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Gleeson D, Bornand R, Brownlee A, Dhaliwal H, Dyson JK, Hails J, Henderson P, Kelly D, Mells GF, Miquel R, Oo YH, Sutton A, Yeoman A, Heneghan MA. British Society of Gastroenterology guidelines for diagnosis and management of autoimmune hepatitis. Gut 2025:gutjnl-2024-333171. [PMID: 40169244 DOI: 10.1136/gutjnl-2024-333171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2024] [Accepted: 10/22/2024] [Indexed: 04/03/2025]
Abstract
Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease which, if untreated, often leads to cirrhosis, liver failure and death. The last British Society of Gastroenterology (BSG) guideline for the management of AIH was published in 2011. Since then, our understanding of AIH has advanced in many areas. This update to the previous guideline was commissioned by the BSG and developed by a multidisciplinary group. The aim of this guideline is to review and summarise the current evidence, in order to inform and guide diagnosis and management of patients with AIH and its variant syndromes. The main focus is on AIH in adults, but the guidelines should also be relevant to older children and adolescents.
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Affiliation(s)
- Dermot Gleeson
- Liver Unit, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
- Division of Clinical Medicine, School of Medicine and Population Science, University of Sheffield, Sheffield, UK
| | | | | | - Harpreet Dhaliwal
- Department of Gastroenterology, Manchester Royal Infirmary, Manchester, UK
| | - Jessica K Dyson
- Liver Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Janeane Hails
- Division of Gastroenterology and Hepatology, Addenbrooke's Hospital, Cambridge, UK
| | - Paul Henderson
- Royal Hospital for Children and Young People, Edinburgh, UK
| | - Deirdre Kelly
- Birmingham Women's & Children's Hospital, Birmingham, UK
- University of Birmingham, Birmingham, UK
| | - George F Mells
- Division of Gastroenterology and Hepatology, Addenbrooke's Hospital, Cambridge, UK
- Academic Department of Medical Genetics, University of Cambridge, Cambridge, UK
| | - Rosa Miquel
- Liver Histopathology Laboratory, Institute of Liver Studies, King's College London, London, UK
| | - Ye H Oo
- Centre for Liver and Gastroenterology research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
- NIHR Biomedical Research Centre, University of Birmingham and University Hospital Birmingham NHS Foundation Trust, Birmingham, UK
- Centre for Rare Diseases, European Reference Network on Hepatological Diseases (ERN-RARE-LIVER) centre, Birmingham, UK
| | - Anthea Sutton
- Sheffield Centre for Health and Related Research, The University of Sheffield, Sheffield, UK
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Peta V, Sandler Y, Deckmyn O, Duroselle O, Vinnitskaya E, Khomeriki S, Noskova K, Poynard T. Diagnostic performance of FibroTest-ActiTest, transient elastography, and the fibrosis-4 index in patients with autoimmune hepatitis using histological reference. World J Hepatol 2025; 17:104534. [DOI: 10.4254/wjh.v17.i3.104534] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Revised: 02/23/2025] [Accepted: 03/06/2025] [Indexed: 03/26/2025] Open
Abstract
BACKGROUND Noninvasive tests are crucial for the management and follow-up of patients with autoimmune hepatitis, but their validation is limited because of insufficient data.
AIM To investigate the diagnostic performance of three fibrosis noninvasive tests [FibroTest, vibration-controlled transient elastography (VCTE), and the fibrosis-4 index (FIB-4) and two activity biomarkers (alanine aminotransferase (ALT) and ActiTest].
METHODS This study enrolled 103 patients for whom liver biopsy, hepatic elastography results, and laboratory markers were available. Diagnostic performance was assessed with receiver operating characteristic (ROC) curves, the Obuchowski measure (OM), and the Bayesian latent class model.
