .05). Incidences of PBC and PSC did not change significantly. In 2016, prevalence values were 27.4 per 100,000 for AIH (95% CI, 23.58-32.0), 9.33 per 100,000 for PBC (95% CI, 7.13-12.05), and 13.17 per 100,000 for PSC (95% CI, 10.56-16.42). CONCLUSIONS In a population-based prospective study, we found that the incidence of AIH was significantly higher in the 2014-2016 period than the 2008-2010 period; incidences of PBC and PSC were unchanged over the same period. Further studies are needed to determine the reasons for changes in incidence of autoimmune liver diseases.
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21
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Sahu R, Mishra R, Majee C. An insight into primary biliary cholangitis and its recent advances in treatment: semi-synthetic analogs to combat ursodeoxycholic-acid resistance. Expert Rev Gastroenterol Hepatol 2020; 14:985-998. [PMID: 32674617 DOI: 10.1080/17474124.2020.1797485] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease which on progression causes cirrhosis; various studies also suggested that several diseases can co-exist in patients. In existing depiction of disease PBC, apart from entire use of ursodeoxycholic acid (UDCA), several patients need to step forward to liver-transplantation or death due to resistance or non-responder with UDCA monotherapy. AREAS COVERED To overcome this non-respondent treatment, novel bile acid semi-synthetic analogs have been identified which shows their potency against for farnesoid X receptor and transmembrane G protein-coupled receptor-5 which are identified as target for many developing analogs which have desirable pharmacokinetic profiles. EXPERT OPINION A range of studies suggests that adding semisynthetic analogs in therapeutic regime improves liver biochemistries in patients with suboptimal response to UDCA. Thus, the aspire of this review is to abridge and compare therapeutic value and current markets affirm of various bile acids semi-synthetic analogs which certainly are having promising effects in PBC monotherapy or in pooled treatment with UDCA for PBC.
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Affiliation(s)
- Rakesh Sahu
- Department of Pharmaceutical Chemistry, Noida Institute of Engineering and Technology (Pharmacy Institute) , Greater Noida, India
| | - Rakhi Mishra
- Department of Pharmaceutical Chemistry, Noida Institute of Engineering and Technology (Pharmacy Institute) , Greater Noida, India
| | - Chandana Majee
- Department of Pharmaceutical Chemistry, Noida Institute of Engineering and Technology (Pharmacy Institute) , Greater Noida, India
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22
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Abstract
Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease with non-suppurative destruction of the intrahepatic bile ducts. The interplay of genetics and environmental triggers contributes to the onset of the disease and subsequently results in cholestasis and progressive fibrosis. Recently, genome-wide association studies (GWAS) have identified multiple genes influencing the susceptibility to PBC in HLA and non-HLA loci. However, it is estimated that the known risk variants merely account for no more than 20% of the heritability of PBC and causes of the remaining heritability remain uncertain. Increasing evidence suggests that the presence of epigenetic abnormalities may explain the "missing heritability" that cannot be captured by GWAS. Among these epigenetic mechanisms, DNA methylation, histone modification, and noncoding RNAs (i.e. miRNA and lncRNA) are involved in the pathogenesis of PBC. Additionally, telomere dysregulation in biliary epithelial cells (BECs) may play a role in disease onset, whereas a deficiency in sex chromosome and skewed gene expression in the X chromosome may to some extent explain the female dominance in PBC.
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23
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French J, van der Mei I, Simpson S, Ng J, Angus P, Lubel J, Nicoll A, Sood S, Roberts SK, Kemp W, Arachchi N, Dev A, Thompson A, Gow PJ. Increasing prevalence of primary biliary cholangitis in Victoria, Australia. J Gastroenterol Hepatol 2020; 35:673-679. [PMID: 31693755 DOI: 10.1111/jgh.14924] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2019] [Revised: 10/16/2019] [Accepted: 10/30/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIM The prevalence of primary biliary cholangitis (PBC) reported in different countries varies significantly and in some parts of the world appears to be increasing. The aim of this study was to determine the 2013 prevalence of PBC in Victoria, Australia, and to determine the time trend by comparing it with previous studies undertaken in 1991 and 2002. METHODS Four case-finding methods were used to identify cases of PBC in Victoria: (1) physicians' survey; (2) tertiary hospital search; (3) liver transplant database search; and (4) private pathology antimitochondrial antibody search. RESULTS The prevalence of PBC in Victoria, Australia, is 189.0 per million using all four methods. The average annual increase in prevalence from 1991 to 2013 was 7.7 per million per year. Using the same case-finding methods as the 1991 Victorian prevalence study (methods 1 and 2), the prevalence of PBC increased from 19.1 per million in 1991 to 49.4 per million in 2002 (P < 0.001) and to 80.7 per million in 2013 (P < 0.001). CONCLUSIONS The current prevalence of PBC in Victoria is significantly higher than previously reported. The use of private pathology-based case-finding methods is important in identifying the maximum number of PBC cases.
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Affiliation(s)
- Janine French
- Department of Gastroenterology, Austin Hospital, Heidelberg, Victoria, Australia
| | - Ingrid van der Mei
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia
| | - Steve Simpson
- Melbourne School of Population and Global Health, University of Melbourne, Carlton, Victoria, Australia.,Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia
| | - Justin Ng
- Department of Gastroenterology, Austin Hospital, Heidelberg, Victoria, Australia
| | - Peter Angus
- Department of Gastroenterology, Austin Hospital, Heidelberg, Victoria, Australia.,University of Melbourne, Parkville, Victoria, Australia
| | - John Lubel
- Department of Gastroenterology, Eastern Health, Box Hill, Victoria, Australia
| | - Amanda Nicoll
- Department of Gastroenterology, Eastern Health, Box Hill, Victoria, Australia.,Department of Gastroenterology and Hepatology, Royal Melbourne Hospital, Parkville, Victoria, Australia
| | - Siddharth Sood
- Department of Gastroenterology and Hepatology, Royal Melbourne Hospital, Parkville, Victoria, Australia.,University of Melbourne, Parkville, Victoria, Australia
| | - Stuart K Roberts
- Department of Gastroenterology and Hepatology, The Alfred, Melbourne, Victoria, Australia.,Monash University, Clayton, Victoria, Australia
| | - William Kemp
- Department of Gastroenterology and Hepatology, The Alfred, Melbourne, Victoria, Australia.,Monash University, Clayton, Victoria, Australia
| | - Niranjan Arachchi
- Department of Gastroenterology and Hepatology, Western Hospital, Footscray, Victoria, Australia
| | - Anouk Dev
- Department of Gastroenterology and Hepatology, Monash Health, Clayton, Victoria, Australia.,Monash University, Clayton, Victoria, Australia
| | - Alexander Thompson
- Department of Gastroenterology, St Vincent's Hospital, Fitzroy, Victoria, Australia.,University of Melbourne, Parkville, Victoria, Australia
| | - Paul J Gow
- Department of Gastroenterology, Austin Hospital, Heidelberg, Victoria, Australia.,University of Melbourne, Parkville, Victoria, Australia
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24
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Abdulkarim M, Zenouzi R, Sebode M, Schulz L, Quaas A, Lohse AW, Schramm C, Weiler-Normann C. Sex differences in clinical presentation and prognosis in patients with primary biliary cholangitis. Scand J Gastroenterol 2019; 54:1391-1396. [PMID: 31692389 DOI: 10.1080/00365521.2019.1683226] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Objectives: Primary biliary cholangitis (PBC) is a chronic inflammatory disease of the small intrahepatic bile ducts disproportionally affecting women. Timely diagnosis and treatment can often prevent progression to liver cirrhosis. We hypothesized PBC diagnosis in male patients is delayed and prognosis impaired. We, therefore, conducted a case-control study and compared clinical and prognostic features among male and female patients with PBC.Materials and methods: 49 male patients with PBC treated at a German tertiary care center between 2006 and 2017 were identified and compared to 98 age-matched female controls. Prospectively collected clinical/biochemical data were analyzed retrospectively. Liver biopsies were scored in a blinded fashion. Prognostic parameters were calculated using established prognostic scores (GLOBE, PBC-UKE). Statistical analysis was performed using Mann-Whitney test and Fisher´s exact test.Results: At PBC diagnosis, male patients reported significantly less PBC-associated symptoms as compared to female controls (34 versus 71%, p < .01). Compared to female patients, median time from onset of PBC-related symptoms and/or first reported elevated cholestatic biochemical parameters to PBC diagnosis was significantly increased in men (36 versus 12 months, p = .02). In addition, male patients underwent liver biopsy to establish PBC diagnosis more frequently, tended to show more advanced fibrosis and showed significantly poorer prognostic PBC score results. Hepatocellular carcinoma was only observed in male patients (n = 3).Conclusions: When compared to women, men with PBC suffer from less PBC-related symptoms, receive PBC diagnosis delayed and have a worse prognosis. Despite its rarity, the diagnosis of PBC should be considered in men with elevated cholestatic parameters.
