|
1
|
Stern C, Ngo A, Villela-Nogueira C, Thabut D, Ratziu V. A Simple and Reliable 2D-Shear Wave Elastography and UltraSound Coefficient Attenuation Parameter Technique in Chronic Liver Diseases. Dig Dis Sci 2024; 69:2648-2654. [PMID: 38678527 DOI: 10.1007/s10620-024-08444-3] [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: 10/16/2023] [Accepted: 04/09/2024] [Indexed: 05/01/2024]
Abstract
BACKGROUND The performance and reliability criteria for Aixplorer MACH30 (SS) in chronic liver diseases (CLD) have not been validated. AIMS The objectives were to define the optimal procedure, the accuracy for fibrosis and steatosis diagnosis, and the reliability criteria using SS. METHODS Patients had 2D-shear wave elastography (SWE) and ultraSound-guided controlled attenuation parameter (SCAP) performed in triplicate at the mid-axillary line (MAL), posterior axillary line (PAL), and anterior axillary line (AAL). Performances of SWE and SCAP were defined using transient elastography (TE ≥ 9.5 kPa) and CAP (≥ 275 dB/m) using Fibroscan (FS) as reference and validated with liver biopsy (LB). RESULTS FS and SS data from 203 CLD patients were analyzed (55 ± 14 years; 59% male; MASLD 58%). Median TE and CAP were 6.4 kPa (2.5-66.9) and 270 dB/m (141-400). The best technique for the diagnosis of advanced fibrosis and significant steatosis was the median of three SWE values and three SCAP values at MAL, PAL, and AAL with an AUROC of 0.96 [95% CI 0.93-0.98] and 0.91 [95% CI 0.86-0.95]. Only skin-to-liver distance ≥ 2.4 cm (p = 0.012, 95% CI 1.37-13.38) was independently associated with discordance. The accuracy of SWE (≥ 8.5 kPa) and SCAP (≥ 0.44) was analyzed in 58 patients with LB. The PPV and NPV were 50% and 94%, and 71% and 88% for fibrosis and steatosis, respectively. CONCLUSION A reliable diagnosis of advanced fibrosis and significant steatosis can be obtained with the median of three measurements in different liver portions using SS. The only non-reliable criterion is skin-to-liver distance ≥ 2.4 cm.
Collapse
Affiliation(s)
- Christiane Stern
- Service d'Hépatologie, Hôpital Beaujon, 100 Boulevard du Général Leclerc, 92110, Clichy, France.
- Service d'Hépato-gastroentérologie, Hôpital Pitié-Salpêtrière, Paris, France.
| | - An Ngo
- Service d'Hépato-gastroentérologie, Hôpital Pitié-Salpêtrière, Paris, France
| | - Cristiane Villela-Nogueira
- Serviço de Hepatologia, Hospital Universitario Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Dominique Thabut
- Service d'Hépato-gastroentérologie, Hôpital Pitié-Salpêtrière, Paris, France
| | - Vlad Ratziu
- Service d'Hépato-gastroentérologie, Hôpital Pitié-Salpêtrière, Paris, France
| |
Collapse
|
|
2
|
Tiniakos DG, Anstee QM, Brunt EM, Burt AD. Fatty Liver Disease. MACSWEEN'S PATHOLOGY OF THE LIVER 2024:330-401. [DOI: 10.1016/b978-0-7020-8228-3.00005-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|
|
3
|
Khan MQ, Hassan S, Lizaola-Mayo BC, Bhat M, Watt KD. Navigating the "specific etiology" steatohepatitis category: Evaluation and management of nonalcoholic/nonmetabolic dysfunction-associated steatohepatitis. Hepatology 2023:01515467-990000000-00637. [PMID: 37939197 DOI: 10.1097/hep.0000000000000674] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Accepted: 10/26/2023] [Indexed: 11/10/2023]
Affiliation(s)
- Mohammad Qasim Khan
- Department of Internal Medicine, Division of Gastroenterology, University of Western Ontario, London, Ontario, Canada
| | - Sara Hassan
- Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Mayo Clinic, Rochester, Minnesota, USA
| | - Blanca C Lizaola-Mayo
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, Arizona, USA
| | - Mamatha Bhat
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Toronto, Toronto, Ontario, Canada
| | - Kymberly D Watt
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| |
Collapse
|
|
4
|
Choi WT, Gill RM. Pathologic features and differential diagnosis of chronic hepatitis. DIAGNOSTIC HISTOPATHOLOGY 2023; 29:12-22. [DOI: 10.1016/j.mpdhp.2022.10.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|
|
5
|
Dalbeni A, Villani R, Bevilacqua M, Sacco F, Faccincani D, Cattazzo F, Cavallone F, Mantovani A, Ceruti V, Ieluzzi D, Paon V, Mantovani A, Serviddio G, Sacerdoti D. Effects of direct-acting antiviral agents on lipid and glucose profile in HCV patients with type 2 diabetes: A real-life Italian experience. J Dig Dis 2022; 23:324-330. [PMID: 35700113 DOI: 10.1111/1751-2980.13103] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Revised: 06/09/2022] [Accepted: 06/10/2022] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Hepatitis C virus (HCV) infection is associated with an increased risk of type 2 diabetes mellitus (T2DM) and cardiovascular diseases. The impact of HCV eradication on the metabolic profile in diabetic patients treated with direct-acting antiviral agents (DAAs) is not well defined. The aim of our study was to evaluate the effects of DAAs on a lipid and glucose profile in a cohort of diabetic patients with different liver fibrotic stages. METHODS T2DM patients with active HCV infection were consecutively enrolled in this prospective trial. Glycolipidic status was assessed, before starting DAA treatment (T0) and at 12 months after the beginning of treatment (T1). Liver fibrotic stage was assessed by FibroScan. RESULTS In all, 131 patients were enrolled and all of them achieved a sustained virologic response. At baseline, no significant differences were found in lipid and glucose profiles in subgroup analysis by liver fibrosis, HCV genotype, and cardiovascular risk factors. At T1, total cholesterol and low-density lipoprotein cholesterol, but not triglycerides, significantly increased irrespective of liver fibrotic stage and baseline anthropometric and clinical profiles, while glycated hemoglobin significantly decreased only in F4 patients. CONCLUSIONS HCV eradication in diabetic patients is associated with a worsening lipid profile that could impact future cardiovascular risk. A careful global monitoring of cardiovascular risk factors in all diabetic patients after HCV eradication is needed.
Collapse
Affiliation(s)
- Andrea Dalbeni
- Division of General Medicine C, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.,Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Rosanna Villani
- Liver Unit, Department of Surgical and Medical Sciences, University of Foggia, Foggia, Italy
| | - Michele Bevilacqua
- Division of General Medicine C, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Federica Sacco
- Liver Unit, Department of Surgical and Medical Sciences, University of Foggia, Foggia, Italy
| | - Diego Faccincani
- Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Filippo Cattazzo
- Division of General Medicine C, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Francesco Cavallone
- Liver Unit, Department of Surgical and Medical Sciences, University of Foggia, Foggia, Italy
| | - Anna Mantovani
- Division of General Medicine C, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Vittoria Ceruti
- Division of General Medicine C, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Donatella Ieluzzi
- Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Veronica Paon
- Division of General Medicine C, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.,Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Alessandro Mantovani
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Gaetano Serviddio
- Liver Unit, Department of Surgical and Medical Sciences, University of Foggia, Foggia, Italy
| | - David Sacerdoti
- Division of General Medicine C, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.,Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| |
Collapse
|
|
6
|
Liu J, Ayada I, Zhang X, Wang L, Li Y, Wen T, Ma Z, Bruno MJ, de Knegt RJ, Cao W, Peppelenbosch MP, Ghanbari M, Li Z, Pan Q. Estimating Global Prevalence of Metabolic Dysfunction-Associated Fatty Liver Disease in Overweight or Obese Adults. Clin Gastroenterol Hepatol 2022; 20:e573-e582. [PMID: 33618024 DOI: 10.1016/j.cgh.2021.02.030] [Citation(s) in RCA: 116] [Impact Index Per Article: 38.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Revised: 02/10/2021] [Accepted: 02/17/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new terminology updated from non-alcoholic fatty liver disease (NAFLD). In this study, we aim to estimate the global prevalence of MAFLD specifically in overweight and obese adults from the general population by performing a systematic review and meta-analysis through mining the existing epidemiological data on fatty liver disease. METHODS We searched Medline, Embase, Web of Science, Cochrane and google scholar database from inception to November, 2020. DerSimonian-Laird random-effects model with Logit transformation was performed for data analysis. Sensitivity analysis and meta-regression were used to explore predictors of MAFLD prevalence in pooled statistics with high heterogeneity. RESULTS We identified 116 relevant studies comprised of 2,667,052 participants in general population with an estimated global MAFLD prevalence as 50.7% (95% CI 46.9-54.4) among overweight/obese adults regardless of diagnostic techniques. Ultrasound was the most commonly used diagnostic technique generating prevalence rate of 51.3% (95% CI, 49.1-53.4). Male (59.0%; 95% CI, 52.0-65.6) had a significantly higher MAFLD prevalence than female (47.5%; 95% CI, 40.7-54.5). Interestingly, MAFLD prevalence rates are comparable based on classical NAFLD and non-NAFLD studies in general population. The pooled estimate prevalence of comorbidities such as type 2 diabetes and metabolic syndrome was 19.7% (95% CI, 12.8-29.0) and 57.5% (95% CI, 49.9-64.8), respectively. CONCLUSIONS MAFLD has an astonishingly high prevalence rate in overweight and obese adults. This calls for attention and dedicated action from primary care physicians, specialists, health policy makers and the general public alike.
Collapse
Affiliation(s)
- Jiaye Liu
- Department of Thyroid and Parathyroid Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Laboratory of Thyroid and Parathyroid Diseases, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - Ibrahim Ayada
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - Xiaofang Zhang
- Department of Epidemiology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - Ling Wang
- Department of Thyroid and Parathyroid Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yang Li
- Department of Thyroid and Parathyroid Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Tianfu Wen
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
| | - Zhongren Ma
- Biomedical Research Center, Northwest Minzu University, Lanzhou, China
| | - Marco J Bruno
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - Robert J de Knegt
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - Wanlu Cao
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - Maikel P Peppelenbosch
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - Mohsen Ghanbari
- Department of Epidemiology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - Zhihui Li
- Department of Thyroid and Parathyroid Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Laboratory of Thyroid and Parathyroid Diseases, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Qiuwei Pan
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands; Biomedical Research Center, Northwest Minzu University, Lanzhou, China.
