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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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Wang H, Li Y, Pu X, Liang X, Tang R, Ma X. MGAT5/TMEM163 variant is associated with prognosis in ursodeoxycholic acid-treated patients with primary biliary cholangitis. J Gastroenterol 2024; 59:66-74. [PMID: 37845416 DOI: 10.1007/s00535-023-02045-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Accepted: 09/20/2023] [Indexed: 10/18/2023]
Abstract
BACKGROUND Primary biliary cholangitis (PBC) is a chronic immune-mediated liver disease. Previous genome-wide meta-analysis has identified the association between variants in TMEM163 with PBC. Here we aimed to evaluate the association between variants near the reported risk loci of TMEM163 at 2q21.3 and prognosis of PBC patients. METHODS We performed a retrospective analysis of 347 PBC patients treated with ursodeoxycholic acid (UDCA) for at least 1 year. We collected clinical data at diagnosis and 1 year after UDCA treatment. SNPs within 200 kb upstream and downstream of the lead variant were genotyped and screened. RESULTS We identified that rs661899 near MGAT5 and TMEM163 showed the strongest association with prognosis in PBC patients. Patients carrying the rs661899 T allele tended to respond incompletely to UDCA treatment and had worse performances in laboratory values including aspartate aminotransferase (53.5 vs 32 vs 28.5 U/L, p = 0.001), alkaline phosphate (157.25 vs 125 vs 113 U/L, p = 0.001), albumin (41.5 vs 42.3 vs 43.7 g/L, p = 0.008) and bilirubin (19.2 vs 14.9 vs 12.85 μmol/L, p = 0.001). GLOBE scores (p = 4.8 × 10-5) and UK-PBC risk scores (p = 4.6 × 10-4) were strongly correlated with rs661899 genotype. Patients with TT genotype had a higher risk for adverse events compared with CC genotype (p = 0.039) during the 1-year follow-up. Results were also verified in an independent cohort. CONCLUSIONS PBC patients carrying the rs661899 T allele are associated with poor prognosis and adverse outcomes after 1-year UDCA therapy.
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Affiliation(s)
- Hanxiao Wang
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, 200001, China
| | - You Li
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, 200001, China
| | - Xiting Pu
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, 200001, China
| | - Xueying Liang
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, 200001, China
| | - Ruqi Tang
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, 200001, China.
| | - Xiong Ma
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, 200001, China.
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Gazda J, Drazilova S, Gazda M, Janicko M, Koky T, Macej M, Carbone M, Jarcuska P. Treatment response to ursodeoxycholic acid in primary biliary cholangitis: A systematic review and meta-analysis. Dig Liver Dis 2023; 55:1318-1327. [PMID: 36593158 DOI: 10.1016/j.dld.2022.12.010] [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: 08/26/2022] [Revised: 11/09/2022] [Accepted: 12/19/2022] [Indexed: 01/04/2023]
Abstract
BACKGROUND Several ursodeoxycholic acid (UDCA) treatment response definitions have been introduced in primary biliary cholangitis (PBC). However, the lack of a gold standard results in heterogeneity in second-line treatment research and clinical practice. AIMS This study aimed to explore which UDCA treatment response endpoint serves as the most accurate predictive model of long-term outcome. METHODS A systematic review and meta-analysis of UDCA treatment response endpoints (and corresponding validations) were performed. RESULTS Sixteen individual UDCA treatment response endpoints and 96 external validations were found. Barcelona, Paris-1, Paris-2, Rotterdam, Toronto and GLOBE and UK-PBC Risk Scores are currently most robustly validated in external populations. The results show that the continuous models (GLOBE and UK-PBC Risk Scores) serve as the most accurate predictive models. Besides standard UDCA treatment response endpoints, the alkaline phosphatase and total bilirubin normalization has been suggested as a new therapeutic target. CONCLUSIONS The GLOBE and UK-PBC Risk Scores are the most suitable for the real-world allocation of second-line therapies (obeticholic acid and fibrates). However, in the wake of the recent findings, alkaline phosphatase and total bilirubin normalization should be the primary outcome in trial research in PBC.
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Affiliation(s)
- Jakub Gazda
- 2nd Department of Internal Medicine, Pavol Jozef Safarik University and Louis Pasteur University Hospital, Trieda SNP 1, 040 12, Kosice, Slovakia
| | - Sylvia Drazilova
- 2nd Department of Internal Medicine, Pavol Jozef Safarik University and Louis Pasteur University Hospital, Trieda SNP 1, 040 12, Kosice, Slovakia.