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Affiliation(s)
- Mosaab Abdulkarim
- I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,Al-Khadra Teaching Hospital, Faculty of Medicine, Tripoli University, Tripoli, Libya
| | - Roman Zenouzi
- I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany
| | - Marcial Sebode
- I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany
| | - Lisa Schulz
- I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany
| | - Alexander Quaas
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,Department of Pathology, University Medical Center Cologne, Cologne, Germany
| | - Ansgar W Lohse
- I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany
| | - Christoph Schramm
- I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.,Martin Zeitz Center for Rare Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Christina Weiler-Normann
- I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.,Martin Zeitz Center for Rare Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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Epidemiology and clinical course of primary biliary cholangitis in the Asia-Pacific region: a systematic review and meta-analysis. Hepatol Int 2019; 13:788-799. [PMID: 31552558 DOI: 10.1007/s12072-019-09984-x] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Accepted: 08/22/2019] [Indexed: 12/12/2022]
Abstract
AIMS Epidemiological studies on primary biliary cholangitis (PBC) show heterogeneity. The aim of the present study was to synthesize the prevalence, incidence and clinical course of PBC in the Asia-Pacific region. METHODS PubMed, Medline, Cochrane library and EMBASE were searched for epidemiology and clinical course of PBC published up to July, 2019. Meta-analysis was conducted on the epidemiology and clinical course (decompensation, hepatocellular carcinoma and death/liver transplantation) of PBC patients. Random-effect model and fixed-effect model were used to evaluate the pooled prevalence, incidence, mortality/liver transplantation and their 95% confidence intervals as appropriate. Subgroup analysis was performed by stratification with gender, pre- and post-UDCA era, sub-region and publication year. Meta-regression was used to examine the heterogeneity. RESULTS Out of 3460 studies, 18 studies from 7 countries/regions were finally included. The overall prevalence of PBC was 118.75 cases per million (95% CI 49.96-187.55) in the Asia-Pacific region, with the high, medium and low prevalence being in Japan and China (191.18 cases per million), New Zealand (99.16 cases per million) and South Korea and Australia (39.09 cases per million), respectively. The incidence of PBC was 8.55 cases per million per year (95% CI 8.05-9.06). The 5-year accumulative incidence of decompensation, HCC and death/liver transplantation in PBC patients was 6.95% (95% CI 2.07-11.83%), 1.54% (95% CI 0.9-2.19%) and 4.02% (95% CI 2.49-5.54%), respectively. CONCLUSION In the Asia-Pacific region, the prevalence and incidence of PBC are higher than once expected. PBC tends to be diagnosed at older age and has a relatively low incidence of HCC in this region.
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26
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Cheung AC, Lammers WJ, Murillo Perez CF, van Buuren HR, Gulamhusein A, Trivedi PJ, Lazaridis KN, Ponsioen CY, Floreani A, Hirschfield GM, Corpechot C, Mayo MJ, Invernizzi P, Battezzati PM, Parés A, Nevens F, Thorburn D, Mason AL, Carbone M, Kowdley KV, Bruns T, Dalekos GN, Gatselis NK, Verhelst X, Lindor KD, Lleo A, Poupon R, Janssen HLA, Hansen BE. Effects of Age and Sex of Response to Ursodeoxycholic Acid and Transplant-free Survival in Patients With Primary Biliary Cholangitis. Clin Gastroenterol Hepatol 2019; 17:2076-2084.e2. [PMID: 30616022 DOI: 10.1016/j.cgh.2018.12.028] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Revised: 12/07/2018] [Accepted: 12/23/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Primary biliary cholangitis (PBC) predominantly affects middle-aged women; there are few data on disease phenotypes and outcomes of PBC in men and younger patients. We investigated whether differences in sex and/or age at the start of ursodeoxycholic acid (UDCA) treatment are associated with response to therapy, based on biochemical markers, or differences in transplant-free survival. METHODS We performed a longitudinal retrospective study of 4355 adults in the Global PBC Study cohort, collected from 17 centers across Europe and North America. Patients received a diagnosis of PBC from 1961 through 2014. We evaluated the effects of sex and age on response to UDCA treatment (based on GLOBE score) and transplant-free survival using logistic regression and Cox regression analyses, respectively. RESULTS Male patients were older at the start of treatment (58.3±12.1 years vs 54.3±11.6 years for women; P<.0001) and had higher levels of bilirubin and lower circulating platelet counts (P<.0001). Younger patients (45 years or younger) had increased serum levels of transaminases than older patients (older than 45 years). Patients older than 45 years at time of treatment initiation had increased odds of a biochemical response to UDCA therapy, based on GLOBE score, compared to younger patients. The greatest odds of response to UDCA were observed in patients older than 65 years (odds ratio compared to younger patients 45 years or younger, 5.48; 95% CI, 3.92-7.67; P<.0001). Risk of liver transplant or death (compared to a general population matched for age, sex, and birth year) decreased significantly with advancing age: hazard ratio for patients 35 years or younger, 14.59 (95% CI, 9.66-22.02) vs hazard ratio for patients older than 65 years, 1.39 (95% CI, 1.23-1.57) (P<.0001). On multivariable analysis, sex was not independently associated with response or transplant-free survival. CONCLUSION In longitudinal analysis of 4355 adults in the Global PBC Study, we associated patient age, but not sex, with response to UDCA treatment and transplant-free survival. Younger age at time of treatment initiation is associated with increased risk of treatment failure, liver transplant, and death.
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Affiliation(s)
- Angela C Cheung
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Willem J Lammers
- Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Carla F Murillo Perez
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Henk R van Buuren
- Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Aliya Gulamhusein
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Palak J Trivedi
- National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, Centre for Liver Research, University of Birmingham, Birmingham, United Kingdom
| | | | - Cyriel Y Ponsioen
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
| | - Annarosa Floreani
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Gideon M Hirschfield
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Christophe Corpechot
- Service d'Hépatologie, Centre national de référence des maladies inflammatoires du foie et des voies biliaires, Hôpital Saint-Antoine, Paris, France
| | - Marlyn J Mayo
- Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Pietro Invernizzi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy
| | | | - Albert Parés
- Liver Unit, Hospital Clínic, IDIBAPS, University of Barcelona, CIBERehd, Barcelona, Spain
| | - Frederik Nevens
- Department of Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium
| | - Douglas Thorburn
- Sheila Sherlock Liver Centre, Royal Free Hospital, London, United Kingdom
| | - Andrew L Mason
- Division of Gastroenterology and Hepatology, University of Alberta, Edmonton, Alberta, Canada
| | - Marco Carbone
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy
| | - Kris V Kowdley
- Liver Care Network, Swedish Medical Center, Seattle, Washington
| | - Tony Bruns
- Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University of Jena, Jena, Germany
| | - George N Dalekos
- Department of Medicine and Research Laboratory of Internal Medicine, University of Thessaly, Larissa, Greece
| | - Nikolaos K Gatselis
- Department of Medicine and Research Laboratory of Internal Medicine, University of Thessaly, Larissa, Greece
| | - Xavier Verhelst
- Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium
| | - Keith D Lindor
- College of Health Solutions, Arizona State University, Phoenix, Arizona
| | - Ana Lleo
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy
| | - Raoul Poupon
- Service d'Hépatologie, Centre national de référence des maladies inflammatoires du foie et des voies biliaires, Hôpital Saint-Antoine, Paris, France
| | - Harry L A Janssen
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Bettina E Hansen
- Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands; Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada.
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Manno V, Gerussi A, Carbone M, Minelli G, Taruscio D, Conti S, Invernizzi P. A National Hospital-Based Study of Hospitalized Patients With Primary Biliary Cholangitis. Hepatol Commun 2019; 3:1250-1257. [PMID: 31497745 PMCID: PMC6719751 DOI: 10.1002/hep4.1407] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2019] [Accepted: 06/18/2019] [Indexed: 12/16/2022] Open
Abstract
Epidemiological studies on primary biliary cholangitis (PBC) have been based primarily on tertiary referral case series. We aimed to estimate the incidence and prevalence and describe comorbidities in hospitalized patients with PBC in Italy using a national hospital-based data source. Data were extracted from the National Hospital Discharge Database, which includes all Italian individuals discharged from any hospital in the country. All adults diagnosed with biliary cirrhosis (International Classification of Diseases, Ninth Revision, Clinical Modification, 571.6) as the primary or secondary diagnosis from 2011 to 2015 were included. To determine whether a comorbidity was either more or less frequent in PBC patients compared with the general hospitalized Italian population, the standardized hospitalization ratio (SHR) was calculated. A total of 5,533 incident cases were identified from 2011 to 2015, 3,790 of whom were females (68.5%; female to male [F:M] ratio, 2.2:1). Prevalent cases were 9,664, of whom 7,209 were females (74.6%; F:M ratio, 2.9:1). The incident rate was 1.03 × 100,000 in males and 1.92 × 100,000 in females; prevalence was 1.89 × 100,000 in males and 4.75 × 100,000 in females. Extrahepatic autoimmune diseases, malignant neoplasms of liver and intrahepatic biliary ducts, and malignant neoplasms of gallbladder and extrahepatic bile ducts were found more frequently in PBC patients than in the general hospitalized population (SHR > 100), whereas cerebrovascular diseases and ischemic heart diseases were less frequent in PBC individuals (SHR < 100). Conclusion: This national study provides a survey of comorbidities associated with PBC. Hospitalized patients with PBC are more likely to have extrahepatic autoimmune diseases, hepatocellular carcinoma, and biliary tract cancers and a low risk of cardiovascular events.
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Affiliation(s)
- Valerio Manno
- Service of StatisticsNational Institute of HealthRomeItaly
| | - Alessio Gerussi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and SurgeryUniversity of Milano‐BicoccaMonzaItaly
| | - Marco Carbone
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and SurgeryUniversity of Milano‐BicoccaMonzaItaly
| | - Giada Minelli
- Service of StatisticsNational Institute of HealthRomeItaly
| | - Domenica Taruscio
- National Center for Rare DiseasesNational Institute of HealthRomeItaly
| | - Susanna Conti
- Service of StatisticsNational Institute of HealthRomeItaly
| | - Pietro Invernizzi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and SurgeryUniversity of Milano‐BicoccaMonzaItaly
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28
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Tanaka A, Mori M, Matsumoto K, Ohira H, Tazuma S, Takikawa H. Increase trend in the prevalence and male-to-female ratio of primary biliary cholangitis, autoimmune hepatitis, and primary sclerosing cholangitis in Japan. Hepatol Res 2019; 49:881-889. [PMID: 30932290 DOI: 10.1111/hepr.13342] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2019] [Revised: 03/26/2019] [Accepted: 03/26/2019] [Indexed: 12/13/2022]
Abstract
AIM Autoimmune liver diseases (AILD) including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) impose a significant burden on public health, and it is important to estimate their prevalence. We carried out a nationwide, hospital-based, epidemiological survey of AIH, PBC, and PSC, and compared the results with those from previous surveys. METHOD We randomly selected health-care facilities used in the survey from a list of all facilities in Japan. The selection rate was determined according to a stratification based on the facility characteristics and scale. We sent questionnaires to the selected facilities enquiring about the number and sex of patients with AILD who visited the facility in 2016. An identical survey was undertaken for AIH/PBC in 2004 and for PSC in 2007; we carried out a comparative analysis of these data. RESULTS We selected 1793 departments from health centers all over Japan. Of them, 1078 (60.1%) responded to the questionnaires. The number of reported patients with AIH, PBC, and PSC was 8505, 10 847, and 906, respectively, and point prevalence was 23.9 (95% confidence interval, 23.3-24.5) for AIH (8.7 in 2004), 33.8 (33.0-34.6) for PBC (11.6 in 2004), and 1.80 (1.75-1.85) for PSC (0.95 in 2007) per 100 000 population. Male-to-female patient ratio of AILD was 1:4.3 for AIH (1:6.9 in 2004), 1:3.9 for PBC (1:7.1 in 2004), and 1:0.88 for PSC (1:1.4 in 2007). CONCLUSION The current study indicates an increasing trend of prevalence as well as male-to-female patient ratio of AILD in Japan.
