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Lan R, Stiles ER, Ward SA, Lajam CM, Bosco JA. Patients With Moderate to Severe Liver Cirrhosis Have Significantly Higher Short-Term Complication Rates Following Total Knee Arthroplasty: A Retrospective Cohort Study. J Arthroplasty 2024; 39:1736-1740. [PMID: 38280615 DOI: 10.1016/j.arth.2024.01.039] [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: 09/11/2023] [Revised: 01/16/2024] [Accepted: 01/21/2024] [Indexed: 01/29/2024] Open
Abstract
BACKGROUND Liver cirrhosis is associated with increased perioperative morbidity. Our study used the Model for End-Stage Liver Disease (MELD) score to assess the impact of cirrhosis severity on postoperative outcomes following total knee arthroplasty (TKA). METHODS A retrospective review identified 59 patients with liver cirrhosis who underwent primary TKA at a large, urban, academic center from January 2013 to August 2022. Cirrhosis was categorized as mild (MELD < 10; n = 47) or moderate-severe (MELD ≥ 10; n = 12). Modified Clavien-Dindo classification was used to grade complications, where grade 2+ denoted significant intervention. Hospital length of stay, nonhome discharge, and mortality were collected. A 1:1 propensity matching was used to control for demographics and selected comorbidities. RESULTS Moderate-severe cirrhosis was associated with significantly higher rates of intrahospital overall (58.33 versus 16.67%, P = .036) complications, 30-day overall complications (75 versus 33.33%, P = .042), and 90-day overall complications (75 versus 33.33%, P = .042) when compared to matched mild cirrhosis patients. Compared to matched noncirrhotic controls, mild cirrhosis patients had no significant increase in complication rate or other outcomes (P > .05). CONCLUSIONS Patients with moderate-severe liver cirrhosis are at risk of short-term complications following primary TKA. Patients with mild cirrhosis have comparable outcomes to matched noncirrhotic patients. Surgeons can use MELD score prior to scheduling TKA to determine which patients require optimization or higher levels of perioperative care.
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Affiliation(s)
- Rae Lan
- Department of Orthopedic Surgery, NYU Langone Health, New York, New York
| | - Elizabeth R Stiles
- Department of Orthopedic Surgery, NYU Langone Health, New York, New York
| | - Spencer A Ward
- Department of Orthopedic Surgery, NYU Langone Health, New York, New York
| | - Claudette M Lajam
- Department of Orthopedic Surgery, NYU Langone Health, New York, New York
| | - Joseph A Bosco
- Department of Orthopedic Surgery, NYU Langone Health, New York, New York
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Li Y, Liu B, Li X. High C-reactive protein-to-albumin ratio levels are associated with osteoporosis in patients with primary biliary cholangitis. Front Endocrinol (Lausanne) 2024; 15:1415488. [PMID: 38872964 PMCID: PMC11169652 DOI: 10.3389/fendo.2024.1415488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Accepted: 05/16/2024] [Indexed: 06/15/2024] Open
Abstract
Objective Inflammation contributes to the development of metabolic bone diseases. The C-reactive protein-to-albumin ratio (CAR) is an inflammation-based marker with a prognostic value for several metabolic diseases. This study investigated the relationship between the CAR and osteoporosis (OP) in patients with primary biliary cholangitis (PBC). Methods Patients with PBC treated at Beijing Ditan Hospital between January 2018 and June 2023 were enrolled. Logistic regression analysis was performed to investigate the factors influencing OP. The predictive value of CAR for OP was evaluated using receiver operating characteristic (ROC) curves. Moreover, a restricted cubic spline (RCS) fitted with a logistic regression model was used to analyze the relationship between CAR and OP. Results The prevalence of OP among the patients with PBC was 26.9% (n = 82). CAR levels were higher in the OP group than in the non-OP group (0.33 (0.09, 0.61) vs. 0.08 (0.04, 0.18), P < 0.001). Logistic regression analysis showed that CAR was an independent predictor of OP in patients with PBC (odds ratio = 2.642, 95% confidence interval = 1.537-4.540, P < 0.001). CAR exhibited a good predictive ability for OP, with an areas under the curve (AUC) of 0.741. We found that individuals with CAR values > 0.1 have higher odds of OP. In addition, high CAR levels were associated with an increased prevalence of fragility fractures and high 10-year fracture risk. Conclusion High CAR levels were associated with greater odds of developing OP, and the CAR could serve as an independent predictor of OP in patients with PBC.
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Affiliation(s)
- Yanyan Li
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Bo Liu
- National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Department of Orthopaedics, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xin Li
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
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Thomson M, Scott A, Trost S, Lake J, Lim N. Low screening rates and high prevalence of osteoporosis in cirrhosis: A real-world retrospective analysis. Aliment Pharmacol Ther 2024; 59:535-546. [PMID: 38059360 DOI: 10.1111/apt.17823] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Revised: 09/23/2023] [Accepted: 11/21/2023] [Indexed: 12/08/2023]
Abstract
BACKGROUND Patients with cirrhosis are at increased risk for osteoporosis, and those who suffer a fracture are at high risk for mortality. Despite this, osteoporosis is often overlooked and undertreated. This study aimed to evaluate osteoporosis screening, management, and adverse osteoporosis medication events in patients with cirrhosis. METHODS We performed a retrospective chart review of adult outpatients with compensated and decompensated cirrhosis seen in single health system over a 6-year period. Patient demographics, liver and bone health comorbidities, DEXA scan results, and medications were abstracted. RESULTS In total, 5398 patients met criteria. The cohort was predominately white (79.1%) and older (age 59). 44.4% were female. 64.6% had decompensated cirrhosis. Median MELD-Na score was 12.8. 23.5% had a DEXA scan ordered, approximately 50% completed this test. Patients who were older, female, white, with more severe liver disease, and other osteoporosis risk factors were more likely to have a DEXA scan ordered. 48.5% of patients had osteopenia and 30.2% had osteoporosis on DEXA scan. Only 22.6% of patients with osteoporosis received treatment, most commonly oral bisphosphonates. Oral bisphosphonate prescription was not associated with variceal bleeding (8.4% without vs. 4.8% with, p = 0.487). CONCLUSION A minority of patients with cirrhosis were screened for osteoporosis. The majority screened had osteopenia or osteoporosis on DEXA scan. Less than a quarter of patients with osteoporosis were started on treatment. Real-world experience of oral bisphosphonate use did not reveal higher rates of gastrointestinal bleeding. There is room for improvement in all aspects of bone health care in cirrhosis.
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Affiliation(s)
- Mary Thomson
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, Minnesota, USA
| | - Adam Scott
- University of Minnesota Medical School, Minneapolis, Minnesota, USA
| | - Suzanne Trost
- Division of Diabetes, Endocrinology and Metabolism, University of Minnesota, Minneapolis, Minnesota, USA
| | - Jack Lake
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, Minnesota, USA
| | - Nicholas Lim
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, Minnesota, USA
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Sánchez-Delgado J, Profitós J, Arévalo M, Lira A, Mármol C, Miquel M, Casas M, Vergara M, Calvet X, Berlanga E, del Rio L, Valero O, Costa E, Larrosa M, Casado Burgos E. Osteoporosis and Fragility Fractures in Patients with Liver Cirrhosis: Usefulness of FRAX ® as a Screening Tool. J Clin Med 2023; 13:188. [PMID: 38202195 PMCID: PMC10780144 DOI: 10.3390/jcm13010188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Revised: 12/16/2023] [Accepted: 12/25/2023] [Indexed: 01/12/2024] Open
Abstract
PURPOSE The purpose of this study is to assess the prevalence of osteoporosis and fragility fractures in patients with liver cirrhosis (LC) and determine the associated risk factors, evaluating the usefulness of FRAX® as a screening method to identify patients at a higher risk of fracture. METHODS This was a cross-sectional study. Demographic, clinical, and analytical data were collected in a randomized sample of LC patients attending the Hepatology Department of a university hospital. We assessed the absolute risk of fracture at 10 years (FRAX®) and based on the bone mineral density (BMD), the presence of morphometric vertebral fracture with a vertebral fracture assessment (VFA), or a thoracic and lumbar X-ray and bone microarchitecture with a trabecular bone score (TBS). RESULTS Ninety-two patients were included (71% male); the mean age was 63 ± 11.3 years. The main etiology of LC was alcoholism (52.2%), and most patients were Child-Pugh A (80.4%), with a mean model for end-stage liver disease (MELD) score of 10.1 ± 3.6. Sixteen patients (17.4%) had osteoporosis, and fifty-four (58.7%) had osteopenia. Eight patients (8.7%) had suffered at least one fragility fracture. The absolute risk of a major fracture according to FRAX without the BMD was 5.7 ± 4.5%. Risk factors associated with osteoporosis were age and the female sex. BMI > 30 was a protective factor. A FRAX cut-off point for a major fracture > 6.6% had a sensitivity of 69% and a specificity of 85% for a diagnosis of osteoporosis. CONCLUSIONS The prevalence of osteoporosis and fractures in patients with LC is high, particularly in older women. FRAX® may be a useful method to identify candidates for bone densitometry. A FRAX value below 6.6% without the BMD can avoid unnecessary testing.
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Affiliation(s)
- Jordi Sánchez-Delgado
- Hepatology Unit, Digestive Disease Department, University Hospital Parc Taulí, I3PT Institute Research, Universitat Autònoma de Barcelona, 08208 Sabadell, Spain; (J.S.-D.); (A.L.); (M.M.); (M.C.); (M.V.); (X.C.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto Carlos III, 28029 Madrid, Spain
| | | | - Marta Arévalo
- Rheumatology Department, University Hospital Parc Taulí, I3PT Institute Research, Universitat Autònoma de Barcelona, 08208 Sabadell, Spain; (M.A.); (E.C.); (M.L.)
| | - Alba Lira
- Hepatology Unit, Digestive Disease Department, University Hospital Parc Taulí, I3PT Institute Research, Universitat Autònoma de Barcelona, 08208 Sabadell, Spain; (J.S.-D.); (A.L.); (M.M.); (M.C.); (M.V.); (X.C.)
| | | | - Mireia Miquel
- Hepatology Unit, Digestive Disease Department, University Hospital Parc Taulí, I3PT Institute Research, Universitat Autònoma de Barcelona, 08208 Sabadell, Spain; (J.S.-D.); (A.L.); (M.M.); (M.C.); (M.V.); (X.C.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto Carlos III, 28029 Madrid, Spain
- Department de Medicina, Universitat de Vic—Universitat Central de Catalunya (UVic-UCC), 08500 Vic, Spain
| | - Meritxell Casas
- Hepatology Unit, Digestive Disease Department, University Hospital Parc Taulí, I3PT Institute Research, Universitat Autònoma de Barcelona, 08208 Sabadell, Spain; (J.S.-D.); (A.L.); (M.M.); (M.C.); (M.V.); (X.C.)
| | - Mercedes Vergara
- Hepatology Unit, Digestive Disease Department, University Hospital Parc Taulí, I3PT Institute Research, Universitat Autònoma de Barcelona, 08208 Sabadell, Spain; (J.S.-D.); (A.L.); (M.M.); (M.C.); (M.V.); (X.C.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto Carlos III, 28029 Madrid, Spain
| | - Xavier Calvet
- Hepatology Unit, Digestive Disease Department, University Hospital Parc Taulí, I3PT Institute Research, Universitat Autònoma de Barcelona, 08208 Sabadell, Spain; (J.S.-D.); (A.L.); (M.M.); (M.C.); (M.V.); (X.C.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto Carlos III, 28029 Madrid, Spain
| | - Eugenio Berlanga
- Clinical Analytics Department, University Hospital Parc Taulí, 08208 Sabadell, Spain;
| | - Luís del Rio
- CETIR Ascires Centre Mèdic, 08029 Barcelona, Spain;
| | - Oliver Valero
- Department of Statistics, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain;
| | - Ester Costa
- Rheumatology Department, University Hospital Parc Taulí, I3PT Institute Research, Universitat Autònoma de Barcelona, 08208 Sabadell, Spain; (M.A.); (E.C.); (M.L.)
| | - Marta Larrosa
- Rheumatology Department, University Hospital Parc Taulí, I3PT Institute Research, Universitat Autònoma de Barcelona, 08208 Sabadell, Spain; (M.A.); (E.C.); (M.L.)
| | - Enrique Casado Burgos
- Rheumatology Department, University Hospital Parc Taulí, I3PT Institute Research, Universitat Autònoma de Barcelona, 08208 Sabadell, Spain; (M.A.); (E.C.); (M.L.)
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DiLeo DA, Gidener T, Aytaman A. Chronic Liver Disease in the Older Patient-Evaluation and Management. Curr Gastroenterol Rep 2023; 25:390-400. [PMID: 37991713 DOI: 10.1007/s11894-023-00908-2] [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] [Accepted: 11/01/2023] [Indexed: 11/23/2023]
Abstract
PURPOSE OF REVIEW As our population ages, the number of elderly patients with advanced chronic liver disease (ACLD) will increase. In this review we explore risk factors for liver injury, noninvasive assessment of liver disease, complications of cirrhosis, and management of frailty and sarcopenia in the older patient with ACLD. RECENT FINDINGS Multiple guidelines regarding ACLD have been updated over the past few years. New cutoffs for FIB-4 and NAFLD (MASLD - Metabolic Dysfunction Associated Steatotic Liver Disease) fibrosis scores for elderly patients are being validated. Older patients with MASLD benefit from caloric restriction, exercise programs, and GLP-1 agonists. Patients with ACLD need to be screened for alcohol use disorder with modified scoring systems, and if positive, benefit from referral to chemical dependency programs. Carvedilol and diuretics may safely be used in the elderly for portal hypertension and ascites, respectively, with careful monitoring. Malnutrition, frailty, sarcopenia, and bone mineral disease are common in older patients with ACLD, and early intervention may improve outcomes. Early identification of ACLD in elderly patients allows us to manage risk factors for liver injury, screen for complications, and implement lifestyle and pharmacological therapy to reduce decompensation and death. Future studies may clarify the role of noninvasive imaging in assessing liver fibrosis in the elderly and optimal interventions for nutrition, frailty, sarcopenia, bone health in addition to reevaluation of antibiotic prophylaxis for liver conditions with rising antibiotic resistance.
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Affiliation(s)
- Daniel Anthony DiLeo
- Department of Gastroenterology, Brooklyn Campus of the Veterans Affairs New York Harbor Healthcare System, 800 Poly Pl, Brooklyn, NY, 11209, USA.
| | - Tolga Gidener
- Department of Medicine, SUNY Downstate Health Sciences University, Brooklyn, NY, 11203, USA
| | - Ayse Aytaman
- Department of Gastroenterology, Brooklyn Campus of the Veterans Affairs New York Harbor Healthcare System, 800 Poly Pl, Brooklyn, NY, 11209, USA
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Prince DS, Nash E, Liu K. Alcohol-Associated Liver Disease: Evolving Concepts and Treatments. Drugs 2023; 83:1459-1474. [PMID: 37747685 PMCID: PMC10624727 DOI: 10.1007/s40265-023-01939-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/03/2023] [Indexed: 09/26/2023]
Abstract
Alcohol is a prominent cause of liver disease worldwide with higher prevalence in developed nations. The spectrum of alcohol-associated liver disease (ALD) encompasses a diverse range of clinical entities, from asymptomatic isolated steatosis to decompensated cirrhosis, and in some cases, acute or chronic liver failure. Consequently, it is important for healthcare practitioners to maintain awareness and systematically screen for ALD. The optimal evaluation and management of ALD necessitates a collaborative approach, incorporating a multidisciplinary team and accounting for concurrent medical conditions. A repertoire of therapeutic interventions exists to support patients in achieving alcohol cessation and sustaining remission, with complete abstinence being the ultimate objective. This review explores the existing therapeutic options for ALD acknowledging geographical discrepancies in accessibility. Recent innovations, including the inclusion of alcohol consumption biomarkers into clinical protocols and the expansion of liver transplantation eligibility to encompass severe alcohol-associated hepatitis, are explored.
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Affiliation(s)
- David Stephen Prince
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
- Department of Gastroenterology and Liver, Liverpool Hospital, Sydney, NSW, Australia.
- Liver Injury and Cancer Program, Centenary Institute, Sydney, NSW, Australia.
- The Ingham Institute for Applied Medical Research, Sydney, NSW, Australia.