RESULTS FibroTest and VCTE outperformed FIB-4 in cases of significant fibrosis (≥ F2), with areas under the ROC curve of 0.83 [95% confidence interval (CI): 0.73-0.90], 0.86 (95%CI: 0.77-0.92), and 0.71 (95%CI: 0.60-0.80), respectively. The mean (standard error) OM values were 0.92 (0.01), 0.93 (0.01), and 0.88 (0.02) for FibroTest, VCTE, and FIB-4, respectively; FibroTest and VCTE performed comparably, and both were superior to FIB-4 (P = 0.03 and P = 0.005). The areas under the ROC curve values for activity biomarkers were 0.86 (95%CI: 0.76-0.92) for ActiTest and 0.84 (95%CI: 0.73-0.90) for ALT (P = 0.06). The OM values for ActiTest and ALT were 0.92 (0.02) and 0.90 (0.02), respectively (P = 0.005).
CONCLUSION FibroTest and VCTE outperformed FIB-4 according to the OM. FibroTest-ActiTest facilitated the evaluation of both fibrosis and activity.
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Affiliation(s)
| | - Yuliya Sandler
- Department of Hepatology, Center for Diagnostics and Treatment of Liver Diseases, Moscow Clinical Scientific and Practical Center, Moscow 111123, Russia
| | | | | | - Elena Vinnitskaya
- Department of Hepatology, Center for Diagnostics and Treatment of Liver Diseases, Moscow Clinical Scientific and Practical Center, Moscow 111123, Russia
| | - Sergey Khomeriki
- Laboratory of Pathomorphology, Moscow Clinical Scientific and Practical Center, Moscow 111123, Russia
| | - Karina Noskova
- Clinical Diagnostic Laboratory, Moscow Clinical Scientific and Practical Center, Moscow 111123, Russia
| | - Thierry Poynard
- BioPredictive, Paris 75007, France
- Sorbonne Université, INSERM Centre de Recherche Saint-Antoine, Paris 75012, France
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Hernandez R, Garcia-Rodriguez NS, Arriaga MA, Perez R, Bala AA, Leandro AC, Diego VP, Almeida M, Parsons JG, Manusov EG, Galan JA. The hepatocellular model of fatty liver disease: from current imaging diagnostics to innovative proteomics technologies. Front Med (Lausanne) 2025; 12:1513598. [PMID: 40109726 PMCID: PMC11919916 DOI: 10.3389/fmed.2025.1513598] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Accepted: 02/06/2025] [Indexed: 03/22/2025] Open
Abstract
Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a prevalent chronic liver condition characterized by lipid accumulation and inflammation, often progressing to severe liver damage. We aim to review the pathophysiology, diagnostics, and clinical care of MASLD, and review highlights of advances in proteomic technologies. Recent advances in proteomics technologies have improved the identification of novel biomarkers and therapeutic targets, offering insight into the molecular mechanisms underlying MASLD progression. We focus on the application of mass spectrometry-based proteomics including single cell proteomics, proteogenomics, extracellular vesicle (EV-omics), and exposomics for biomarker discovery, emphasizing the potential of blood-based panels for noninvasive diagnosis and personalized medicine. Future research directions are presented to develop targeted therapies and improve clinical outcomes for MASLD patients.