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Affiliation(s)
- Atsushi Tanaka
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Mitsuru Mori
- Hokkaido Chitose College of Rehabilitation, Chitose, Japan
| | - Kosuke Matsumoto
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Hiromasa Ohira
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Susumu Tazuma
- Department of General Medicine, Graduate School of Medical Science, Programs of Applied Medicine and Clinical Pharmacotherapy, Hiroshima University,, Hiroshima, Japan
| | - Hajime Takikawa
- Faculty of Medical Technology, Teikyo University, Tokyo, Japan
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Chen S, Duan W, Li M, Li S, Lv T, Tian Q, Wang Q, Wu X, Zhao X, Wang X, Wang Y, Kong Y, Ma H, Ou X, You H, Jia J. Prognosis of 732 ursodeoxycholic acid-treated patients with primary biliary cholangitis: A single center follow-up study from China. J Gastroenterol Hepatol 2019; 34:1236-1241. [PMID: 30365184 DOI: 10.1111/jgh.14521] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2018] [Revised: 10/04/2018] [Accepted: 10/15/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM The impact of male sex and past hepatitis B virus (HBV) infection on survival of primary biliary cholangitis (PBC) are issues at discussion. The aim of the present study was to identify risk factors for transplant-free survival (TRS) in Chinese PBC patients who received ursodeoxycholic acid (UDCA), with special focus on the impact of male sex and past HBV infection. METHODS We followed up PBC patients who received UDCA at our institute between January 2000 and December 2017 until their death, liver transplantation, or censored on April 1, 2018, by interview and review of medical records. We used Cox proportional hazards model and Kaplan-Meier method. RESULTS Out of 976 PBC patients, 732 UDCA-treated patients (female : male = 6.2:1) with required clinical and laboratory data were enrolled in this study. The median follow-up period were 4.8 years (interquartile range: 2.8-7.1 years). The overall 5-, 10-, and 15-year TRS rates were 86.7% (95% CI: 83.8-88.1), 71.1% (95% CI: 65.0-77.2), and 59.2% (95% CI: 44.5-73.9), respectively. The survival was significantly worse for male patients and older patients (≥ 55 years) (log-rank test: P < 0.05 for both). On multivariate analysis, male sex, cirrhosis, serum bilirubin, and serum albumin were independent predictors for TRS. There was no significant difference in survivals between patients with (n = 167) and without (n = 219) past HBV infection (log-rank test: P = 0.293). CONCLUSIONS In this large Chinese cohort of UDCA-treated PBC patients, male sex was associated with shorter survival, whereas past HBV infection was not associated with poorer outcome.
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Affiliation(s)
- Sha Chen
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Translational Medicine on Cirrhosis, Capital Medical University, Beijing, China.,National Clinical Research Center for Digestive Diseases, Capital Medical University, Beijing, China
| | - Weijia Duan
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Translational Medicine on Cirrhosis, Capital Medical University, Beijing, China.,National Clinical Research Center for Digestive Diseases, Capital Medical University, Beijing, China
| | - Min Li
- Center for Clinical Epidemiology and EBM, Beijing Friendship Hospital, Capital Medical University, Beijing, China.,National Clinical Research Center for Digestive Diseases, Capital Medical University, Beijing, China
| | - Shuxiang Li
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Translational Medicine on Cirrhosis, Capital Medical University, Beijing, China.,National Clinical Research Center for Digestive Diseases, Capital Medical University, Beijing, China
| | - Tingting Lv
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Translational Medicine on Cirrhosis, Capital Medical University, Beijing, China.,National Clinical Research Center for Digestive Diseases, Capital Medical University, Beijing, China
| | - Qiuju Tian
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Translational Medicine on Cirrhosis, Capital Medical University, Beijing, China.,National Clinical Research Center for Digestive Diseases, Capital Medical University, Beijing, China
| | - Qianyi Wang
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Translational Medicine on Cirrhosis, Capital Medical University, Beijing, China.,National Clinical Research Center for Digestive Diseases, Capital Medical University, Beijing, China
| | - Xiaoning Wu
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Translational Medicine on Cirrhosis, Capital Medical University, Beijing, China.,National Clinical Research Center for Digestive Diseases, Capital Medical University, Beijing, China
| | - Xinyan Zhao
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Translational Medicine on Cirrhosis, Capital Medical University, Beijing, China.,National Clinical Research Center for Digestive Diseases, Capital Medical University, Beijing, China
| | - Xiaoming Wang
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Translational Medicine on Cirrhosis, Capital Medical University, Beijing, China.,National Clinical Research Center for Digestive Diseases, Capital Medical University, Beijing, China
| | - Yu Wang
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Translational Medicine on Cirrhosis, Capital Medical University, Beijing, China.,National Clinical Research Center for Digestive Diseases, Capital Medical University, Beijing, China
| | - Yuanyuan Kong
- Center for Clinical Epidemiology and EBM, Beijing Friendship Hospital, Capital Medical University, Beijing, China.,National Clinical Research Center for Digestive Diseases, Capital Medical University, Beijing, China
| | - Hong Ma
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Translational Medicine on Cirrhosis, Capital Medical University, Beijing, China.,National Clinical Research Center for Digestive Diseases, Capital Medical University, Beijing, China
| | - Xiaojuan Ou
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Translational Medicine on Cirrhosis, Capital Medical University, Beijing, China.,National Clinical Research Center for Digestive Diseases, Capital Medical University, Beijing, China
| | - Hong You
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Translational Medicine on Cirrhosis, Capital Medical University, Beijing, China.,National Clinical Research Center for Digestive Diseases, Capital Medical University, Beijing, China
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Translational Medicine on Cirrhosis, Capital Medical University, Beijing, China.,National Clinical Research Center for Digestive Diseases, Capital Medical University, Beijing, China
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30
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Lin CY, Cheng YT, Chang ML, Chien RN. The extrahepatic events of Asian patients with primary biliary cholangitis: A 30-year cohort study. Sci Rep 2019; 9:7577. [PMID: 31110209 PMCID: PMC6527707 DOI: 10.1038/s41598-019-44081-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2018] [Accepted: 05/09/2019] [Indexed: 12/16/2022] Open
Abstract
The extrahepatic complications of primary biliary cholangitis (PBC) in Asian patients remain elusive. A 30-year cohort study of 150 Taiwanese PBC patients treated with ursodeoxycholic acid (UDCA) was conducted. Patients with alkaline phosphatase levels >1.67 × ULN after 1-year treatment were considered suboptimal responders. At baseline, of 150 patients (mean age: 53.75 years), 128 (85.3%) were females, and 34 (22.8%) had cirrhosis. The cumulative incidences of various incident events were all-cause mortality or liver transplantation: 46.7%; extrahepatic mortality: 24.5%; extrahepatic malignancies: 8.1%; hypertension: 46.2%; dyslipidemia: 44.1%; diabetes: 30.6%; hyperuricemia: 11.2%; acute coronary syndrome: 3.1%; cerebral vascular accident (CVA): 8.9%; autoimmune diseases: 16%; and osteoporosis: 20.9%. The 5- to 20-year cumulative incidences for all-cause mortality or liver transplantation and extrahepatic mortality were 16.2–41.3% and 3.1–11.9%, respectively. Baseline associations were age and alpha-fetoprotein levels with extrahepatic mortality, 80% due to sepsis; age with extrahepatic malignancies and hypertension; gender and hyperuricemia with CVA; and UDCA response with autoimmune disease. Conclusions: Sepsis accounted for most extrahepatic mortality in PBC patients, and the longer the follow-up was, the higher the extrahepatic/all-cause mortality ratio. Baseline age is crucial for incident extrahepatic events and only CVA shows gender-dimorphism; the association between UDCA response and autoimmune disease requires further investigation.
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Affiliation(s)
- Cheng-Yu Lin
- Liver Research Center, Division of Gastroenterology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Ya-Ting Cheng
- Liver Research Center, Division of Gastroenterology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Ming-Ling Chang
- Liver Research Center, Division of Gastroenterology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan. .,Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
| | - Rong-Nan Chien
- Liver Research Center, Division of Gastroenterology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan. .,Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
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Shahab O, Sayiner M, Paik J, Felix S, Golabi P, Younossi ZM. Burden of Primary Biliary Cholangitis Among Inpatient Population in the United States. Hepatol Commun 2019; 3:356-364. [PMID: 30859148 PMCID: PMC6396368 DOI: 10.1002/hep4.1314] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Accepted: 12/21/2018] [Indexed: 12/14/2022] Open
Abstract
Primary biliary cholangitis (PBC) is an autoimmune liver disease that can lead to cirrhosis and liver failure. Our aim was to assess the recent trends in the mortality rates and health care utilization of patients with PBC seen in the inpatient setting in the United States. We used the National (Nationwide) Inpatient Sample data (2005‐2014). The study population included adults with PBC, using International Classification of Diseases, Ninth Revision codes. Trends in PBC‐related discharges, total charges, length of stay (LoS), and in‐hospital mortality were evaluated. Hierarchical generalized linear models were performed for determining predictors of mortality and total hospital charges. Between the study years of 2005 and 2014, a total of 22,665 hospitalized cases with PBC were identified (mean age 63 years; 84% female, 76% white). The number of PBC‐related discharges increased from 3.24 per 100,000 in 2005 to 3.68 per 100,000 in 2014, with an average annual increase of 1.4% (95% confidence interval [CI]: 0.4%‐2.4%). Fifty‐seven percent had Medicare as their primary payer, 37% had cirrhosis, and 1.3% had hepatocellular carcinoma. Between 2005 and 2014, the average total charges for PBC increased from $53,901 to $57,613 (annual percent change [APC], 1.7%; 95% CI: −0.2%‐3.5%), LoS decreased from 6.9 days to 5.4 days (APC, −2.2%; 95% CI: −3.2% to −1.1%), and mortality rate decreased from 3.8% to 2.8% (APC, −5.4%; 95% CI: −8.4% to −2.4%). Multivariable analysis revealed that ascites were independently associated with increased risk of in‐hospital mortality (odds ratio: 1.77; 95% CI: 1.50‐2.08), increased charge (percent change: 22.5%; 95% CI: 18.6%‐26.7%), and increased LoS (percent change: 29.7%; 95% CI: 25.7%‐33.9%). Conclusion: The number of PBC cases has increased in recent years. Mortality and LoS have decreased, and the total charges have remained the same.