| | - Matej Gazda
- Intelligent Information Systems Laboratory, Technical University of Kosice, Bozeny Nemcovej 32, 04201 Kosice, Slovakia
| | - Martin Janicko
- 2nd Department of Internal Medicine, Pavol Jozef Safarik University and Louis Pasteur University Hospital, Trieda SNP 1, 040 12, Kosice, Slovakia
| | - Tomas Koky
- 2nd Department of Internal Medicine, Pavol Jozef Safarik University and Louis Pasteur University Hospital, Trieda SNP 1, 040 12, Kosice, Slovakia
| | - Marian Macej
- 2nd Department of Internal Medicine, Pavol Jozef Safarik University and Louis Pasteur University Hospital, Trieda SNP 1, 040 12, Kosice, Slovakia
| | - Marco Carbone
- Division of Gastroenterology and Centre for Autoimmune Liver Disease, University of Milano-Bicocca, Piazza dell'Ateneo Nuovo, 1, 20126 Milano, Italy
| | - Peter Jarcuska
- 2nd Department of Internal Medicine, Pavol Jozef Safarik University and Louis Pasteur University Hospital, Trieda SNP 1, 040 12, Kosice, Slovakia
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Li SZ, Liu SH, Hao M, Yu T, Hu S, Liu L, Liu ZL. Thrombocytopenia as an important determinant of poor prognosis in patients with pyogenic liver abscess: a retrospective case series. Front Surg 2023; 10:1192523. [PMID: 37560317 PMCID: PMC10407093 DOI: 10.3389/fsurg.2023.1192523] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Accepted: 06/30/2023] [Indexed: 08/11/2023] Open
Abstract
BACKGROUND Thrombocytopenia and poor prognosis in severe conditions are associated. However, the clinical significance of thrombocytopenia in pyogenic liver abscess (PLA) has not been evaluated. OBJECTIVE To evaluate the association between thrombocytopenia and the prognosis of patients with PLA. METHODS A consecutive case series of 458 adult patients with PLA hospitalized at Tongji Hospital (Wuhan, China) between October 2011 and June 2021 was included in this cross-sectional analysis. Patient data were compared between the thrombocytopenia and non-thrombocytopenia groups. Multivariate logistic regression, receiver operating characteristic (ROC) curve and propensity score -matched analyses (PSM) were performed. RESULTS Of the 458 patients with PLA, 94 (20.5%) developed thrombocytopenia, 19 (4.1%) developed septic shock, 14 (3.1%) were admitted to the ICU, and 15 (3.3%) died during hospitalization. Thrombocytopenia was independently associated with shock (95%CI = 3.529-57.944, P < 0.001), ICU admission (95%CI = 1.286-25.733, P = 0.022), and mortality (95%CI = 1.947-34.223, P = 0.004) in multivariate regression analysis. ROC analysis showed that thrombocytopenia may be an identified marker of shock [area under the ROC curve (AUC), 0.8119; cut-off, 92.50; P < 0.0001], ICU admission (AUC, 0.7484; cut-off, 82.50; P < 0.0015), and mortality (AUC, 0.7827; cut-off, 122.50; P < 0.002). These findings remained consistent across 86 pairs of patients analyzed for PSM analyses. CONCLUSIONS Thrombocytopenia is an independent risk factor for poor prognosis in PLA and patients may be more prone to adverse outcomes.
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Affiliation(s)
- Sheng-zhong Li
- Department of Surgery, Wuhan Jinyintan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shao-hua Liu
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, China
| | - Meng Hao
- Department of Gastroenterology, Zigui County People’s Hospital, Yichang, China
| | - Tian Yu
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, China
| | - Song Hu
- Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Li Liu
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, China
| | - Zhe-long Liu
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, China
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Huang LX, Wang ZL, Jin R, Chen HS, Feng B. Incomplete response to ursodeoxycholic acid in primary biliary cholangitis: criteria, epidemiology, and possible mechanisms. Expert Rev Gastroenterol Hepatol 2022; 16:1065-1078. [PMID: 36469627 DOI: 10.1080/17474124.2022.2153672] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
INTRODUCTION As a common autoimmune disease with the characteristic of early complication, primary biliary cholangitis (PBC) leads to an increasing number of mortalities among people with end-stage liver disease (ESLD) waiting for liver transplantation. Ursodeoxycholic acid (UDCA) is the only approved first-line medicine for PBC, and a good response to treatment could acquire an ideal prognosis. Patients with poor UDCA response usually have more adverse outcomes and worse survival, therefore, the management of this group become a major consideration. AREAS COVERED Due to the complexity of race and environment for PBC, different criteria for UDCA response exhibit various predictive performances. Factors affecting UDCA response conditions include gender, age, ethnicity, serum indicators, auto-antibodies, and autoimmune comorbidities, while no agreement has been reached. In this review, we mainly focus on cellular senescence, immune-mediated damage, and vitamin D deficiency as possible mechanisms for UDCA non-responders. EXPERT OPINION The pathogenesis of PBC has yet to be clarified. Immunology-related mechanisms and therapy targets ought to be the main effort made for further study. Irrespective of the response condition, UDCA is recommended for routine administration in all PBC patients without contraindication. Ongoing clinical trials of second-line and additional therapy exhibit promising prospects.