| |
Collapse
|
|
7
|
Kusano H, Kondo R, Ogasawara S, Omuraya M, Okudaira M, Mizuochi S, Mihara Y, Kinjo Y, Yano Y, Nakayama M, Naito Y, Akiba J, Nakashima O, Yano H. Utility of sonic hedgehog and keratin 8/18 immunohistochemistry for detecting ballooned hepatocytes. Histopathology 2022; 80:974-981. [DOI: 10.1111/his.14631] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Revised: 02/21/2022] [Accepted: 02/21/2022] [Indexed: 11/28/2022]
Affiliation(s)
- Hironori Kusano
- Department of Pathology Kurume University School of Medicine Kurume Japan
- Department of Clinical Laboratory, National Hospital Organization Kokura Medical Center, Kitakyushu Japan
| | - Reiichiro Kondo
- Department of Pathology Kurume University School of Medicine Kurume Japan
| | - Sachiko Ogasawara
- Department of Pathology Kurume University School of Medicine Kurume Japan
| | | | | | - Shinji Mizuochi
- Department of Pathology Kurume University School of Medicine Kurume Japan
| | - Yutaro Mihara
- Department of Pathology Kurume University School of Medicine Kurume Japan
| | - Yoshinao Kinjo
- Department of Pathology Kurume University School of Medicine Kurume Japan
| | - Yuta Yano
- Department of Pathology Kurume University School of Medicine Kurume Japan
| | - Masamichi Nakayama
- Department of Pathology Kurume University School of Medicine Kurume Japan
| | - Yoshiki Naito
- Department of Diagnostic Pathology Kurume University Hospital Kurume Japan
| | - Jun Akiba
- Department of Diagnostic Pathology Kurume University Hospital Kurume Japan
| | - Osamu Nakashima
- Department of Clinical Laboratory Medicine Kurume University Hospital Kurume Japan
| | - Hirohisa Yano
- Department of Pathology Kurume University School of Medicine Kurume Japan
| |
Collapse
|
|
8
|
Castera L. Assessment of Liver Disease Severity. HEPATITIS C: CARE AND TREATMENT 2021:1-20. [DOI: 10.1007/978-3-030-67762-6_1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
9
|
Kierepa A, Witkowska A, Kaczmarek M, Książek K, Mikuła-Pietrasik J, Żeromski J, Kowala-Piaskowska A, Mozer-Lisewska I. Impact of chronic HCV treatment on quality of life of patients with metabolic disorders in context of immunological disturbances. Sci Rep 2020; 10:10388. [PMID: 32587314 PMCID: PMC7316785 DOI: 10.1038/s41598-020-67296-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Accepted: 04/20/2020] [Indexed: 12/20/2022] Open
Abstract
Chronic viral hepatitis C (CHC) and its complications have a negative effect on patient's quality of life. We evaluated the impact of a successful interferon-free treatment on the quality of life of patients with obesity and metabolic disorders in the context of immunological disturbances. Twenty overweight or obese (BMI > 25) patients with CHC were tested before the therapy and after a successful treatment regimen. After the therapy, patient's emotional well-being improved (p = 0.02), while physical well-being remained unchanged. There was a decrease of patient's liver fibrosis and an increase of steatosis along with body mass. Among HCV-infected individuals, the expression of toll-like receptor 3 (TLR3) on lymphocytes was higher than in the control group (p = 0.03), but it decreased (p = 0.001) after the treatment. There was also a decrease of the intensity of immunofluorescence of FoxP3+ after the treatment (p = 0.04). Our study showed an improvement in mental aspects of patient's quality of life after the treatment. Unfortunately, probably due to rapid immunological changes, patient's BMI, serum cholesterol levels and hepatic steatosis have a tendency to increase and may lead to cardiovascular and other complications, like hepatocellular carcinoma.
Collapse
Affiliation(s)
- Agata Kierepa
- Chair and Department of Infectious Diseases, Hepatology and Acquired Immunodeficiencies, Karol Marcinkowski University of Medical Sciences, Poznań, Poland.
| | - Aleksandra Witkowska
- Chair and Department of Infectious Diseases, Hepatology and Acquired Immunodeficiencies, Karol Marcinkowski University of Medical Sciences, Poznań, Poland
| | - Mariusz Kaczmarek
- Chair of Clinical Immunology, Karol Marcinkowski University of Medical Sciences, Poznań, Poland
| | - Krzysztof Książek
- Department of Hypertensiology, Angiology and Internal Medicine, Karol Marcinkowski University of Medical Sciences, Poznań, Poland
| | - Justyna Mikuła-Pietrasik
- Department of Hypertensiology, Angiology and Internal Medicine, Karol Marcinkowski University of Medical Sciences, Poznań, Poland
| | - Jan Żeromski
- Chair of Clinical Immunology, Karol Marcinkowski University of Medical Sciences, Poznań, Poland
| | - Arleta Kowala-Piaskowska
- Chair and Department of Infectious Diseases, Hepatology and Acquired Immunodeficiencies, Karol Marcinkowski University of Medical Sciences, Poznań, Poland
| | - Iwona Mozer-Lisewska
- Chair and Department of Infectious Diseases, Hepatology and Acquired Immunodeficiencies, Karol Marcinkowski University of Medical Sciences, Poznań, Poland
| |
Collapse
|
|
10
|
Soldevila L, Tenesa M, Horneros J, Bechini J, López JJ, Pérez R, Martínez MÀ, Ouchi D, Franco S, Perez-Àlvarez N, Buccione D, Clotet B, Tural C. Association Between Visceral Abdominal Fat Accumulation and Severity of Liver Fibrosis in Nondiabetic Individuals Coinfected by Human Immunodeficiency Virus and Hepatitis C Virus. AIDS Res Hum Retroviruses 2020; 36:205-213. [PMID: 31564109 DOI: 10.1089/aid.2019.0097] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Our primary objective was to assess the independent association between liver fibrosis (LF) and abdominal fat accumulation (AFA) and fatty liver disease (FLD). We also aimed to determine the diagnostic accuracy of AFA and FLD for the prediction of cirrhosis measured using unenhanced low-dose computed tomography (CT). This is a cross-sectional study in stable human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients with active HCV replication. CT was used to quantify fat content in segments III and VI of the liver and AFA. Transient elastometry was used to stage LF. Multivariate logistic regression, receiver operating characteristic curve analysis, and linear mixed model analysis were applied. One hundred fifteen HIV/HCV-coinfected patients were included. Cirrhosis was detected in 20.8% (24 patients). There was a high correlation between anthropometric characteristics and radiological variables. The factors independently associated with cirrhosis were albumin concentration [odds ratio (OR), 0.69; 95% confidence interval (CI), 0.58-0.83; p < .0001] and visceral fat accumulation (OR, 1.02; 95% CI, 1.01-1.04; p = .0003). Multinomial analysis showed that visceral fat area (VFA) was the factor independently associated with stage F2 (OR, 1.02; 95% CI, 1.0-1.03; p < .005) and albumin concentration with stage F3 (OR, 0.75; 95% CI, 0.64-0.89; p < .001). VFA was the only radiological variable with an area under the curve >0.7 for the prediction of cirrhosis. There was no inter- or intraobserver variability in the measurement of AFA; however, high interobserver variability was recorded in the measurement of FLD. The association of VFA with cirrhosis, the high reproducibility of CT for the measurement of VFA, and the ability of VFA to predict cirrhosis make CT a suitable technique for identifying HIV/HCV-coinfected patients for closer surveillance.
Collapse
Affiliation(s)
- Laura Soldevila
- Internal Medicine Department, University Hospital Germans Trias I Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Montserrat Tenesa
- Radiology Department, University Hospital Germans Trias I Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Judith Horneros
- Radiology Department, University Hospital Germans Trias I Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Jordi Bechini
- Radiology Department, University Hospital Germans Trias I Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Juan José López
- Internal Medicine Department, University Hospital Germans Trias I Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Ricardo Pérez
- Radiology Department, University Hospital Germans Trias I Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain
| | | | - Dan Ouchi
- IrsiCaixa Laboratory, University Hospital Germans Trias I Pujol, Barcelona, Spain
| | - Sandra Franco
- IrsiCaixa Laboratory, University Hospital Germans Trias I Pujol, Barcelona, Spain
| | - Nuria Perez-Àlvarez
- Statistics and Operations Research Department, Technical University of Catalonia, Barcelona, Spain
| | - Daniela Buccione
- Internal Medicine Department, University Hospital Germans Trias I Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Bonaventura Clotet
- IrsiCaixa Laboratory, University Hospital Germans Trias I Pujol, Barcelona, Spain
- Infectious Diseases Department, University Hospital Germans Trias I Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Cristina Tural
- Internal Medicine Department, University Hospital Germans Trias I Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain
| |
Collapse
|
|
11
|
Munsterman ID, van Erp M, Weijers G, Bronkhorst C, de Korte CL, Drenth JPH, van der Laak JAWM, Tjwa ETTL. A Novel Automatic Digital Algorithm that Accurately Quantifies Steatosis in NAFLD on Histopathological Whole-Slide Images. CYTOMETRY PART B-CLINICAL CYTOMETRY 2019; 96:521-528. [PMID: 31173462 PMCID: PMC6899563 DOI: 10.1002/cyto.b.21790] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Revised: 04/21/2019] [Accepted: 05/17/2019] [Indexed: 12/14/2022]
Abstract
Background Accurate assessment of hepatic steatosis is a key to grade disease severity in non‐alcoholic fatty liver disease (NAFLD). Methods We developed a digital automated quantification of steatosis on whole‐slide images (WSIs) of liver tissue and performed a validation study. Hematoxylin–eosin stained liver tissue slides were digitally scanned, and steatotic areas were manually annotated. We identified thresholds for size and roundness parameters by logistic regression to discriminate steatosis from surrounding liver tissue. The resulting algorithm produces a steatosis proportionate area (SPA; ratio of steatotic area to total tissue area described as percentage). The software can be implemented as a Java plug‐in in FIJI, in which digital WSI can be processed automatically using the Pathomation extension. Results We obtained liver tissue specimens from 61 NAFLD patients and 18 controls. The area under the curve of correctly classified steatosis by the algorithm was 0.970 (95% CI 0.968–0.973), P < 0.001. Accuracy of the algorithm was 91.9%, with a classification error of 8.1%. SPA correlated significantly with steatosis grade (Rs = 0.845, CI: 0.749–0.902, P < 0.001) and increased significantly with each individual steatosis grade, except between Grade 2 and 3. Conclusions We have developed a novel digital analysis algorithm that accurately quantifies steatosis on WSIs of liver tissue. This algorithm can be incorporated when quantification of steatosis is warranted, such as in clinical trials studying efficacy of new therapeutic interventions in NAFLD. © 2019 The Authors. Cytometry Part B: Clinical Cytometry published by Wiley Periodicals, Inc. on behalf of International Clinical Cytometry Society.
Collapse
Affiliation(s)
- Isabelle D Munsterman
- Department of Gastroenterology and Hepatology, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Merijn van Erp
- Department of Pathology, Radboud University Medical Centre, Nijmegen, The Netherlands.,Microscopic Imaging Centre, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Gert Weijers
- Medical UltraSound Imaging Centre (MUSIC), Department of Radiology and Nuclear Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Carolien Bronkhorst
- Department of Pathology, Jeroen Bosch Ziekenhuis's-Hertogenbosch, The Netherlands
| | - Chris L de Korte
- Medical UltraSound Imaging Centre (MUSIC), Department of Radiology and Nuclear Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Joost P H Drenth
- Department of Gastroenterology and Hepatology, Radboud University Medical Centre, Nijmegen, The Netherlands
| | | | - Eric T T L Tjwa
- Department of Gastroenterology and Hepatology, Radboud University Medical Centre, Nijmegen, The Netherlands
| |
Collapse
|
|
12
|
|
|
13
|
Abstract
Metabolic disorders are common in patients with chronic hepatitis C virus (HCV) infection. Epidemiologic and clinical data indicate an overprevalence of lipids abnormalite, steatosis, insuline resistance (IR) and diabetes mellitus in HCV patients, suggesting that HCV itself may interact with glucido-lipidic metabolism. HCV interacts with the host lipid metabolism by several mechanisms leading to hepatic steatosis and hypolipidemia which are reversible after viral eradication. Liver and peripheral IR are HCV genotype/viral load dependent and improved after viral eradication. This article examines examine the relationship between HCV, lipid abnormalities, steatosis, IR, and diabetes and the pathogenic mechanisms accounting for these events in HCV-infected patients.