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Affiliation(s)
- Omer Shahab
- Center for Liver Disease, Department of Medicine Inova Fairfax Hospital Falls Church VA
| | - Mehmet Sayiner
- Center for Liver Disease, Department of Medicine Inova Fairfax Hospital Falls Church VA
| | - James Paik
- Betty and Guy Beatty Center for Integrated Research Inova Health System Falls Church VA
| | - Sean Felix
- Betty and Guy Beatty Center for Integrated Research Inova Health System Falls Church VA
| | - Pegah Golabi
- Betty and Guy Beatty Center for Integrated Research Inova Health System Falls Church VA
| | - Zobair M Younossi
- Center for Liver Disease, Department of Medicine Inova Fairfax Hospital Falls Church VA.,Betty and Guy Beatty Center for Integrated Research Inova Health System Falls Church VA
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32
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Martin ML, Stassek L, Blum SI, Joshi AV, Jones D. Development and adaptation of patient-reported outcome measures for patients who experience itch associated with primary biliary cholangitis. J Patient Rep Outcomes 2019; 3:2. [PMID: 30645706 PMCID: PMC6333594 DOI: 10.1186/s41687-018-0090-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2018] [Accepted: 12/04/2018] [Indexed: 12/18/2022] Open
Abstract
PURPOSE To conduct qualitative interviews to evaluate and refine the Itch Diary (ID) and weekly version of the PBC-40 in patients with itching associated with primary biliary cholangitis (PBC). METHODS Twenty adults with self-reported PBC diagnoses and recent/ongoing itching of at least moderate intensity participated in face-to-face qualitative combined concept elicitation (CE) interviews and cognitive interviews after completing the morning and evening versions of the ID and weekly version of the PBC-40. These questionnaires were evaluated to confirm saturation of concepts of interest and cognitively test the English language versions of the measures in patients with PBC in the US and Canada. Transcripts were organized into descriptions of PBC-related symptoms and symptom-related impacts using a structured coding framework. Two waves of interviews were conducted; revisions made after wave 1 were further tested in wave 2. RESULTS Interview results confirmed the relevance of concepts presented in the PBC-40 and ID to patients' experiences. Saturation of concept was achieved. Itching-related signs and symptoms (46%) were the most commonly expressed symptom concept in the CE interviews followed by energy-related (14%) and additional signs/symptoms (13%). Several changes to the ID were made in response to cognitive interview results. Changes to the PBC-40 included adaptations from British to North American English, and the appropriateness of a 7-day recall period was confirmed. CONCLUSIONS Relevance of the symptom and impact concepts in the ID to measure PBC-related itch were confirmed. Adaptation of the PBC-40 to a weekly recall period and for North American English was successful.
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Affiliation(s)
- Mona L Martin
- Health Research Associates, Inc., 6505 216th St. SW, Suite 105, Mountlake Terrace, WA, 98043, USA.
| | - Larissa Stassek
- Health Research Associates, Inc., 6505 216th St. SW, Suite 105, Mountlake Terrace, WA, 98043, USA
| | - Steven I Blum
- , GlaxoSmithKline, 1250 S. Collegeville Road, Collegeville, PA, 19426, USA
| | - Ashish V Joshi
- , GlaxoSmithKline, 1250 S. Collegeville Road, Collegeville, PA, 19426, USA
| | - David Jones
- Newcastle University, Newcastle upon Tyne, UK
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Sayiner M, Golabi P, Stepanova M, Younossi I, Nader F, Racila A, Younossi ZM. Primary Biliary Cholangitis in Medicare Population: The Impact on Mortality and Resource Use. Hepatology 2019; 69:237-244. [PMID: 30015376 DOI: 10.1002/hep.30174] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2017] [Accepted: 07/11/2018] [Indexed: 01/02/2023]
Abstract
Primary biliary cholangitis (PBC) is a disease of small bile ducts, which can lead to morbidity and mortality. Our aim was to assess recent trends in mortality and healthcare use of PBC patients in the Medicare program. Data from Medicare beneficiaries between 2005 and 2015 (5% random samples) were used. The diagnosis of PBC was established with International Classification of Diseases-9 code 571.6 used for both primary and secondary diagnoses. Mortality was assessed by Medicare-linked death registry. Healthcare use included episodes of care, length of stay, and total charges/payments. Independent predictors of outcomes were evaluated in multiple generalized linear or logistic regression models. The study cohort included a total of 6,375 inpatient/outpatient Medicare beneficiaries (mean age 69.8 years, 17% male, 88% white, and 18% with disability). Over the study period, 1-year mortality remained stable (9.1% to 14.3%, P = 0.11). Independent predictors of 1-year mortality were older age, male gender, black race, the presence of ascites, encephalopathy, hepatocellular carcinoma, and higher Charlson score. Outpatient total yearly charges and payments per beneficiary with PBC increased from $3,065 and $777 (2005) to $5,773 and $967 (2014), respectively. Similarly, inpatient total yearly charges and payments per beneficiary with PBC increased from $59,765 and $19,406 (2007), to $98,941 and $27,948 (2013), respectively (P < 0.05). The presence of ascites, portal hypertension, and higher Charlson score were independent predictors of higher payments for both inpatient and outpatient resource use, and the presence of hepatic encephalopathy was an additional predictor of higher inpatient resource use (all P < 0.02). Conclusion: The prevalence of PBC among the Medicare beneficiaries has increased. Despite stable mortality rates, resource use for Medicare patients with PBC continues to rise.
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Affiliation(s)
- Mehmet Sayiner
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA.,Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA
| | - Pegah Golabi
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA
| | - Maria Stepanova
- Center for Outcomes Research in Liver Diseases, Washington, DC
| | - Issah Younossi
- Center for Outcomes Research in Liver Diseases, Washington, DC
| | - Fatema Nader
- Center for Outcomes Research in Liver Diseases, Washington, DC
| | - Andrei Racila
- Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA.,Center for Outcomes Research in Liver Diseases, Washington, DC
| | - Zobair M Younossi
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA.,Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA
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Rodrigues PM, Perugorria MJ, Santos-Laso A, Bujanda L, Beuers U, Banales JM. Primary biliary cholangitis: A tale of epigenetically-induced secretory failure? J Hepatol 2018; 69:1371-1383. [PMID: 30193962 DOI: 10.1016/j.jhep.2018.08.020] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2018] [Revised: 08/14/2018] [Accepted: 08/24/2018] [Indexed: 12/16/2022]
Abstract
Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease associated with autoimmune-related destruction of small to medium size intrahepatic bile ducts. The aetiology of PBC is unknown and its pathogenesis remains obscure. Both genetic variants and environmental factors have been linked to increased PBC susceptibility, with other alterations known to cooperate in disease pathobiology. Increasing evidence indicates the presence of epigenetic abnormalities in PBC, particularly alterations of cholangiocellular microRNAs (miRNAs or miRs). This review highlights and discusses the most relevant epigenetic alterations found in patients with PBC, focusing on the role of miR-506 in the promotion of cholestasis and immune activation.
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Affiliation(s)
- Pedro M Rodrigues
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain
| | - Maria J Perugorria
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain; National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, "Instituto de Salud Carlos III"), Spain; Ikerbasque, Basque Foundation for Science, Bilbao, Spain
| | - Alvaro Santos-Laso
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain
| | - Luis Bujanda
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain; National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, "Instituto de Salud Carlos III"), Spain
| | - Ulrich Beuers
- Tytgat Institute for Liver and Intestinal Research and Department of Gastroenterology & Hepatology, Amsterdam Gastroenterology and Metabolism, AMC, Amsterdam, The Netherlands
| | - Jesus M Banales
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain; National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, "Instituto de Salud Carlos III"), Spain; Ikerbasque, Basque Foundation for Science, Bilbao, Spain.
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Parés A, Albillos A, Andrade RJ, Berenguer M, Crespo J, Romero-Gómez M, Vergara M, Vendrell B, Gil A. Primary biliary cholangitis in Spain. Results of a Delphi study of epidemiology, diagnosis, follow-up and treatment. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2018; 110:641-649. [PMID: 30032637 DOI: 10.17235/reed.2018.5665/2018] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
INTRODUCTION primary biliary cholangitis (PBC) is a rare disease with limited data regarding its epidemiology and standard clinical management in Spain. OBJECTIVE to gain insight into the epidemiology, patient flow, diagnosis, follow-up and treatment of PBC in Spain. METHODS a review of the literature and Delphi study involving 28 specialists in two rounds of consultations and an in-person results validation workshop. RESULTS there are approximately 9,400 patients with PBC in Spain, with an annual incidence of 0.51-3.86 cases/100,000 population. Albeit, a high error margin may be presumed due to the scarcity of relevant studies on this subject. Several months may elapse from suspicion to a confirmed diagnosis, usually by a gastroenterologist or hepatologist. The role of the liver biopsy for diagnosis and follow-up is heterogeneous. Overall, 95% of patients are treated with ursodeoxycholic acid (UDCA) and response is primarily monitored using the Barcelona criteria. Follow-up is performed every six months, with a heterogeneous use of the various available techniques. No recommendations or second-line commercial drugs are available in the case of no response, inadequate response or intolerance to UDCA. CONCLUSIONS while epidemiology may be estimated based on expert opinions, national registries are needed to provide accurate, up-to-date information on epidemiological parameters, disease stage and response to treatment in patients with PBC. Furthermore, novel therapies are required for selected patient groups.