- Faculty of Medicine and Health, The University of New South Wales, Sydney, NSW, Australia.
| | - Emily Nash
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia
- Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
| | - Ken Liu
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia
- Liver Injury and Cancer Program, Centenary Institute, Sydney, NSW, Australia
- Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
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Yang Y, Zeng J, Zhang T, Wang J, Fan X, Wang Q, Wang X, Qi Z, Fang Y. Association between resolved hepatitis B virus infection and femoral and spinal bone mineral density in American adults: a cross-sectional study. Front Endocrinol (Lausanne) 2023; 14:1237618. [PMID: 37829687 PMCID: PMC10565481 DOI: 10.3389/fendo.2023.1237618] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Accepted: 08/18/2023] [Indexed: 10/14/2023] Open
Abstract
Background Hepatitis B virus (HBV) infection is a global health concern that can potentially affect bone health. However, the specific association between resolved HBV infection and bone mineral density (BMD) remains unclear. This cross-sectional study aimed to investigate the potential association between resolved HBV infection and femoral and spinal BMD in adults in the United States. Methods This cross-sectional study included participants aged 20-79 years with negative HBV surface antigen (HBsAg) from the 2005-2010, 2013-2014, and 2017-2018 cycles of the National Health and Nutrition Examination Survey. Resolved HBV infection was defined as negative HBsAg with positive HBV core antibody. BMD was measured using dual-energy X-ray absorptiometry. Propensity score matching (PSM) was performed to balance baseline characteristics. Results A total of 10,333 eligible participants were identified and matched, of whom 737 (7.1%) had resolved HBV infection. Men with resolved HBV infection had significantly lower femoral and spinal BMD compared to those with no HBV infection, both before and after PSM. In the matched population, resolved HBV infection in men was negatively associated with femoral BMD (β= -0.024, 95% CI: -0.047 to -0.002, p = 0.0332) and spinal BMD (β= -0.025, 95% CI: -0.048 to -0.002, p = 0.0339). Postmenopausal women exhibited similar trends to men, while premenopausal women showed a tendency towards higher BMD, although statistical significance was not consistently achieved. Subgroup and sensitivity analyses supported the robustness of the findings. Conclusion The study suggests a negative association between resolved HBV infection and femoral and spinal BMD in adult men in the United States. It highlights the importance of routine bone density assessments and the consideration of anti-osteoporotic therapy, if necessary, in individuals with resolved HBV infection.
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Affiliation(s)
- Yan Yang
- Department of Endocrinology, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Jing Zeng
- Department of Endocrinology, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Tingting Zhang
- Department of Endocrinology, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Jinjing Wang
- Department of Endocrinology, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Xiaojing Fan
- Department of Endocrinology, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Qiaomin Wang
- Department of Endocrinology, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Xuan Wang
- Department of Endocrinology, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Zhengrong Qi
- Department of Orthopedics, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Yi Fang
- Department of Endocrinology, The Fifth Medical Center of PLA General Hospital, Beijing, China
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Mariano da Rocha CR, Guaragna-Filho G, Kieling CO, Adami MR, Guedes RR, Gonçalves Vieira SM. Daily Vitamin D Supplementation Improves Vitamin D Deficiency in Patients With Chronic Liver Disease. J Pediatr Gastroenterol Nutr 2023; 76:723-730. [PMID: 36917843 DOI: 10.1097/mpg.0000000000003769] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/16/2023]
Abstract
OBJECTIVE The objective of this article is to evaluate the response to 6000 IU oral cholecalciferol (OC) treatment in children with chronic liver disease (CLD) and 25(OH)D deficiency. METHODS This historical cohort included non-transplanted CLD patients younger than 18 years old, which were analyzed for serum 25(OH)D, liver function, bone metabolism, Child-Pugh classification, and anthropometry. Patients with 25(OH)D deficiency (defined as 25(OH)D < 20 ng/mL) who received 6000 IU/day of OC were analyzed pre- and post-intervention, and considered responders if 25(OH)D > 20 ng/mL after at least 60 days. We compared clinical and laboratory data from patients with and without 25(OH)D deficiency, responders and nonresponders. RESULTS We studied 96 patients, of which 57.2% had biliary atresia. The prevalence of 25(OH)D deficiency was 67.7% (65/96). These patients were younger ( P < 0.001), had higher Child-Pugh scores ( P < 0.001), higher levels of total bilirubin (TB) ( P < 0.001), gamma-glutamyl transferase ( P < 0.001), and alkaline phosphatase ( P = 0.002), as well as lower levels of phosphorus ( P = 0.009) compared with patients without 25(OH)D deficiency. The median treatment length was 126 days (70-307 days). At the end of treatment, we observed a higher median of 25(OH)D ( P < 0.001), and lower median of parathyroid hormone (PTH) ( P = 0.023). Nine patients (29%) restored 25(OH)D to normal range; they had lower Child-Pugh score ( P = 0.001), lower TB levels ( P = 0.001), and higher level of phosphorus ( P = 0.003) after treatment. CONCLUSION Despite an increase in 25(OH)D and decrease in PTH levels, 6000 IU/day of OC was not sufficient to restore 25(OH)D deficiency in most of the patients in this study.
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Affiliation(s)
- Carolina Roos Mariano da Rocha
- From the Post Graduate Program in Children and Adolescent Health, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
| | - Guilherme Guaragna-Filho
- the Pediatric Endocrinology Unit, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
- the Pediatrics Department, Medical School, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
| | - Carlos Oscar Kieling
- the Pediatric Liver Transplantation Program, Pediatric Gastroenterology and Hepatology Unit, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
| | - Marina Rossato Adami
- the Pediatric Liver Transplantation Program, Pediatric Gastroenterology and Hepatology Unit, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
| | - Renata Rostirola Guedes
- the Pediatric Liver Transplantation Program, Pediatric Gastroenterology and Hepatology Unit, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
| | - Sandra Maria Gonçalves Vieira
- From the Post Graduate Program in Children and Adolescent Health, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
- the Pediatrics Department, Medical School, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
- the Pediatric Liver Transplantation Program, Pediatric Gastroenterology and Hepatology Unit, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
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Bégin MJ, Ste-Marie LG, Huard G, Dorais M, Räkel A. Increased Imminent Fracture Risk in Liver Transplant Recipients Despite Bisphosphonate Therapy. Transplant Proc 2023; 55:576-585. [PMID: 37012143 DOI: 10.1016/j.transproceed.2023.02.060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Revised: 01/29/2023] [Accepted: 02/24/2023] [Indexed: 04/03/2023]
Abstract
BACKGROUND Bone loss is significant after orthotopic liver transplant (OLT) and is associated with increased fracture risk and decreased quality of life. In post-transplant fracture prevention, the cornerstone of therapeutic management is bisphosphonates. METHODS We conducted a retrospective study in a cohort of 155 OLT recipients who received a bisphosphonate prescription at hospital discharge between 2012 and 2016 to investigate post-OLT fragility fracture incidence and predictive risk factors. RESULTS Before OLT, 14 patients presented a T score < -2.5 SD, and 23 patients (14.8%) had a history of fracture. During follow-up, the cumulative incidence of fractures on bisphosphonates (99.4% risedronate/alendronate) was 9.7% at 12 months and 13.1% at 24 months. The median time to first fragility fracture was 10 months (IQR, 3-22 months) and thus within the first 2 years of follow-up. Predictive factors of fragility fractures in multivariate Cox regression analyses included age 60 years or older (hazard ratio [HR], 2.61; 95% CI, 1.14-6.01; P = .02), post-transplant diabetes mellitus (HR, 3.82; 95% CI, 1.55-9.44; P = .004), and cholestatic disease (HR, 5.93; 95% CI, 2.30-15.26; P = .0002). Additionally, the female sex was associated with a strong trend toward increased fracture risk in univariate analysis (HR, 2.27; 95% CI, 1.00-5.15; P = .05), as well as a post-transplant absolute decrease in bone mineral density at the femoral neck and total hip (P = .08). CONCLUSIONS This real-world study reports a high incidence of fractures post-OLT despite bisphosphonate therapy. Age 60 years or older, post-transplant diabetes mellitus, cholestatic disease, female sex, and femoral neck and/or total hip bone mineral density loss contribute to increased imminent fracture risk in liver transplant recipients.
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Muacevic A, Adler JR, Puli SR. Prevalence of Osteoporosis in Cirrhosis: A Systematic Review and Meta-Analysis. Cureus 2023; 15:e33721. [PMID: 36788896 PMCID: PMC9922208 DOI: 10.7759/cureus.33721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/12/2023] [Indexed: 01/14/2023] Open
Abstract
The prevalence of osteoporosis in individuals with cirrhosis varies based on the diagnostic approach and etiology of the underlying liver disease. This systematic review aims to evaluate the prevalence of osteoporosis in individuals with cirrhosis. Electronic databases were searched for studies reporting the prevalence of osteoporosis among patients with cirrhosis. The primary outcome was the presence of osteoporosis, as determined by a dual-energy x-ray absorptiometry (DEXA) scan. Secondary outcomes were levels of biochemical markers of bone metabolism, including calcium, vitamin D, phosphorus, and parathormone (PTH) levels. A cohort of 836 patients from 10 studies was included in the final analysis. The pooled rate of osteoporosis was 14.80% (95% CI: 14.19-15.49). Pooled levels of biochemical markers of bone metabolism were as follows: calcium 9.09 mg/dL (95% CI: 8.73-9.45), 25-hydroxyvitamin D (25-OH vitamin D) 15.41 ng/mL (95% CI: 14.79-16.03), phosphorus 15.41 mg/dL (95% CI: 2.99-3.51), and PTH 26.58 pg/mL (95% CI: 25.45-27.71). Pooled levels of liver biochemistries were: bilirubin 3.04 mg/dL (95% CI: 2.84-3.25), aspartate aminotransferase (AST) 65.35 U/L (95% CI: 61.39-69.31), alanine aminotransferase (ALT) 50.17 U/L (95% CI: 46.18-54.10), alkaline phosphatase 133.31 U/L (95% CI: 124.89-141.73), and albumin 3.25 g/dL (95% CI: 3.05-3.45). Cirrhosis appears to be associated with an increased risk for osteoporosis, with a pooled prevalence of 15%. This can include men and individuals younger than 50 years of age, a cohort not typically considered to be at an increased risk of osteoporosis. Levels of 25-hydroxyvitamin D and insulin-like growth factor-1 (IGF-1) were also significantly low. Further studies are required to evaluate the risk of osteoporosis based on the etiology and stage of cirrhosis, especially in younger males, to incorporate this into future prediction models for fragility fractures.
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Wester A, Ndegwa N, Hagström H. Risk of Fractures and Subsequent Mortality in Alcohol-Related Cirrhosis: A Nationwide Population-Based Cohort Study. Clin Gastroenterol Hepatol 2022; 21:1271-1280.e7. [PMID: 35811047 DOI: 10.1016/j.cgh.2022.05.048] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 05/08/2022] [Accepted: 05/31/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Alcohol-related cirrhosis is linked to increased risk of fractures, but this has seldom been quantified nationally or compared against control subjects without cirrhosis. Here, we determined the rate and risk of fractures and postfracture mortality in patients with alcohol-related cirrhosis compared with individuals from the general population. METHODS In this nationwide population-based cohort study, data were retrieved from the Swedish National Patient Registry on 25,090 patients with alcohol-related cirrhosis from 1969-2016. Patients were matched for sex, age, and municipality with 239,458 control subjects from the Swedish Total Population Registry. Cox regression models were fitted to investigate the rates of fractures and postfracture mortality. The cumulative incidence of fractures was calculated while accounting for competing risks (death or liver transplantation). RESULTS A total of 48,635 fractures occurred during 3,468,860 person-years of follow-up. Patients with alcohol-related cirrhosis had a higher fracture rate per 1000 person-years (38.7) than control subjects (13.3; adjusted hazard ratio, 3.8; 95% confidence interval, 3.6-3.9). The cumulative incidence of fractures was elevated for patients the first 19 years of follow-up, with a 5-year risk of 9.6% compared with 4.5% for control subjects. Patients with alcohol-related cirrhosis had a higher postfracture mortality rate compared with control subjects who also experienced a fracture, at both 30 days (adjusted hazard ratio, 1.6; 95% confidence interval, 1.4-1.8) and 1 year (adjusted hazard ratio, 1.8; 95% confidence interval, 1.7-2.0). CONCLUSIONS Alcohol-related cirrhosis is associated with an almost 4-fold increased fracture rate, a higher risk of fractures the first 2 decades after initial diagnosis, and higher postfracture mortality. Preventive interventions to reduce modifiable fracture risk factors in this population are justified.
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Affiliation(s)
- Axel Wester
- Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
| | - Nelson Ndegwa
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Division of Surgery, Department of Clinical Science Intervention and Technology, Karolinska Institutet, Stockholm, Sweden; Esophageal and Gastric Cancer Unit, Department of Upper GI, Karolinska University Hospital, Stockholm, Sweden
| | - Hannes Hagström
- Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden; Division of Hepatology, Department of Upper GI, Karolinska University Hospital, Stockholm, Sweden; Clinical Epidemiology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden
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Xu L, Yuan Y, Che Z, Tan X, Wu B, Wang C, Xu C, Xiao J. The Hepatoprotective and Hepatotoxic Roles of Sex and Sex-Related Hormones. Front Immunol 2022; 13:939631. [PMID: 35860276 PMCID: PMC9289199 DOI: 10.3389/fimmu.2022.939631] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Accepted: 06/13/2022] [Indexed: 12/18/2022] Open
Abstract
Most liver diseases, including acute liver injury, drug-induced liver injury, viral hepatitis, metabolic liver diseases, and end-stage liver diseases, are strongly linked with hormonal influences. Thus, delineating the clinical manifestation and underlying mechanisms of the "sexual dimorphism" is critical for providing hints for the prevention, management, and treatment of those diseases. Whether the sex hormones (androgen, estrogen, and progesterone) and sex-related hormones (gonadotrophin-releasing hormone, luteinizing hormone, follicle-stimulating hormone, and prolactin) play protective or toxic roles in the liver depends on the biological sex, disease stage, precipitating factor, and even the psychiatric status. Lifestyle factors, such as obesity, alcohol drinking, and smoking, also drastically affect the involving mechanisms of those hormones in liver diseases. Hormones deliver their hepatic regulatory signals primarily via classical and non-classical receptors in different liver cell types. Exogenous sex/sex-related hormone therapy may serve as a novel strategy for metabolic liver disease, cirrhosis, and liver cancer. However, the undesired hormone-induced liver injury should be carefully studied in pre-clinical models and monitored in clinical applications. This issue is particularly important for menopause females with hormone replacement therapy (HRT) and transgender populations who want to receive gender-affirming hormone therapy (GAHT). In conclusion, basic and clinical studies are warranted to depict the detailed hepatoprotective and hepatotoxic mechanisms of sex/sex-related hormones in liver disease. Prolactin holds a promising perspective in treating metabolic and advanced liver diseases.
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Affiliation(s)
- Linlin Xu
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yuan Yuan
- Clinical Medicine Research Institute, Department of Metabolic and Bariatric Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Zhaodi Che
- Clinical Medicine Research Institute, Department of Metabolic and Bariatric Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Xiaozhi Tan
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Bin Wu
- Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Cunchuan Wang
- Clinical Medicine Research Institute, Department of Metabolic and Bariatric Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Chengfang Xu
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jia Xiao
- Clinical Medicine Research Institute, Department of Metabolic and Bariatric Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China
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Reshetnyak VI, Maev IV. Mechanism for development of malnutrition in primary biliary cholangitis. World J Meta-Anal 2022; 10:81-98. [DOI: 10.13105/wjma.v10.i3.81] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Revised: 04/14/2022] [Accepted: 05/23/2022] [Indexed: 02/06/2023] Open
Abstract
Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease that is associated with impaired biliary excretion processes. Along with the development of cholestasis, there is a deficient flow of bile acids into the intestinal lumen causing malnutrition (MN) that is manifested in deficiencies of both macro- and micronutrients. The mechanism for development of trophological insufficiency is multifactorial. However, the trigger of MN in PBC is impaired enterohepatic circulation of bile acids. The ingress of bile acids with a detergent effect into the general bloodstream, followed by elimination via the kidneys and skin, triggers a cascade of metabolic disturbances, which leads to the gradual development and progression of calorie MN. The latter gradually transforms into protein-calorie MN (PСM) (as marasmus) due to the insufficient entry of bile acids into the duodenum, which is accompanied by a decrease in the emulsification, hydrolysis, and absorption of fats and fat-soluble vitamins, as well as disturbance of intestinal motility and bacterial overgrowth. Fat-soluble vitamin deficiencies complement PСM with vitamin and mineral MN. The development of hepatocellular failure enhances the progression of PСM due to the impaired protein synthetic function of hepatocytes in the advanced stage of PBC, which results in deficiency of not only the somatic but also the visceral pool of proteins. A mixed PСM form of marasmus and kwashiorkor develops. Early recognition of energy, protein, micronutrient, and macronutrient deficiencies is of great importance because timely nutritional support can improve liver function and quality of life in patients with PBC. In this case, it is important to know what type (energy, protein-calorie, vitamin, and vitamin-mineral) and form (marasmus, marasmus-kwashiorkor) of MN is present in the patient and how it is associated with the stage of the disease. Therefore, it is recommended to screen all patients with PBC for MN, from the early asymptomatic stage of the disease in order to identify and avoid preventable complications, such as fatigue, malaise, performance decrement, sarcopenia, osteoporosis, and hepatic encephalopathy, which will be able to provide appropriate nutritional support for correction of the trophological status.