Collapse
Affiliation(s)
- Lawrence Serfaty
- Hepatology Department, INSERM UMR_S 938, APHP, Saint-Antoine Hospital, UPMC Univ Paris 06, Paris, France.
| |
Collapse
|
|
14
|
Brunt EM. Nonalcoholic fatty liver disease and the ongoing role of liver biopsy evaluation. Hepatol Commun 2017; 1:370-378. [PMID: 29404465 PMCID: PMC5721411 DOI: 10.1002/hep4.1055] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2017] [Revised: 05/02/2017] [Accepted: 05/10/2017] [Indexed: 12/11/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is one of the most common underlying causes of chronically elevated liver tests and liver disease in adults and children worldwide and may be strongly suspected if not diagnosed by ever evolving and available serologic and imaging‐based noninvasive tests. However, the definitive diagnosis of the most progressive form of NAFLD, nonalcoholic steatohepatitis, and the identification of fibrosis stage still require liver biopsy evaluation as noninvasive testing has not replaced some of the specifics or the totality of information obtainable from liver biopsy. In this review, both the role and value of a liver biopsy evaluation in NAFLD/ nonalcoholic steatohepatitis are examined from publications related to a selected variety of settings. Details of the most commonly used semiquantitative methods of analysis are discussed, and some useful potential pitfalls for differential diagnostic consideration in liver biopsy interpretation are given. (Hepatology Communications 2017;1:370–378)
Collapse
Affiliation(s)
- Elizabeth M Brunt
- Department of Pathology and Immunology Washington University School of Medicine St Louis MO
| |
Collapse
|
|
15
|
Abstract
Hepatitis C virus (HCV) represents a significant global disease burden, with an estimated 130-150 million people worldwide living with chronic HCV infection. Within the six major clinical HCV genotypes, genotype 3 represents 22-30% of all infection and is described as a unique entity with higher rates of steatosis, faster progression to cirrhosis, and higher rates of hepatocellular carcinoma. Hepatic steatosis in the setting of hepatitis C genotype 3 (HCV-3) is driven by viral influence on three major pathways: microsomal triglyceride transfer protein, sterol regulatory element-binding protein-1c, and peroxisome proliferator-associated receptor-α. Historically with direct-acting antivirals, the rates of cure for HCV-3 therapies lagged behind the other genotypes. As current therapies for HCV-3 continue to close this gap, it is important to be cognizant of common drug interactions such as acid-suppressing medication and amiodarone. In this review, we discuss the rates of steatosis in HCV-3, the mechanisms behind HCV-3-specific steatosis, and current and future therapies.
Collapse
Affiliation(s)
- Austin Chan
- Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, NC, USA
- Infectious Diseases Research, Duke Clinical Research Institute, Durham, NC, USA
| | - Keyur Patel
- Toronto Center for Liver Disease, University of Toronto, Toronto, ON, Canada
| | - Susanna Naggie
- Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
- Infectious Diseases Research, Duke Clinical Research Institute, Durham, NC, USA.
| |
Collapse
|
|
16
|
Abstract
Non-invasive diagnosis and quantification of hepatic steatosis rely on two different but complementary approaches: biomarkers or imaging techniques, either ultrasound-based such as liver ultrasonography and controlled attenuation parameter (CAP), or computed tomography (CT) and magnetic resonance imaging (MRI). Scores for the detection of steatosis have not gained much popularity in clinical practice so far. CAP, using the M probe, is the most promising technique but needs to be implemented with the XL probe and compared to ultrasound that, despite its limitations, remains the most widely used method. CT, owing to its low sensitivity and the fact that it involves a potential radiation hazard, is inappropriate. Finally, proton density fat fraction measurement by MRI is currently the most accurate and sensitive imaging method, simpler and more practical than magnetic resonance spectroscopy, but restricted, up to now, just to research and clinical trials.
Collapse
|
|
17
|
Natural History of Patients Presenting with Autoimmune Hepatitis and Coincident Nonalcoholic Fatty Liver Disease. Dig Dis Sci 2016; 61:2710-20. [PMID: 27262844 PMCID: PMC6357773 DOI: 10.1007/s10620-016-4213-3] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2016] [Accepted: 05/26/2016] [Indexed: 12/24/2022]
Abstract
BACKGROUND Given the increase of nonalcoholic fatty liver disease (NAFLD) in the general population, a similar rise might be expected in autoimmune hepatitis (AIH) patients. AIMS We sought to determine the clinical outcome of patients with coincident AIH and NAFLD. METHODS We identified all intradepartmental AIH cases, and those meeting study criteria were placed into one of three cohorts: AIH only, AIH and simple steatosis (SS), and AIH and nonalcoholic steatohepatitis (NASH). The following outcome and clinical data were analyzed: incidence of all-cause mortality, incidence of liver-related mortality, incidence of liver-related adverse outcomes, and prevalence of cirrhosis at index biopsy. RESULTS Out of a total 73 study patients, 14 % classified as AIH with SS and 16 % as AIH and NASH. Fifty percent of AIH and NASH patients had cirrhosis at index biopsy as compared to 18 % of AIH-only patients (p = 0.032). Patients with AIH and NASH had a relative risk of 7.65 (95 % CI 1.43-40.8) for liver-related mortality and 2.55 (95 % CI 0.92-7.09) for liver-related adverse outcomes, as compared to the AIH-only cohort. No significant difference in outcome measures existed in comparing (AIH only) with (AIH and SS) cohorts. DISCUSSION Patients with coincident AIH and NASH were more likely to present with cirrhosis and more likely to develop adverse clinical outcome with decreased survival as compared to AIH-only patients. These findings suggest that simultaneous exposure confers a clinically significant increased risk, which may warrant closer follow-up and surveillance.
Collapse
|
|
18
|
Eslam M, Mangia A, Berg T, Chan HLY, Irving WL, Dore GJ, Abate ML, Bugianesi E, Adams LA, Najim MAM, Miele L, Weltman M, Mollison L, Cheng W, Riordan S, Fischer J, Romero-Gomez M, Spengler U, Nattermann J, Rahme A, Sheridan D, Booth DR, McLeod D, Powell E, Liddle C, Douglas MW, van der Poorten D, George J. Diverse impacts of the rs58542926 E167K variant in TM6SF2 on viral and metabolic liver disease phenotypes. Hepatology 2016; 64:34-46. [PMID: 26822232 DOI: 10.1002/hep.28475] [Citation(s) in RCA: 88] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2015] [Accepted: 01/27/2016] [Indexed: 01/03/2023]
Abstract
UNLABELLED A genome-wide exome association study has identified the transmembrane 6 superfamily member 2 (TM6SF2) rs58542926 variant encoding an E167K substitution as a genetic determinant of hepatic steatosis in nonalcoholic fatty liver disease (NAFLD). The roles of this variant across a spectrum of liver diseases and pathologies and on serum lipids comparing viral hepatitis to NAFLD and viral load in chronic viral hepatitis, as well as its intrahepatic molecular signature, have not been well characterized. We undertook detailed analyses in 3260 subjects with viral and nonviral liver diseases and in healthy controls. Serum inflammatory markers and hepatic expression of TM6SF2 and genes regulating lipid metabolism were assessed in a subset with chronic hepatitis C (CHC). The rs58542926 T allele was more prevalent in 502 NAFLD patients than controls (P = 0.02) but not different in cohorts with CHC (n = 2023) and chronic hepatitis B (n = 507). The T allele was associated with alterations in serum lipids and hepatic steatosis in all diseases and with reduced hepatic TM6SF2 and microsomal triglyceride transfer protein expression. Interestingly, the substitution was associated with reduced CHC viral load but increased hepatitis B virus DNA. The rs58542926 T allele had no effect on inflammation, impacted ≥F2 fibrosis in CHC and NAFLD assessed cross-sectionally (odds ratio = 1.39, 95% confidence interval 1.04-1.87, and odds ratio = 1.62, 95% confidence interval 1.03-2.52, respectively; P < 0.03 for both), but had no effect on fibrosis progression in 1174 patients with CHC and a known duration of infection. CONCLUSION The TM6SF2 E167K substitution promotes steatosis and lipid abnormalities in part by altering TM6SF2 and microsomal triglyceride transfer protein expression and differentially impacts CHC and chronic hepatitis B viral load, while effects on fibrosis are marginal. (Hepatology 2016;64:34-46).
Collapse
Affiliation(s)
- Mohammed Eslam
- Storr Liver Centre, Westmead Millennium Institute and Westmead Hospital, University of Sydney, NSW, Australia
| | - Alessandra Mangia
- Division of Hepatology, Ospedale Casa Sollievo della Sofferenza, IRCCS, San Giovanni Rotondo, Italy
| | - Thomas Berg
- Section of Hepatology, Clinic for Gastroenterology and Rheumatology, University Clinic Leipzig, Leipzig, Germany
| | - Henry Lik Yuen Chan
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
| | - William L Irving
- NIHR Biomedical Research Unit in Gastroenterology and the Liver, University of Nottingham, Nottingham, UK
| | - Gregory J Dore
- Kirby Institute, The University of New South Wales, Sydney, NSW, Australia
- St. Vincent's Hospital, Sydney, NSW, Australia
| | - Maria Lorena Abate
- Division of Gastroenterology and Hepatology, Department of Medical Science, University of Turin, Turin, Italy
| | - Elisabetta Bugianesi
- Division of Gastroenterology and Hepatology, Department of Medical Science, University of Turin, Turin, Italy
| | - Leon A Adams
- School of Medicine and Pharmacology, Sir Charles Gairdner Hospital Unit, University of Western Australia, Nedlands, WA, Australia
| | - Mustafa A M Najim
- Storr Liver Centre, Westmead Millennium Institute and Westmead Hospital, University of Sydney, NSW, Australia
- Department of Medical Laboratories Technology, Faculty of Applied Medical Sciences, Taibah University, Medina, Saudi Arabia
| | - Luca Miele
- Department of Internal Medicine, Catholic University of the Sacred Heart, Rome, Italy
| | - Martin Weltman
- Department of Gastroenterology and Hepatology, Nepean Hospital, Sydney, NSW, Australia
| | - Lindsay Mollison
- Department of Gastroenterology and Hepatology, Fremantle Hospital, Fremantle, WA, Australia
| | - Wendy Cheng
- Department of Gastroenterology & Hepatology, Royal Perth Hospital, WA, Australia
| | - Stephen Riordan
- Gastrointestinal and Liver Unit, Prince of Wales Hospital and University of New South Wales, Sydney, NSW, Australia
| | - Janett Fischer
- Section of Hepatology, Clinic for Gastroenterology and Rheumatology, University Clinic Leipzig, Leipzig, Germany
| | - Manuel Romero-Gomez
- Unit for the Clinical Management of Digestive Diseases and CIBERehd, Hospital Universitario de Valme, Sevilla, Spain
| | - Ulrich Spengler
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | - Jacob Nattermann
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | - Antony Rahme
- Storr Liver Centre, Westmead Millennium Institute and Westmead Hospital, University of Sydney, NSW, Australia
| | - David Sheridan
- Institute of Translational and Stratified Medicine, Plymouth University, UK
| | - David R Booth
- Institute of Immunology and Allergy Research, Westmead Hospital and Westmead Millennium Institute, University of Sydney, NSW, Australia
| | - Duncan McLeod
- Department of Anatomical Pathology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Sydney, Australia
| | - Elizabeth Powell
- The University of Queensland, School of Medicine, Princess Alexandra Hospital, Woolloongabba, QLD, Australia
| | - Christopher Liddle
- Storr Liver Centre, Westmead Millennium Institute and Westmead Hospital, University of Sydney, NSW, Australia
| | - Mark W Douglas
- Storr Liver Centre, Westmead Millennium Institute and Westmead Hospital, University of Sydney, NSW, Australia
- Centre for Infectious Diseases and Microbiology, Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney at Westmead Hospital, Westmead, NSW, Australia
| | - David van der Poorten
- Storr Liver Centre, Westmead Millennium Institute and Westmead Hospital, University of Sydney, NSW, Australia
| | - Jacob George
- Storr Liver Centre, Westmead Millennium Institute and Westmead Hospital, University of Sydney, NSW, Australia
| |
Collapse
|
|
19
|
Serfaty L. Clinical Implications of Concomitant Alcohol Use, Obesity, and Viral Hepatitis. Gastroenterology 2016; 150:1718-22. [PMID: 26873400 DOI: 10.1053/j.gastro.2016.02.001] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2015] [Revised: 02/04/2016] [Accepted: 02/04/2016] [Indexed: 12/11/2022]
Affiliation(s)
- Lawrence Serfaty
- AP-HP, Hôpital Saint-Antoine, Service d'Hépatologie and UPMC Univ Paris 6, Paris, France.