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Affiliation(s)
- Albert Parés
- Unidad de Hepatología. Hospital Clínic, IDIBAPS, CIBERehd, Universidad de Barcelona, Barcelona
| | - Agustín Albillos
- Servicio Gastroenterología y Hepatología. Hospital Universitario Ramón y Cajal, IRYCIS, CIBERehd, Un
| | - Raul Jesús Andrade
- Unidad Aparato Digestivo. Complejo Hospitalario de Especialidades Virgen de la Victoria, Málaga
| | - Marina Berenguer
- Servicio Aparato Digestivo. Hospital Universitari i Politècnic la Fe, Universidad de Valencia, CIBER
| | - Javier Crespo
- Servicio Aparato Digestivo. Hospital Universitario Marqués de Valdecilla, Santander
| | | | - Mercè Vergara
- Unidad de Hepatología. Servicio Aparato Digestivo. Parc Taulí Sabadell. Institut d'Investigació i In
| | | | - Alicia Gil
- CEO Market Access, Omakase Consulting, España
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Yoshida EM, Mason A, Peltekian KM, Shah H, Thiele S, Borrelli R, Fischer A. Epidemiology and liver transplantation burden of primary biliary cholangitis: a retrospective cohort study. CMAJ Open 2018; 6:E664-E670. [PMID: 30578275 PMCID: PMC6303180 DOI: 10.9778/cmajo.20180029] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND There is a wealth of data documenting the epidemiology of primary biliary cholangitis (PBC) globally; however, the epidemiology of PBC has not been as well studied in Canada. Our study characterized the Canadian prevalence of PBC and the number of liver transplantations because of PBC. METHODS For this retrospective cohort study we used national hospital administrative records from the Canadian Institute for Health Information, with the exception of Quebec for the prevalence estimate and Quebec and British Columbia for the transplant analysis. Prevalent patients were identified through a diagnostic code for PBC of the Canadian version of the 10th revision of the International Classification of Diseases. PBC transplant patients were identified from their transplant record. Descriptive statistics were used to summarize the characteristics of the study cohorts. RESULTS In 2015, 8680 patients with PBC were identified in Canada, translating to a prevalence of 318 cases per million. Annual prevalence by province varied, ranging from 283 (95% confidence interval [CI] 269-297) cases per million to 465 (95% CI 426-504) cases per million, and the 6-year PBC liver transplantation rate ranged from 3.17 (95% CI 1.27-6.54) to 5.92 (95% CI 3.71-9.08) per million. The Atlantic provinces exhibited the highest PBC prevalence and close to the highest 6-year liver transplantation rate (465 [95% CI 426-504] cases per million and 5.70 [95% CI 426-504, 3.19-9.56] cases per million, respectively). We observed the lowest PBC prevalence (283 [95% CI 269-297] cases per million) and the second lowest 6-year liver transplantation rate in Ontario (3.37 [95% CI 2.47-4.50] cases per million). INTERPRETATION The prevalence of PBC that we found in Canada is similar to the prevalence reported in other studies, but our work also indicates geographic variation within this country. Given our finding of geographic clustering of PBC across Canada, we hypothesize that environmental and genetic factors contribute to the pathogenesis of this condition.
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Affiliation(s)
- Eric M Yoshida
- Division of Gastroenterology (Yoshida), University of British Columbia, Vancouver, BC; Division of Gastroenterology (Mason), University of Alberta, Edmonton, Alta.; Division of Digestive Care & Endoscopy (Peltekian), Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax, NS; Toronto Centre for Liver Disease (Shah), University Health Network, Toronto, Ont.; IQVIA (Thiele, Borrelli, Fischer), Mississauga, Ont
| | - Andrew Mason
- Division of Gastroenterology (Yoshida), University of British Columbia, Vancouver, BC; Division of Gastroenterology (Mason), University of Alberta, Edmonton, Alta.; Division of Digestive Care & Endoscopy (Peltekian), Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax, NS; Toronto Centre for Liver Disease (Shah), University Health Network, Toronto, Ont.; IQVIA (Thiele, Borrelli, Fischer), Mississauga, Ont
| | - Kevork M Peltekian
- Division of Gastroenterology (Yoshida), University of British Columbia, Vancouver, BC; Division of Gastroenterology (Mason), University of Alberta, Edmonton, Alta.; Division of Digestive Care & Endoscopy (Peltekian), Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax, NS; Toronto Centre for Liver Disease (Shah), University Health Network, Toronto, Ont.; IQVIA (Thiele, Borrelli, Fischer), Mississauga, Ont
| | - Hemant Shah
- Division of Gastroenterology (Yoshida), University of British Columbia, Vancouver, BC; Division of Gastroenterology (Mason), University of Alberta, Edmonton, Alta.; Division of Digestive Care & Endoscopy (Peltekian), Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax, NS; Toronto Centre for Liver Disease (Shah), University Health Network, Toronto, Ont.; IQVIA (Thiele, Borrelli, Fischer), Mississauga, Ont
| | - Sherri Thiele
- Division of Gastroenterology (Yoshida), University of British Columbia, Vancouver, BC; Division of Gastroenterology (Mason), University of Alberta, Edmonton, Alta.; Division of Digestive Care & Endoscopy (Peltekian), Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax, NS; Toronto Centre for Liver Disease (Shah), University Health Network, Toronto, Ont.; IQVIA (Thiele, Borrelli, Fischer), Mississauga, Ont
| | - Richard Borrelli
- Division of Gastroenterology (Yoshida), University of British Columbia, Vancouver, BC; Division of Gastroenterology (Mason), University of Alberta, Edmonton, Alta.; Division of Digestive Care & Endoscopy (Peltekian), Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax, NS; Toronto Centre for Liver Disease (Shah), University Health Network, Toronto, Ont.; IQVIA (Thiele, Borrelli, Fischer), Mississauga, Ont
| | - Aren Fischer
- Division of Gastroenterology (Yoshida), University of British Columbia, Vancouver, BC; Division of Gastroenterology (Mason), University of Alberta, Edmonton, Alta.; Division of Digestive Care & Endoscopy (Peltekian), Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax, NS; Toronto Centre for Liver Disease (Shah), University Health Network, Toronto, Ont.; IQVIA (Thiele, Borrelli, Fischer), Mississauga, Ont.
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Hirschfield GM, Dyson JK, Alexander GJM, Chapman MH, Collier J, Hübscher S, Patanwala I, Pereira SP, Thain C, Thorburn D, Tiniakos D, Walmsley M, Webster G, Jones DEJ. The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut 2018; 67:1568-1594. [PMID: 29593060 PMCID: PMC6109281 DOI: 10.1136/gutjnl-2017-315259] [Citation(s) in RCA: 213] [Impact Index Per Article: 30.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2017] [Revised: 01/22/2018] [Accepted: 01/23/2018] [Indexed: 12/12/2022]
Abstract
Primary biliary cholangitis (formerly known as primary biliary cirrhosis, PBC) is an autoimmune liver disease in which a cycle of immune mediated biliary epithelial cell injury, cholestasis and progressive fibrosis can culminate over time in an end-stage biliary cirrhosis. Both genetic and environmental influences are presumed relevant to disease initiation. PBC is most prevalent in women and those over the age of 50, but a spectrum of disease is recognised in adult patients globally; male sex, younger age at onset (<45) and advanced disease at presentation are baseline predictors of poorer outcome. As the disease is increasingly diagnosed through the combination of cholestatic serum liver tests and the presence of antimitochondrial antibodies, most presenting patients are not cirrhotic and the term cholangitis is more accurate. Disease course is frequently accompanied by symptoms that can be burdensome for patients, and management of patients with PBC must address, in a life-long manner, both disease progression and symptom burden. Licensed therapies include ursodeoxycholic acid (UDCA) and obeticholic acid (OCA), alongside experimental new and re-purposed agents. Disease management focuses on initiation of UDCA for all patients and risk stratification based on baseline and on-treatment factors, including in particular the response to treatment. Those intolerant of treatment with UDCA or those with high-risk disease as evidenced by UDCA treatment failure (frequently reflected in trial and clinical practice as an alkaline phosphatase >1.67 × upper limit of normal and/or elevated bilirubin) should be considered for second-line therapy, of which OCA is the only currently licensed National Institute for Health and Care Excellence recommended agent. Follow-up of patients is life-long and must address treatment of the disease and management of associated symptoms.