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Affiliation(s)
- Vasiliy Ivanovich Reshetnyak
- Department of Propaedeutic of Internal Diseases and Gastroenterology, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow 127473, Russia
| | - Igor Veniaminovich Maev
- Department of Propaedeutic of Internal Diseases and Gastroenterology, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow 127473, Russia
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Hundersmarck D, Groot OQ, Schuijt HJ, Hietbrink F, Leenen LPH, Heng M. Hip Fractures in Patients With Liver Cirrhosis: Worsening Liver Function Is Associated with Increased Mortality. Clin Orthop Relat Res 2022; 480:1077-1088. [PMID: 34978539 PMCID: PMC9263483 DOI: 10.1097/corr.0000000000002088] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Accepted: 11/29/2021] [Indexed: 01/31/2023]
Abstract
BACKGROUND Liver cirrhosis is associated with osteoporosis, imbalance leading to falls, and subsequent fragility fractures. Knowing the prognosis of patients with liver cirrhosis of varying severity at the time of hip fracture would help physicians determine the course of treatment in this complex patient popultaion. QUESTIONS/PURPOSES (1) Is there an association between liver cirrhosis of varying severity and mortality in patients with hip fractures? (2) Is there an association between liver cirrhosis of varying severity and the in-hospital, 30-day, and 90-day postoperative complications of symptomatic thromboembolism and infections including wound complications, pneumonia, and urinary tract infections? METHODS Between 2015 and 2019, we identified 128 patients with liver cirrhosis who were treated for hip fractures at one of two Level I trauma centers. Patients younger than 18 years, those with incomplete medical records, fractures other than hip fractures or periprosthetic hip fractures, noncirrhotic liver disease, status after liver transplantation, and metastatic cancer other than hepatocellular carcinoma were excluded. Based on these exclusions, 77% (99 of 128) of patients were eligible; loss to follow-up was 0% within 1 year and 4% (4 of 99) at 2 years. The median follow-up duration was 750 days (interquartile range 232 to 1000). Ninety-four patients were stratified based on Model for End-stage Liver Disease (MELD) score subgroup (MELD scores of 6-9 [MELD6-9], 10-19 [MELD10-19], and 20-40 [MELD20-40]), and 99 were stratified based on compensation or decompensation status, both measures for liver cirrhosis severity. MELD scores combine laboratory parameters related to liver disease and are used to predict cirrhosis-related mortality based on metabolic abnormalities. Decompensation, however, is the clinical finding of acute deterioration in liver function characterized by ascites, hepatic encephalopathy, and variceal hemorrhage, associated with increased mortality. MELD analyses excluded 5% (5 of 99) of patients due to missing laboratory values. Median age at the time of hip fracture was 69 years (IQR 62 to 78), and 55% (54 of 99) of patients were female. The primary outcome of mortality was determined at 90 days, 1 year, and 2 years after surgery. Secondary outcomes were symptomatic thromboembolism and infections, defined as any documented surgical wound complications, pneumonia, or urinary tract infections requiring treatment. These were determined by chart review at three timepoints: in-hospital and within 30 days or 90 days after discharge. The primary outcome was assessed using a Cox proportional hazard analysis for the MELD score and compensation or decompensation classifications; secondary outcomes were analyzed using the Fisher exact test. RESULTS Patients in the MELD20-40 group had higher 90-day (hazard ratio 3.95 [95% CI 1.39 to 12.46]; p = 0.01), 1-year (HR 4.12 [95% CI 1.52 to 11.21]; p < 0.001), and 2-year (HR 3.65 [95% CI 1.68 to 7.93]; p < 0.001) mortality than those in the MELD6-9 group. Patients with decompensation had higher in-hospital (9% versus 0%; p = 0.04), 90-day (HR 3.35 [95% CI 1.10 to 10.25]; p = 0.03), 1-year (HR 4.39 [95% CI 2.02 to 9.54]; p < 0.001), and 2-year (HR 3.80 [95% CI 2.02 to 7.15]; p < 0.001) mortality than did patients with compensated disease. All in-hospital deaths were related to liver failure and within 30 days of surgery. The 1-year mortality was 55% for MELD20-40 and 53% for patients with decompensated disease, compared with 16% for patients with MELD6-9 and 15% for patients with compensated disease. In both the MELD and (de)compensation analyses, in-hospital and postdischarge 30-day symptomatic thromboembolic and infectious complications were not different among the groups (all p > 0.05). Ninety-day symptomatic thromboembolism was higher in the MELD20-40 group compared with the other two MELD classifications (13% for MELD20-40 and 0% for both MELD6-9 and MELD10-19; p = 0.02). CONCLUSION The mortality of patients with preexisting liver cirrhosis who sustain a hip fracture is high, and it is associated with the degree of cirrhosis and decline in liver function, especially in those with signs of decompensation, defined as ascites, hepatic encephalopathy, and variceal hemmorrhage. Patients with mild-to-moderate cirrhosis (MELD score < 20) and those with compensated disease may undergo routine fracture treatment based on their prognosis. Those with severe (MELD score > 20) or decompensated liver cirrhosis should receive multidisciplinary, individualized treatment, with consideration given to palliative and nonsurgical treatment given their high risk of death within 1 year after surgery. LEVEL OF EVIDENCE Level III, therapeutic study.
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Affiliation(s)
- Dennis Hundersmarck
- Department of Orthopaedic Surgery, Harvard Medical School Orthopaedic Trauma Initiative, Massachusetts General Hospital, Boston, MA, USA
- Department of Surgery, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Olivier Q. Groot
- Department of Orthopaedic Surgery, Harvard Medical School Orthopaedic Trauma Initiative, Massachusetts General Hospital, Boston, MA, USA
| | - Henk J. Schuijt
- Department of Orthopaedic Surgery, Harvard Medical School Orthopaedic Trauma Initiative, Massachusetts General Hospital, Boston, MA, USA
| | - Falco Hietbrink
- Department of Surgery, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Luke P. H. Leenen
- Department of Surgery, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Marilyn Heng
- Department of Orthopaedic Surgery, Harvard Medical School Orthopaedic Trauma Initiative, Massachusetts General Hospital, Boston, MA, USA
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Ebeling PR, Nguyen HH, Aleksova J, Vincent AJ, Wong P, Milat F. Secondary Osteoporosis. Endocr Rev 2022; 43:240-313. [PMID: 34476488 DOI: 10.1210/endrev/bnab028] [Citation(s) in RCA: 139] [Impact Index Per Article: 46.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Indexed: 02/07/2023]
Abstract
Osteoporosis is a global public health problem, with fractures contributing to significant morbidity and mortality. Although postmenopausal osteoporosis is most common, up to 30% of postmenopausal women, > 50% of premenopausal women, and between 50% and 80% of men have secondary osteoporosis. Exclusion of secondary causes is important, as treatment of such patients often commences by treating the underlying condition. These are varied but often neglected, ranging from endocrine to chronic inflammatory and genetic conditions. General screening is recommended for all patients with osteoporosis, with advanced investigations reserved for premenopausal women and men aged < 50 years, for older patients in whom classical risk factors for osteoporosis are absent, and for all patients with the lowest bone mass (Z-score ≤ -2). The response of secondary osteoporosis to conventional anti-osteoporosis therapy may be inadequate if the underlying condition is unrecognized and untreated. Bone densitometry, using dual-energy x-ray absorptiometry, may underestimate fracture risk in some chronic diseases, including glucocorticoid-induced osteoporosis, type 2 diabetes, and obesity, and may overestimate fracture risk in others (eg, Turner syndrome). FRAX and trabecular bone score may provide additional information regarding fracture risk in secondary osteoporosis, but their use is limited to adults aged ≥ 40 years and ≥ 50 years, respectively. In addition, FRAX requires adjustment in some chronic conditions, such as glucocorticoid use, type 2 diabetes, and HIV. In most conditions, evidence for antiresorptive or anabolic therapy is limited to increases in bone mass. Current osteoporosis management guidelines also neglect secondary osteoporosis and these existing evidence gaps are discussed.
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Affiliation(s)
- Peter R Ebeling
- Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria 3168, Australia.,Department of Endocrinology, Monash Health, Clayton, Victoria 3168, Australia
| | - Hanh H Nguyen
- Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria 3168, Australia.,Department of Endocrinology, Monash Health, Clayton, Victoria 3168, Australia.,Department of Endocrinology and Diabetes, Western Health, Victoria 3011, Australia
| | - Jasna Aleksova
- Department of Endocrinology, Monash Health, Clayton, Victoria 3168, Australia.,Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia
| | - Amanda J Vincent
- Department of Endocrinology, Monash Health, Clayton, Victoria 3168, Australia.,Monash Centre for Health Research and Implementation, School of Public Health and Preventative Medicine, Monash University, Clayton, Victoria 3168, Australia
| | - Phillip Wong
- Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria 3168, Australia.,Department of Endocrinology, Monash Health, Clayton, Victoria 3168, Australia.,Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia
| | - Frances Milat
- Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria 3168, Australia.,Department of Endocrinology, Monash Health, Clayton, Victoria 3168, Australia.,Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia
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SIQUEIRA MDMLG, CASULARI LA, FREITAS WMD, CARNEIRO MDV, MENDES LSC. RISK FACTORS ASSOCIATED WITH FRACTURE OF THE LUMBOSACRAL SPINE AND ITS COMPROMISE IN THE QUALITY OF LIFE OF CIRRHOTICS. ARQUIVOS DE GASTROENTEROLOGIA 2022; 59:9-15. [DOI: 10.1590/s0004-2803.202200001-03] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Accepted: 08/23/2021] [Indexed: 11/21/2022]
Abstract
ABSTRACT Background Chronic hepatic disease is associated with osteoporosis, osteopenia or osteomalacia. Osteoporosis and fractures due to bone fragility present high prevalences and are more frequent in patients with liver cirrhosis than in the general population. The search for a diagnosis of osteopenia and osteoporosis in this population may allow early intervention and modify unfavorable outcomes. Objective To know the prevalence of osteopenia or osteoporosis and of fracture due to bone fragility in individuals with liver cirrhosis, the associated risk factors, and its compromise in their quality of life (QoL). Methods Observational, transversal study performed with 71 liver cirrhosis patients of the Hepatology Service of the Hospital de Base do Distrito Federal, Brasília, DF, Brazil, between July 2017 and December 2018. The patients were submitted to bone densitometry (DXA) of the lumbar spine and of the femoral neck, to x-ray of the lumbosacral spine and to the Chronic Liver Disease Questionnaire (CLDQ) for the evaluation of quality of life (QoL). The Fracture Risk Assessment (FRAX) major was calculated for patients >50 years old. The analyses were performed for the evaluation of the risk factors associated with lumbosacral spine fracture. Results The majority (62%) of the 71 evaluated patients was diagnosed with osteoporosis or osteopenia on DXA. Of the 44 patients with osteopenia or osteoporosis, 52.3% were female, with a mean age of 62.6±9.51 years old, with the majority (72.7%) being Child A, cirrhotics of alcoholic etiology (36.4%), and with an intermediate QoL according to the CLDQ (3.3). Regarding the patients with lumbosacral spine fracture, the mean age was 61.6±11.1 years old, 60% were female, most of them Child A (66.7%), of alcoholic etiology (46.7%), and with an intermediary QoL according to the CLDQ (3.5). The presence of osteopenia and/or osteoporosis was associated with lumbosacral fracture (P<0.001), without correlation with the other analyzed variables: age, body mass index, gender, presence and absence of ascites, Child-Pugh classification, vitamin D, calcium, and phosphorus serum concentration, cirrhosis etiology and FRAX major. Conclusion The prevalence of hepatic osteodystrophy was high, and the occurrence of lumbosacral spine fracture was more associated with osteoporosis and/or osteopenia among the cirrhotic patients studied. The QoL was intermediate and with no differences between cirrhotics with and without fracture.
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Yoo J, Lee BJ. Anthropometric, biochemical, and nutritional risk factors for osteoporosis in Korean adults based on a large cross-sectional study. PLoS One 2021; 16:e0261361. [PMID: 34898647 PMCID: PMC8668121 DOI: 10.1371/journal.pone.0261361] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Accepted: 11/25/2021] [Indexed: 11/18/2022] Open
Abstract
Background Osteoporosis a common bone disorder characterized by decreases in bone mass, tension, and strength. Although many previous studies worldwide have sought to identify the risk factors for osteoporosis, studies that simultaneously examine a variety of factors, such as biochemical, anthropometric and nutritional components, are very rare. Therefore, the objective of this study was to simultaneously examine the association of osteoporosis with biochemical profiles, anthropometric factors, and nutritional components in a large-scale cross-sectional study. Method This cross-sectional study was based on data from the Korea National Health and Nutrition Examination Survey (KNHANES VI-VII) from 2015 to 2018. Based on data from 16,454 participants, logistic regression was used to examine the association between various parameters in a crude analysis and in models adjusted for confounders. Results In men, osteoporosis was significantly associated with the anthropometric variables height and weight; the biochemical components hemoglobin, hematocrit, urea nitrogen and urine pH and creatinine; and the nutritional components total food intake, energy, water, protein, phosphorus, and kalium. However, these associations disappeared in adjusted model 2. In women, osteoporosis was significantly related to the anthropometric measures height, weight, and systolic blood pressure; the biochemical components hemoglobin, hematocrit and urine pH; and the nutritional components total food intake, water, calcium, phosphorus, and kalium. Most of these associations were maintained in the adjusted models. Conclusion Osteoporosis was linked to various anthropometric, biochemical and urine and nutritional components in Korean women, but the association between osteoporosis and risk factors differed according to sex.
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Affiliation(s)
- Junghun Yoo
- KM Data Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea
| | - Bum Ju Lee
- Digital Health Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea
- * E-mail:
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Bone loss in hepatitis B virus-infected patients can be associated with greater osteoclastic activity independently of the retroviral use. Sci Rep 2021; 11:10162. [PMID: 33986322 PMCID: PMC8119499 DOI: 10.1038/s41598-021-89486-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Accepted: 04/20/2021] [Indexed: 01/04/2023] Open
Abstract
Nucleoside/nucleotide analogs such as tenofovir, have been used as long-term therapy for the treatment of hepatitis B and side effects such as the reduction in bone mineral density have been associated with their use. To determine the relationships between bone, hormonal, biochemical, and mineral parameters in patients with hepatitis B treated with nucleoside/nucleotide antiviral. A cross-sectional study was conducted with 81 adult patients with chronic hepatitis B infection. Dual-energy X-ray absorptiometry (DXA) was performed to assess bone mineral density. Biochemical analyses were performed for osteocalcin, deoxypyridinoline, parathyroid hormone, vitamin D, IGF-1, TSH, testosterone, estradiol, FSH, transaminases, urea, creatinine, calcium, serum and urinary phosphorus, magnesium, and FGF-23, body composition was performed by DXA. Participants, both gender, were divided according to the use of antiretrovirals: Group1: 27 inactive virus carriers without medication; Group2: 27 patients using tenofovir; and Group3: 27 patients using lamivudine or entecavir. DXA readings diagnosed osteopenia in the lumbar spine for 7.4% of individuals in Group1, 15% in Group2, and 3.7% in Group3. For all groups, we observed normal values in bone formation markers, osteocalcin levels as well as parathyroid hormone, insulin growth factor 1, and FGF-23. In all groups, we found increased levels of urinary deoxypyridinoline, a bone resorption marker. Increased levels in the bone resorption markers indicated a high resorptive activity of bone tissue. These data suggested high resorption activity of bone tissue in hepatitis B virus-infected patients independent of the use of antiretrovirals.