| |
Collapse
|
|
20
|
Adinolfi LE, Rinaldi L, Guerrera B, Restivo L, Marrone A, Giordano M, Zampino R. NAFLD and NASH in HCV Infection: Prevalence and Significance in Hepatic and Extrahepatic Manifestations. Int J Mol Sci 2016; 17:ijms17060803. [PMID: 27231906 PMCID: PMC4926337 DOI: 10.3390/ijms17060803] [Citation(s) in RCA: 67] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2016] [Revised: 05/15/2016] [Accepted: 05/19/2016] [Indexed: 02/06/2023] Open
Abstract
The aim of this paper is to review and up to date the prevalence of hepatitis C virus (HCV)-associated non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) and their significance in both accelerating progression of HCV-related liver disease and development of HCV-associated extrahepatic diseases. The reported mean prevalence of HCV-related NAFLD was 55%, whereas NASH was reported in 4%–10% of cases. HCV genotype 3 directly induces fatty liver deposition, namely “viral steatosis” and it is associated with the highest prevalence and degree of severity, whereas, HCV non-3 genotype infection showed lower prevalence of steatosis, which is associated with metabolic factors and insulin resistance. The host’s genetic background predisposes him or her to the development of steatosis. HCV’s impairment of lipid and glucose metabolism causes fatty liver accumulation; this seems to be a viral strategy to optimize its life cycle. Irrespective of insulin resistance, HCV-associated NAFLD, in a degree-dependent manner, contributes towards accelerating the liver fibrosis progression and development of hepatocellular carcinoma by inducing liver inflammation and oxidative stress. Furthermore, NAFLD is associated with the presence of metabolic syndrome, type 2 diabetes, and atherosclerosis. In addition, HCV-related “metabolic steatosis” impairs the response rate to interferon-based treatment, whereas it seems that “viral steatosis” may harm the response rate to new oral direct antiviral agents. In conclusion, a high prevalence of NAFLD occurs in HCV infections, which is, at least in part, induced by the virus, and that NAFLD significantly impacts progression of the liver disease, therapeutic response, and some extrahepatic diseases.
Collapse
Affiliation(s)
- Luigi Elio Adinolfi
- Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, Second University of Naples, Naples 80100, Italy.
| | - Luca Rinaldi
- Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, Second University of Naples, Naples 80100, Italy.
| | - Barbara Guerrera
- Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, Second University of Naples, Naples 80100, Italy.
| | - Luciano Restivo
- Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, Second University of Naples, Naples 80100, Italy.
| | - Aldo Marrone
- Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, Second University of Naples, Naples 80100, Italy.
| | - Mauro Giordano
- Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, Second University of Naples, Naples 80100, Italy.
| | - Rosa Zampino
- Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, Second University of Naples, Naples 80100, Italy.
| |
Collapse
|
|
21
|
Abstract
Nonalcoholic fatty liver disease (NAFLD) covers a spectrum of histological lesions ranging from steatosis to a complex pattern with hepatocyte injury and inflammation in an appropriate clinical context. The disease has been artificially dichotomized into NAFL (steatosis) and NASH (steatosis with hepatocellular injury and inflammation), but it is increasingly clear that intermediate patterns may exist. More than NASH, the stage of fibrosis was shown to govern prognosis, and for such evaluation, a liver biopsy of adequate size and width is needed. Like for any other chronic liver diseases, semi-quantitative histologic scores have been proposed. They are not useful in clinical practice but concur to categorize homogeneous group of patients according to their histology. Pediatric NAFLD is a growing concern. While a subgroup of children may harbor different but characteristic histological patterns, most of them display a mixed pattern or features similar to the adults. Today, liver histology is the mainstay for clinical trials. Biopsy is used both for enrollment and for assessing benefit of clinical trials. End points such as reversion of NASH or regression of fibrosis are acceptable but require a clear histological definition.
Collapse
Affiliation(s)
- Pierre Bedossa
- Hôpital Beaujon, Assistance Publique - Hôpitaux de Paris, Université Paris-Diderot, Paris, France.
| |
Collapse
|
|
22
|
Valva P, Ríos DA, De Matteo E, Preciado MV. Chronic hepatitis C virus infection: Serum biomarkers in predicting liver damage. World J Gastroenterol 2016; 22:1367-1381. [PMID: 26819506 PMCID: PMC4721972 DOI: 10.3748/wjg.v22.i4.1367] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2015] [Revised: 08/04/2015] [Accepted: 10/13/2015] [Indexed: 02/06/2023] Open
Abstract
Currently, a major clinical challenge in the management of the increasing number of hepatitis C virus (HCV) infected patients is determining the best means for evaluating liver impairment. Prognosis and treatment of chronic hepatitis C (CHC) are partly dependent on the assessment of histological activity, namely cell necrosis and inflammation, and the degree of liver fibrosis. These parameters can be provided by liver biopsy; however, in addition to the risks related to an invasive procedure, liver biopsy has been associated with sampling error mostly due to suboptimal biopsy size. To avoid these pitfalls, several markers have been proposed as non-invasive alternatives for the diagnosis of liver damage. Distinct approaches among the currently available non-invasive methods are (1) the physical ones based on imaging techniques; and (2) the biological ones based on serum biomarkers. In this review, we discuss these approaches with special focus on currently available non-invasive serum markers. We will discuss: (1) class I serum biomarkers individually and as combined panels, particularly those that mirror the metabolism of liver extracellular matrix turnover and/or fibrogenic cell changes; (2) class II biomarkers that are indirect serum markers and are based on the evaluation of common functional alterations in the liver; and (3) biomarkers of liver cell death, since hepatocyte apoptosis plays a significant role in the pathogenesis of HCV infection. We highlight in this review the evidence behind the use of these markers and assess the diagnostic accuracy as well as advantages, limitations, and application in clinical practice of each test for predicting liver damage in CHC.
Collapse
|
|
23
|
Ress C, Kaser S. Mechanisms of intrahepatic triglyceride accumulation. World J Gastroenterol 2016; 22:1664-1673. [PMID: 26819531 PMCID: PMC4721997 DOI: 10.3748/wjg.v22.i4.1664] [Citation(s) in RCA: 83] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2015] [Revised: 08/20/2015] [Accepted: 09/30/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatic steatosis defined as lipid accumulation in hepatocytes is very frequently found in adults and obese adolescents in the Western World. Etiologically, obesity and associated insulin resistance or excess alcohol intake are the most frequent causes of hepatic steatosis. However, steatosis also often occurs with chronic hepatitis C virus (HCV) infection and is also found in rare but potentially life-threatening liver diseases of pregnancy. Clinical significance and outcome of hepatic triglyceride accumulation are highly dependent on etiology and histological pattern of steatosis. This review summarizes current concepts of pathophysiology of common causes of hepatic steatosis, including non-alcoholic fatty liver disease (NAFLD), alcoholic fatty liver disease, chronic HCV infections, drug-induced forms of hepatic steatosis, and acute fatty liver of pregnancy. Regarding the pathophysiology of NAFLD, this work focuses on the close correlation between insulin resistance and hepatic triglyceride accumulation, highlighting the potential harmful effects of systemic insulin resistance on hepatic metabolism of fatty acids on the one side and the role of lipid intermediates on insulin signalling on the other side. Current studies on lipid droplet morphogenesis have identified novel candidate proteins and enzymes in NAFLD.
Collapse
|
|
24
|
Wang Y, Hou JL. Fibrosis assessment: impact on current management of chronic liver disease and application of quantitative invasive tools. Hepatol Int 2016; 10:448-61. [DOI: 10.1007/s12072-015-9695-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2015] [Accepted: 12/07/2015] [Indexed: 12/15/2022]
|
|
25
|
Serfaty L. Follow-up of patients with chronic hepatitis C and a sustained viral response. Liver Int 2016; 36 Suppl 1:67-71. [PMID: 26725900 DOI: 10.1111/liv.13016] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2015] [Accepted: 11/03/2015] [Indexed: 12/12/2022]
Abstract
Patients with chronic hepatitis C who achieve a sustained virological response (SVR) after antiviral treatment have improved survival and liver-related morbidity compared to non-SVR patients. However, long-term follow-up studies in SVR patients have shown that the regression of fibrosis varies and the risk of liver-related complications remains, even in the absence of cirrhosis. While patients with cirrhosis are still at risk of hepatocellular carcinoma, comorbidities such as diabetes, obesity or alcohol consumption may play a major role in the outcome of liver disease in SVR patients without cirrhosis. The risk of re-infection is high in patients with a persistent risk of contamination such as IV drug users or men who have sex with men. Thus, in the era of highly efficient DAAs regimens, monitoring after a cure of HCV infection remains a major challenge in SVR patients. This review describes long-term HCV infection and liver-related outcomes in SVR patients, as well as the profile of patients who are still at risk of progression, and monitoring techniques including non-invasive markers for the assessment of fibrosis.
Collapse
Affiliation(s)
- Lawrence Serfaty
- AP-HP, Service d'Hépatologie, Hôpital Saint-Antoine, F75012, Paris, France.,UPMC Univ Paris 6, UMR_S938, F75012, Paris, France
| |
Collapse
|
|
26
|
Martini A, Fattovich G, Guido M, Bugianesi E, Biasiolo A, Ieluzzi D, Gallotta A, Fassina G, Merkel C, Gatta A, Negro F, Pontisso P. HCV genotype 3 and squamous cell carcinoma antigen (SCCA)-IgM are independently associated with histological features of NASH in HCV-infected patients. J Viral Hepat 2015; 22:800-8. [PMID: 25611978 DOI: 10.1111/jvh.12394] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2014] [Accepted: 12/07/2014] [Indexed: 12/13/2022]
Abstract
Nonalcoholic steatohepatitis (NASH) enhances the risk of progressive liver disease. In chronic hepatitis C (CHC), liver steatosis is frequent, especially in genotype 3, but its clinical significance is debated. As squamous cell carcinoma antigen (SCCA)-IgM has been associated with advanced liver disease and risk of tumour development, we evaluated its occurrence in CHC and the possible relation with NASH at liver biopsy. Using a validated ELISA, serum SCCA-IgM was measured in 91 patients with CHC at the time of liver biopsy performed before antiviral treatment, at the end of treatment and 6 months thereafter, and in 93 HCV-negative patients with histological diagnosis of nonalcoholic fatty liver disease, as controls. SCCA-IgM was detected in 33% of CHC patients and in 4% of controls. This biomarker was found more elevated in CHC patients with histological NASH, and at multivariate analysis, SCCA-IgM and HCV genotype 3 were independently associated with NASH [OR (95% CI): 6.94 (1.21-40) and 27.02 (4.44-166.6)]. As predictors of NASH, HCV genotype 3 and SCCA-IgM had a specificity and a sensitivity of 97% and 44%, and of 95% and 27%, respectively. PPV and NPV were 80% and 86% for HCV genotype 3 vs 73% and 72% for SCCA-IgM. In patients with sustained virologic response to therapy, SCCA-IgM levels decreased significantly, while these remained unchanged in nonresponders. In conclusion, SCCA-IgM is detectable in one-third of patients with CHC and significantly correlates with histological NASH.