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Affiliation(s)
- Gideon M Hirschfield
- NIHR Birmingham Biomedical Research Centre, Birmingham, UK
- University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
- Centre for Liver Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - Jessica K Dyson
- Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
- Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
- NIHR Newcastle Biomedical Research Centre, Newcastle, United Kingdom
| | - Graeme J M Alexander
- Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust, London, UK
- UCL Institute for Liver and Digestive Health, Division of Medicine, University College London, London, UK
| | - Michael H Chapman
- Department of Gastroenterology, University College London Hospitals NHS Foundation Trust, London, UK
| | - Jane Collier
- Translational Gastroenterology Unit, Oxford University Hospitals, University of Oxford, Oxford, UK
| | - Stefan Hübscher
- Centre for Liver Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
- Department of Cellular Pathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Imran Patanwala
- Department of Gastroenterology, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK
- University of Liverpool, Liverpool, UK
| | - Stephen P Pereira
- Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust, London, UK
- UCL Institute for Liver and Digestive Health, Division of Medicine, University College London, London, UK
- Department of Gastroenterology, University College London Hospitals NHS Foundation Trust, London, UK
| | | | - Douglas Thorburn
- Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust, London, UK
- UCL Institute for Liver and Digestive Health, Division of Medicine, University College London, London, UK
| | - Dina Tiniakos
- Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
| | | | - George Webster
- Department of Gastroenterology, University College London Hospitals NHS Foundation Trust, London, UK
| | - David E J Jones
- Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
- Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
- NIHR Newcastle Biomedical Research Centre, Newcastle, United Kingdom
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38
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Terziroli Beretta-Piccoli B, Stirnimann G, Cerny A, Semela D, Hessler R, Helbling B, Stickel F, Kalid-de Bakker C, Bihl F, Giostra E, Filipowicz Sinnreich M, Oneta C, Baserga A, Invernizzi P, Carbone M, Mertens J. Geoepidemiology of Primary Biliary Cholangitis: Lessons from Switzerland. Clin Rev Allergy Immunol 2018; 54:295-306. [PMID: 29181702 DOI: 10.1007/s12016-017-8656-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
No data on primary biliary cholangitis (PBC) are available in Switzerland. We established a national patient cohort to obtain information on PBC phenotypes and disease course in Switzerland. Local databases in all university hospitals and in two large secondary centers were searched for case finding. In addition, all primary care physicians, gastroenterologists, rheumatologists, and dermatologists were invited to contribute patients from their own medical records. PBC diagnosis was centrally reviewed. Five hundred one PBC patients were identified, 474 were included in data analysis, and 449 of them were enrolled by tertiary centers. The catchment area accounts for approximately one third of the Swiss population or approximately 2.8 million inhabitants. The median age at diagnosis was 53 years, 84% were women, and 86% were anti-mitochondrial antibody positive. The median follow-up was 5.4 years, 12.6% experienced a liver-related endpoint. Splenomegaly was present at diagnosis in one quarter of patients and in half of male patients. Approximately one third were non-responders to ursodeoxycholic acid (UDCA). The median transplant-free survival at 10 years was 85%. The following variables were independently associated with poor outcome: low platelet count at baseline (HR = 0.99, p < 0.0001), elevated alkaline phosphatase at baseline (HR = 1.36, p < 0.0001), elevated bilirubin at baseline (HR = 1.11, p = 0.001), and elevated alanine aminotransaminase (HR = 1.35, p = 0.04) after 12 months of UDCA therapy. The AUROC for the UK-PBC risk score at 5, 10, and 15 years was 0.82. The AUROC for the Globe score at 5, 10, and 15 years was 0.77. Patients included in this study are currently being enrolled in a prospective nationwide registry with biobank, taking advantage of the collaboration network generated by this study. Our study provides the first snapshot of PBC in Switzerland, describing a diagnostic delay with one quarter of patients diagnosed when already in the cirrhotic stage. We were also able to externally validate the UK-PBC risk score and the Globe score. The ongoing nationwide prospective registry will be fundamental to improve disease awareness and interdisciplinary collaborations and will serve as a platform for clinical and translational research. TRIAL REGISTRATION NUMBER clinicaltrials.gov : NCT02846896; SNCTP000001870.
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Affiliation(s)
| | - Guido Stirnimann
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Andreas Cerny
- Epatocentro Ticino, via Soldino 5, 6900, Lugano, Switzerland
| | - David Semela
- Hepatologie, Kantonsspital St. Gallen, St. Gallen, Switzerland
| | - Roxane Hessler
- Department of Gastroenterology and Hepatology, Centre Hôpitalier Universitaire Vaudois, Lausanne, Switzerland
| | | | - Felix Stickel
- Hepatologie Hirslanden Bern, Bern, Switzerland.,Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | | | - Florian Bihl
- Servizio Epatologia EOC, Bellinzona, Switzerland
| | | | | | - Carl Oneta
- Medical office for Gastroenterology and Hepatology, Winterthur, Switzerland
| | - Adriana Baserga
- Epatocentro Ticino, via Soldino 5, 6900, Lugano, Switzerland
| | - Pietro Invernizzi
- Center for Autoimmune Liver Diseases, Division of Gastroenterology, University of Milan Bicocca, Milan, Italy
| | - Marco Carbone
- Center for Autoimmune Liver Diseases, Division of Gastroenterology, University of Milan Bicocca, Milan, Italy
| | - Joachim Mertens
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
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Factors Associated With Prevalence and Treatment of Primary Biliary Cholangitis in United States Health Systems. Clin Gastroenterol Hepatol 2018; 16:1333-1341.e6. [PMID: 29066370 DOI: 10.1016/j.cgh.2017.10.018] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2017] [Revised: 10/06/2017] [Accepted: 10/07/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Reported prevalence of primary biliary cholangitis (PBC) varies widely. Demographic features and treatment patterns are not well characterized in the United States (US). We analyzed data from the Fibrotic Liver Disease (FOLD) Consortium, drawn from 11 geographically diverse health systems, to investigate epidemiologic factors and treatment of PBC in the US. METHODS We developed a validated electronic health record-based classification model to identify patients with PBC in the FOLD database from 2003 through 2014. We used multivariable modeling to assess the effects of factors associated with PBC prevalence and treatment with ursodeoxycholic acid (UDCA). RESULTS We identified 4241 PBC cases among over 14.5 million patients in FOLD health systems; median follow-up was 5 years. Accuracy of the classification model was excellent, with an area under the receiver operating characteristic curve value of 93%, 94% sensitivity, and 87% specificity. The average patient age at diagnosis was 60 years; 21% were Hispanic, 8% were African American, and 7% were Asian American/American Indian/Pacific Islander. Half of the cohort (49%) had elevated levels of alkaline phosphatase, and overall, 70% were treated with UDCA. The estimated 12-year prevalence of PBC was 29.3 per 100,000 persons. Adjusted prevalence values were highest among women (42.8 per 100,000), White patients (29.6 per 100,000), and patients 60-70 years old (44.7 per 100,000). Prevalence was significantly lower among men and African Americans (10.7 and 19.7 per 100,000, respectively) than women and whites; men and African Americans were also less likely to receive UDCA treatment (odds ratios, 0.6 and 0.5, respectively; P < .05). CONCLUSIONS In an analysis of a large cohort of patients with PBC receiving routine clinical care, we observed significant differences in PBC prevalence and treatment by gender, race, and age.
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40
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Lu M, Zhou Y, Haller IV, Romanelli RJ, VanWormer JJ, Rodriguez CV, Anderson H, Boscarino JA, Schmidt MA, Daida YG, Sahota A, Vincent J, Bowlus CL, Lindor K, Zhang T, Trudeau S, Li J, Rupp LB, Gordon SC. Increasing Prevalence of Primary Biliary Cholangitis and Reduced Mortality With Treatment. Clin Gastroenterol Hepatol 2018; 16:1342-1350.e1. [PMID: 29277621 DOI: 10.1016/j.cgh.2017.12.033] [Citation(s) in RCA: 70] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2017] [Revised: 12/08/2017] [Accepted: 12/12/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS There are few data from longitudinal studies of trends in primary biliary cholangitis (PBC) among patients under routine clinical care in the United States. We collected data from the Fibrotic Liver Disease consortium to investigate changes in the incidence and prevalence of PBC and the effects of patient demographics, clinical features, and treatment on mortality. METHODS We collected demographic and clinical data for the general patient population as well as PBC patients receiving care from 11 health systems in different regions of the United States (Northeast, Midwest, Northwest, and South) from January 1, 2003, through December 31, 2014. Annual percentage changes in PBC prevalence and incidence were estimated using join-point Poisson regression. Differences based on race, age, and gender were calculated with rate ratios. All-cause mortality was estimated using Cox regression with adjustment for patient characteristics and treatment with ursodeoxycholic acid (UDCA). Propensity scores were used to adjust for treatment selection bias. Analyses were adjusted by geographic regions. RESULTS In our racially diverse cohort of 3488 patients with PBC (21% Hispanic, 8% African American, 7% Asian American), 70% had ever received UDCA. From 2006 through 2014, the prevalence of PBC increased from 21.7 to 39.2 per 100,000 persons. Adjusted annual percentage changes in prevalence differed among age groups (≤40 y, 41-50 y, 51-60 y, 61-70 y, and >70 y), ranging from 3.0% to 7.5% (P < .05). Incidence did not change significantly during the study period (4.2 vs 4.3 per 100,000 person-years in 2006 and 2014, respectively; P = .98). Ratios of prevalence for women vs men (3.9:1) and incidence for women vs men (3.2:1) were consistent over the study period. Among African Americans, the prevalence of PBC increased from 16.9 to 30.8 per 100,000 during the study period, and annual incidence ranged from 2.6 to 6.6 per 100,000 person-years. In adjusted analyses, an increased level of alkaline phosphatase at baseline was associated with significantly higher mortality (adjusted hazard ratios [aHR], 1.24; 95% CI, 1.04-1.48 for patients with levels 1-2 times the upper limit of normal and aHR, 2.27; 95% CI, 1.88-2.73 for patients with levels more than 3 times the upper limit of normal). UDCA treatment was associated with significantly reduced mortality (aHR, 0.57; 95% CI, 0.52-0.64). CONCLUSIONS In an analysis of data from patients receiving routine clinical care in Fibrotic Liver Disease Consortium health systems, we found that the prevalence of PBC increased from 2004 through 2014, despite steady incidence. Patient demographic and clinical characteristics, as well as UDCA treatment, affected mortality.
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Affiliation(s)
- Mei Lu
- Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan.
| | - Yueren Zhou
- Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan
| | - Irina V Haller
- Essentia Institute of Rural Health, Essentia Health, Duluth, Minnesota
| | | | | | - Carla V Rodriguez
- Center for Health Research, Kaiser Permanente Mid-Atlantic Research Institute, Rockville, Maryland
| | - Heather Anderson
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, Colorado
| | - Joseph A Boscarino
- Department of Epidemiology and Health Services Research, Geisinger Clinic, Danville, Pennsylvania
| | - Mark A Schmidt
- Center for Health Research, Kaiser Permanente Northwest, Portland, Oregon
| | - Yihe G Daida
- Center for Health Research Hawai'i, Kaiser Permanente, Honolulu, Hawaii
| | - Amandeep Sahota
- Department of Research and Evaluation, Kaiser Permanente Southern California, Los Angeles, California
| | | | | | - Keith Lindor
- College of Health Solutions, Arizona State University, Phoenix, Arizona
| | - Talan Zhang
- Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan
| | - Sheri Trudeau
- Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan
| | - Jia Li
- Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan
| | - Loralee B Rupp
- Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, Michigan
| | - Stuart C Gordon
- Department of Gastroenterology and Hepatology, Henry Ford Health System, Detroit, Michigan
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Abstract
Primary biliary cholangitis (PBC) is considered a model autoimmune disease, characterized by circulating anti-mitochondrial antibodies and a selective autoimmune destruction of intrahepatic cholangiocytes. PBC is heterogeneous in its presentation, symptomatology, disease progression, and response to therapy. The pathogenesis is still largely unknown and epidemiologic studies have facilitated the identification of risk factors and the understanding of disease prevalence, geographic variations, heterogeneity, and differences in sex ratio. Recent studies from large international cohorts have better identified prognostic factors suggesting a change in patient management based on risk-stratification tools to identify subgroups at greatest potential benefit from second-line therapies.