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Bukhari T, Jafri L, Majid H, Khan AHH, Siddiqui I. Determining Bone Turnover Status in Patients With Chronic Liver Disease. Cureus 2021; 13:e14479. [PMID: 33996337 PMCID: PMC8120131 DOI: 10.7759/cureus.14479] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/28/2020] [Indexed: 11/05/2022] Open
Abstract
Introduction Hepatic osteodystrophy is an osteoporotic bone disease that occurs in chronic liver disease patients. The global prevalence of osteoporosis in patients with chronic liver disease is 30% to 40%. The pathogenesis of hepatic bone disease is not clear, but it occurs due to unstable bone remodeling with increased bone resorption and decreases bone formation. There has been an interest in determining the clinical utility of bone turnover markers (BTMs) in the assessment of osteoporosis in chronic liver patients. Methods This was a cross-sectional study conducted in patients with chronic liver disease at the section of chemical pathology, department of pathology and laboratory medicine, Aga Khan University (AKU). A total of 50 patients with age >8 years and a history of liver disease >6 months were recruited from January to October 2019. Liver function tests, i.e. aspartate aminotransferase (AST), alanine transaminase (ALT), albumin, and bilirubin, along with clinical signs of liver disease chronicity, were noted. The samples for BTMs, i.e. total serum alkaline phosphatase (ALP) and serum C-terminal telopeptide of type-1 collagen (CTX) were withdrawn and analyzed on Microlab (ELItech Group, Puteaux, France) and ADVIA Centaur (Siemens Diagnostics, NY), respectively. Results The majority of patients were males (n=34, 68%). Twenty-four (48%) patients suffered from fibrosis while 26 (52%) were without fibrosis. Median platelet count (68×109/L (102.5-50)) and median cholesterol levels (102.5 mg/dl (147-99.5)) were decreased, whereas gamma-glutamyl transferase (GGT) levels were higher in the fibrosis group as compared to the non-fibrosis group. The median levels of total ALP were 91.5 IU/L (103-82), and the median levels of CTX were 0.24 pg/ml (0.34-0.21). Conclusion In the present study, no significant difference was found in the BTMs of patients with and without chronic liver disease (CLD). However, there was a positive and significant correlation of BTMs, particularly CTX with age, bilirubin levels, and hepatomegaly.
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Affiliation(s)
- Tayyaba Bukhari
- Pathology & Laboratory Medicine, Aga Khan University Hospital, Karachi, PAK
| | - Lena Jafri
- Pathology & Laboratory Medicine, Aga Khan University Hospital, Karachi, PAK
| | - Hafsa Majid
- Pathology & Laboratory Medicine, Aga Khan University Hospital, Karachi, PAK
| | - Aysha Habib H Khan
- Pathology & Laboratory Medicine, Aga Khan University Hospital, Karachi, PAK
| | - Imran Siddiqui
- Pathology & Laboratory Medicine, Aga Khan University Hospital, Karachi, PAK
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20
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Puri P, Dhiman RK, Taneja S, Tandon P, Merli M, Anand AC, Arora A, Acharya SK, Benjamin J, Chawla YK, Dadhich S, Duseja A, Eapan C, Goel A, Kalra N, Kapoor D, Kumar A, Madan K, Nagral A, Pandey G, Rao PN, Saigal S, Saraf N, Saraswat VA, Saraya A, Sarin SK, Sharma P, Shalimar, Shukla A, Sidhu SS, Singh N, Singh SP, Srivastava A, Wadhawan M. Nutrition in Chronic Liver Disease: Consensus Statement of the Indian National Association for Study of the Liver. J Clin Exp Hepatol 2021; 11:97-143. [PMID: 33679050 PMCID: PMC7897902 DOI: 10.1016/j.jceh.2020.09.003] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Accepted: 09/22/2020] [Indexed: 02/06/2023] Open
Abstract
Malnutrition and sarcopenia are common in patients with chronic liver disease and are associated with increased risk of decompensation, infections, wait-list mortality and poorer outcomes after liver transplantation. Assessment of nutritional status and management of malnutrition are therefore essential to improve outcomes in patients with chronic liver disease. This consensus statement of the Indian National Association for Study of the Liver provides a comprehensive review of nutrition in chronic liver disease and gives recommendations for nutritional screening and treatment in specific clinical scenarios of malnutrition in cirrhosis in adults as well as children with chronic liver disease and metabolic disorders.
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Key Words
- ACLF, acute on chronic liver failure
- ASM, appendicular skeletal muscle mass
- BCAA, branched chain amino acids
- BIA, bioimpedance analysis
- BMD, bone mineral densitometry
- BMI, body mass index
- CLD, chronic liver disease
- CS, corn-starch
- CT, computed tomography
- CTP, Child–Turcotte–Pugh
- DEXA, dual-energy X-ray absorptiometry
- EASL, European Association for the Study of the Liver
- ESPEN, European society for Clinical Nutrition and Metabolism
- GSD, glycogen storage disease
- HGS, hand-grip strength
- IBW, ideal body weight
- IEM, inborn error of metabolism
- INASL, Indian National Association for Study of the Liver
- L3, third lumbar
- LFI, Liver Frailty Index
- MCT, medium-chain triglyceride
- MELD, model for end-stage liver disease
- MLD, metabolic liver disease
- MRI, magnetic resonance imaging
- RDA, recommended daily allowance
- REE, NASH
- RFH-NPT, Royal Free Hospital-Nutritional Prioritizing Tool
- SMI, skeletal muscle index
- Sarcopenia
- TEE, total energy expenditure
- chronic liver disease
- cirrhosis
- malnutrition
- non-alcoholic liver disease, resting energy expenditure
- nutrition
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Affiliation(s)
- Pankaj Puri
- Fortis Escorts Liver & Digestive Diseases Institute, New Delhi, 110025, India
| | - Radha K. Dhiman
- Department of Hepatobiliary Sciences, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India
| | - Sunil Taneja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Puneeta Tandon
- Department of Medicine, University of Alberta, Edmonton, AB T6G 2R3, Canada
| | - Manuela Merli
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, 00185, Italy
| | - Anil C. Anand
- Kalinga Institute of Medical Sciences, Bhubhaneswar, 751024, Odisha, India
| | - Anil Arora
- Institute of Liver, Gastroenterology and Pancreatico-Biliary Sciences of Sir Ganga Ram Hospital, New Delhi, 110060, India
| | - Subrat K. Acharya
- Fortis Escorts Liver & Digestive Diseases Institute, New Delhi, 110025, India
| | - Jaya Benjamin
- Institute of Liver and Biliary Sciences, Vasant Kunj, New Delhi, 110070, India
| | - Yogesh K. Chawla
- Kalinga Institute of Medical Sciences, Bhubhaneswar, 751024, Odisha, India
| | - Sunil Dadhich
- Department of Gastroenterology SN Medical College, Jodhpur, 342003, India
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - C.E. Eapan
- Department of Gastroenterology, Christian Medical College, Vellore, 632004, India
| | - Amit Goel
- Department of Hepatobiliary Sciences, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India
| | - Naveen Kalra
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Dharmesh Kapoor
- Department of Gastroenterology, Global Hospital, Hyderabad, 500004, India
| | - Ashish Kumar
- Institute of Liver, Gastroenterology and Pancreatico-Biliary Sciences of Sir Ganga Ram Hospital, New Delhi, 110060, India
| | - Kaushal Madan
- Max Smart Super Speciality Hospital, New Delhi, India
| | - Aabha Nagral
- Department of Gastroenterology, Jaslok Hospital, Mumbai, 400026, India
| | - Gaurav Pandey
- Department of Hepatobiliary Sciences, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India
| | - Padaki N. Rao
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, 500082, India
| | - Sanjiv Saigal
- Department of Hepatology, Medanta Hospital, Gurugram, 122001, India
| | - Neeraj Saraf
- Department of Hepatology, Medanta Hospital, Gurugram, 122001, India
| | - Vivek A. Saraswat
- Department of Hepatobiliary Sciences, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India
| | - Anoop Saraya
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110016, India
| | - Shiv K. Sarin
- Institute of Liver and Biliary Sciences, Vasant Kunj, New Delhi, 110070, India
| | - Praveen Sharma
- Institute of Liver, Gastroenterology and Pancreatico-Biliary Sciences of Sir Ganga Ram Hospital, New Delhi, 110060, India
| | - Shalimar
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110016, India
| | - Akash Shukla
- Department of Gastroenterology, Seth GSMC & KEM Hospital, Mumbai, 400022, India
| | - Sandeep S. Sidhu
- Department of Gastroenterology, SPS Hospital, Ludhiana, 141001, India
| | - Namrata Singh
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110016, India
| | - Shivaram P. Singh
- Department of Gastroenterology, SCB Medical College, Cuttack, 753007, India
| | - Anshu Srivastava
- Department of Hepatobiliary Sciences, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India
| | - Manav Wadhawan
- Institute of Liver & Digestive Diseases, BL Kapur Memorial Hospital, New Delhi, 110005, India
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21
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Zhang Y, Gao X, Liu T, Gao P, Li H, Liu N, Gao L, Wan G, Zhang Y, Duan X. Association between osteoporosis and hepatitis B cirrhosis: a case-control study. Afr Health Sci 2020; 20:1610-1616. [PMID: 34394221 PMCID: PMC8351827 DOI: 10.4314/ahs.v20i4.13] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Background and aims Hepatitis B virus (HBV)-related cirrhosis is associated with decreased bone mineral density (BMD); however, the mechanism is yet unknown. To assess the incidence of osteoporosis in patients with HBV-associated cirrhosis and relevant mechanisms. Methods A total of 80 hospitalized patients with HBV-associated cirrhosis and 80 healthy controls were enrolled. The levels of serum osteocalcin, total procollagen type 1 amino-terminal propeptide, β-C-terminal telopeptide of type I collagen (β-CTX), and 25-hydroxy vitamin D3 (25(OH)D3) was evaluated in the cirrhosis group. Results The BMDs of the lumbar spine (P<0.001) and hip joints (P=0.015) in the cirrhosis group were significantly lower than those in the controls. The incidence of osteoporosis in the cirrhosis group was significantly higher than that in the control group (P<0.001). Compared to the patients of the Child-Pugh grade A and B, the BMD of lumbar spine and 25(OH)D3 was significantly decreased in patients of grade C, while β-CTX was elevated. Patients in the cirrhosis group faced a higher risk of osteoporosis as compared to the controls(P<0.001). Conclusions Enhanced bone resorption accounted for increased risk of osteoporosis in severe cirrhosis. Thus, HBV-associated cirrhosis was a risk factor for osteoporosis.
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Affiliation(s)
- Yijin Zhang
- Department of General Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xuesong Gao
- Department of General Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ting Liu
- Clinical data and sample repository, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ping Gao
- Department of General Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Hongjie Li
- Department of General Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Nan Liu
- Department of General Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Lili Gao
- Department of General Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Gang Wan
- Department of Medical Record, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yaonan Zhang
- Department of Orthopedics, Beijing Hospital, National Center of Gerontology, Beijing, China
| | - Xuefei Duan
- Department of General Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
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22
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De A, Ray D, Lamoria S, Sharma V, Khurana TR. Hepatic osteodystrophy and fracture risk prediction using FRAX tool in Indian patients with cirrhosis. JGH OPEN 2020; 4:945-949. [PMID: 33102768 PMCID: PMC7578334 DOI: 10.1002/jgh3.12369] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Revised: 04/22/2020] [Accepted: 05/19/2020] [Indexed: 01/05/2023]
Abstract
Background and Aim The main clinical relevance of hepatic osteodystrophy is the increased risk of fractures. Dual‐energy X ray absorptiometry (DEXA)‐based assessment of bone mineral density, the current gold standard for diagnosing osteoporosis, is not the sole determinant of fracture risk. Other clinical risk factors also play an important role. This study was carried out to assess the prevalence and risk factors of hepatic osteodystrophy and estimate the entailed fracture risk by using the FRAX tool in a cohort of Indian cirrhotics. Methods Consecutive patients with cirrhosis (n = 120) were recruited. Etiologic workup, liver function tests, serum calcium, phosphate, 25(OH)D, HbA1c, and DEXA scan were performed. Hepatic osteodystrophy was defined as a T score of < −1. FRAX scores were calculated using the Indian calculator. Results The study cohort was predominantly male (86.7%) with a median age of 49 (40–65) years. Alcohol was the most common etiology (80%). All patients had Child‐Turcotte‐Pugh class B (63.3%) or class B (36.7%) cirrhosis. Hepatic osteodystrophy was present in 83.3% patients. On multivariate analysis, smoking (odds ratio [OR]: 3.1 [1.76–4.7], P < 0.001) and serum 25(OH)D (OR: 0.23 [0.09–0.94]; P = 0.03) showed significant association with hepatic osteodystrophy. The 10‐year probability of major osteoporotic fracture and hip fracture was 5.7% (2.1–28.9) and 2.5% (1.4–7.4), respectively. Using a FRAX probability cut‐off of 20% for major osteoporotic fracture and 3% for hip fracture, 30% patients qualified for osteoporosis treatment. Conclusion Hepatic osteodystrophy is widely prevalent among Indian patients with cirrhosis and entails a high risk of fractures. Approximately one‐third of patients with cirrhosis need treatment to reduce the risk of osteoporotic fractures.
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Affiliation(s)
- Arka De
- Department of Hepatology Post Graduate Institute of Medical Education and Research Chandigarh India
| | - Debadrita Ray
- Department of Laboratory Oncology All India Institute of Medical Sciences New Delhi India
| | - Sandeep Lamoria
- Department of Medicine Post Graduate Institute of Medical Education and Research, Dr RML Hospital New Delhi India
| | - Vishal Sharma
- Department of Gastroenterology Post Graduate Institute of Medical Education and Research Chandigarh India
| | - Tilak Raj Khurana
- Department of Medicine Post Graduate Institute of Medical Education and Research, Dr RML Hospital New Delhi India
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23
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Hidalgo DF, Boonpheng B, Sikandar S, Nasr L, Hidalgo J. Chronic Liver Disease and the Risk of Osteoporotic Fractures: A Meta-Analysis. Cureus 2020; 12:e10483. [PMID: 33083184 PMCID: PMC7567329 DOI: 10.7759/cureus.10483] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Introduction Chronic liver disease (CLD) causes more than 1 million deaths every year and remains a pandemic in the last decade affecting more than 600,000 patients in the United States. Previous studies found patients with CLD had increased risk of osteoporosis, so fractures were inferred to be complications of this condition. The aim of this meta-analysis is to summarize the best evidence that correlates CLD patients and the risk to develop osteoporotic fractures versus control patients without CLD. Methods A review of the literature using MEDLINE and EMBASE database was performed during December 2017. We included cross-sectional and cohort studies that reported relative risks (RR), odds ratios (OR) and hazard ratios (HR) comparing the risk of developing osteoporotic fractures among patients with CLD versus patients without CLD. Pooled OR and 95% confidence interval (CI) were calculated using generic inverse- variance method. The Newcastle-Ottawa scale was used to determine the quality of the studies. Effect estimates from the individual study were extracted and combined using the random-effect, generic inverse variance method of DerSimonian and Laird. Results After the review of the literature, seven studies fulfilled the eligibility criteria established during the analysis. Significant association was found between CLD and osteoporotic fractures with a pooled OR of 2.13 (95% CI, 1.79 - 2.52). High heterogeneity among the studies was found (I2=88.5). No publication bias was found using Egger regression test (p=0.44). Conclusion We found a significant association between CLD and the risk of developing osteoporotic fractures. The calculated risk was 2.13 times higher for patients with CLD when compared with controls. The results showed high heterogeneity but no publication bias. More prospective studies are needed to fully understand the mechanisms involved in loss of bone density and osteoporotic fractures in order to improve the morbidity associated with this disease.