Collapse
Affiliation(s)
- A Martini
- Department of Medicine, University of Padua, Padua, Italy
| | - G Fattovich
- Division of Gastroenterology and Endoscopy, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.,Department of Medicine, University of Verona, Verona, Italy
| | - M Guido
- Department of Medicine, University of Padua, Padua, Italy
| | - E Bugianesi
- Division of Gastroenterology and Hepatology, Department of Medical Sciences, University of Torino, Torino, Italy
| | - A Biasiolo
- Department of Medicine, University of Padua, Padua, Italy
| | - D Ieluzzi
- Division of Gastroenterology and Endoscopy, Azienda Ospedaliera Universitaria Integrata, Verona, Italy
| | | | | | - C Merkel
- Department of Medicine, University of Padua, Padua, Italy
| | - A Gatta
- Department of Medicine, University of Padua, Padua, Italy
| | - F Negro
- Division of Clinical Pathology, University Hospitals of Geneva, Geneva, Switzerland.,Division Gastroenterology and Hepatology, University Hospitals of Geneva, Geneva, Switzerland
| | - P Pontisso
- Department of Medicine, University of Padua, Padua, Italy
| |
Collapse
|
|
27
|
Uraki S, Tameda M, Sugimoto K, Shiraki K, Takei Y, Nobori T, Ito M. Substitution in Amino Acid 70 of Hepatitis C Virus Core Protein Changes the Adipokine Profile via Toll-Like Receptor 2/4 Signaling. PLoS One 2015; 10:e0131346. [PMID: 26121241 PMCID: PMC4487891 DOI: 10.1371/journal.pone.0131346] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2015] [Accepted: 06/01/2015] [Indexed: 12/28/2022] Open
Abstract
Background & Aims It has been suggested that amino acid (aa) substitution at position 70 from arginine (70R) to glutamine (70Q) in the genotype 1b hepatitis C virus (HCV) core protein is associated with insulin resistance and worse prognosis. However, the precise mechanism is still unclear. The aim of this study was to investigate the impact of the substitution at position 70 in HCV core protein on adipokine production by murine and human adipocytes. Methods The influence of treatment with HCV core protein (70R or 70Q) on adipokine production by both 3T3-L1 and human adipocytes were examined with real-time PCR and enzyme-linked immunosorbent assay (ELISA), and triglyceride content was also analyzed. The effects of toll-like receptor (TLR)2/4 inhibition on IL-6 production by 3T3-L1 induced by HCV core protein were examined. Results IL-6 production was significantly increased and adiponectin production was reduced without a change in triglyceride content by treatment with 70Q compared to 70R core protein in both murine and human adipocytes. IL-6 induction of 3T3-L1 cells treated by 70Q HCV core protein was significantly inhibited with anti-TLR2 antibody by 42%, and by TLR4 inhibitor by 40%. Conclusions Our study suggests that extracellular HCV core protein with substitution at position 70 enhanced IL-6 production and reduced adiponectin production from visceral adipose tissue, which can cause insulin resistance, hepatic steatosis, and ultimately development of HCC.
Collapse
Affiliation(s)
- Satoko Uraki
- First Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan
| | - Masahiko Tameda
- First Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan
- Department of Molecular and Laboratory Medicine, Mie University School of Medicine, 2–174 Edobashi, Tsu, Mie, 514–8507, Japan
- Department of Gastroenterology and Hepatology, Mie University School of Medicine, Tsu, Japan
| | - Kazushi Sugimoto
- First Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan
- Department of Molecular and Laboratory Medicine, Mie University School of Medicine, 2–174 Edobashi, Tsu, Mie, 514–8507, Japan
- Department of Gastroenterology and Hepatology, Mie University School of Medicine, Tsu, Japan
- * E-mail:
| | - Katsuya Shiraki
- First Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan
- Department of Gastroenterology and Hepatology, Mie University School of Medicine, Tsu, Japan
| | - Yoshiyuki Takei
- Department of Gastroenterology and Hepatology, Mie University School of Medicine, Tsu, Japan
| | - Tsutomu Nobori
- Department of Molecular and Laboratory Medicine, Mie University School of Medicine, 2–174 Edobashi, Tsu, Mie, 514–8507, Japan
| | - Masaaki Ito
- First Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan
| |
Collapse
|
|
28
|
Petta S, Vanni E, Bugianesi E, Rosso C, Cabibi D, Cammà C, Di Marco V, Eslam M, Grimaudo S, Macaluso FS, McLeod D, Pipitone RM, Abate ML, Smedile A, George J, Craxì A. PNPLA3 rs738409 I748M is associated with steatohepatitis in 434 non-obese subjects with hepatitis C. Aliment Pharmacol Ther 2015; 41:939-948. [PMID: 25801076 DOI: 10.1111/apt.13169] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2014] [Revised: 01/28/2015] [Accepted: 03/02/2015] [Indexed: 12/18/2022]
Abstract
BACKGROUND The PNPLA3/Adiponutrin rs738409 C/G single nucleotide polymorphism is associated with the severity of steatosis, steatohepatitis and fibrosis in patients with non-alcoholic fatty liver disease, as well as the severity of steatosis and fibrosis in patients with chronic hepatitis C (CHC). AIM To test in genotype 1(G1)-CHC patients, the putative association between the PNPLA3 variant and histological features of steatohepatitis, as well as their impact on the severity of fibrosis. METHODS Four hundred and thirty-four consecutively biopsied Caucasian G1-CHC patients were genotyped for PNPLA3 rs738409, its effect evaluated by using an additive model. Histological features of steatohepatitis in CHC were assessed using the Bedossa classification. Hepatic expression of PNPLA3 mRNA was evaluated in 63 patients. RESULTS The prevalence of steatohepatitis increased from 16.5% in patients with PNPLA3 CC, to 23.2% in CG and 29.2% in the GG genotype (P = 0.02). By multiple logistic regression, PNPLA3 genotype (OR 1.54, 95% CI 1.03-2.30, P = 0.03), together with age (OR 1.03, 95% CI 1.00-1.05, P = 0.02), BMI ≥ 30 (OR 2.06, 95% CI 1.04-4.10, P = 0.03) and homoeostasis model assessment (HOMA, OR 1.18, 95% CI 1.04-1.32, P = 0.006) were independently linked to steatohepatitis. When stratifying for obesity, PNPLA3 was associated with NASH in non-obese patients only (12.0% in CC vs. 18.3% in CG vs. 27.3% in GG, P = 0.01), including after correction for metabolic confounders (OR 2.06, 95% CI 1.26-3.36, P = 0.004). We showed an independent association between steatohepatitis (OR 2.05, 95% CI 1.05-4.02, P = 0.003) and severe fibrosis. Higher liver PNPLA3 mRNA was associated both with the severity of steatosis (adjusted P = 0.03) and steatohepatitis after adjusting for gender, age, BMI and HOMA (P = 0.002). CONCLUSION In patients with genotype 1 hepatitis C, the PNPLA3 G variant is associated with a higher risk of steatosis severity and steatohepatitis, particularly among non-obese subjects.
Collapse
Affiliation(s)
- S Petta
- Section of Gastroenterology, Di.Bi.M.I.S., University of Palermo, Palermo, Italy
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
29
|
Cauchy F, Belghiti J. A clinical perspective of the link between metabolic syndrome and hepatocellular carcinoma. J Hepatocell Carcinoma 2015; 2:19-27. [PMID: 27508191 PMCID: PMC4918280 DOI: 10.2147/jhc.s44521] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Metabolic syndrome (MS), which is defined as a constellation of clinico-biological features closely related to insulin-resistance has reached epidemic levels in Western Europe and Northern America. Non-alcoholic fatty liver disease (NAFLD) represents the hepatic manifestation of MS. As its incidence parallels that of MS, NAFLD is currently becoming one of the most frequent chronic liver diseases in Western countries. On one hand, MS favors the development of hepatocellular carcinoma (HCC) either through NAFLD liver parenchymal alterations (steatosis; steatohepatitis; fibrosis), or in the absence of significant underlying liver parenchyma changes. In this setting, HCC are often diagnosed incidentally, tend to be larger than in patients developing HCC on cirrhosis and therefore frequently require major liver resections. On the other hand, MS patients are at increased risk of both liver-related postoperative complications and increased cardiorespiratory events leading to non-negligible mortality rates following liver surgery. These deleterious effects seem to be related to the existence of impaired liver function even in the absence of severe fibrosis but also higher cardiorespiratory sensitivity in a setting of MS/NAFLD. Hence, specific medical and surgical improvements in the perioperative management of these patients are required. These include complete preoperative cardiorespiratory work-up and the wide use of preoperative liver volume modulation. Finally, the long-term prognosis after curative surgery for MS-related HCC does not seem to be worse than for other HCC occurring on classical chronic liver diseases. This is probably related to less aggressive tumor behavior with lower micro vascular invasion and decreased rates of poorly differentiated lesions. In this setting, several medical therapies including metformin could be of value in the prevention of both occurrence and recurrence of HCC.
Collapse
Affiliation(s)
- François Cauchy
- HPB and Liver Transplantation Unit, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France
| | - Jacques Belghiti
- HPB and Liver Transplantation Unit, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France
| |
Collapse
|
|
30
|
Abenavoli L, Masarone M, Peta V, Milic N, Kobyliak N, Rouabhia S, Persico M. Insulin resistance and liver steatosis in chronic hepatitis C infection genotype 3. World J Gastroenterol 2014; 20:15233-15240. [PMID: 25386071 PMCID: PMC4223256 DOI: 10.3748/wjg.v20.i41.15233] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2014] [Revised: 04/28/2014] [Accepted: 06/13/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infection is a common chronic liver disease worldwide. Non-alcoholic fatty liver disease and insulin resistance (IR) are the major determinants of fibrosis progression and response to antiviral therapy. The pathogenetic link between IR and chronic HCV infection is complex, and is associated with HCV genotype. Liver steatosis is the most common in the patients infected with genotype 3 virus, possibly due to direct effects of genotype 3 viral proteins. To the contrary, hepatic steatosis in the patients infected with other genotypes is thought to be mostly due to the changes in host metabolism, involving IR. In HCV genotype 3, liver steatosis correlates with viral load, reverts after reaching the sustained virologic response and reoccurs in the relapsers. A therapeutic strategy to improve IR and liver steatosis and subsequently the response to antiviral treatment in these patients is warranted.
Collapse
|
|
31
|
Negro F. Facts and fictions of HCV and comorbidities: steatosis, diabetes mellitus, and cardiovascular diseases. J Hepatol 2014; 61:S69-78. [PMID: 25443347 DOI: 10.1016/j.jhep.2014.08.003] [Citation(s) in RCA: 121] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2014] [Revised: 07/16/2014] [Accepted: 08/01/2014] [Indexed: 12/16/2022]
Abstract
The hepatitis C virus (HCV) is a major cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma worldwide. A significant portion of the morbidity and mortality associated with HCV is a consequence of numerous HCV-associated comorbidities. Type 2 diabetes and atherosclerosis, two known complications of the metabolic syndrome, are noteworthy, because HCV has been suggested to play a role in their pathogenesis. In addition, HCV also causes steatosis, which may increase the risk of cardiovascular events. This review summarizes the evidence supporting the association between HCV and steatosis, insulin resistance/type 2 diabetes and cardiovascular morbidity and mortality. Their diagnostic, prognostic and management aspects are discussed.