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Affiliation(s)
- Renee Hernandez
- Division of Human Genetics, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, United States
| | - Natasha S Garcia-Rodriguez
- Division of Human Genetics, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, United States
| | - Marco A Arriaga
- Division of Human Genetics, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, United States
| | - Ricardo Perez
- Division of Human Genetics, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, United States
| | - Auwal A Bala
- Division of Human Genetics, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, United States
| | - Ana C Leandro
- Division of Human Genetics, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, United States
- South Texas Diabetes and Obesity Institute, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, United States
| | - Vince P Diego
- Division of Human Genetics, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, United States
- South Texas Diabetes and Obesity Institute, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, United States
| | - Marcio Almeida
- Division of Human Genetics, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, United States
- South Texas Diabetes and Obesity Institute, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, United States
| | - Jason G Parsons
- Division of Human Genetics, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, United States
| | - Eron G Manusov
- Division of Human Genetics, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, United States
| | - Jacob A Galan
- Division of Human Genetics, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, United States
- South Texas Diabetes and Obesity Institute, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, United States
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Huang J, Zhang X, Su L, Liu M, Xu M, Zhuang B, Liu B, Huang T, Hu H, Xie X, Xie X, Lin M. Comparison of Two-Dimensional Shear Wave Elastography Between Two Different Instruments for Hepatocellular Carcinoma Patients. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2025; 44:209-219. [PMID: 39400409 DOI: 10.1002/jum.16597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Revised: 09/22/2024] [Accepted: 09/23/2024] [Indexed: 10/15/2024]
Abstract
OBJECTIVES This study aimed to investigate and compare 2-dimensional shear wave elastography (2D-SWE) measurements and influencing factors among 2 different devices and to evaluate the ability and influencing factors of these measurements to assess liver fibrosis. METHODS From October 2022 to September 2023, 290 hepatocellular carcinoma (HCC) patients and 30 healthy volunteers were prospectively included. The 2D-SWE measurements were performed using AixPlorer V (SEmean) and APLIO i900 (CEmean). This study compared 2D-SWE measurements between instruments for evaluating the liver fibrosis stage and analyzed the potential influencing factors. RESULTS The 2D-SWE measurements obtained by the 2 instruments were significantly different (P < .001), but the differences were significant only for patients with stage F4 liver fibrosis (P < .001) and not for volunteers or patients with stage F0-F3 liver fibrosis (all P > .050). Multivariate linear regression analysis revealed that the factors independently influencing the SEmean were alanine aminotransferase (ALT) (P = .034) and liver fibrosis stage (P < .001), while fibrosis stage (P = .028) was the only factor influencing the CEmean. CONCLUSIONS Although 2D-SWE from the 2 different instruments was capable of detecting liver fibrosis, it yielded varying results in HCC patients. These discrepancies were predominantly observed in patients with F4 liver fibrosis but not in healthy adults or patients with F0-F3 liver fibrosis. One potential contributing factor to the differences between instruments could be ALT levels.
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Affiliation(s)
- Jiayao Huang
- Department of Medical Ultrasonics, Sun Yat-sen University First Affiliated Hospital, Guangzhou, China
| | - Xiaoer Zhang
- Department of Medical Ultrasonics, Sun Yat-sen University First Affiliated Hospital, Guangzhou, China
| | - Liya Su
- Department of Medical Ultrasonics, Sun Yat-sen University First Affiliated Hospital, Guangzhou, China
| | - Ming Liu
- Department of Medical Ultrasonics, Sun Yat-sen University First Affiliated Hospital, Guangzhou, China
| | - Ming Xu
- Department of Medical Ultrasonics, Sun Yat-sen University First Affiliated Hospital, Guangzhou, China
| | - Bowen Zhuang
- Department of Medical Ultrasonics, Sun Yat-sen University First Affiliated Hospital, Guangzhou, China
| | - Baoxian Liu
- Department of Medical Ultrasonics, Sun Yat-sen University First Affiliated Hospital, Guangzhou, China
| | - Tongyi Huang
- Department of Medical Ultrasonics, Sun Yat-sen University First Affiliated Hospital, Guangzhou, China
| | - Hangtong Hu
- Department of Medical Ultrasonics, Sun Yat-sen University First Affiliated Hospital, Guangzhou, China
| | - Xiaohua Xie
- Department of Medical Ultrasonics, Sun Yat-sen University First Affiliated Hospital, Guangzhou, China
| | - Xiaoyan Xie