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Affiliation(s)
- Diego F Hidalgo
- Geriatrics, Jackson Memorial Hospital, University of Miami, Miami, USA
| | | | - Sehrish Sikandar
- Geriatrics, Miami Geriatric Research Education and Clinical Center Veterans Successful Aging for Frail Elders (VSAFE), Miami, USA
| | - Lubna Nasr
- Geriatrics, University of Miami Miller School of Medicine, Miami, USA.,Geriatrics, Miami Geriatric Research Education and Clinical Center Veterans Successful Aging for Frail Elders (VSAFE), Miami, USA
| | - Jessica Hidalgo
- Internal Medicine, San Francisco de Quito University, Quito, ECU
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24
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Lima TB, Santos LAA, Nunes HRDC, Silva GF, Caramori CA, Qi X, Romeiro FG. Safety and efficacy of risedronate for patients with esophageal varices and liver cirrhosis: a non-randomized clinical trial. Sci Rep 2019; 9:18958. [PMID: 31831865 PMCID: PMC6908659 DOI: 10.1038/s41598-019-55603-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Accepted: 11/22/2019] [Indexed: 02/07/2023] Open
Abstract
Despite the high prevalence of osteoporosis in liver cirrhosis, the indication of bisphosphonates for patients with esophageal varices has been avoided due to risk of digestive mucosal damage. Therefore, this study aimed to evaluate the safety profile of risedronate treatment for patients with osteoporosis, liver cirrhosis and esophageal varices with low risk of bleeding. A total of 120 patients were allocated into two groups according to their bone mineral density measured by dual-energy X-ray absorptiometry. In the intervention group, 57 subjects with osteoporosis received oral risedronate at 35 mg weekly plus daily calcium and vitamin D supplementation. In the control group, 63 subjects with osteopenia received only calcium and vitamin D. The groups received the treatment for one year and underwent surveillance endoscopies at six and 12 months, as well as a control dual-energy X-ray absorptiometry after a 12-month follow-up. The study received Institutional Review Board approval. The groups had not only comparable Model for End-stage Liver Disease score and esophageal varices degree, but also similar incidence of digestive adverse effects. A significant improvement was achieved in the intervention group in the lumbar spine T score (p < 0.001). The results suggest that risedronate may be safely used in liver cirrhosis and esophageal varices with low bleeding risk under endoscopic surveillance, thus allowing bone mass recovery.
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Affiliation(s)
- Talles Bazeia Lima
- Internal Medicine Department, Gastroenterology Division - São Paulo State University (UNESP), Botucatu Medical School, São Paulo, Brazil
| | - Lívia Alves Amaral Santos
- Internal Medicine Department, Gastroenterology Division - São Paulo State University (UNESP), Botucatu Medical School, São Paulo, Brazil
| | | | - Giovanni Faria Silva
- Internal Medicine Department, Gastroenterology Division - São Paulo State University (UNESP), Botucatu Medical School, São Paulo, Brazil
| | - Carlos Antonio Caramori
- Internal Medicine Department, Gastroenterology Division - São Paulo State University (UNESP), Botucatu Medical School, São Paulo, Brazil
| | - Xingshun Qi
- General Hospital of Shenyang Military Command, Liaoning, Sheng, China
| | - Fernando Gomes Romeiro
- Internal Medicine Department, Gastroenterology Division - São Paulo State University (UNESP), Botucatu Medical School, São Paulo, Brazil.
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25
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Jeong HM, Kim DJ. Bone Diseases in Patients with Chronic Liver Disease. Int J Mol Sci 2019; 20:4270. [PMID: 31480433 PMCID: PMC6747370 DOI: 10.3390/ijms20174270] [Citation(s) in RCA: 64] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Revised: 08/25/2019] [Accepted: 08/28/2019] [Indexed: 02/07/2023] Open
Abstract
Osteoporosis is a frequently observed complication in patients with chronic liver disease, particularly liver cirrhosis and cholestatic liver diseases. In addition, osteoporosis is critical in patients receiving a liver transplant. Nevertheless, few studies have evaluated bone diseases in patients with more frequently observed chronic liver disease, such as chronic viral hepatitis, nonalcoholic fatty liver disease and alcoholic liver disease. Osteoporosis is a disease caused by an imbalance in the activities of osteoblasts and osteoclasts. Over the last few decades, many advances have improved our knowledge of the pathogenesis of osteoporosis. Importantly, activated immune cells affect the progression of osteoporosis, and chronic inflammation may exert an additional effect on the existing pathophysiology of osteoporosis. The microbiota of the intestinal tract may also affect the progression of bone loss in patients with chronic liver disease. Recently, studies regarding the effects of chronic inflammation on dysbiosis in bone diseases have been conducted. However, mechanisms underlying osteoporosis in patients with chronic liver disease are complex and precise mechanisms remain unknown. The following special considerations in patients with chronic liver disease are reviewed: bone diseases in patients who underwent a liver transplant, the association between chronic hepatitis B virus infection treatment and bone diseases, the association between sarcopenia and bone diseases in patients with chronic liver disease, and the association between chronic liver disease and avascular necrosis of the hip. Few guidelines are currently available for the management of low bone mineral density or bone diseases in patients with chronic liver disease. Due to increased life expectancy and therapeutic advances in chronic liver disease, the importance of managing osteoporosis and other bone diseases in patients with chronic liver disease is expected to increase. Consequently, specific guidelines need to be established in the near future.
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Affiliation(s)
- Hae Min Jeong
- Department of Internal Medicine, Hallym University Chuncheon Sacred Heart Hospital, Chuncheon, Gangwon-do 24253, Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Gangwon-do 24253, Korea
| | - Dong Joon Kim
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Gangwon-do 24253, Korea.
- Department of Internal Medicine, Hallym University College of Medicine, Seoul 05355, Korea.
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26
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Chapman MH, Thorburn D, Hirschfield GM, Webster GGJ, Rushbrook SM, Alexander G, Collier J, Dyson JK, Jones DE, Patanwala I, Thain C, Walmsley M, Pereira SP. British Society of Gastroenterology and UK-PSC guidelines for the diagnosis and management of primary sclerosing cholangitis. Gut 2019; 68:1356-1378. [PMID: 31154395 PMCID: PMC6691863 DOI: 10.1136/gutjnl-2018-317993] [Citation(s) in RCA: 172] [Impact Index Per Article: 28.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2018] [Revised: 02/21/2019] [Accepted: 03/24/2019] [Indexed: 12/11/2022]
Abstract
These guidelines on the management of primary sclerosing cholangitis (PSC) were commissioned by the British Society of Gastroenterology liver section. The guideline writing committee included medical representatives from hepatology and gastroenterology groups as well as patient representatives from PSC Support. The guidelines aim to support general physicians, gastroenterologists and surgeons in managing adults with PSC or those presenting with similar cholangiopathies which may mimic PSC, such as IgG4 sclerosing cholangitis. It also acts as a reference for patients with PSC to help them understand their own management. Quality of evidence is presented using the AGREE II format. Guidance is meant to be used as a reference rather than for rigid protocol-based care as we understand that management of patients often requires individual patient-centred considerations.
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Affiliation(s)
- Michael Huw Chapman
- GI Division, UCL Hospitals NHS Foundation Trust, London, UK
- Liver Unit, Royal Free London NHS Foundation Trust, London, UK
| | | | - Gideon M Hirschfield
- Toronto Centre for Liver Disease, University Health Network and University of Toronto, Toronto, Canada
| | | | - Simon M Rushbrook
- Department of Hepatology, Norfolk and Norwich University Hospitals NHS Trust, Norwich, UK
| | | | | | - Jessica K Dyson
- Hepatology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK
- Institute of Cellular Medicine, Newcastle University, Newcastle, UK
| | - David Ej Jones
- Institute of Cellular Medicine, Newcastle University, Newcastle, UK
| | - Imran Patanwala
- Gastroenterology, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK
- University of Liverpool, Liverpool, UK
| | | | | | - Stephen P Pereira
- GI Division, UCL Hospitals NHS Foundation Trust, London, UK
- Institute for Liver & Digestive Health, University College London, London, UK
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27
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Chen YY, Fang WH, Wang CC, Kao TW, Chang YW, Yang HF, Wu CJ, Sun YS, Chen WL. Crosssectional Assessment of Bone Mass Density in Adults with Hepatitis B Virus and Hepatitis C Virus Infection. Sci Rep 2019; 9:5069. [PMID: 30911051 PMCID: PMC6433944 DOI: 10.1038/s41598-019-41674-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2018] [Accepted: 03/13/2019] [Indexed: 12/13/2022] Open
Abstract
Osteoporosis is one of the major complications in chronic hepatitis B virus (HBV) and hepatitis C (HCV) infection. However, few studies had examined the relationship between hepatic viral infection with bone loss. Our aim was to investigate the association between hepatic viral infection with bone mineral density (BMD) in a cross-sectional study. Participants who attended the health examinations at the Tri-Service General Hospital (TSGH), Taiwan, were enrolled in the study. Diagnosis of viral hepatitis was confirmed by the serum viral markers of hepatitis B surface antigen (HBsAg) and anti-HCV, and BMD measurement was performed by the bone densitometry. Subjects were divided into four groups by the presence of viral markers. The association between hepatic viral infection and BMD was examined by a multivariate linear regression model. HBV infection was inversely associated with BMD after full adjusting with β values of -0.17 (95% CI: -0.29, -0.05) (p < 0.05). The relationship remained significant in males (β = -0.16, 95% CI = -0.31, -0.01) (p < 0.05). In subjects with body mass index less than 30 HBV infection was associated with reduced BMD (β = -0.16, 95% CI = -0.29, -0.02) (p < 0.05). However, HCV infection was only associated with an increase in BMD in patients with BMI less than 30 (β = 0.17, 95% CI = 0.21, 0.32) (p < 0.05). Chronic HBV infection was significantly associated with reduced BMD in males. The impact of viral hepatitis on bone health deserves further investigation for the potential pathophysiological mechanisms.
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Affiliation(s)
- Yuan-Yuei Chen
- Department of Internal Medicine, Tri-Service General Hospital Songshan Branch; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China.,Division of Family Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China
| | - Wen-Hui Fang
- Division of Family Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China
| | - Chung-Ching Wang
- Division of Family Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China
| | - Tung-Wei Kao
- Division of Family Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China.,Division of Geriatric Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China.,Graduate Institute of Clinical Medical, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China
| | - Yaw-Wen Chang
- Division of Family Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China.,Division of Geriatric Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China
| | - Hui-Fang Yang
- Division of Family Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China.,Division of Geriatric Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China
| | - Chen-Jung Wu
- Division of Family Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China.,Division of Geriatric Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China.,Division of Family Medicine, Department of Community Medicine, Taoyuan Armed Forces General Hospital, Taoyuan, Taiwan, Republic of China
| | - Yu-Shan Sun
- Division of Family Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China.,Division of Geriatric Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China
| | - Wei-Liang Chen
- Division of Family Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China. .,Division of Geriatric Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China.
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28
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Lin MS, Chen PH, Wang PC, Lin HS, Huang TJ, Chang ST, Chiu WN, Chen MY. Association between hepatitis C virus infection and osteoporotic fracture risk among postmenopausal women: a cross-sectional investigation in Taiwan. BMJ Open 2019; 9:e021990. [PMID: 30782676 PMCID: PMC6340457 DOI: 10.1136/bmjopen-2018-021990] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Revised: 08/24/2018] [Accepted: 11/05/2018] [Indexed: 01/13/2023] Open
Abstract
PURPOSE Early low bone mass is a risk factor for osteoporotic fractures associated with multiple factors, including menopause and chronic liver diseases. Hepatitis C virus (HCV) also plays a major role in chronic liver disease and has many extrahepatic consequences, such as decreased bone mineral density (BMD). This study aimed to examine the hypothesis that HCV seropositivity is independently associated with menopausal BMD loss. METHODS This community-based, cross-sectional study was based in two rural townships in Yunlin County, Taiwan. A total of 636 menopausal women aged 45-80 years who underwent annual health checks were included. Viral markers of HCV, dual-energy X-ray absorptiometry and fracture risk assessment tool (FRAX) scores were measured. Logistic regression analysis was performed to assess the association between various predictors and the presence of low BMD. RESULTS The participants (median age: 65 years) had a HCV seropositivity rate of 32.2%. BMD was significantly lower in the HCV-seropositive participants in different anatomic locations than in the seronegative individuals (lumbar spine: -1.5 vs -1.1; total hip: -0.9 vs -0.6; femoral neck: -1.2 vs -1.0; p<0.05). HCV-seropositive subjects had higher rates of major osteoporotic fractures (11.3%±7.6%vs 9.0±6.8%; p<0.001) and hip fractures (3.4%±4.7%vs 2.3±4.9%; p=0.006) and a higher risk of lower BMD (osteopenia and osteoporosis) based on a multivariable regression analysis (adjusted OR: 1.8; 95% CI 1.16 to 2.81; p=0.009). CONCLUSIONS HCV infection may be an independent risk factor for menopausal BMD loss and fractures predicted by FRAX.
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Affiliation(s)
- Ming-Shyan Lin
- Department of Cardiology, Chang Gung Memorial Hospital, Chiayi, Taiwan
- Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Po-Han Chen
- Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Yunlin, Taiwan
| | - Po-Chang Wang
- Department of Cardiology, Chang Gung Memorial Hospital, Chiayi, Taiwan
- Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Huang-Shen Lin
- Department of Infectious Diseases, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Tung-Jung Huang
- Department of Pulmonary Disease and Critical Care, Chang Gung Memorial Hospital, Yunlin, Taiwan
- Department of Respiratory Care, Chang Gung University of Science and Technology, Chiayi, Taiwan
| | - Shih-Tai Chang
- Department of Cardiology, Chang Gung Memorial Hospital, Chiayi, Taiwan
- Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Wen-Nan Chiu
- Department of Hepato-Gastroenterology, Chang Gung Memorial Hospital, Yunlin, Taiwan
| | - Mei-Yen Chen
- Department of Cardiology, Chang Gung Memorial Hospital, Chiayi, Taiwan
- Department of Nursing, Chang Gung University of Science and Technology, Chiayi, Taiwan
- Department of Nursing, Chang Gung University, Taoyuan, Taiwan
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Otete H, Deleuran T, Fleming KM, Card T, Aithal GP, Jepsen P, West J. Hip fracture risk in patients with alcoholic cirrhosis: A population-based study using English and Danish data. J Hepatol 2018; 69:697-704. [PMID: 29673756 DOI: 10.1016/j.jhep.2018.04.002] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2017] [Revised: 04/04/2018] [Accepted: 04/06/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Cirrhosis, the prevalence of which is increasing, is a risk factor for osteoporosis and fractures. However, little is known of the actual risk of hip fractures in patients with alcoholic cirrhosis. Using linked primary and secondary care data from the English and Danish nationwide registries, we quantified the hip fracture risk in two national cohorts of patients with alcoholic cirrhosis. METHODS We followed 3,706 English and 17,779 Danish patients with a diagnosis of alcoholic cirrhosis, and we identified matched controls from the general populations. We estimated hazard ratios (HR) of hip fracture for patients vs. controls, adjusted for age, sex and comorbidity. RESULTS The five-year hip fracture risk was raised both in England (2.9% vs. 0.8% for controls) and Denmark (4.6% vs. 0.9% for controls). With confounder adjustment, patients with cirrhosis had fivefold (adjusted HR 5.5; 95% CI 4.3-6.9), and 8.5-fold (adjusted HR 8.5; 95% CI 7.8-9.3) increased rates of hip fracture, in England and Denmark, respectively. This association between alcoholic cirrhosis and risk of hip fracture showed significant interaction with age (p <0.001), being stronger in younger age groups (under 45 years, HR 17.9 and 16.6 for English and Danish patients, respectively) than in patients over 75 years (HR 2.1 and 2.9, respectively). In patients with alcoholic cirrhosis, 30-day mortality following a hip fracture was 11.1% in England and 10.0% in Denmark, giving age-adjusted post-fracture mortality rate ratios of 2.8(95% CI 1.9-3.9) and 2.0(95% CI 1.5-2.7), respectively. CONCLUSIONS Patients with alcoholic cirrhosis have a markedly increased risk of hip fracture and post-hip fracture mortality compared with the general population. These findings support the need for more effort towards fracture prevention in this population, to benefit individuals and reduce the societal burden. LAY SUMMARY Alcoholic cirrhosis creates a large public health burden and is a risk factor for bone fractures. Based on data from England and Denmark, we found that hip fractures occur more than five times more frequently in people with alcoholic cirrhosis than in people without the disease. Additionally, the aftermath of the hip fracture is severe, such that up to 11% of patients with alcoholic cirrhosis die within 30 days after their hip fracture. These results suggest that efforts directed towards fracture prevention in people with alcoholic cirrhosis could be beneficial.