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Affiliation(s)
- Lin-Xiang Huang
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, PR China
| | - Zi-Long Wang
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, PR China
| | - Rui Jin
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, PR China
| | - Hong-Song Chen
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, PR China
| | - Bo Feng
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, PR China
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Simplified 6-month prediction scores for primary biliary cholangitis patients treated with ursodeoxycholic acid. Eur J Gastroenterol Hepatol 2022; 34:411-416. [PMID: 34074987 DOI: 10.1097/meg.0000000000002216] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES To develop a prognostic score evaluating treatment response at 6 months after ursodeoxycholic acid (UDCA) initiation in primary biliary cholangitis (PBC) patients. METHODS Adult PBC patients who were newly prescribed UDCA at our institution (n = 292) were included. Significant determinants of liver-related adverse events in the multivariable Cox model were used for score development, weighted by β-coefficients. Discrimination ability was assessed using Harrell's C-statistic. The performance of our model was compared to the previous models. RESULTS Our model included the following variables evaluated at 6 months: (1) alkaline phosphatase decline of less than 50% from baseline and >upper limit normal (ULN) (2 points); (2) bilirubin >ULN (2 points); (3) albumin <lower limit normal (1 point). The score ranged from 0 to 5 points. C-statistic estimates were 0.87 (overall cohort), 0.87 (no cirrhosis) and 0.77 (cirrhosis), indicating good discrimination of treatment response. Patients with scores ≥3 points had significant shorter transplant-free survival (TFS) than scores <3 points (P < 0.001). The TFS rates for patients with score ≥3 points at 5, 10 and 15 years were 52, 26 and 7%, and for patients with scores <3 points were 96, 92 and 82%, respectively. There was no significant difference between the performance of our 6-month model and the previous models (Paris I, Paris II, Barcelona, Rotterdam and GLOBE scores evaluated at 12 months) in predicting liver-related outcomes (all P = NS). CONCLUSION This novel 6-month prognostic model showed good prognostic performance. Utilization of this score would identify patients with suboptimal responses to UDCA earlier.
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Berzigotti A, Tsochatzis E, Boursier J, Castera L, Cazzagon N, Friedrich-Rust M, Petta S, Thiele M. EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis - 2021 update. J Hepatol 2021; 75:659-689. [PMID: 34166721 DOI: 10.1016/j.jhep.2021.05.025] [Citation(s) in RCA: 947] [Impact Index Per Article: 236.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 05/28/2021] [Indexed: 02/07/2023]
Abstract
Non-invasive tests are increasingly being used to improve the diagnosis and prognostication of chronic liver diseases across aetiologies. Herein, we provide the latest update to the EASL Clinical Practice Guidelines on the use of non-invasive tests for the evaluation of liver disease severity and prognosis, focusing on the topics for which relevant evidence has been published in the last 5 years.
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Natarajan Y, Tansel A, Patel P, Emologu K, Shukla R, Qureshi Z, El-Serag HB, Thrift AP, Kanwal F. Incidence of Hepatocellular Carcinoma in Primary Biliary Cholangitis: A Systematic Review and Meta-Analysis. Dig Dis Sci 2021; 66:2439-2451. [PMID: 32743773 DOI: 10.1007/s10620-020-06498-7] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Accepted: 07/18/2020] [Indexed: 01/17/2023]
Abstract
BACKGROUND The risk and determinants of HCC in patients with primary biliary cholangitis (PBC) are unclear. We conducted a systematic review and meta-analysis of the incidence of HCC and risk factors associated with HCC risk among patients with PBC. METHODS We searched PubMed, EMBASE, MEDLINE, Cochrane databases and reference lists from relevant articles to identify cohort studies that examined incidence of HCC in patients with PBC from inception through November 2019. RESULTS A total of 29 studies including 22,615 patients met the eligibility criteria. The median cohort size was 292 patients followed for an average of 76 months. The pooled incidence rate for patients with PBC was 4.17 per 1000 patient-years (95% CI 3.17-5.47). On subgroup analysis, the incidence of HCC in patients with PBC cirrhosis was 15.7 per 1000 patient-years (95% CI 8.73-28.24). The HCC incidence rate was 9.82 per 1000 person-years (95% CI 5.92-16.28) in men and 3.82 per 1000 person-years (95% CI 2.85-5.11) in women. CONCLUSIONS Cirrhosis is the strongest risk factor for HCC in patients with PBC. Male gender was also a risk factor. Our meta-analysis supports current recommendations of HCC surveillance in patients with PBC cirrhosis. Further studies are needed to evaluate risk factors in this population.
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Affiliation(s)
- Yamini Natarajan
- Section of Gastroenterology and Hepatology and Clinical Epidemiology and Comparative Effectiveness Program in the Health Services Research, Michael E. DeBakey VA Medical Center, Baylor College of Medicine, 2002 Holcombe Blvd (MS152), Houston, TX, 77030, USA.