Collapse
Affiliation(s)
- Francesco Negro
- Divisions of Gastroenterology and Hepatology, University Hospitals, Geneva, Switzerland; Division of Clinical Pathology, University Hospitals, Geneva, Switzerland.
| |
Collapse
|
|
32
|
Sato M, Kato N, Tateishi R, Muroyama R, Kowatari N, Li W, Goto K, Otsuka M, Shiina S, Yoshida H, Omata M, Koike K. Impact of PNPLA3 polymorphisms on the development of hepatocellular carcinoma in patients with chronic hepatitis C virus infection. Hepatol Res 2014; 44:E137-E144. [PMID: 24125181 DOI: 10.1111/hepr.12258] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2013] [Revised: 10/02/2013] [Accepted: 10/04/2013] [Indexed: 02/06/2023]
Abstract
AIM The PNPLA3 rs738409 C>G polymorphism (encoding for I148M) has recently been identified as a susceptibility factor for steatosis-mediated liver damage. We evaluated the influence of this polymorphism on hepatocarcinogenesis in patients with chronic hepatitis C (CHC) virus infection. METHODS We genotyped the rs738409 single nucleotide polymorphism in 358 hepatitis C-associated hepatocellular carcinoma (HCC) patients and correlated the age at onset of HCC and the interval between hepatitis C virus (HCV) infection and the development of HCC in patients with each genotype. RESULTS The frequencies of CC, CG and GG genotypes were 27.9% (100/358), 49.2% (176/358) and 22.9% (82/358), respectively, and were in Hardy-Weinberg equilibrium. The median age at onset of HCC for the GG genotype was significantly younger compared to for non-GG genotypes (67.81 vs 69.87 years, P < 0.001), and the median interval between HCV infection and the development of HCC was significantly shorter in patients with the GG genotype (39.96 vs 40.85 years, P = 0.008). PNPLA3 GG genotype was also associated with a higher aspartate aminotransferase level (69.5 vs 59.0 IU/L, P = 0.02), lower prothrombin time (73.0% vs 78.0%, P = 0.008) and a higher prevalence of histological steatosis (40.0% vs. 22.2%, P = 0.01) at the time of HCC onset. CONCLUSION The PNPLA3 genotype GG may be associated with accelerated hepatocarcinogenesis in CHC patients through increased steatosis in the liver.
Collapse
Affiliation(s)
- Masaya Sato
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
33
|
Treeprasertsuk S, Komolmit P, Tanyaowalak W. Adipokines, insulin resistance, hepatic steatosis, and necroinflammation in patients with chronic viral hepatitis. ASIAN BIOMED 2014; 8:557-564. [DOI: 10.5372/1905-7415.0804.327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2025]
Abstract
Abstract
Background: Hypoadiponectinemia and hyperleptinemia, and reductions in the ratio of adiponectin to leptin (A/L ratio) are associated with the development of hepatic necroinflammation in nonalcoholic fatty liver, but the association of the adipokines with hepatic steatosis in chronic viral hepatitis is unclear.
Objective: To investigate the relationship between serum A/L ratio, insulin resistance, degree of hepatic steatosis, and necroinflammation in patients with chronic viral hepatitis.
Methods: We measured serum adiponectin, leptin, and resistin levels, insulin resistance, and analyzed the association between liver histopathology and the level of the adipokines in 44 patients with chronic viral hepatitis before they started treatment.
Results: We found that insulin resistance, leptin, and resistin levels tended to increase in the group with a greater degree of hepatic steatosis and necroinflammation, but that the increase was not significant. The adiponectin/leptin ratio (A/L ratio) in a group with a low degree of hepatic steatosis was significantly higher than it was in the group with a high degree of hepatic steatosis (3.1 ± 3.1 vs 1.2 ± 0.8; P = 0.008). The A/L ratio in a group with low histological activity index (HAI) scores was significantly higher than in the group with high HAI scores (3.7 ± 3.4 vs 1.1 ± 1.1; P = 0.006). Abdominal obesity was the only variable that showed a significant association with the HAI score (P = 0.03).
Conclusion: The serum A/L ratio in patients with chronic viral hepatitis showed a significant inverse association with their degree of hepatic steatosis and necroinflammation.
Collapse
Affiliation(s)
- Sombat Treeprasertsuk
- MD, PhD, Division of Gastroenterology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
| | - Piyawat Komolmit
- Division of Gastroenterology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
| | | |
Collapse
|
|
34
|
Quantification of portal-bridging fibrosis area more accurately reflects fibrosis stage and liver stiffness than whole fibrosis or perisinusoidal fibrosis areas in chronic hepatitis C. Mod Pathol 2014; 27:1035-45. [PMID: 24390214 DOI: 10.1038/modpathol.2013.225] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2013] [Accepted: 10/13/2013] [Indexed: 12/11/2022]
Abstract
Morphometry provides an objective evaluation of fibrosis in liver diseases. We developed an image analysis algorithm using automated thresholding and segmentation to separately quantify the areas and the fractal dimensions of portal-bridging fibrosis and perisinusoidal fibrosis in chronic hepatitis C liver biopsies. We studied 427 digitized liver biopsies and compared the automated measures of the different fibrosis compartments with (1) the Metavir F (fibrosis) and A (activity) histological scores, (2) the digitally assessed area of steatosis, and (3) the liver stiffness measured by elastography (Fibroscan). The perisinusoidal fibrosis area was higher than that of portal fibrosis in stages ≤F2; it reached its highest value in F2 stage and stabilized thereafter. The F3 stage was characterized by equal proportions of portal-bridging and perisinusoidal fibrosis, whereas portal-bridging area was predominant in cirrhosis. Measurement of portal-bridging fibrosis showed highly significantly different values between contiguous F stages; the ratio of portal-bridging fibrosis/perisinusoidal fibrosis displayed less overlap between Metavir stages than did the whole fibrosis area values. Fractal dimension showed that portal-bridging fibrosis tended to display a homogeneous surface-like spatial organization, whereas perisinusoidal fibrosis appeared more heterogeneous according to stage and curvilinear. The portal-bridging fibrosis area was low in cases with low Metavir activity and little steatosis, and became predominant with increasing activity and steatosis. Using stepwise multiple linear regression analysis, the liver stiffness was independently correlated to the portal-bridging fibrosis area (first step, P<0.001), the steatosis area (second step, P<0.001), and the Metavir A grade (third step, P=0.001), but not to the perisinusoidal fibrosis area. Automated quantification in a large cohort of chronic hepatitis C showed that perisinusoidal fibrosis progressively grew in early fibrosis stages but did not increase in septal or cirrhotic stages and that the portal-bridging fibrosis area appeared as a more accurate tool to assess fibrosis progression than the whole fibrosis area.
Collapse
|
|
35
|
Lonardo A, Adinolfi LE, Restivo L, Ballestri S, Romagnoli D, Baldelli E, Nascimbeni F, Loria P. Pathogenesis and significance of hepatitis C virus steatosis: an update on survival strategy of a successful pathogen. World J Gastroenterol 2014; 20:7089-7103. [PMID: 24966582 PMCID: PMC4064057 DOI: 10.3748/wjg.v20.i23.7089] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2013] [Revised: 01/17/2014] [Accepted: 04/01/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) is a successful pathogen on the grounds that it exploits its host's metabolism to build up viral particles; moreover it favours its own survival by inducing chronic disease and the development of specific anatomic changes in the infected organ. Steatosis, therefore, is associated with HCV infection by necessity rather than by chance alone. Approximately 6% of HCV patients have steatohepatitis. Interestingly, HCV steatosis occurs in the setting of multiple metabolic abnormalities (hyperuricemia, reversible hypocholesterolemia, insulin resistance, arterial hypertension and expansion of visceral adipose tissue) collectively referred to as "hepatitis C-associated dysmetabolic syndrome" (HCADS). General, nonalcoholic fatty liver disease (NAFLD)-like, mechanisms of steatogenesis (including increased availability of lipogenic substrates and de novo lipogenesis; decreased oxidation of fatty substrates and export of fatty substrates) are shared by all HCV genotypes. However, genotype 3 seemingly amplifies such steatogenic molecular mechanisms reported to occur in NAFLD via more profound changes in microsomal triglyceride transfer protein; peroxisome proliferator-activated receptor alpha; sterol regulatory element-binding proteins and phosphatase and tensin homologue. HCV steatosis has a remarkable clinical impact in as much as it is an acknowledged risk factor for accelerated fibrogenesis; for impaired treatment response to interferon and ribavirin; and development of hepatocellular carcinoma. Recent data, moreover, suggest that HCV-steatosis contributes to premature atherogenesis via both direct and indirect mechanisms. In conclusion, HCV steatosis fulfills all expected requirements necessary to perpetuate the HCV life cycle. A better understanding of the physiology of HCADS will likely result in a more successful handling of disease with improved antiviral success rates.
Collapse
|
|
36
|
Fonseca AL, Cha CH. Hepatocellular carcinoma: a comprehensive overview of surgical therapy. J Surg Oncol 2014; 110:712-9. [PMID: 24894746 DOI: 10.1002/jso.23673] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2014] [Accepted: 05/13/2014] [Indexed: 12/21/2022]
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, with a rising incidence in the United States. The increase in medical and locally ablative therapies have improved prognosis, however surgery, either liver resection or transplantation, remains the mainstay of therapy. An increased understanding of liver anatomy, improved imaging modalities and refinements of surgical technique have all led to improved outcomes after surgery. Both resection and transplantation may be used in a complementary manner. Resection remains the treatment of choice for HCC when feasible. Liver transplantation, which removes both the tumor and the underlying diseased liver offers excellent outcomes in patients that meet the Milan criteria. While both these modalities have relatively well defined roles, the treatment of these patients must be tailored individually, using a multidisciplinary approach, to maximize survival, quality of life and allocation of scarce organs.
Collapse
Affiliation(s)
- Annabelle L Fonseca
- Department of Surgery, Yale University School of Medicine, New Haven, Connecticut
| | | |
Collapse
|
|
37
|
Cauchy F, Fuks D, Zarzavadjian Le Bian A, Belghiti J, Costi R. Metabolic syndrome and non-alcoholic fatty liver disease in liver surgery: The new scourges? World J Hepatol 2014; 6:306-14. [PMID: 24868324 PMCID: PMC4033288 DOI: 10.4254/wjh.v6.i5.306] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2013] [Revised: 01/01/2014] [Accepted: 01/17/2014] [Indexed: 02/06/2023] Open
Abstract
The aim of this topic highlight is to review relevant evidence regarding the influence of the metabolic syndrome (MS) and its associated liver manifestation, non-alcoholic fatty liver disease (NAFLD), on the development of liver cancer as well as their impact on the results of major liver surgery. MS and NAFLD, whose incidences are significantly increasing in Western countries, are leading to a changing profile of the patients undergoing liver surgery. A MEDLINE search was performed for relevant articles using the key words "metabolic syndrome", "liver resection", "liver transplantation", "non alcoholic fatty liver disease", "non-alcoholic steatohepatitis" and "liver cancer". On one hand, the MS favors the development of primary liver malignancies (hepatocellular carcinoma and cholangiocarcinoma) either through NAFLD liver parenchymal alterations (steatosis, steatohepatitis, fibrosis) or in the absence of significant underlying liver parenchyma changes. Also, the existence of NAFLD may have a specific impact on colorectal liver metastases recurrence. On the other hand, the postoperative period following partial liver resection and liver transplantation is at increased risk of both postoperative complications and mortality. These deleterious effects seem to be related to the existence of liver specific complications but also higher cardio-vascular sensitivity in a setting of MS/NAFLD. Finally, the long-term prognosis after curative surgery joins that of patients operated on with other types of underlying liver diseases. An increased rate of patients with MS/NAFLD referred to hepatobiliary units has to be expected. The higher operative risk observed in this subset of patients will require specific improvements in their perioperative management.