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Affiliation(s)
- Harmony Otete
- Division of Epidemiology and Public Health, University of Nottingham, City Hospital Campus, Nottingham NG5 1PB, United Kingdom; School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, United Kingdom; School of Medicine, University of Central Lancashire, Harrington building 242, Preston PR1 2HE, United Kingdom.
| | - Thomas Deleuran
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg Denmark
| | - Kate M Fleming
- Department of Public Health and Policy, University of Liverpool, Liverpool L69 3GB, United Kingdom
| | - Tim Card
- Division of Epidemiology and Public Health, University of Nottingham, City Hospital Campus, Nottingham NG5 1PB, United Kingdom; Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK; NIHR Nottingham Biomedical Research Centre at the Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
| | - Guru P Aithal
- Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK; NIHR Nottingham Biomedical Research Centre at the Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
| | - Peter Jepsen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
| | - Joe West
- Division of Epidemiology and Public Health, University of Nottingham, City Hospital Campus, Nottingham NG5 1PB, United Kingdom; Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK; NIHR Nottingham Biomedical Research Centre at the Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
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Schiavo L, Busetto L, Cesaretti M, Zelber-Sagi S, Deutsch L, Iannelli A. Nutritional issues in patients with obesity and cirrhosis. World J Gastroenterol 2018; 24:3330-3346. [PMID: 30122874 PMCID: PMC6092576 DOI: 10.3748/wjg.v24.i30.3330] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Revised: 06/15/2018] [Accepted: 06/25/2018] [Indexed: 02/06/2023] Open
Abstract
Obesity and metabolic syndrome are considered as responsible for a condition known as the non-alcoholic fatty liver disease that goes from simple accumulation of triglycerides to hepatic inflammation and may progress to cirrhosis. Patients with obesity also have an increased risk of primary liver malignancies and increased body mass index is a predictor of decompensation of liver cirrhosis. Sarcopenic obesity confers a risk of physical impairment and disability that is significantly higher than the risk induced by each of the two conditions alone as it has been shown to be an independent risk factor for chronic liver disease in patients with obesity and a prognostic negative marker for the evolution of liver cirrhosis and the results of liver transplantation. Cirrhotic patients with obesity are at high risk for depletion of various fat-soluble, water-soluble vitamins and trace elements and should be supplemented appropriately. Diet, physical activity and protein intake should be carefully monitored in these fragile patients according to recent recommendations. Bariatric surgery is sporadically used in patients with morbid obesity and cirrhosis also in the setting of liver transplantation. The risk of sarcopenia, micronutrient status, and the recommended supplementation in patients with obesity and cirrhosis are discussed in this review. Furthermore, the indications and contraindications of bariatric surgery-induced weight loss in the cirrhotic patient with obesity are discussed.
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Affiliation(s)
- Luigi Schiavo
- Department of Translational Medical Science, University of Campania “Luigi Vanvitelli”, Naples 80131, Italy
- IX Division of General Surgery, Vascular Surgery and Applied Biotechnology, Naples University Policlinic, Naples 80131, Italy
| | - Luca Busetto
- Department of Medicine, University of Padua, Padua 35128, Italy
- Center for the Study and the Integrated Management of Obesity, University Hospital of Padua, Padua 35128, Italy
| | - Manuela Cesaretti
- Department of HPB Surgery and Liver Transplantation, Hôpital Beaujon, AP-HP, Clichy 92110, France
- Department of Nanophysics, Italian Institute of Technology, Genova 16163, Italy
| | - Shira Zelber-Sagi
- School of Public Health, University of Haifa, Haifa 3498838, Israel
- Department of Gastroenterology and Liver disease, Tel Aviv Medical Center, 62431, Tel-Aviv 62431, Israel
| | - Liat Deutsch
- Department of Gastroenterology and Liver disease, Tel Aviv Medical Center, 62431, Tel-Aviv 62431, Israel
- The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 62431, Israel
| | - Antonio Iannelli
- Digestive Unit, Archet 2 Hospital, University Hospital of Nice, F-06202, Nice, France; Inserm, U1065, Team 8 “Hepatic complications of obesity”, Nice F-06204, France
- University of Nice Sophia-Antipolis, Nice F-06107, France
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Moctezuma-Velázquez C, Low G, Mourtzakis M, Ma M, Burak KW, Tandon P, Montano-Loza AJ. Association between Low Testosterone Levels and Sarcopenia in Cirrhosis: A Cross-sectional Study. Ann Hepatol 2018; 17:615-623. [PMID: 29893704 DOI: 10.5604/01.3001.0012.0930] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND AIM Sarcopenia is an independent predictor of mortality in cirrhosis. Hypogonadism is common in cirrhosis and has been associated with sarcopenia in non-cirrhotic chronic liver disease populations. The aim of this study is to investigate if sarcopenia is associated with low testosterone levels in patients with cirrhosis. MATERIAL AND METHODS This is a retrospective analysis of prospectively collected data of 211 cirrhotic patients undergoing evaluation for liver transplantation. Sarcopenia was defined by computed tomography (CT) scan using specific cutoffs of the 3rd lumbar vertebra skeletal muscle index (L3 SMI). Morning testosterone levels were obtained in all patients. RESULTS Of the 211 patients, sarcopenia was noted in 94 (45%). Testosterone levels were lower in sarcopenic patients (10.7 ± 1.1 vs. 13.7 ± 1.4 nmol/L, p = 0.03) and hypotestosteronemia was more frequent in them too (34 vs. 16%, p = 0.004). In males, those with sarcopenia had lower testosterone levels (14.6 ± 1.4 vs. 21.9 ± 1.8, p = 0.002), and the corresponding frequency of hypotestosteronemia (42 vs. 19%, p = 0.006) was also higher. There were no significant differences in female patients. There was a weak correlation between L3 SMI and testosterone levels (r 0.37, p < 0.001). On multivariable regression analysis including sex, body mass index (BMI), hypotestosteronemia, MELD and etiology of cirrhosis, only hypotestosteronemia (RR 2.76, p = 0.005) and BMI (RR 0.88, p < 0.001) were independently associated with sarcopenia. CONCLUSION Low testosterone levels are associated with sarcopenia in male cirrhotic patients. The potential therapeutic effect of testosterone to reverse sarcopenia in these patients warrants evaluation in future trials.
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Affiliation(s)
| | - Gavin Low
- Department of Radiology, University of Alberta Hospital, Edmonton, Alberta, Canada
| | - Marina Mourtzakis
- Department of Rehabilitation Medicine, University of Waterloo, Ontario, Canada
| | - Mang Ma
- Liver Unit, University of Alberta Hospital, Edmonton, Alberta, Canada
| | | | - Puneeta Tandon
- Liver Unit, University of Alberta Hospital, Edmonton, Alberta, Canada
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Sajith KG, Kapoor N, Shetty S, Goel A, Zachariah U, Eapen CE, Paul TV. Bone Health and Impact of Tenofovir Treatment in Men with Hepatitis-B Related Chronic Liver Disease. J Clin Exp Hepatol 2018; 8:23-27. [PMID: 29743793 PMCID: PMC5938523 DOI: 10.1016/j.jceh.2017.05.009] [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: 01/06/2017] [Accepted: 05/02/2017] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Chronic Liver Disease (CLD) has been shown to have an adverse impact on bone health. Hepatitis-B related CLD and its treatment with tenofovir may have additional effects on skeleton. OBJECTIVE To study the impact of HBV related CLD and its treatment with Tenofovir on bone health in Indian subjects. METHODS This cross sectional study included men (18-60 years) and comprised of three groups: Group-1 was treatment naïve HBV related CLD (n = 79), Group-2 those with HBV related CLD on tenofovir for at least 1 year (n = 136), Group-3 age, sex and Body Mass Index (BMI) matched healthy controls (n = 58). Bone biochemistry and Bone Mineral Density (BMD) at spine, Femoral Neck (FN) and forearm were studied. Independent t-test or ANOVA was used to compare the means of continuous variables and chi-square test for categorical variables. Multiple logistic regression was used to assess the factors causing Low Bone Mass (LBM) at FN. RESULTS A significantly greater proportion (P < 0.05) of patients (40%) with CLD (group 1 and group 2) had vitamin D deficiency (<20 ng/ml) in comparison with control group (22%). The mean serum C-Terminal telopeptide was significantly higher (P < 0.05) and the mean BMD was significantly lower (P < 0.05) in subjects with HBV related CLD than controls. The prevalence of LBM was higher in group 1 at the spine (31%) and forearm (18.4%) when compared to controls (8.1% and 7.8% respectively) (P < 0.05). The proportion of patients with LBM at FN was highest in group 2 (12.3%) compared to those in group 1 (8%) and group 3 (4%) (P < 0.05). Advanced age, low BMI, and high viral load (>10,000 IU/ml) emerged as significant risk factors for LBM at FN. CONCLUSION The impact of hepatitis-B related CLD as well as its treatment on bone health is significant. Bone health need to be periodically evaluated in these subjects especially in older men who are lean and have a higher viral load.
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Affiliation(s)
- Kattiparambil G. Sajith
- Professor, Department of Hepatology, Christian Medical College and Hospital, Vellore, Tamil Nadu, India
| | - Nitin Kapoor
- Associate Professor, Department of Endocrinology, Diabetes and Metabolism, Christian Medical College and Hospital, Vellore, Tamil Nadu, India
| | - Sahana Shetty
- Assistant Professor, Department of Endocrinology, Diabetes and Metabolism, Christian Medical College and Hospital, Vellore, Tamil Nadu, India
| | - Ashish Goel
- Professor, Department of Hepatology, Christian Medical College and Hospital, Vellore, Tamil Nadu, India
| | - Uday Zachariah
- Professor, Department of Hepatology, Christian Medical College and Hospital, Vellore, Tamil Nadu, India
| | - Chundamannil E. Eapen
- Professor & Head, Department of Hepatology, Christian Medical College and Hospital, Tamil Nadu, India
| | - Thomas V. Paul
- Professor, Department of Endocrinology, Diabetes and Metabolism, Christian Medical College and Hospital, Vellore, Tamil Nadu, India
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Assessment of bone mineral density in patients with cirrhosis treated with third-generation nucleos(t)ide analogues: comparison between tenofovir and entecavir. Eur J Gastroenterol Hepatol 2018; 30:284-290. [PMID: 29309397 DOI: 10.1097/meg.0000000000001051] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
BACKGROUND AND AIM Tenofovir and entecavir are nowadays the first-line treatment in hepatitis B virus (HBV)-related cirrhosis. Both drugs were shown to be effective in HBV suppression and well tolerated. The effects of tenofovir on bone mineral density (BMD), however, were shown to worsen the rate of osteoporosis, which is already a common feature in cirrhosis. In contrast, entecavir seems to have no effect on mineral metabolism. The aim of our study was to compare the effects of nucleos(t)ide analogs on bone density in HBV-related cirrhosis. PATIENTS AND METHODS Fourty-eight patients were treated with tenofovir and 22 patients were treated with entecavir, and were followed prospectively from 2008 to 2013. To evaluate BMD, laboratory examinations, dual-X-ray absorptiometry, and Fracture Risk Assessment Tool were assessed. RESULTS During the study, no difference was found between the two groups in the plasmatic concentration of calcium, phosphate, vitamin D, parathyroid hormone, or creatinine. Dual-X-ray absorptiometry showed no difference in the T-score and Fracture Risk Assessment Tool showed no significant difference in the 10-year risk of osteoporotic fractures in the two groups. On univariate and multivariate analyses, the only predictors of osteoporosis development were the prognostic scores of liver disease and BMI. CONCLUSION Both tenofovir and entecavir are effective in treating HBV in cirrhotic patients. The known effects of tenofovir on BMD do not worsen osteoporotic fractures risk compared with entecavir in these patients.
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Liu Z, Han T, Werner H, Rosen CJ, Schaffler MB, Yakar S. Reduced Serum IGF-1 Associated With Hepatic Osteodystrophy Is a Main Determinant of Low Cortical but Not Trabecular Bone Mass. J Bone Miner Res 2018; 33:123-136. [PMID: 28902430 PMCID: PMC5771972 DOI: 10.1002/jbmr.3290] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2017] [Revised: 08/31/2017] [Accepted: 09/06/2017] [Indexed: 12/11/2022]
Abstract
Hepatic osteodystrophy is multifactorial in its pathogenesis. Numerous studies have shown that impairments of the hepatic growth hormone/insulin-like growth factor-1 axis (GH/IGF-1) are common in patients with non-alcoholic fatty liver disease, chronic viral hepatitis, liver cirrhosis, and chronic cholestatic liver disease. Moreover, these conditions are also associated with low bone mineral density (BMD) and greater fracture risk, particularly in cortical bone sites. Hence, we addressed whether disruptions in the GH/IGF-1 axis were causally related to the low bone mass in states of chronic liver disease using a mouse model of liver-specific GH-receptor (GHR) gene deletion (Li-GHRKO). These mice exhibit chronic hepatic steatosis, local inflammation, and reduced BMD. We then employed a crossing strategy to restore liver production of IGF-1 via hepatic IGF-1 transgene (HIT). The resultant Li-GHRKO-HIT mouse model allowed us to dissect the roles of liver-derived IGF-1 in the pathogenesis of osteodystrophy during liver disease. We found that hepatic IGF-1 restored cortical bone acquisition, microarchitecture, and mechanical properties during growth in Li-GHRKO-HIT mice, which was maintained during aging. However, trabecular bone volume was not restored in the Li-GHRKO-HIT mice. We found increased bone resorption indices in vivo as well as increased basal reactive oxygen species and increased mitochondrial stress in osteoblast cultures from Li-GHRKO and the Li-GHRKO-HIT compared with control mice. Changes in systemic markers such as inflammatory cytokines, osteoprotegerin, osteopontin, parathyroid hormone, osteocalcin, or carboxy-terminal collagen cross-links could not fully account for the diminished trabecular bone in the Li-GHRKO-HIT mice. Thus, the reduced serum IGF-1 associated with hepatic osteodystrophy is a main determinant of low cortical but not trabecular bone mass. © 2017 American Society for Bone and Mineral Research.
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Affiliation(s)
- Zhongbo Liu
- David B. Kriser Dental Center, Department of Basic Science and Craniofacial Biology New York University College of Dentistry New York, NY 10010-4086
| | - Tianzhen Han
- David B. Kriser Dental Center, Department of Basic Science and Craniofacial Biology New York University College of Dentistry New York, NY 10010-4086
| | - Haim Werner
- Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
| | | | | | - Shoshana Yakar
- David B. Kriser Dental Center, Department of Basic Science and Craniofacial Biology New York University College of Dentistry New York, NY 10010-4086
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Muhsen IN, AlFreihi O, Abaalkhail F, AlKhenizan A, Khan M, Eldali A, Alsohaibani F. Bone mineral density loss in patients with cirrhosis. Saudi J Gastroenterol 2018; 24:342-347. [PMID: 29943736 PMCID: PMC6253916 DOI: 10.4103/sjg.sjg_74_18] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND/AIMS Evidence of increased risk of osteoporosis and osteopenia in chronic liver disease and cirrhosis is inconsistent. This study aims to investigate this relationship and to identify the predictors of increased loss of bone mineral density in Saudi patients. PATIENTS AND METHODS One hundred and sixty-four patients and controls who are age and gender matched, were included in this study with 1:1 ratio. Patients' included in this study were adults with confirmed liver cirrhosis. Bone mineral densitometry (BMD) at both lumbar spine (LS) and femoral neck (FN) were collected for both groups. Univariate and multivariate regression analyses were performed to identify predictors of BMD loss. RESULTS Results showed that cirrhotic patients are at higher risk of developing osteoporosis or osteopenia at LS (OR 2.23, 95% CI [1.19-4.19], P = 0.01) but not at FN, when compared to control sample. Patients with cirrhosis were found to have lower vitamin D and PTH levels (P = 0.0005) and (P = 0.006), respectively. Of the possible predictors tested (gender, age, body mass index [BMI], phosphorus, calcium, parathyroid hormone (PTH), vitamin D, and Model for End Stage Liver Disease [MELD] score), female gender was the main predictor of loss of BMD at LS only (OR 4.80, 95% CI [1.47-15.73], P = 0.01). CONCLUSIONS The study showed that cirrhotic patients are at increased susceptibility of having decreased BMD, particularly at the LS and it highlights the need for preventive measures, especially for female patients.