| | - Aylin Tansel
- Section of Gastroenterology and Hepatology and Clinical Epidemiology and Comparative Effectiveness Program in the Health Services Research, Michael E. DeBakey VA Medical Center, Baylor College of Medicine, 2002 Holcombe Blvd (MS152), Houston, TX, 77030, USA
| | - Parth Patel
- Section of Gastroenterology and Hepatology and Clinical Epidemiology and Comparative Effectiveness Program in the Health Services Research, Michael E. DeBakey VA Medical Center, Baylor College of Medicine, 2002 Holcombe Blvd (MS152), Houston, TX, 77030, USA
| | - Kingsley Emologu
- Section of Gastroenterology and Hepatology and Clinical Epidemiology and Comparative Effectiveness Program in the Health Services Research, Michael E. DeBakey VA Medical Center, Baylor College of Medicine, 2002 Holcombe Blvd (MS152), Houston, TX, 77030, USA
| | - Richa Shukla
- Section of Gastroenterology and Hepatology and Clinical Epidemiology and Comparative Effectiveness Program in the Health Services Research, Michael E. DeBakey VA Medical Center, Baylor College of Medicine, 2002 Holcombe Blvd (MS152), Houston, TX, 77030, USA
| | - Zeeshan Qureshi
- Section of Gastroenterology and Hepatology and Clinical Epidemiology and Comparative Effectiveness Program in the Health Services Research, Michael E. DeBakey VA Medical Center, Baylor College of Medicine, 2002 Holcombe Blvd (MS152), Houston, TX, 77030, USA
| | - Hashem B El-Serag
- Section of Gastroenterology and Hepatology and Clinical Epidemiology and Comparative Effectiveness Program in the Health Services Research, Michael E. DeBakey VA Medical Center, Baylor College of Medicine, 2002 Holcombe Blvd (MS152), Houston, TX, 77030, USA.,Clinical Epidemiology and Comparative Effectiveness Program, Section of Health Services Research (IQuESt), Michael E. DeBakey VA Medical Center, Baylor College of Medicine, Houston, TX, USA.,Texas Medical Center Digestive Disease Center, Houston, TX, USA.,Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine, Houston, TX, USA
| | - Aaron P Thrift
- Section of Gastroenterology and Hepatology and Clinical Epidemiology and Comparative Effectiveness Program in the Health Services Research, Michael E. DeBakey VA Medical Center, Baylor College of Medicine, 2002 Holcombe Blvd (MS152), Houston, TX, 77030, USA.,Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine, Houston, TX, USA
| | - Fasiha Kanwal
- Section of Gastroenterology and Hepatology and Clinical Epidemiology and Comparative Effectiveness Program in the Health Services Research, Michael E. DeBakey VA Medical Center, Baylor College of Medicine, 2002 Holcombe Blvd (MS152), Houston, TX, 77030, USA.,Clinical Epidemiology and Comparative Effectiveness Program, Section of Health Services Research (IQuESt), Michael E. DeBakey VA Medical Center, Baylor College of Medicine, Houston, TX, USA.,Texas Medical Center Digestive Disease Center, Houston, TX, USA.,Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine, Houston, TX, USA
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Mehta TI, Weissman S, Fung BM, Tabibian JH. Geoepidemiologic variation in outcomes of primary sclerosing cholangitis. World J Hepatol 2020; 12:116-124. [PMID: 32685104 PMCID: PMC7336294 DOI: 10.4254/wjh.v12.i4.116] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Revised: 03/15/2020] [Accepted: 03/24/2020] [Indexed: 02/06/2023] Open
Abstract
Primary sclerosing cholangitis (PSC) is a chronic, progressive, hepatobiliary disease characterized by inflammation and fibrosis of the intra- and extra-hepatic bile ducts. Its natural history is one that generally progresses towards cirrhosis, liver failure, cholangiocarcinoma, and ultimately disease-related death, with a median liver transplantation-free survival time of approximately 15-20 years. However, despite its lethal nature, PSC remains a heterogenous disease with significant variability in outcomes amongst different regions of the world. There are also many regions where the outcomes of PSC have not been studied, limiting the overall understanding of this disease worldwide. In this review, we present the geoepidemiologic variations in outcomes of PSC, with a focus on survival pre- and post-liver transplantation as well as the concurrence of inflammatory bowel disease and hepatobiliary neoplasia.