Collapse
Affiliation(s)
- François Cauchy
- François Cauchy, David Fuks, Jacques Belghiti, Service de Chirurgie Hépato-Bilio-Pancréatique et Transplantation Hépatique, Hôpital Beaujon, Assistance Publique - Hôpitaux de Paris, 92110 Clichy, France
| | - David Fuks
- François Cauchy, David Fuks, Jacques Belghiti, Service de Chirurgie Hépato-Bilio-Pancréatique et Transplantation Hépatique, Hôpital Beaujon, Assistance Publique - Hôpitaux de Paris, 92110 Clichy, France
| | - Alban Zarzavadjian Le Bian
- François Cauchy, David Fuks, Jacques Belghiti, Service de Chirurgie Hépato-Bilio-Pancréatique et Transplantation Hépatique, Hôpital Beaujon, Assistance Publique - Hôpitaux de Paris, 92110 Clichy, France
| | - Jacques Belghiti
- François Cauchy, David Fuks, Jacques Belghiti, Service de Chirurgie Hépato-Bilio-Pancréatique et Transplantation Hépatique, Hôpital Beaujon, Assistance Publique - Hôpitaux de Paris, 92110 Clichy, France
| | - Renato Costi
- François Cauchy, David Fuks, Jacques Belghiti, Service de Chirurgie Hépato-Bilio-Pancréatique et Transplantation Hépatique, Hôpital Beaujon, Assistance Publique - Hôpitaux de Paris, 92110 Clichy, France
| |
Collapse
|
|
38
|
Pais R, Rusu E, Ratziu V. The impact of obesity and metabolic syndrome on chronic hepatitis B and drug-induced liver disease. Clin Liver Dis 2014; 18:165-78. [PMID: 24274872 DOI: 10.1016/j.cld.2013.09.015] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Steatosis and insulin resistance (IR) are no more frequent in chronic hepatitis B (CHB) than in the general population. Although experimental studies suggest that the HBx protein induces liver fat, human studies have shown that steatosis and IR are related to coexistent metabolic risk factors, thus epidemiologically linked rather than virally induced. Diabetes and obesity are associated with advanced fibrosis and increased risk of hepatocellular carcinoma in CHB. Despite abundant experimental data showing that fatty liver is more susceptible to liver injury, drug-induced liver disease seems no more frequent in NAFLD patients, except, possibly, a higher incidence but not severity of acetaminophen hepatotoxicity.
Collapse
Affiliation(s)
- Raluca Pais
- Department of Hepatogastroenterology, Université Pierre et Marie Curie, Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Inserm UMR_S 938, Paris 75013, France
| | | | | |
Collapse
|
|
39
|
Industrial, not fruit fructose intake is associated with the severity of liver fibrosis in genotype 1 chronic hepatitis C patients. J Hepatol 2013; 59:1169-76. [PMID: 23933265 DOI: 10.1016/j.jhep.2013.07.037] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2013] [Revised: 07/08/2013] [Accepted: 07/15/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Unhealthy food intake, specifically fructose, has been associated with metabolic alterations and with the severity of liver fibrosis in patients with non-alcoholic fatty liver disease. In a cohort of patients with genotype 1 chronic hepatitis C (G1 CHC), we tested the association of fructose intake with the severity of liver histology. METHODS Anthropometric and metabolic factors, including waist circumference (WC), waist-to-hip ratio (WHR), dorso-cervical lipohypertrophy and HOMA were assessed in 147 consecutive biopsy-proven G1 CHC patients. Food intake, namely industrial and fruit fructose, was investigated by a three-day structured interview and a computed database. All biopsies were scored by an experienced pathologist for staging and grading (Scheuer classification), and graded for steatosis, which was considered moderate-severe if ≥ 20%. Features of non-alcoholic steatohepatitis (NASH) in CHC were also assessed (Bedossa classification). RESULTS Mean daily intake of total, industrial and fruit fructose was 18.0±8.7g, 6.0±4.7g, and 11.9±7.2g, respectively. Intake of industrial, not fruit fructose, was independently associated with higher WHR (p=0.02) and hypercaloric diet (p<0.001). CHC patients with severe liver fibrosis (⩾F3) reported a significantly higher intake of total (20.8±10.2 vs. 17.2±8.1g/day; p=0.04) and industrial fructose (7.8±6.0 vs. 5.5±4.2; p=0.01), not fruit fructose (12.9±8.0 vs. 11.6±7.0; p=0.34). Multivariate logistic regression analysis showed that older age (OR 1.048, 95% CI 1.004-1.094, p=0.03), severe necroinflammatory activity (OR 3.325, 95% CI 1.347-8.209, p=0.009), moderate-severe steatosis (OR 2.421, 95% CI 1.017-6.415, p=0.04), and industrial fructose intake (OR 1.147, 95% CI 1.047-1.257, p=0.003) were independently linked to severe fibrosis. No association was found between fructose intake and liver necroinflammatory activity, steatosis, and the features of NASH. CONCLUSIONS The daily intake of industrial, not fruit fructose is a risk factor for metabolic alterations and the severity of liver fibrosis in patients with G1 CHC.
Collapse
|
|
40
|
Li Vecchi V, Giannitrapani L, Di Carlo P, Mazzola G, Colletti P, La Spada E, Vizzini G, Montalto G, Soresi M. Non-invasive assessment of liver steatosis and fibrosis in HIV/HCV- and HCV- infected patients. Ann Hepatol 2013; 12:740-748. [PMID: 24018492 DOI: 10.1016/s1665-2681(19)31315-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/15/2023]
Abstract
BACKGROUND Conflicting data have been reported on the prevalence of liver steatosis, its risk factors and its relationship with fibrosis in patients with human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infection or with HCV mono-infection. AIM The study aims were to assess steatosis prevalence and its risk factors in both HCV groups. We also evaluated whether steatosis was linked with advanced fibrosis. Sixty-eight HIV/HCV co-infected and 69 HCV mono-infected patients were consecutively enrolled. They underwent liver ultrasonography and transient elastography. Bright liver echo-pattern was used to diagnose steatosis; advanced fibrosis was defined as liver stiffness ≥ 9.5 kPa and FIB-4 values ≥ 3.25. The optimal stiffness cut-off according to FIB-4 ≥ 3.25 was evaluated by ROC analysis. RESULTS No significant difference was found in steatosis-prevalence between mono- and co-infected patients (46.3 vs. 51.4%). Steatosis was associated with triglycerides and impaired fasting glucose/diabetes in HCV mono-infected, with lipodystrophy, metabolic syndrome, total-cholesterol and triglycerides in co-infected patients. Stiffness ≥ 9.5 was significantly more frequent in co-infection (P < 0.003). Advanced fibrosis wasn't significantly associated with steatosis. The area under the ROC curve was 0.85 (95% CI 0.79-0.9). On multivariate analysis steatosis was associated with triglycerides in both HCV mono- and co-infected groups (P < 0.02; P < 0.03). CONCLUSION Although steatosis was common in both HCV mono- and co-infected patients, it was not linked with advanced fibrosis. Triglycerides were independent predictors of steatosis in either of the HCV-groups. Dietary interventions and lifestyle changes should be proposed to prevent metabolic risk factors.
Collapse
Affiliation(s)
- Valentina Li Vecchi
- Biomedical Department of Internal Medicine and Specialties, University of Palermo, Via del Vespro 141, 90127 Palermo, Italy
| | | | | | | | | | | | | | | | | |
Collapse
|
|
41
|
Tosello-Trampont AC, Landes SG, Nguyen V, Novobrantseva TI, Hahn YS. Kuppfer cells trigger nonalcoholic steatohepatitis development in diet-induced mouse model through tumor necrosis factor-α production. J Biol Chem 2012; 287:40161-72. [PMID: 23066023 DOI: 10.1074/jbc.m112.417014] [Citation(s) in RCA: 341] [Impact Index Per Article: 26.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND The mechanisms triggering nonalcoholic steatohepatitis (NASH) remain poorly defined. RESULTS Kupffer cells are the first responding cells to hepatocyte injuries, leading to TNFα production, chemokine induction, and monocyte recruitment. The silencing of TNFα in myeloid cells reduces NASH progression. CONCLUSION Increase of TNFα-producing Kupffer cells is crucial for triggering NASH via monocyte recruitment. SIGNIFICANCE Myeloid cells-targeted silencing of TNFα might be a tenable therapeutic approach. Nonalcoholic steatohepatitis (NASH), characterized by lipid deposits within hepatocytes (steatosis), is associated with hepatic injury and inflammation and leads to the development of fibrosis, cirrhosis, and hepatocarcinoma. However, the pathogenic mechanism of NASH is not well understood. To determine the role of distinct innate myeloid subsets in the development of NASH, we examined the contribution of liver resident macrophages (i.e. Kupffer cells) and blood-derived monocytes in triggering liver inflammation and hepatic damage. Employing a murine model of NASH, we discovered a previously unappreciated role for TNFα and Kupffer cells in the initiation and progression of NASH. Sequential depletion of Kupffer cells reduced the incidence of liver injury, steatosis, and proinflammatory monocyte infiltration. Furthermore, our data show a differential contribution of Kupffer cells and blood monocytes during the development of NASH; Kupffer cells increased their production of TNFα, followed by infiltration of CD11b(int)Ly6C(hi) monocytes, 2 and 10 days, respectively, after starting the methionine/choline-deficient (MCD) diet. Importantly, targeted knockdown of TNFα expression in myeloid cells decreased the incidence of NASH development by decreasing steatosis, liver damage, monocyte infiltration, and the production of inflammatory chemokines. Our findings suggest that the increase of TNFα-producing Kupffer cells in the liver is crucial for the early phase of NASH development by promoting blood monocyte infiltration through the production of IP-10 and MCP-1.
Collapse
|
|
42
|
Tosello-Trampont AC, Landes SG, Nguyen V, Novobrantseva TI, Hahn YS. Kuppfer cells trigger nonalcoholic steatohepatitis development in diet-induced mouse model through tumor necrosis factor-α production. J Biol Chem 2012. [PMID: 23066023 DOI: 10.10747/jbc.m112.417014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND The mechanisms triggering nonalcoholic steatohepatitis (NASH) remain poorly defined. RESULTS Kupffer cells are the first responding cells to hepatocyte injuries, leading to TNFα production, chemokine induction, and monocyte recruitment. The silencing of TNFα in myeloid cells reduces NASH progression. CONCLUSION Increase of TNFα-producing Kupffer cells is crucial for triggering NASH via monocyte recruitment. SIGNIFICANCE Myeloid cells-targeted silencing of TNFα might be a tenable therapeutic approach. Nonalcoholic steatohepatitis (NASH), characterized by lipid deposits within hepatocytes (steatosis), is associated with hepatic injury and inflammation and leads to the development of fibrosis, cirrhosis, and hepatocarcinoma. However, the pathogenic mechanism of NASH is not well understood. To determine the role of distinct innate myeloid subsets in the development of NASH, we examined the contribution of liver resident macrophages (i.e. Kupffer cells) and blood-derived monocytes in triggering liver inflammation and hepatic damage. Employing a murine model of NASH, we discovered a previously unappreciated role for TNFα and Kupffer cells in the initiation and progression of NASH. Sequential depletion of Kupffer cells reduced the incidence of liver injury, steatosis, and proinflammatory monocyte infiltration. Furthermore, our data show a differential contribution of Kupffer cells and blood monocytes during the development of NASH; Kupffer cells increased their production of TNFα, followed by infiltration of CD11b(int)Ly6C(hi) monocytes, 2 and 10 days, respectively, after starting the methionine/choline-deficient (MCD) diet. Importantly, targeted knockdown of TNFα expression in myeloid cells decreased the incidence of NASH development by decreasing steatosis, liver damage, monocyte infiltration, and the production of inflammatory chemokines. Our findings suggest that the increase of TNFα-producing Kupffer cells in the liver is crucial for the early phase of NASH development by promoting blood monocyte infiltration through the production of IP-10 and MCP-1.