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Affiliation(s)
- Ana Lleo
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, Milan 20090, Italy; Liver Unit, Center for Autoimmune Liver Diseases, Humanitas Clinical and Research Center, Rozzano 20089, Milan, Italy.
| | - Francesca Colapietro
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, Milan 20090, Italy
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42
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Goet JC, Harms MH, Carbone M, Hansen BE. Risk stratification and prognostic modelling in primary biliary cholangitis. Best Pract Res Clin Gastroenterol 2018; 34-35:95-106. [PMID: 30343715 DOI: 10.1016/j.bpg.2018.06.006] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2018] [Accepted: 06/08/2018] [Indexed: 01/31/2023]
Abstract
Primary biliary cholangitis (PBC) is a slowly progressive chronic cholestatic liver disease that, in a subgroup of patients, may result in liver failure or death. The definition of specific risk profiles, i.e. risk stratification, is of critical importance for the identification of these subgroups and thereby the targeting of care. Over the last few years large multicentre cohort studies have improved our knowledge regarding factors associated with progressive disease. Stratification based on biochemical response to ursodoxycholic acid provides a readily available measure to identify groups that might benefit from additional therapies to further improve prognosis. In addition, serum total bilirubin and alkaline phosphatase are now considered the most robustly validated biomarkers of long-term outcome in PBC and are used as endpoints in clinical trials. The GLOBE score and UK-PBC risk score enable us to quantify the risk of future events for the individual patient, allowing more individualized risk prediction. In this review, we discuss both established prognostic factors and newly developed tools to estimate prognosis in PBC, highlighting their strengths, limitations and applicability in clinical practice.
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Affiliation(s)
- Jorn C Goet
- Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
| | - Maren H Harms
- Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
| | - Marco Carbone
- Division of Gastroenterology and Program for Autoimmune Liver Diseases, International Center for Digestive Health, Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy.
| | - Bettina E Hansen
- Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands; Toronto Centre for Liver Disease, Toronto General Hospital, Toronto, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada.
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43
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Harms MH, van Buuren HR, van der Meer AJ. Improving prognosis in primary biliary cholangitis - Therapeutic options and strategy. Best Pract Res Clin Gastroenterol 2018; 34-35:85-94. [PMID: 30343714 DOI: 10.1016/j.bpg.2018.06.004] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Accepted: 06/08/2018] [Indexed: 01/31/2023]
Abstract
Overall survival in primary biliary cholangitis is diminished. As patients are often asymptomatic, the disease may silently progress towards cirrhosis and liver failure. Timely diagnosis and effective treatment options are of vital importance to improve the prognosis of affected patients. Ursodeoxycholic acid is the standard of care first-line therapy and is associated with a reduced risk of liver transplantation and death. Treatment with UDCA is relevant for all patients, irrespective of disease stage or biochemical response. In case of incomplete biochemical response according to internationally accepted criteria, second-line treatment should be considered to improve long-term prognosis. Ursodeoxycholic acid has been the only accepted treatment for PBC during the last decades. Recent research, however, has identified a number of new therapeutic targets and agents, including obeticholic acid, fibrates and budesonide. While these agents all qualify as potentially beneficial second-line treatment, obeticholic acid is currently the only drug specifically approved for the treatment of PBC. Although long-term follow-up studies for these agents are mostly lacking, improvement of biochemical surrogate markers of clinical outcome induced by these drugs suggests a therapeutic benefit. The authors of this review aim to provide a summary of the results of previous and current studies evaluating medical treatments, and propose a treatment strategy based on the evidence available today.
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Affiliation(s)
- Maren H Harms
- Erasmus University Medical Center, Rotterdam, The Netherlands.
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44
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Rosa R, Cristoferi L, Tanaka A, Invernizzi P. Geoepidemiology and (epi-)genetics in primary biliary cholangitis. Best Pract Res Clin Gastroenterol 2018; 34-35:11-15. [PMID: 30343705 DOI: 10.1016/j.bpg.2018.05.011] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2018] [Accepted: 05/14/2018] [Indexed: 01/31/2023]
Abstract
Primary biliary cholangitis (PBC) is a rare female preponderant chronic autoimmune cholestatic liver disease, characterized by intrahepatic ductopenia and progressive fibrosis. During last decades incidence and prevalence showed an increasing rate which vary widely worldwide demonstrating an important interaction between environmental and genetic factors. Heritability suggested by familial occurrence and monozygotic twins concordance have been confirmed in more studies. Epigenetics mechanisms such as histone modification and DNA methylation can partially explain predisposition and inheritance of this disease. Nevertheless, an association with specific class II human leukocyte antigen (HLA) variants have been reported, showing an increase risk in susceptibility. More recently, data regarding a strong protective association between PBC and HLA alleles confirmed this association. After recent genome-wide association studies (GWAS), a more intricate interaction between PBC and the HLA region has been shown. Furthermore, GWAS also identified several immune-related-genes implicated. More genome-wide association studies on this disease are needed to reach a complete and systematic knowledge of this disease. In this review we discuss more recent issued data on geoepidemiology of PBC and the role of (epi-)genetic mechanisms in its pathogenesis.
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Affiliation(s)
- Roberto Rosa
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy
| | - Laura Cristoferi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy
| | - Atsushi Tanaka
- Department of Medicine, Teikyo University School of Medicine, 2-11-1, Kaga, Itabashi-ku, Tokyo, Japan
| | - Pietro Invernizzi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy.
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45
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46
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Murillo Perez CF, Goet JC, Lammers WJ, Gulamhusein A, van Buuren HR, Ponsioen CY, Carbone M, Mason A, Corpechot C, Invernizzi P, Mayo MJ, Battezzati PM, Floreani A, Pares A, Nevens F, Kowdley KV, Bruns T, Dalekos GN, Thorburn D, Hirschfield G, LaRusso NF, Lindor KD, Zachou K, Poupon R, Trivedi PJ, Verhelst X, Janssen HLA, Hansen BE. Milder disease stage in patients with primary biliary cholangitis over a 44-year period: A changing natural history. Hepatology 2018; 67:1920-1930. [PMID: 29220537 DOI: 10.1002/hep.29717] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2017] [Revised: 11/21/2017] [Accepted: 12/02/2017] [Indexed: 01/03/2023]
Abstract
UNLABELLED Changes over time in the presenting features and clinical course of patients with primary biliary cholangitis are poorly described. We sought to describe temporal trends in patient and disease characteristics over a 44-year period across a large international primary biliary cholangitis cohort of 4,805 patients diagnosed between 1970 and 2014, from 17 centers across Europe and North America. Patients were divided into five cohorts according to their year of diagnosis: 1970-1979 (n = 143), 1980-1989 (n = 858), 1990-1999 (n = 1,754), 2000-2009 (n = 1,815), and ≥2010 (n = 235). Age at diagnosis, disease stage, response to ursodeoxycholic acid, and clinical outcomes were compared. Mean age at diagnosis increased incrementally by 2-3 years per decade from 46.9 ± 10.1 years in the 1970s to 57.0 ± 12.1 years from 2010 onward (P < 0.001). The female to male ratio (9:1) and antimitochondrial antibody positivity (90%) were not significantly variable. The proportion of patients presenting with mild biochemical disease (according to Rotterdam staging) increased from 41.3% in the 1970s to 72.2% in the 1990s (P < 0.001) and remained relatively stable thereafter. Patients with a mild histological stage at diagnosis increased from 60.4% (1970-1989) to 76.5% (1990-2014) (P < 0.001). Correspondingly, response to ursodeoxycholic acid according to Paris-I criteria increased; 51.7% in the 1970s and 70.5% in the 1990s (P < 0.001). Recent decades were also characterized by lower decompensation rates (18.5% in the 1970s to 5.8% in the 2000s, P < 0.001) and higher 10-year transplant-free survival (48.4%, 68.7%, 79.7%, and 80.1% for each respective cohort; P < 0.001). CONCLUSION In recent decades, a pattern of primary biliary cholangitis presentation consistent with an older age at diagnosis alongside reduced disease severity has been noted; the observed trends may be explained by an increase in routine testing of liver function and/or a changing environmental trigger. (Hepatology 2018;67:1920-1930).