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Affiliation(s)
- Tej I Mehta
- Department of Medicine, University of South Dakota Sanford School of Medicine, Sioux Falls, SD 57108, United States
| | - Simcha Weissman
- Department of Medicine, Hackensack University-Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Brian M Fung
- Department of Medicine, Olive View-UCLA Medical Center, Sylmar, CA 91342, United States
| | - James H Tabibian
- Department of Medicine, UCLA-Olive View Medical Center, Sylmar, CA 91342, and Health Sciences Clinical Associate Professor, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, United States
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Alomari M, Covut F, Al Momani L, Chadalavada P, Hitawala A, Young MF, Romero-Marrero C. Evaluation of the United Kingdom-primary biliary cholangitis and global primary biliary cholangitis group prognostic models for primary biliary cholangitis patients treated with ursodeoxycholic acid in the U.S. population. JGH OPEN 2019; 4:132-139. [PMID: 32280755 PMCID: PMC7144790 DOI: 10.1002/jgh3.12223] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Accepted: 06/06/2019] [Indexed: 01/25/2023]
Abstract
Background and Aim The United Kingdom‐primary biliary cholangitis (UK‐PBC) and global primary biliary cholangitis group (GLOBE) prognostic models have been recently developed to predict long‐term outcomes in primary biliary cholangitis (PBC). However, these predictive scores have not yet been well evaluated in the U.S. population. Methods We retrospectively reviewed newly diagnosed PBC patients at the Cleveland Clinic between November 1998 and February 2017. Adverse events were defined as liver transplantation, liver‐related mortality, and all‐cause mortality. Transplant‐free survival (TFS) was estimated using the Kaplan–Meier method. Predictive performances of all prognostic models were evaluated using the C‐statistic. Results We identified 352 patients who used ursodeoxycholic acid therapy. Of them, 311 (88.4%) only had PBC, while 41 (11.6%) were diagnosed with PBC‐autoimmune hepatitis overlap. A total of 22 (6%), 47 (13%), and 55 (16%) patients had adverse events within 5, 10, and 15 years after diagnosis, respectively. In patients with PBC only, the C‐statistic in predicting 15‐year adverse events was 0.75 per GLOBE compared to 0.74 per UK‐PBC (P = 0.94), 0.73 per Rotterdam (P = 0.44), 0.66 per Barcelona (P = 0.004), 0.65 per Paris 1 (P = 0.005), 0.62 per Paris 2 (P < 0.0001), 0.60 per Toronto (P < 0.0001), and 0.60 per Mayo (P < 0.0001) scores. Median follow‐up was 9.2 years. Ten‐year TFS for patients who had optimal versus suboptimal treatment response was 92 versus 74% per Paris 1 (P < 0.0001), 95 versus 79% per Paris 2 (P = 0.0002), 93 versus 65% per Barcelona (P < 0.0001), and 96 versus 68% per Rotterdam (P < 0.0001) risk scores, respectively. Conclusion In our cohort of PBC patients, the UK‐PBC and GLOBE scores were both accurate and reasonably valid prognostic models in the U.S. population.
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Affiliation(s)
- Mohammad Alomari
- Department of Internal Medicine Cleveland Clinic Foundation Cleveland Ohio USA
| | - Fahrettin Covut
- Department of Internal Medicine Cleveland Clinic Foundation Cleveland Ohio USA
| | - Laith Al Momani
- Department of Internal Medicine East Tennessee State University Johnson City Tennessee USA
| | | | - Asif Hitawala
- Department of Internal Medicine Cleveland Clinic Foundation Cleveland Ohio USA
| | - Mark F Young
- Department of Gastroenterology and Hepatology East Tennessee State University Johnson City Tennessee USA
| | - Carlos Romero-Marrero
- Department of Gastroenterology Hepatology and Nutrition, Cleveland Clinic Foundation Cleveland Ohio USA
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11
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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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12
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Validation of Risk Scoring Systems in Ursodeoxycholic Acid-Treated Patients With Primary Biliary Cholangitis. Am J Gastroenterol 2019; 114:1101-1108. [PMID: 31241547 DOI: 10.14309/ajg.0000000000000290] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Risk stratification based on biochemical variables is a useful tool for monitoring ursodeoxycholic acid (UDCA)-treated patients with primary biliary cholangitis (PBC). Several UDCA response criteria and scoring systems have been proposed for risk prediction in PBC, but these have not been validated in large external cohorts. METHODS We performed a study on data of 1746 UDCA-treated patients with PBC from 25 centers in Europe, United States, and Canada. The prognostic performance of the risk scoring systems (GLOBE and UK-PBC) and the UDCA response criteria (Barcelona, Paris I, Paris II, Rotterdam, and Toronto) were evaluated. We regarded cirrhosis-related complications (ascites, variceal bleeding, and/or hepatic encephalopathy) as clinical end points. RESULTS A total of 171 patients reached a clinical end point during a median 7 years (range 1-16 years) of follow-up. The 5-, 10- and 15-year adverse outcome-free survivals were 95%, 85%, and 77%. The GLOBE and UK-PBC scores predicted cirrhosis-related complications better than the UDCA response criteria. The hazard ratio (HR) for a 1 standard deviation increase was HR 5.05 (95% confidence interval (CI): 4.43-5.74, P < 0.001) for the GLOBE score and HR 3.39 (95% CI: 3.10-3.72, P < 0.001) for the UK-PBC score. Overall, the GLOBE and UK-PBC risk scores showed similar and excellent prognostic performance (C-statistic, 0.93; 95% CI: 0.91%-95% vs 0.94; 95% CI: 0.91%-0.96%). DISCUSSION In our international, multicenter PBC cohort, the GLOBE and UK-PBC risk scoring systems were good predictors of future cirrhosis-related complications.