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Affiliation(s)
- Ibrahim N. Muhsen
- College of Medicine, Alfaisal University, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Omar AlFreihi
- College of Medicine, Alfaisal University, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Faisal Abaalkhail
- College of Medicine, Alfaisal University, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia,Liver Transplantation and Hepatobiliary Surgery, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Abdullah AlKhenizan
- Department of Family Medicine, Section of Gastroenterology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Mohammed Khan
- Department of Medicine, Section of Gastroenterology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Abdelmoneim Eldali
- Department of Biostatistics, Epidemiology and Scientific Computing, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Fahad Alsohaibani
- Department of Medicine, Section of Gastroenterology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia,Address for correspondence: Dr. Fahad Alsohaibani, Department of Medicine, Section of Gastroenterology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. E-mail:
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Huang Z, Wei H, Cheng C, Yang S, Wang J, Liu X. Low bone mineral density in chronic hepatitis B virus infection: A case-control study. Pak J Med Sci 2017; 33:457-461. [PMID: 28523056 PMCID: PMC5432723 DOI: 10.12669/pjms.332.12099] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
Objective: Osteoporosis is the well-known major complication in chronic hepatitis B virus (HBV) infection. Fewer reports are available of the relationship between bone loss and chronic HBV infection. We investigated the bone mineral density (BMD) and prevalence of osteoporosis in chronic HBV patients in comparison with healthy subjects. Methods: We assessed 148 chronic HBV patients and 148 age- and gender-matched healthy controls by dual energy X-ray absorptiometry (DEXA) for determination of BMD. T-score was used to define bone status according to the World Health Organization’s classification. Results: The BMD values were significantly lower in HBV patients in all scan of specific regions compared with the controls (P < 0.05). The prevalence of osteoporosis in either of lumbar spine (LS), total hip (TH) or the femoral neck (FN) was significantly higher in the HBV patients group compared with the healthy controls. The rate of osteopenia and osteoporosis for HBV patients aged 45–54 years was significantly higher than that of the healthy controls. Conclusions: Chronic HBV infection was associated with low BMD and increased the risk of developing subsequent osteoporosis.
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Affiliation(s)
- Zengfa Huang
- Zengfa Huang, Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hui Wei
- Hui Wei, Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Cheng Cheng
- Cheng Cheng, Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shuhua Yang
- Shuhua Yang, Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jing Wang
- Jing Wang, Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xianzhe Liu
- Xianzhe Liu, Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Buzzetti E, Parikh PM, Gerussi A, Tsochatzis E. Gender differences in liver disease and the drug-dose gender gap. Pharmacol Res 2017; 120:97-108. [PMID: 28336373 DOI: 10.1016/j.phrs.2017.03.014] [Citation(s) in RCA: 57] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2016] [Revised: 03/17/2017] [Accepted: 03/17/2017] [Indexed: 12/14/2022]
Abstract
Although gender-based medicine is a relatively recent concept, it is now emerging as an important field of research, supported by the finding that many diseases manifest differently in men and women and therefore, might require a different treatment. Sex-related differences regarding the epidemiology, progression and treatment strategies of certain liver diseases have long been known, but most of the epidemiological and clinical trials still report results only about one sex, with consequent different rate of response and adverse reactions to treatment between men and women in clinical practice. This review reports the data found in the literature concerning the gender-related differences for the most representative hepatic diseases.
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Affiliation(s)
- Elena Buzzetti
- UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK.
| | - Pathik M Parikh
- UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
| | - Alessio Gerussi
- UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK; Internal Medicine Unit, Department of Experimental and Clinical Medical Sciences, University of Udine, Udine, Italy
| | - Emmanuel Tsochatzis
- UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
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Diagnosis and Management of Cirrhosis-Related Osteoporosis. BIOMED RESEARCH INTERNATIONAL 2016; 2016:1423462. [PMID: 27840821 PMCID: PMC5093239 DOI: 10.1155/2016/1423462] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/09/2016] [Accepted: 10/03/2016] [Indexed: 12/20/2022]
Abstract
Management of cirrhosis complications has greatly improved, increasing survival and quality of life of the patients. Despite that, some of these complications are still overlooked and scarcely treated, particularly those that are not related to the liver. This is the case of osteoporosis, the only cirrhosis complication that is not solved after liver transplantation, because bone loss often increases after immunosuppressant therapy. In this review, the definitions of bone conditions in cirrhotic patients are analyzed, focusing on the more common ones and on those that have the largest impact on this population. Risk factors, physiopathology, diagnosis, screening strategies, and treatment of osteoporosis in cirrhotic patients are discussed, presenting the more striking data on this issue. Therapies used for particular conditions, such as primary biliary cirrhosis and liver transplantation, are also presented.
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Chinnaratha MA, Chaudhary S, Doogue M, McCormick RJ, Woodman RJ, Wigg AJ. Prevalence of hepatic osteodystrophy and vitamin D deficiency in cirrhosis. Intern Med J 2016; 45:1230-5. [PMID: 26247615 DOI: 10.1111/imj.12866] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2015] [Accepted: 07/20/2015] [Indexed: 01/19/2023]
Abstract
BACKGROUND Hepatic osteodystrophy (HO) is a major complication of cirrhosis. However, the prevalence of HO in a general cirrhotic patient population is not well defined as previous studies were in single aetiology or pre-liver transplant patients. AIMS The aims of this study were to investigate the prevalence of HO and vitamin D deficiency in patients with cirrhosis of mixed aetiology and disease severity and to determine the risk factors for HO. METHODS This is a single-centre cross-sectional study of all patients newly diagnosed with cirrhosis between September 2009 and December 2012. All patients underwent bone mineral density assessment using dual energy X-ray absorptiometry within 3 months of diagnosis. Demographic and biochemical factors, severity of underlying liver disease, previous fragility fractures, smoking status and alcohol use were collected on diagnosis. Logistic regression analysis was used to assess risk factors for HO. RESULTS Among the 406 patients (67% males), the median (range) age was 56 years (21-85) and most (84%) were Childs-Pugh A or B with a median (range) model for end-stage liver disease score of 11 (5-40). Alcohol (41%) was the most common underlying aetiology. The prevalence of HO and vitamin D deficiency (≤50 nmol/L) was 56% and 54%, respectively, and previous fragility fractures had occurred in 3%. Increasing age (odds ratio (95% confidence interval): 1.49 per 10 years (1.02-2.18), P = 0.04), excessive alcohol intake (2.34 (1.03-5.32), P = 0.04) and lower body mass index (0.92 per kg/m2 (0.87-0.98), P = 0.009) were independent risk factors for HO. CONCLUSION There is a high prevalence of HO and vitamin D deficiency in patients with cirrhosis at presentation irrespective of disease severity or underlying aetiology.
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Affiliation(s)
- M A Chinnaratha
- Hepatology and Liver Transplant Medicine Unit, Flinders Medical Centre, Adelaide, South Australia, Australia.,School of Medicine, Flinders University of South Australia, Adelaide, South Australia, Australia
| | - S Chaudhary
- Hepatology and Liver Transplant Medicine Unit, Flinders Medical Centre, Adelaide, South Australia, Australia
| | - M Doogue
- Southern Adelaide Diabetes and Endocrine Services, Southern Area Local Health Network, Adelaide, South Australia, Australia
| | - R J McCormick
- Hepatology and Liver Transplant Medicine Unit, Flinders Medical Centre, Adelaide, South Australia, Australia
| | - R J Woodman
- School of Medicine, Flinders University of South Australia, Adelaide, South Australia, Australia
| | - A J Wigg
- Hepatology and Liver Transplant Medicine Unit, Flinders Medical Centre, Adelaide, South Australia, Australia.,School of Medicine, Flinders University of South Australia, Adelaide, South Australia, Australia
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Karoli Y, Karoli R, Fatima J, Manhar M. Study of Hepatic Osteodystrophy in Patients with Chronic Liver Disease. J Clin Diagn Res 2016; 10:OC31-4. [PMID: 27656483 DOI: 10.7860/jcdr/2016/21539.8367] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2016] [Accepted: 07/04/2016] [Indexed: 12/31/2022]
Abstract
INTRODUCTION Chronic Liver Disease (CLD) is a major cause of morbidity and mortality worldwide. It involves haemodynamic and metabolic complications. Hepatic Osteodystrophy is a metabolic bone disease that may occur in individuals with chronic liver disease. It can significantly affect morbidity and quality of life of these patients. Fractures are also associated with an excess mortality. It has been an under recognized and inadequately studied complication among Indian population. An early diagnosis is essential to correct reversible risk factors which predispose to bone mass loss. AIM To assess the prevalence of metabolic bone disease and identify the risk factors associated with hepatic osteodystrophy in patients with cirrhosis. MATERIALS AND METHODS This was an observational, cross-sectional, hospital based study conducted at a medical college hospital. All patients more than 20-year-old, diagnosed with chronic liver disease/Cirrhosis were enrolled. They were subjected to haematological, biochemical investigations, evaluation of Vitamin D and other hormonal parameters. Bone Mineral Density (BMD) was estimated by Dual Energy X-ray Absorptiometry (DEXA). RESULTS A total of 72 patients with mean age 50.04±11.24 years were included in the study. Amongst causes of chronic liver disease were alcoholic liver disease 22 (30.6%), CLD due to hepatitis B 24 (33.3%) and chronic hepatitis C 26 (36.1%). Twenty one (29.2%) patients had normal BMD while 51 (70.8%) had a low BMD. Out of these 51 patients, 36 (70.6%) were diagnosed of osteopenia and 15 (29.4%) others were found to have osteoporosis. Vitamin D levels and severity of liver disease had correlation with low BMD. CONCLUSION Low BMD is highly prevalent in patients with chronic liver disease of variable aetiologies. We advocate more randomised and prospective studies to be conducted on homogeneous groups with chronic liver disease in its various stages. In view of numerous therapeutic options available both for liver disease and bone disease, it is prudent to characterize this condition in order to give these patients a better chance of survival with good quality of life.
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Affiliation(s)
- Yogesh Karoli
- Senior Consultant Orthopaedic Surgeon, Department of Orthopaedics, Ram Manohar Lohia Combined Hospital , Gomti Nagar, Lucknow, Uttar Pradesh, India
| | - Ritu Karoli
- Professor, Department of Medicine, Era's Lucknow Medical College , Sarfarzganj, Lucknow, Uttar Pradesh, India
| | - Jalees Fatima
- Professor and Head, Department of Medicine, Era's Lucknow Medical College , Sarfarzganj, Lucknow, Uttar Pradesh, India
| | - Mohammad Manhar
- Postgraduate Student, Department of Medicine, Era's Lucknow Medical College , Sarfarzganj, Lucknow, Uttar Pradesh, India
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Bone health and vitamin D status in alcoholic liver disease. Indian J Gastroenterol 2016; 35:253-9. [PMID: 27246833 DOI: 10.1007/s12664-016-0652-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2015] [Accepted: 03/26/2016] [Indexed: 02/07/2023]
Abstract
Alcohol consumption is harmful to many organs and tissues, including bones, and it leads to osteoporosis. Hepatic osteodystrophy is abnormal bone metabolism that has been defined in patients with chronic liver disease (CLD), including osteopenia, osteoporosis, and osteomalacia. Decreased bone density in patients with CLD results from decreased bone formation or increased bone resorption. The prevalence of osteopenia in alcoholic liver disease (ALD) patients is between 34 % and 48 %, and the prevalence of osteoporosis is between 11 % and 36 %. Cirrhosis is also a risk factor for osteoporosis. The liver has an important role in vitamin D metabolism. Ninety percent of patients with alcoholic liver cirrhosis have vitamin D inadequacy (<80 nmol/L). The lowest serum vitamin D levels were observed in patients with Child-Pugh class C. Bone densitometry is used for the definitive diagnosis of osteoporosis in ALD. There are no specific controlled clinical studies on the treatment of osteoporosis in patients with ALD. Alcohol cessation and abstinence are principal for the prevention and treatment of osteoporosis in ALD patients, and the progression of osteopenia can be stopped in this way. Calcium and vitamin D supplementation is recommended, and associated nutritional deficiencies should also be corrected. The treatment recommendations of osteoporosis in CLD tend to be extended to ALD. Bisphosphonates have been proven to be effective in increasing bone mineral density (BMD) in chronic cholestatic disease and post-transplant patients, and they can be used in ALD patients. Randomized studies assessing the management of CLD-associated osteoporosis and the development of new drugs for osteoporosis may change the future. Here, we will discuss bone quality, vitamin D status, mechanism of bone effects, and diagnosis and treatment of osteoporosis in ALD.
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Fracture risk calculation tool enhances dual-energy X-ray absorptiometry scan referral pathway in cirrhosis patients. Eur J Gastroenterol Hepatol 2016; 28:757-61. [PMID: 27254536 DOI: 10.1097/meg.0000000000000585] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
OBJECTIVES Liver cirrhosis is associated with osteoporosis leading to an increased risk of fractures. We aimed to establish whether a risk stratification strategy using a fracture risk calculation tool (FRAX) to determine which patients should receive a dual-energy X-ray absorptiometry (DXA) scan is effective in reducing scan rates without compromising sensitivity for detecting osteoporosis. METHODS A retrospective analysis of 252 patients with liver cirrhosis attending hepatoma surveillance clinics. Receiver operating characteristic analysis was performed to assess sensitivity and specificity at 10-year fracture risk thresholds of 5, 10 and 15%. RESULTS DXA scans were performed among 252 patients. Mean age was 61.6±10.2 years, of which 53.2% were male. Cirrhosis aetiology was largely a result of alcohol excess (n=33.3%), chronic hepatitis C virus infection (n=20.2%) and nonalcoholic fatty liver disease (n=15.9%). The majority of patients were in good prognostic groups (87.4% Child-Pugh A, 11.3% Child-Pugh B, 1.3% Child-Pugh C). Osteoporosis was present in 19.0% of those who underwent DXA scanning. The optimum 10-year fracture risk threshold was found to be 10% using the FRAX tool. This retained a high sensitivity of 95.8%, specificity 64.7%, and negative predictive value 98.5%. Introduction of a 10% FRAX threshold would result in a reduction of the DXA scanning rate to 46.8% of the current rate. CONCLUSION A risk stratification strategy for DXA scanning using a fracture risk assessment tool (FRAX) and a 10-year fracture risk threshold of 10% leads to a significant reduction in scan rates without compromising osteoporosis detection rates.
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Lampertico P, Chan HLY, Janssen HLA, Strasser SI, Schindler R, Berg T. Review article: long-term safety of nucleoside and nucleotide analogues in HBV-monoinfected patients. Aliment Pharmacol Ther 2016; 44:16-34. [PMID: 27198929 DOI: 10.1111/apt.13659] [Citation(s) in RCA: 95] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2015] [Revised: 01/15/2016] [Accepted: 04/21/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND Nucleos(t)ide analogues (NUCs) for chronic hepatitis B treatment achieve high rates of viral suppression and are generally well tolerated. Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are the currently preferred first-line agents. The safety of these agents in clinical practice is particularly relevant since long-term treatment is usually required. AIM To summarise and critically discuss recent real-world evidence on the safety of treatment with ETV or TDF in hepatitis B virus (HBV)-monoinfected patients. METHODS PubMed and conference proceedings up to 15th June 2015 were searched using the terms ((((Hepatitis_B) OR HBV) AND ((tenofovir) OR entecavir)) AND (((lactic_acidosis) OR bone) OR renal)). RESULTS In selected populations included in registration studies, both ETV and TDF were well tolerated with no clinically significant renal toxicity or lactic acidosis. Growing 'real-world' clinical experience with these agents includes some reports of ETV-associated lactic acidosis and TDF-associated renal impairment; however, evidence from cohort studies appears to be conflicting. In the case of ETV-related lactic acidosis, a small number of cases have been reported, all in patients with decompensated cirrhosis. The degree of association between TDF treatment and changes in markers of renal function varies between studies: discrepancies may result from the use of different definitions and cut-offs for reporting renal toxicities, and differences in patient populations. CONCLUSIONS Pre-treatment and on-treatment monitoring of eGFR and phosphorus, with prompt appropriate dose adjustment or treatment switch can minimise the impact of NUC renal toxicity. Standardisation of measures of renal impairment and identification of early molecular markers remain an unmet need.