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Affiliation(s)
- Carla F Murillo Perez
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, ON, Canada.,Insitute of Medical Science, University of Toronto, Toronto, ON, Canada
| | - Jorn C Goet
- Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Willem J Lammers
- Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Aliya Gulamhusein
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, ON, Canada
| | - Henk R van Buuren
- Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Cyriel Y Ponsioen
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
| | - Marco Carbone
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy
| | - Andrew Mason
- Divison of Gastroenterology and Hepatology, University of Alberta, Edmonton, AB, Canada
| | - Christophe Corpechot
- Centre de Référence des Maladies Inflammatoires des VoiesBiliaires, Hôpital Saint-Antoine, Paris, France
| | - Pietro Invernizzi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy
| | - Marlyn J Mayo
- Digestive and Liver diseases, UT Southwestern Medical Center, Dallas, TX
| | | | - Annarosa Floreani
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Albert Pares
- Liver Unit, Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Frederik Nevens
- Department of Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium
| | | | - Tony Bruns
- Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University of Jena, Jena, Germany
| | - George N Dalekos
- Department of Medicine and Research Laboratory of Internal Medicine, University of Thessaly, Larissa, Greece
| | - Douglas Thorburn
- The Sheila Sherlock Liver Centre, The Royal Free Hospital, London, UK
| | - Gideon Hirschfield
- NIHR, Biomedical Research Centre and Centre for Liver Research, University of Birmingham, Birmingham, UK
| | | | | | - Kalliopi Zachou
- Department of Medicine and Research Laboratory of Internal Medicine, University of Thessaly, Larissa, Greece
| | - Raoul Poupon
- Centre de Référence des Maladies Inflammatoires des VoiesBiliaires, Hôpital Saint-Antoine, Paris, France
| | - Palak J Trivedi
- NIHR, Biomedical Research Centre and Centre for Liver Research, University of Birmingham, Birmingham, UK
| | - Xavier Verhelst
- Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium
| | - Harry L A Janssen
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, ON, Canada
| | - Bettina E Hansen
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, ON, Canada.,Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.,Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada
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47
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Shaheen AA, Kaplan GG, Almishri W, Vallerand I, Frolkis AD, Patten S, Swain MG. The impact of depression and antidepressant usage on primary biliary cholangitis clinical outcomes. PLoS One 2018; 13:e0194839. [PMID: 29617396 PMCID: PMC5884515 DOI: 10.1371/journal.pone.0194839] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2018] [Accepted: 02/14/2018] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Depression is prevalent in primary biliary cholangitis (PBC) patients. Our aims were to examine the effects of depression and antidepressants on hepatic outcomes of PBC patients. METHODS We used the UK Health Improvement Network database to identify PBC patients between 1974 and 2007. Our primary outcome was one of three clinical events: decompensated cirrhosis, liver transplantation and death. We assessed depression and each class of antidepressant medication in adjusted multivariate Cox proportional hazards models to identify independent predictors of outcomes. In a sensitivity analysis, the study population was restricted to PBC patients using ursodeoxycholic acid (UDCA). RESULTS We identified 1,177 PBC patients during our study period. In our cohort, 86 patients (7.3%) had a depression diagnosis prior to PBC diagnosis, while 79 patients (6.7%) had a depression diagnosis after PBC diagnosis. Ten-year incidence of mortality, decompensated cirrhosis, and liver transplantation were 13.4%, 6.6%, and 2.0%, respectively. In our adjusted models, depression status was not a predictor of poor outcomes. After studying all classes of antidepressants, using the atypical antidepressant mirtazapine after PBC diagnosis was significantly protective (Adjusted HR 0.23: 95% CI 0.07-0.72) against poor liver outcomes (decompensation, liver transplant, mortality), which remained statistically significant in patients using UCDA (HR 0.21: 95% CI 0.05-0.83). CONCLUSIONS In our study, depression was not associated with poor clinical outcomes. However, using the antidepressant mirtazapine was associated with decreased mortality, decompensated cirrhosis and liver transplantation in PBC patients. These findings support further assessment of mirtazapine as a potential treatment for PBC patients.
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Affiliation(s)
- Abdel-Aziz Shaheen
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
- * E-mail:
| | - Gilaad G. Kaplan
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Wagdi Almishri
- Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Isabelle Vallerand
- Departments of Community Health Sciences and Psychiatry, University of Calgary, Calgary, Alberta, Canada
| | - Alexandra D. Frolkis
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
- Departments of Community Health Sciences and Psychiatry, University of Calgary, Calgary, Alberta, Canada
| | - Scott Patten
- Departments of Community Health Sciences and Psychiatry, University of Calgary, Calgary, Alberta, Canada
| | - Mark G. Swain
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
- Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
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48
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Pan HY, Dai YN, Zheng JN, Shi KQ, Van Poucke S, Zou H, Zheng MH. National incidence of autoimmune liver diseases and its relationship with the human development index. Oncotarget 2018; 7:46273-46282. [PMID: 27323833 PMCID: PMC5216797 DOI: 10.18632/oncotarget.10090] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2016] [Accepted: 06/02/2016] [Indexed: 12/24/2022] Open
Abstract
Objective Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), autoimmune hepatitis (AIH) and immunoglobulin G4 related cholangitis represent the major autoimmune liver diseases (AILD). However, the relationship between AILD incidence and socioeconomic development levels is yet to be explored. Results A total of 43 studies were included. There was a positive but not significant correlation between the PBC incidence and HDI on a global level (r=0.348, P=0.082). However, in Europe, a significantly positive correlation existed between the PBC incidence and HDI (r=0.455, P=0.044). No statistical correlation between PSC incidence and HDI was observed (r=0.116, P=0.706). The incidence of AIH revealed a positive correlation with the national HDI both globally (r=0.638, P=0.014) and in Europe (r=0.644, P=0.045). Moreover, the PBC incidence demonstrated a positive correlation with the health index (r=0.422, P=0.036), but a negative correlation with the education index (r= −0.650, P<0.01). Moreover, the income index presented a positive correlation with both the PSC incidence (r=0.599, P=0.031) and the AIH incidence (r=0.649, P=0.012). Methods PubMed was searched to identify relevant epidemiological studies on AILD. The human development index (HDI) was applied as an indicator for socioeconomic development. HDI data were obtained and calculated based on the 2014 Human Development Report. Pearson coefficient and linear regression analysis were conducted to estimate the correlation between incidence and HDI. Conclusions There is positive association between the national incidence of AILD and the socioeconomic status, as measured by HDI. In less-developed countries, the incidence of AILD, especially PBC and AIH, might be less common.
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Affiliation(s)
- Hong-Ying Pan
- Department of Infection Diseases, Zhejiang Provincial People's Hospital, Hangzhou, China
| | - Yi-Ning Dai
- Department of Infection Diseases, Zhejiang Provincial People's Hospital, Hangzhou, China
| | - Ji-Na Zheng
- Department of Hepatology, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.,School of The First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Ke-Qing Shi
- Department of Hepatology, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.,Institute of Hepatology, Wenzhou Medical University, Wenzhou, China
| | - Sven Van Poucke
- Department of Anesthesiology, Intensive Care, Emergency Medicine and Pain Therapy, Ziekenhuis Oost-Limburg, Genk, Belgium
| | - Hai Zou
- Department of Infection Diseases, Zhejiang Provincial People's Hospital, Hangzhou, China
| | - Ming-Hua Zheng
- Department of Hepatology, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.,Institute of Hepatology, Wenzhou Medical University, Wenzhou, China
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Lleo A, Marzorati S, Anaya JM, Gershwin ME. Primary biliary cholangitis: a comprehensive overview. Hepatol Int 2017; 11:485-499. [PMID: 29164395 DOI: 10.1007/s12072-017-9830-1] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2017] [Accepted: 10/05/2017] [Indexed: 12/15/2022]
Abstract
Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by biliary destruction, progressive cholestasis, and potentially liver cirrhosis. Patients develop a well-orchestrated immune reaction, both innate and adaptive, against mitochondrial antigens that specifically targets intrahepatic biliary cells. A puzzling feature of PBC is that the immune attack is predominantly organ specific, although the mitochondrial autoantigens are found in all nucleated cells. The disease results from a combination of genetic and environmental risk factors; however, the exact pathogenesis remains unclear. Serologically, PBC is characterized by presence of antimitochondrial antibodies, which are present in 90-95 % of patients and are often detectable years before clinical signs appear. Like other complex disorders, PBC is heterogeneous in its presentation, symptomatology, disease progression, and response to therapy. A significant number of patients develop end-stage liver disease and eventually require liver transplantation. Recent studies from large international cohorts have better identified prognostic factors, suggesting a change in patient management based on risk stratification. Therapeutic options are changing. In this review we discuss data on the autoimmune responses and treatment of the disease.
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Affiliation(s)
- Ana Lleo
- Liver Unit and Center for Autoimmune Liver Diseases, Humanitas Clinical and Research Center, Rozzano, MI, Italy.,Department of Biomedical Sciences, Humanitas University, Rozzano, MI, Italy
| | - Simona Marzorati
- Liver Unit and Center for Autoimmune Liver Diseases, Humanitas Clinical and Research Center, Rozzano, MI, Italy
| | - Juan-Manuel Anaya
- Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia
| | - M Eric Gershwin
- Division of Rheumatology, Allergy, and Clinical Immunology, University of California at Davis, Davis, CA, USA.
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50
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Cheung KS, Seto WK, Fung J, Lai CL, Yuen MF. Epidemiology and Natural History of Primary Biliary Cholangitis in the Chinese: A Territory-Based Study in Hong Kong between 2000 and 2015. Clin Transl Gastroenterol 2017; 8:e116. [PMID: 28858291 PMCID: PMC5587844 DOI: 10.1038/ctg.2017.43] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2017] [Accepted: 07/17/2017] [Indexed: 02/06/2023] Open
Abstract
Objectives: Studies on the epidemiology of primary biliary cholangitis (PBC) in the Chinese population are lacking. We aimed to determine the epidemiology of PBC in Hong Kong (HK) with a population of 7.3 million. Methods: We retrieved data from the electronic database of the HK Hospital Authority, the only public healthcare provider in Hong Kong. PBC cases between 2000 and 2015 were identified by International Classification of Diseases (ICD)-9 code. We estimated the age-/sex-adjusted incidence rate and prevalence of PBC, and analyzed the adverse outcomes (hepatocellular carcinoma (HCC), liver transplantation, and death). Results: One thousand and sixteen PBC patients aged ≥20 years were identified (female-to-male ratio 4:1; median age 60.6 years, interquartile range (IQR) 51.8–72.6 years; median follow-up 5.6 years, IQR 1.6–8.7 years). The average age/sex-adjusted annual incidence rate and prevalence were 8.4 per million person-years and 56.4 per million, respectively. Between 2000 and 2015, the age/sex-adjusted annual incidence rate increased from 6.7 to 8.1 per million person-years (Poisson P=0.002), while age/sex-adjusted prevalence increased from 31.1 to 82.3 per million (Poisson P<0.001). Fifty patients developed HCC, and 49 underwent liver transplantation. Case fatality risk decreased from 10.8 to 6.4% (Poisson P=0.003). The 5- and 10-year overall survival rates were 81.5 and 78.3%, whereas the transplant-free survival rates were 78.0% and 74.3%, respectively. Increasing age, cirrhosis and being treatment-naïve were associated with lower transplant-free survival. Conclusions: There is a considerable increase in the incidence and prevalence of PBC in the Chinese population over the past 16 years, with significant morbidity and mortality.
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Affiliation(s)
- Ka-Shing Cheung
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong
| | - Wai-Kay Seto
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong.,State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, Hong Kong
| | - James Fung
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong.,State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, Hong Kong
| | - Ching-Lung Lai
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong.,State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, Hong Kong
| | - Man-Fung Yuen
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong.,State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, Hong Kong
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