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13
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Brunet E, Hernández L, Miquel M, Sánchez-Delgado J, Dalmau B, Valero O, Vergara M, Casas M. Análisis de los índices predictores de respuesta al tratamiento con ácido ursodeoxicólico en pacientes con colangitis biliar primaria. Med Clin (Barc) 2019; 152:377-383. [DOI: 10.1016/j.medcli.2018.08.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2018] [Revised: 08/14/2018] [Accepted: 08/15/2018] [Indexed: 01/25/2023]
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14
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Yoo JJ, Cho EJ, Lee B, Kim SG, Kim YS, Lee YB, Lee JH, Yu SJ, Kim YJ, Yoon JH. Prognostic Value of Biochemical Response Models for Primary Biliary Cholangitis and the Additional Role of the Neutrophil-to-Lymphocyte Ratio. Gut Liver 2019; 12:714-721. [PMID: 30400732 PMCID: PMC6254625 DOI: 10.5009/gnl18271] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2018] [Revised: 07/21/2018] [Accepted: 07/27/2018] [Indexed: 12/11/2022] Open
Abstract
Background/Aims Recently reported prognostic models for primary biliary cholangitis (PBC) have been shown to be effective in Western populations but have not been well-validated in Asian patients. This study aimed to compare the performance of prognostic models in Korean patients and to investigate whether inflammation-based scores can further help in prognosis prediction. Methods This study included 271 consecutive patients diagnosed with PBC in Korea. The following prognostic models were evaluated: the Barcelona model, the Paris-I/II model, the Rotterdam criteria, the GLOBE score and the UK-PBC score. The neutrophil-to-lymphocyte ratio (NLR) was analyzed with reference to its association with prognosis. Results For predicting liver transplant or death at the 5-year and 10-year follow-up examinations, the UK-PBC score (areas under the receiver operating characteristic curve [AUCs], 0.88 and 0.82) and GLOBE score (AUCs, 0.85 and 0.83) were significantly more accurate in predicting prognosis than the other scoring systems (all p＜0.05). There was no significant difference between the performance of the UK-PBC and GLOBE scores. In addition to the prognostic models, a high NLR (＞2.46) at baseline was an independent predictor of reduced transplant-free survival in the multivariate analysis (adjusted hazard ratio, 3.74; p＜0.01). When the NLR was applied to the prognostic models, it significantly differentiated the prognosis of patients. Conclusions The UK-PBC and GLOBE scores showed good prognostic performance in Korean patients with PBC. In addition, a high NLR was associated with a poorer prognosis. Including the NLR in prognostic models may further help to stratify patients with PBC.
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Affiliation(s)
- Jeong-Ju Yoo
- Department of Gastroenterology and Hepatology, Soonchunhyang University School of Medicine, Seoul, Korea
| | - Eun Ju Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Bora Lee
- Department of Statistics, Graduate School, Chung-Ang University, Seoul, Korea
| | - Sang Gyune Kim
- Department of Gastroenterology and Hepatology, Soonchunhyang University School of Medicine, Seoul, Korea
| | - Young Seok Kim
- Department of Gastroenterology and Hepatology, Soonchunhyang University School of Medicine, Seoul, Korea
| | - Yun Bin Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Su Jong Yu
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Yoon Jun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jung-Hwan Yoon
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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15
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Past hepatitis B virus infection was not associated with poorer response or the UK-PBC risk score in ursodeoxycholic acid-treated patients with primary biliary cirrhosis. Eur J Gastroenterol Hepatol 2019; 31:277. [PMID: 30575642 DOI: 10.1097/meg.0000000000001320] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
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16
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Abstract
Primary biliary cholangitis is a progressive, autoimmune disease of the interlobular bile ducts, leading to secondary damage of hepatocytes that may progress to cirrhosis and liver failure. Until recently, the only approved treatment was ursodeoxycholic acid. However, 40% of patients do not have an adequate response. Obeticholic acid was approved for treatment as add-on therapy in this group of patients. Off-label use of fibrates has also been reported to be effective. Several new therapies are in development and may further add to the treatment options available to patients with primary biliary cholangitis.
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Affiliation(s)
- Kimberly A Wong
- Department of Internal Medicine, UC Davis School of Medicine, 4150 V Street, PSSB 3000, Sacramento, CA 95817, USA
| | - Runalia Bahar
- Department of Internal Medicine, UC Davis School of Medicine, 4150 V Street, PSSB 3000, Sacramento, CA 95817, USA
| | - Chung H Liu
- Division of Gastroenterology and Hepatology, UC Davis School of Medicine, 4150 V Street, PSSB 3500, Sacramento, CA 95817, USA
| | - Christopher L Bowlus
- Division of Gastroenterology and Hepatology, UC Davis School of Medicine, 4150 V Street, PSSB 3500, Sacramento, CA 95817, USA.
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17
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Abstract
Primary biliary cholangitis (PBC) is a chronic progressive cholestatic disease characterized by destruction of small- and medium-sized intrahepatic bile ducts. It is no longer a rare disease, since many new asymptomatic cases are incidentally identified. Liver biopsy is diagnostically critical but not always feasible or practical to be performed. Many potential, noninvasive, markers have been proposed to replace liver biopsy and further provide the assessment of disease severity and ultimate prognosis. In this review, we evaluated serum biomarkers proposed for diagnosis, extent of fibrosis, disease prognosis and attempts for early prediction of treatment response. Older biochemical and immunological markers are presented along with recent reports including the role of microRNAs and promising results based on proteomics and metabolomics.