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Affiliation(s)
- P Lampertico
- Division of Gastroenterology and Hepatology, "A.M. and A. Migliavacca" Center for Liver Disease, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - H L Y Chan
- Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong
| | - H L A Janssen
- Toronto Centre for Liver Diseases, University Health Network, Toronto, ON, Canada
| | - S I Strasser
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia
| | - R Schindler
- Department of Nephrology and Intensive Care, Campus Virchow, Charité - Universitätsmedizin, Berlin, Germany
| | - T Berg
- Section Hepatology, Clinic for Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany
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Guarino M, Loperto I, Camera S, Cossiga V, Di Somma C, Colao A, Caporaso N, Morisco F. Osteoporosis across chronic liver disease. Osteoporos Int 2016; 27:1967-77. [PMID: 26846777 DOI: 10.1007/s00198-016-3512-z] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2015] [Accepted: 01/29/2016] [Indexed: 02/06/2023]
Abstract
Osteoporosis is a complication of chronic liver disease, with impact on morbidity, quality of life, and survival. The progress of medicine and the new therapies stretched the disease's natural history and improved the survival of patients with liver disease. So, it is fundamental to make better the quality of life and to prevent complications. Metabolic bone disorders are common complications of chronic liver disease (CLD). Patients with CLD have an increased risk of bone fractures, with significant impact on morbidity, quality of life, and even on survival. Bone diseases, including osteomalacia, osteoporosis, and osteopenia, are frequently observed in many types of liver disease. The pathogenesis of damage and the mechanisms of bone loss are different in relation to the specific liver disease. The relevance of these conditions induced many authors to create a new nosographic entity known as "hepatic osteodystrophy", although this term is rarely used anymore and it is now commonly referred to as osteopenia or osteoporosis associated with chronic liver disease. This review is based on the personal experiences of the authors and upon research done of the available literature on this subject matter. The authors searched the PubMed database for publications containing the term "liver disease" in combination with "bone disease", "hepatic osteodistrophy", "osteoporosis", "osteopenia", "osteomalacia", and "fractures". They selected publications from the past 10 years but did not exclude older seminal publications, especially for colestatic liver diseases. This review of literature shows that osteoporosis crosses all CLD. It is important to underline that the progress of medicine and the new therapies stretched the disease's natural history and improved the survival of patients with CLD. It is fundamental to make better the quality of life and it is mandatory to prevent complications and in particular the osteoporotic ones, especially fractures.
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Affiliation(s)
- M Guarino
- Department of Clinical Medicine and Surgery, Gastroenterology Unit, University of Naples "Federico II", via Sergio Pansini, 5, 80131, Napoli, Italy
| | - I Loperto
- Department of Clinical Medicine and Surgery, Gastroenterology Unit, University of Naples "Federico II", via Sergio Pansini, 5, 80131, Napoli, Italy
| | - S Camera
- Department of Clinical Medicine and Surgery, Gastroenterology Unit, University of Naples "Federico II", via Sergio Pansini, 5, 80131, Napoli, Italy
| | - V Cossiga
- Department of Clinical Medicine and Surgery, Gastroenterology Unit, University of Naples "Federico II", via Sergio Pansini, 5, 80131, Napoli, Italy
| | - C Di Somma
- Department of Clinical Medicine and Surgery, Endocrinology Unit, University of Naples "Federico II", via Sergio Pansini, 5, 80131, Napoli, Italy
| | - A Colao
- Department of Clinical Medicine and Surgery, Endocrinology Unit, University of Naples "Federico II", via Sergio Pansini, 5, 80131, Napoli, Italy
| | - N Caporaso
- Department of Clinical Medicine and Surgery, Gastroenterology Unit, University of Naples "Federico II", via Sergio Pansini, 5, 80131, Napoli, Italy
| | - F Morisco
- Department of Clinical Medicine and Surgery, Gastroenterology Unit, University of Naples "Federico II", via Sergio Pansini, 5, 80131, Napoli, Italy.
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Handzlik-Orlik G, Holecki M, Wilczyński K, Duława J. Osteoporosis in liver disease: pathogenesis and management. Ther Adv Endocrinol Metab 2016; 7:128-35. [PMID: 27293541 PMCID: PMC4892399 DOI: 10.1177/2042018816641351] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Osteoporosis affects a substantial proportion of patients with chronic liver disease. Pathologic fracture in osteoporosis significantly affects quality of life and life expectancy. By some estimates, 40% of patients with chronic liver disease may experience osteoporotic fracture. In this study we review the pathogenesis, diagnosis and treatment of specific liver disease entities and their relation to osteoporosis.
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Affiliation(s)
| | - Michał Holecki
- Department of Internal Medicine and Metabolic Diseases, School of Health Science, Medical University of Silesia, Katowice, Poland
| | - Krzysztof Wilczyński
- Department of Internal Medicine and Metabolic Diseases, School of Health Science, Medical University of Silesia, Katowice, Poland
| | - Jan Duława
- Department of Internal Medicine and Metabolic Diseases, School of Health Science, Medical University of Silesia, Katowice, Poland
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46
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Dyson JK, Anstee QM, McPherson S. Republished: Non-alcoholic fatty liver disease: a practical approach to treatment. Postgrad Med J 2016; 91:92-101. [PMID: 25655252 PMCID: PMC4345831 DOI: 10.1136/postgradmedj-2013-100404rep] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) affects up to a third of the population in many developed countries. Between 10% and 30% of patients with NAFLD have non-alcoholic steatohepatitis (NASH) that can progress to cirrhosis. There are metabolic risk factors common to both NAFLD and cardiovascular disease, so patients with NASH have an increased risk of liver-related and cardiovascular death. Management of patients with NAFLD depends largely on the stage of disease, emphasising the importance of careful risk stratification. There are four main areas to focus on when thinking about management strategies in NAFLD: lifestyle modification, targeting the components of the metabolic syndrome, liver-directed pharmacotherapy for high risk patients and managing the complications of cirrhosis.
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Affiliation(s)
- J K Dyson
- Liver Unit, Freeman Hospital, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Q M Anstee
- Liver Unit, Freeman Hospital, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
| | - S McPherson
- Liver Unit, Freeman Hospital, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
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Prieto-Frías C, Conchillo M, Payeras M, Iñarrairaegui M, Davola D, Frühbeck G, Salvador J, Rodríguez M, Richter JÁ, Mugueta C, Gil MJ, Herrero I, Prieto J, Sangro B, Quiroga J. Factors related to increased resting energy expenditure in men with liver cirrhosis. Eur J Gastroenterol Hepatol 2016; 28:139-45. [PMID: 26560751 DOI: 10.1097/meg.0000000000000516] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVE Hypermetabolism in cirrhosis is associated with a high risk of complications and mortality. However, studies about underlying mechanisms are usually focussed on isolated potential determinants and specific etiologies, with contradictory results. We aimed at investigating differences in nutrition, metabolic hormones, and hepatic function between hypermetabolic and nonhypermetabolic men with cirrhosis of the liver. PATIENTS AND METHODS We prospectively enrolled 48 male cirrhotic inpatients. We evaluated their resting energy expenditure (REE) and substrate utilization by indirect calorimetry, body composition by dual-energy X-ray absorptiometry, liver function, and levels of major hormones involved in energy metabolism by serum sample tests. Patients with ascites, specific metabolic disturbances, and hepatocellular carcinoma were excluded. RESULTS REE and REE adjusted per fat-free mass (FFM) were significantly increased in cirrhotic patients. Overall, 58.3% of cirrhotic patients were classified as hypermetabolic. Groups did not differ significantly in age, etiology of cirrhosis, liver function, presence of ascites, use of diuretics, β-blockers, or presence of transjugular intrahepatic portosystemic shunts. Hypermetabolic cirrhotic patients had lower weight, BMI (P<0.05), nonprotein respiratory quotient (P<0.01), leptin (P<0.05), and leptin adjusted per fat mass (FM) (P<0.05), but higher FFM% (P<0.05) and insulin resistance [homeostatic model assessment-insulin resistance (HOMA-IR)] (P<0.05). Only HOMA-IR, leptin/FM, and FFM% were independently related to the presence of hypermetabolism. CONCLUSION Hypermetabolic cirrhotic men are characterized by lower weight, higher FFM%, insulin resistance, and lower leptin/FM when compared with nonhypermetabolic men. HOMA-IR, FFM%, and leptin/FM were independently associated with hypermetabolism, and may serve as easily detectable markers of this condition in daily clinical practice.
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Affiliation(s)
- César Prieto-Frías
- aDepartment of Gastroenterology bLiver Unit, Department of Medicine cDepartment of Endocrinology dDepartment of Nuclear Medicine eDepartment of Laboratory Medicine, Clínica Universidad de Navarra fInstitute for Biomedical Research in Navarra (IDISNA), Pamplona gBiomedical Research Network in Liver and Digestive Diseases (CIBEREHD), Madrid, Spain
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Gunewardena SS, Yoo B, Peng L, Lu H, Zhong X, Klaassen CD, Cui JY. Deciphering the Developmental Dynamics of the Mouse Liver Transcriptome. PLoS One 2015; 10:e0141220. [PMID: 26496202 PMCID: PMC4619800 DOI: 10.1371/journal.pone.0141220] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2015] [Accepted: 10/06/2015] [Indexed: 02/06/2023] Open
Abstract
During development, liver undergoes a rapid transition from a hematopoietic organ to a major organ for drug metabolism and nutrient homeostasis. However, little is known on a transcriptome level of the genes and RNA-splicing variants that are differentially regulated with age, and which up-stream regulators orchestrate age-specific biological functions in liver. We used RNA-Seq to interrogate the developmental dynamics of the liver transcriptome in mice at 12 ages from late embryonic stage (2-days before birth) to maturity (60-days after birth). Among 21,889 unique NCBI RefSeq-annotated genes, 9,641 were significantly expressed in at least one age, 7,289 were differently regulated with age, and 859 had multiple (> = 2) RNA splicing-variants. Factor analysis showed that the dynamics of hepatic genes fall into six distinct groups based on their temporal expression. The average expression of cytokines, ion channels, kinases, phosphatases, transcription regulators and translation regulators decreased with age, whereas the average expression of peptidases, enzymes and transmembrane receptors increased with age. The average expression of growth factors peak between Day-3 and Day-10, and decrease thereafter. We identified critical biological functions, upstream regulators, and putative transcription modules that seem to govern age-specific gene expression. We also observed differential ontogenic expression of known splicing variants of certain genes, and 1,455 novel splicing isoform candidates. In conclusion, the hepatic ontogeny of the transcriptome ontogeny has unveiled critical networks and up-stream regulators that orchestrate age-specific biological functions in liver, and suggest that age contributes to the complexity of the alternative splicing landscape of the hepatic transcriptome.
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Affiliation(s)
- Sumedha S. Gunewardena
- Department of Molecular and Integrative Physiology, Department of Biostatistics, University of Kansas Medical Center, Kansas City, Kansas, 66160, United States of America
| | - Byunggil Yoo
- Children's Mercy Hospital, Kansas City, Missouri, 64108, United States of America
| | - Lai Peng
- Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut, 06269, United States of America
| | - Hong Lu
- Department of Pharmacology, State University of New York Upstate Medical University, Syracuse, New York, 13210, United States of America
| | - Xiaobo Zhong
- Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut, 06269, United States of America
| | - Curtis D. Klaassen
- Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington, 98195, United States of America
| | - Julia Yue Cui
- Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington, 98195, United States of America
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Pawlowska M, Kapeluto JE, Kendler DL. A case report of osteomalacia unmasking primary biliary cirrhosis. Osteoporos Int 2015; 26:2035-8. [PMID: 25801184 DOI: 10.1007/s00198-015-3102-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2014] [Accepted: 03/04/2015] [Indexed: 10/23/2022]
Abstract
Osteomalacia, a metabolic bone disease characterized by the inability to mineralize new osteoid, can be caused by vitamin D deficiency. We report a patient with symptomatic, biochemical, and imaging evidence of osteomalacia due to vitamin D deficiency, who as a result of work up for bone disease was diagnosed with early primary biliary cirrhosis. Osteomalacia was treated with high-dose vitamin D and serial bone density scans showed evidence of increasing bone mineral density suggesting osteoid mineralization in response to treatment. The diagnosis of cholestatic liver disease should be considered in all patients presenting with osteomalacia due to vitamin D deficiency, particularly if other cholestatic liver enzymes are elevated in addition to alkaline phosphatase.
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Affiliation(s)
- M Pawlowska
- Prohealth Clinical Research Center, Prohealth, 150-943W Broadway, Vancouver, BC, V5Z 4E1, Canada,
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50
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Hajiabbasi A, Shafaghi A, Fayazi HS, Shenavar Masooleh I, Hedayati Emami MH, Ghavidel Parsa P, Amir Maafi A. The factors affecting bone density in cirrhosis. HEPATITIS MONTHLY 2015; 15:e26871. [PMID: 25977695 PMCID: PMC4428083 DOI: 10.5812/hepatmon.15(4)2015.26871] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/10/2015] [Revised: 02/17/2015] [Accepted: 03/15/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND Bone loss is common in cirrhosis. However, the prevalence of osteopenia and osteoporosis has been heterogeneous in different reports. Reduction in bone formation with or without increase in bone resorption appears to be responsible for bone loss in these patients. OBJECTIVES We aimed to investigate bone loss in patients with cirrhosis at different anatomical sites and key factors that might affect it. PATIENTS AND METHODS In this cross-sectional study, 97 patients with cirrhosis who were referred to Razi Hospital, Rasht, Iran, from 2008 to 2010, were studied. Cirrhosis was diagnosed using biopsy and/or clinical and paraclinical findings. Bone mineral densitometry was done in L2 through L4 lumbar spine (LS) and femoral neck (FN), using dual-energy X-ray absorptiometry (DEXA) (QDR 1000, Hologic DEXA Inc, Waltham, Massachusetts, the United States). Statistical analysis was performed using SPSS 18. A P value < 0.05 was considered statistically significant. RESULTS A total of 97 patients with cirrhosis (55.7% male) and the mean age of 51 ± 13 years and median body mass index (BMI) of 22.7 kg/m(2) were recruited over a two-year period. Etiologies of cirrhosis were hepatitis C (40.2%), hepatitis B (26.8%), cryptogenic (21.6%), and other causes (11.4%). Child A, B, and C, were seen in 16.5%, 47.4%, and 36.1% of patients, respectively. The DEXA results were abnormal in 78.4% of our participants (osteopenia, 45.4%; osteoporosis, 33%). BMI and calculated glomerular filtration rate (GFRc) had moderate positive and Child score had moderate negative significant correlation with T score in both anatomical sites. There was no significant association between abnormal DEXA and the causes of cirrhosis. The univariate analysis showed that the risk of abnormal results in DEXA was significantly higher in those with low BMI, current smoking, higher Child score, and low GFRc; however, in multivariate analysis, the abnormal results were more frequent in those with lower vitamin D, higher Child score, and less GFRc. CONCLUSIONS Abnormal DEXA was highly prevalent among patients with cirrhosis. The risk of this finding was increased by lower vitamin D levels, advanced disease, and impaired renal function.
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Affiliation(s)
- Asghar Hajiabbasi
- Guilan Rheumatology Research Center, Razi Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, IR Iran
| | - Afshin Shafaghi
- Gasteroenterology and Liver Disease Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, IR Iran
- Corresponding Author: Afshin Shafaghi, Gasteroenterology and Liver Disease Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, IR Iran. Tel: +98-9111368274, Fax: +98-1315530169, E-mail:
| | - Haniyeh Sadat Fayazi
- Razi Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, IR Iran
| | - Irandokht Shenavar Masooleh
- Guilan Rheumatology Research Center, Razi Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, IR Iran
| | - Mohammad Hassan Hedayati Emami
- Guilan Rheumatology Research Center, Razi Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, IR Iran
| | - Pooneh Ghavidel Parsa
- Guilan Rheumatology Research Center, Razi Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, IR Iran
| | - Alireza Amir Maafi
- Student Research Center, Guilan University of Medical Sciences, Rasht, IR Iran
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