Collapse
|
|
43
|
Chung WJ. [Chronic hepatitis C and insulin resistance]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2012; 59:268-74. [PMID: 22544023 DOI: 10.4166/kjg.2012.59.4.268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Insulin resistance is frequently associated with chronic liver disease, and the interaction between hepatitis C virus (HCV) infection and insulin resistance is a major public health issue, bound to increase in the near term. Because of their potential synergism on liver disease severity, a better understanding of the clinical consequences of the relationship between HCV infection and insulin resistance is needed. This translates into accelerated liver disease progression, reduced response to anti-viral agents and, in susceptible individuals, increased risk of developing type 2 diabetes. HCV may also cause hepatic steatosis, especially in patients infected with genotype 3, although the clinical impact of viral steatosis is debated. Little is known regarding the effect of anti-diabetic agents on HCV infection, and a possible association between use of exogenous insulin or a sulfonylurea agents and the development of hepatocellular carcinoma has recently been reported. Thus, modified lifestyle and pharmacological modalities are urgently warranted in chronic hepatitis C with metabolic alterations.
Collapse
Affiliation(s)
- Woo Jin Chung
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea.
| |
Collapse
|
|
44
|
Ratziu V, Cadranel JF, Serfaty L, Denis J, Renou C, Delassalle P, Bernhardt C, Perlemuter G. A survey of patterns of practice and perception of NAFLD in a large sample of practicing gastroenterologists in France. J Hepatol 2012; 57:376-83. [PMID: 22521354 DOI: 10.1016/j.jhep.2012.03.019] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2011] [Revised: 03/18/2012] [Accepted: 03/20/2012] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Most studies on non-alcoholic fatty liver disease (NAFLD) originate from tertiary care centers with an academic interest. How this emerging entity is accepted and managed by a wider body of gastroenterologists is unknown, despite significant implications for the diagnosis of at-risk subjects and the utilization of healthcare resources. METHODS We conducted a survey among 352 French, board-certified gastroenterologists from a large variety of practices to understand the clinical burden, perceived severity, and management patterns of NAFLD. RESULTS Half of participants saw >30 new cases (equal to HCV) of NAFLD and 40% >5 new cases of NASH-cirrhosis yearly. Only 20% of patients were referred by endocrinologists; conversely, gastroenterologists overwhelmingly referred NAFLD patients for assessment of metabolic co-morbidities. In patients with metabolic risk factors, a majority of physicians considered the diagnosis of NAFLD, even if other liver diseases co-existed. The diagnosis heavily relies on aminotransferases, hence patients with normal ALT are usually not diagnosed. Liver biopsy is performed for fibrosis staging but not for the diagnosis/grading of steatohepatitis, and mainly decided based on non-invasive fibrosis procedures. Pharmacological treatment is used despite a lack of clear evidence of efficacy. Physicians monitor patients themselves, usually twice a year. CONCLUSIONS NAFLD is recognized and accepted as a disease in itself with potentially severe outcomes. Most at-risk patients are currently missed because of non-referral by endocrinologists and no exploration of those with normal aminotransferases. The medical need for the diagnosis and treatment of NAFLD is real in the community of gastroenterologists at large.
Collapse
Affiliation(s)
- Vlad Ratziu
- Université Pierre et Marie Curie, Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, INSERM UMR_S 938, France.
| | | | | | | | | | | | | | | |
Collapse
|
|
45
|
Reddy SK, Steel JL, Chen HW, DeMateo DJ, Cardinal J, Behari J, Humar A, Marsh JW, Geller DA, Tsung A. Outcomes of curative treatment for hepatocellular cancer in nonalcoholic steatohepatitis versus hepatitis C and alcoholic liver disease. Hepatology 2012; 55:1809-19. [PMID: 22183968 DOI: 10.1002/hep.25536] [Citation(s) in RCA: 184] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2011] [Accepted: 12/06/2011] [Indexed: 12/11/2022]
Abstract
UNLABELLED Concomitant increasing incidences of hepatocellular carcinoma (HCC) and nonalcoholic steatohepatitis (NASH) suggest that a substantial proportion of HCC arises as a result of hepatocellular injury from NASH. The aim of this study was to determine differences in severity of liver dysfunction at HCC diagnosis and long-term survival outcomes between patients undergoing curative therapy for HCC in the background of NASH compared to hepatitis C virus (HCV) and/or alcoholic liver disease (ALD). Patient demographics and comorbidities, clinicopathologic data, and long-term outcomes among patients who underwent liver transplantation, hepatic resection, or radiofrequency ablation for HCC were reviewed. From 2000 to 2010, 303 patients underwent curative treatment of HCC; 52 (17.2%) and 162 (53.5%) patients had NASH and HCV and/or alcoholic liver disease. At HCC diagnosis, NASH patients were older (median age 65 versus 58 years), were more often female (48.1% versus 16.7%), more often had the metabolic syndrome (45.1% versus 14.8%), and had lower model for end-stage liver disease scores (median 9 versus 10) (all P < 0.05). NASH patients were less likely to have hepatic bridging fibrosis or cirrhosis (73.1% versus 93.8%; P < 0.001). After a median follow-up of 50 months after curative treatment, the most frequent cause of death was liver failure. Though there were no differences in recurrence-free survival after curative therapy (median, 60 versus 56 months; P = 0.303), NASH patients had longer overall survival (OS) (median not reached versus 52 months; P = 0.009) independent of other clinicopathologic factors and type of curative treatment. CONCLUSION Patients with HCC in the setting of NASH have less severe liver dysfunction at HCC diagnosis and better OS after curative treatment compared to counterparts with HCV and/or alcoholic liver disease.
Collapse
Affiliation(s)
- Srinevas K Reddy
- Departments of Surgery, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
46
|
Cauchy F, Fuks D, Belghiti J. HCC: current surgical treatment concepts. Langenbecks Arch Surg 2012; 397:681-95. [DOI: 10.1007/s00423-012-0911-2] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2012] [Accepted: 01/17/2012] [Indexed: 12/28/2022]
|
|
47
|
Graft fibrosis and recipient survival in postorthotopic liver transplant nonalcoholic fatty liver disease. EGYPTIAN LIVER JOURNAL 2012. [DOI: 10.1097/01.elx.0000407755.75559.9f] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
|
|
48
|
Rakoski MO, Brown MB, Fontana RJ, Bonkovsky HL, Brunt EM, Goodman ZD, Lok AS, Omary MB. Mallory-Denk bodies are associated with outcomes and histologic features in patients with chronic hepatitis C. Clin Gastroenterol Hepatol 2011; 9:902-909.e1. [PMID: 21782771 PMCID: PMC3400531 DOI: 10.1016/j.cgh.2011.07.006] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2011] [Revised: 06/29/2011] [Accepted: 07/13/2011] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Mallory-Denk bodies (MDBs) are inclusions found in hepatocytes of patients with chronic liver diseases. Their clinical significance and prognostic value are not understood. METHODS We performed cross-sectional and longitudinal analyses of patients with chronic hepatitis C (CHC) enrolled in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial to identify clinical features associated with MDBs and changes in MDBs over time. Biopsy specimens were obtained at baseline and 1.5 and 3.5 years after patients were assigned to groups for the HALT-C trial; and patients were followed up to assess clinical and histologic outcomes. RESULTS Of biopsy samples collected from 1050 patients, MDBs were present in 15%. They were associated with insulin resistance and laboratory and histologic markers of advanced liver disease (higher levels of periportal fibrosis, pericellular fibrosis, steatosis, and inflammation). After adjusting for disease severity (the ratio of aspartate aminotransferase to alanine aminotransferase, albumin, platelets, fibrosis, steatosis), the presence of MDBs was associated with histologic progression (odds ratio, 1.97; P = .04). Of the 844 patients from whom serial biopsy samples were collected, 61 (7.2%) developed MDBs (MDB gain) and 101 (12.0%) lost MDBs (MDB loss). The presence or absence of diabetes mellitus was associated with MDB gain (P = .006) or loss (P = .024), respectively. Development of MDBs was associated with decompensation (adjusted hazard ratio, 2.81; P < .001) and histologic signs of progression (adjusted odds ratio, 4.02; P = .004). CONCLUSIONS The presence of MDBs in liver biopsy samples from patients with CHC is associated independently with fibrosis progression. Gain of MDBs over time is associated with decompensation and progression to cirrhosis; and occurs most frequently among diabetic patients. MDBs might be used as prognostic factors for patients with CHC.
Collapse
Affiliation(s)
- Mina O Rakoski
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.
| | | | | | | | | | | | | | | |
Collapse
|
|
49
|
Basaranoglu M, Basaranoglu G. Pathophysiology of insulin resistance and steatosis in patients with chronic viral hepatitis. World J Gastroenterol 2011; 17:4055-62. [PMID: 22039318 PMCID: PMC3203355 DOI: 10.3748/wjg.v17.i36.4055] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2011] [Revised: 05/16/2011] [Accepted: 05/23/2011] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis due to any cause leads to cirrhosis and end-stage liver disease. A growing body of literature has also shown that fatty liver due to overweight or obesity is a leading cause of cirrhosis. Due to the obesity epidemic, fatty liver is now a significant problem in clinical practice. Steatosis has an impact on the acceleration of liver damage in patients with chronic hepatitis due to other causes. An association between hepatitis C virus (HCV) infection, steatosis and the onset of insulin resistance has been reported. Insulin resistance is one of the leading factors for severe fibrosis in chronic HCV infections. Moreover, hyperinsulinemia has a deleterious effect on the management of chronic HCV. Response to therapy is increased by decreasing insulin resistance by weight loss or the use of thiazolidenediones or metformin. The underlying mechanisms of this complex interaction are not fully understood. A direct cytopathic effect of HCV has been suggested. The genomic structure of HCV (suggesting that some viral sequences are involved in the intracellular accumulation of triglycerides), lipid metabolism, the molecular links between the HCV core protein and lipid droplets (the core protein of HCV and its transcriptional regulatory function which induce a triglyceride accumulation in hepatocytes) and increased neolipogenesis and inhibited fatty acid degradation in mitochondria have been investigated.
Collapse
|
|
50
|
Fukuda S, Komori A, Itoh M, Mihara Y, Hashimoto S, Bae SK, Nagaoka S, Abiru S, Yatsuhashi H, Ishibashi H. Histological Remission during Corticosteroid Therapy of Overlapping Nonalcoholic Steatohepatitis and Autoimmune Hepatitis: Case Report and Literature Review. Case Rep Gastroenterol 2011; 5:553-7. [PMID: 22110414 PMCID: PMC3219477 DOI: 10.1159/000332152] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
Concurrence of nonalcoholic steatohepatitis (NASH) with autoimmune hepatitis (AIH) is a rare condition that is challenging to diagnosis, due to the relatively high prevalence of autoantibodies in NASH. It is also difficult to determine the most effective treatment as corticosteroids are likely to worsen NASH despite being effective in the treatment of AIH. In this case report, we present a female diagnosed with NASH-AIH overlap with accompanying diabetes mellitus, who successfully achieved normalization of serum alanine aminotransferase levels following prednisolone therapy and weight loss. A follow-up liver biopsy performed 40 months after the initial diagnosis showed only minimal inflammatory infiltrates in the portal area without any NASH histology. Resolution of NASH, in conjunction with a reduction in hepatic fibrosis, might suggest that prednisolone itself does not aggravate steatohepatitis, but rather prevents disease progression. Appropriate immunosuppressive treatment may therefore be an important component of the optimum therapy for NASH-AIH overlap.
Collapse
Affiliation(s)
- Shinichiroh Fukuda
- Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Nagasaki University Graduate School of Biomedical Sciences, Omura, Japan
| | | | | | | | | | | | | | | | | | | |
Collapse
|