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Affiliation(s)
- Elias Kouroumalis
- Department of Gastroenterology, University Hospital and Medical School, University of Crete, Heraklion, Crete, Greece
| | - Demetrius Samonakis
- Department of Gastroenterology, University Hospital of Heraklion, Crete, Greece
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18
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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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19
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Patterns of disease progression and incidence of complications in primary biliary cholangitis (PBC). Best Pract Res Clin Gastroenterol 2018; 34-35:71-83. [PMID: 30343713 DOI: 10.1016/j.bpg.2018.06.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2018] [Accepted: 06/08/2018] [Indexed: 02/07/2023]
Abstract
Clinical outcome for patients with primary biliary cholangitis (PBC) is dictated by development of cirrhosis, portal hypertension and its associated complications; including for some, a predisposition toward hepatocellular carcinoma. However rates of clinical progression vary, and accurately identifying disease course is of critical importance to patients, clinicians, as well as industry, who are committed to developing new effective and life-prolonging therapy as well as treating symptoms that appear disproportionate to underlying disease severity. Patients seek reassurance and guidance as to their own prognosis, and clinicians wish to confidently recognise those at highest risk of poor outcomes as equally as they strive to reassure individuals with a more favourable disease trajectory. International registries have facilitated a much greater knowledge of disease incidence and heterogeneity of presenting phenotypes. In so doing they highlight the opportunity to provide a more individualized estimate of the clinical course that patients experience, and have led to a renewed approach to risk stratification; both in terms of 'hard outcomes' and also disease-associated complications in PBC specifically.
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21
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Carbone M, Harms MH, Lammers WJ, Marmon T, Pencek R, MacConell L, Shapiro D, Jones DE, Mells GF, Hansen BE. Clinical application of the GLOBE and United Kingdom-primary biliary cholangitis risk scores in a trial cohort of patients with primary biliary cholangitis. Hepatol Commun 2018; 2:683-692. [PMID: 29881820 PMCID: PMC5983203 DOI: 10.1002/hep4.1180] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Revised: 02/22/2018] [Accepted: 03/02/2018] [Indexed: 12/15/2022] Open
Abstract
The GLOBAL Primary Biliary Cholangitis (PBC) Study Group and United Kingdom‐PBC (UK‐PBC) Consortium have demonstrated that dichotomous response criteria are not as accurate as continuous equations at predicting mortality or liver transplantation in PBC. The aim of this analysis was to assess the clinical utility of the GLOBE and UK‐PBC risk scores using data from POISE, a phase 3 trial investigating obeticholic acid (OCA) in patients with PBC. Data (N = 216) at baseline and month 12 were used to calculate the GLOBE and UK‐PBC risk scores to assess the projected change in risk with OCA versus placebo. Additionally, the benefit of OCA was assessed in patients not meeting the POISE primary endpoint. Both the GLOBE and UK‐PBC risk scores predicted a significant reduction in long‐term risk of death and liver transplantation after OCA treatment (P < 0.0001). The differences in the relative risk reduction from baseline in the 10‐year event risk after 1 year for OCA 10 mg versus placebo was 26% (GLOBE) and 37% (UK‐PBC). The scores also predicted a significantly decreased risk in patients treated with OCA who did not meet POISE response criteria after 1 year of treatment compared to an increased risk with placebo (P < 0.0001). Conclusion: This analysis demonstrates the use of the GLOBE and UK‐PBC risk scores to assess risk reduction of a cohort treated with OCA. While validation of this risk reduction in studies with clinical outcomes is needed, this study highlights the potential use of these scores in individualizing risk prediction in PBC both in clinical practice and therapeutic trials. (Hepatology Communications 2018;2:683‐692)
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Affiliation(s)
- Marco Carbone
- Academic Department of Medical Genetics University of Cambridge Cambridge United Kingdom.,Division of Gastroenterology University of Milan-Bicocca Milan Italy
| | - Maren H Harms
- Department of Gastroenterology and Hepatology Erasmus University Medical Center Rotterdam the Netherlands
| | - Willem J Lammers
- Department of Gastroenterology and Hepatology Erasmus University Medical Center Rotterdam the Netherlands
| | | | | | | | | | - David E Jones
- Institute of Cellular Medicine Newcastle University Newcastle United Kingdom
| | - George F Mells
- Academic Department of Medical Genetics University of Cambridge Cambridge United Kingdom
| | - Bettina E Hansen
- Department of Gastroenterology and Hepatology Erasmus University Medical Center Rotterdam the Netherlands.,Toronto Centre for Liver Disease Toronto General Hospital Toronto ONT Canada
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22
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Bahar R, Wong KA, Liu CH, Bowlus CL. Update on New Drugs and Those in Development for the Treatment of Primary Biliary Cholangitis. Gastroenterol Hepatol (N Y) 2018; 14:154-163. [PMID: 29928160 PMCID: PMC6004046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
Primary biliary cholangitis (PBC) is an autoimmune inflammatory liver disease of the interlobular bile ducts that can lead to cirrhosis and liver failure. Until recently, the only effective treatment was ursodeoxycholic acid (UDCA). However, up to 40% of PBC patients have an inadequate response to UDCA and may continue to have disease progression. Several models have been developed, including the UK-PBC and GLOBE scores, to assist in identifying patients who may benefit from second-line therapies, such as the farnesoid X receptor (FXR) agonist obeticholic acid (OCA). The addition of OCA can significantly improve serum alkaline phosphatase and total bilirubin, which are strong surrogate markers of clinical outcomes in PBC. Other alternatives, including the peroxisome proliferator-activated receptor (PPAR)-α agonists fenofibrate and bezafibrate, may also improve liver biochemistries in PBC patients with an inadequate response to UDCA, but further study is needed to demonstrate their safety and long-term efficacy. Other novel agents, including those targeting the FXR pathway and PPAR-δ agonists, have shown promising results and may alter the therapeutic landscape of PBC in the near future. For now, OCA remains the only approved second-line agent for PBC patients with an inadequate response to UDCA while results of long-term studies of its safety and clinical benefit are awaited.
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Affiliation(s)
- Runalia Bahar
- Dr Bahar is a hospitalist at the University of California Davis Medical Center in Sacramento, California. Dr Wong is a chief resident in the Department of Internal Medicine at the University of California Davis School of Medicine in Sacramento, California. Mr Liu is a staff member and Dr Bowlus is the Lena Valente Professor and Chief of the Division of Gastroenterology and Hepatology at the University of California Davis School of Medicine
| | - Kimberly A Wong
- Dr Bahar is a hospitalist at the University of California Davis Medical Center in Sacramento, California. Dr Wong is a chief resident in the Department of Internal Medicine at the University of California Davis School of Medicine in Sacramento, California. Mr Liu is a staff member and Dr Bowlus is the Lena Valente Professor and Chief of the Division of Gastroenterology and Hepatology at the University of California Davis School of Medicine
| | - Chung H Liu
- Dr Bahar is a hospitalist at the University of California Davis Medical Center in Sacramento, California. Dr Wong is a chief resident in the Department of Internal Medicine at the University of California Davis School of Medicine in Sacramento, California. Mr Liu is a staff member and Dr Bowlus is the Lena Valente Professor and Chief of the Division of Gastroenterology and Hepatology at the University of California Davis School of Medicine
| | - Christopher L Bowlus
- Dr Bahar is a hospitalist at the University of California Davis Medical Center in Sacramento, California. Dr Wong is a chief resident in the Department of Internal Medicine at the University of California Davis School of Medicine in Sacramento, California. Mr Liu is a staff member and Dr Bowlus is the Lena Valente Professor and Chief of the Division of Gastroenterology and Hepatology at the University of California Davis School of Medicine
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Cheung KS, Seto WK, Fung J, Mak LY, Lai CL, Yuen MF. Prediction of hepatocellular carcinoma development by aminotransferase to platelet ratio index in primary biliary cholangitis. World J Gastroenterol 2017; 23:7863-7874. [PMID: 29209127 PMCID: PMC5703915 DOI: 10.3748/wjg.v23.i44.7863] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2017] [Revised: 09/25/2017] [Accepted: 09/28/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the usefulness of aspartate aminotransferase to platelet ratio index (APRI) in predicting hepatocellular carcinoma (HCC) risk in primary biliary cholangitis (PBC).
METHODS We identified PBC patients between 2000 and 2015 by searching the electronic medical database of a tertiary center. The hazard ratio (HR) of HCC with different risk factors was determined by Cox proportional hazards model.
RESULTS One hundred and forty-four PBC patients were recruited. Patients were diagnosed at a median age of 57.8 years [interquartile range (IQR): 48.7-71.5 years), and 41 (28.5%) patients had cirrhosis at baseline. The median follow-up duration was 6.9 years (range: 1.0-26.3 years). Twelve patients developed HCC, with an incidence rate of 10.6 cases per 1000 patient-years. The overall 5-, 10- and 15-year cumulative incidences of HCC were 2.3% 95%CI: 0%-4.8%), 8.4% (95%CI: 1.8%-14.5%) and 21.6% (6.8%-34.1%), respectively. Older age (HR = 1.07), cirrhosis (HR = 4.38) and APRI at 1 year after treatment (APRI-r1) > 0.54 (HR = 3.94) were independent factors for HCC development. APRI-r1, when combined with treatment response, further stratified HCC risk (log rank P < 0.05). The area under receiver operating curve of APRI-r1 in predicting HCC was 0.77 (95%CI: 0.64-0.88).
CONCLUSION APRI-r1 can be used to predict the development of HCC in PBC patients. Combination of APRI-r1 with treatment response can further stratify the HCC risk.
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Affiliation(s)
- Ka-Shing Cheung
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
| | - Wai-Kay Seto
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
- State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China
| | - James Fung
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
- State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China
| | - Lung-Yi Mak
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
| | - Ching-Lung Lai
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
- State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China
| | - Man-Fung Yuen
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
- State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China
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