- Department of Medical Ultrasonics, Sun Yat-sen University First Affiliated Hospital, Guangzhou, China
| | - Manxia Lin
- Department of Medical Ultrasonics, Sun Yat-sen University First Affiliated Hospital, Guangzhou, China
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Duarte-Rojo A, Taouli B, Leung DH, Levine D, Nayfeh T, Hasan B, Alsawaf Y, Saadi S, Majzoub AM, Manolopoulos A, Haffar S, Dundar A, Murad MH, Rockey DC, Alsawas M, Sterling RK. Imaging-based noninvasive liver disease assessment for staging liver fibrosis in chronic liver disease: A systematic review supporting the AASLD Practice Guideline. Hepatology 2025; 81:725-748. [PMID: 38489521 DOI: 10.1097/hep.0000000000000852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Accepted: 01/19/2024] [Indexed: 03/17/2024]
Abstract
BACKGROUND AND AIMS Transient elastography (TE), shear wave elastography, and/or magnetic resonance elastography (MRE), each providing liver stiffness measurement (LSM), are the most studied imaging-based noninvasive liver disease assessment (NILDA) techniques. To support the American Association for the Study of Liver Diseases guidelines on NILDA, we summarized the evidence on the accuracy of these LSM methods to stage liver fibrosis (F). APPROACH AND RESULTS A comprehensive search for studies assessing LSM by TE, shear wave elastography, or MRE for the identification of significant fibrosis (F2-4), advanced fibrosis (F3-4), or cirrhosis (F4), using histopathology as the standard of reference by liver disease etiology in adults or children from inception to April 2022 was performed. We excluded studies with <50 patients with a single disease entity and mixed liver disease etiologies (with the exception of HCV/HIV coinfection). Out of 9447 studies, 240 with 61,193 patients were included in this systematic review. In adults, sensitivities for the identification of F2-4 ranged from 51% to 95%, for F3-4 from 70% to 100%, and for F4 from 60% to 100% across all techniques/diseases, whereas specificities ranged from 36% to 100%, 74% to 100%, and 67% to 99%, respectively. The largest body of evidence available was for TE; MRE appeared to be the most accurate method. Imaging-based NILDA outperformed blood-based NILDA in most comparisons, particularly for the identification of F3-4/F4. In the pediatric population, imaging-based NILDA is likely as accurate as in adults. CONCLUSIONS LSM from TE, shear wave elastography, and MRE shows acceptable to outstanding accuracy for the detection of liver fibrosis across various liver disease etiologies. Accuracy increased from F2-4 to F3-4 and was the highest for F4. Further research is needed to better standardize the use of imaging-based NILDA, particularly in pediatric liver diseases.
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Affiliation(s)
- Andres Duarte-Rojo
- Division of Gastroenterology and Hepatology, Northwestern Medicine and Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Bachir Taouli
- Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Daniel H Leung
- Department of Pediatrics, Baylor College of Medicine and Division of Gastroenterology, Hepatology and Nutrition, Texas Children's Hospital, Houston, Texas, USA
| | - Deborah Levine
- Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Tarek Nayfeh
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Bashar Hasan
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Yahya Alsawaf
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Samer Saadi
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | | | | | - Samir Haffar
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Ayca Dundar
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - M Hassan Murad
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Don C Rockey
- Digestive Disease Research Center, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Mouaz Alsawas
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Richard K Sterling
- Section of Hepatology, Department of Medicine, Virginia Commonwealth University, Richmond, Virginia, USA
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Olivas I, Arvaniti P, Gabeta S, Torres S, Del Barrio M, Díaz-González A, Esteban P, Riveiro-Barciela M, Mauro E, Rodríguez-Tajes S, Zachou K, Dalekos GN, Londoño MC. Liver stiffness measurement predicts clinical outcomes in autoimmune hepatitis. JHEP Rep 2024; 6:101213. [PMID: 39524208 PMCID: PMC11550196 DOI: 10.1016/j.jhepr.2024.101213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Revised: 07/26/2024] [Accepted: 09/02/2024] [Indexed: 11/16/2024] Open
Abstract
Background & Aims Liver stiffness measurement (LSM) has been shown to adequately predict outcomes in patients with liver disease. However, the value of LSM as a predictor of disease progression in autoimmune hepatitis (AIH) remains to be determined. This study aimed to evaluate the role of LSM as a predictor of disease progression and decompensation of cirrhosis in patients with AIH. Methods This multicentre cohort study included 439 patients with histologically confirmed AIH and at least one LSM during follow-up. The association between the first LSM performed at least 6 months after treatment initiation (baseline LSM [BLSM]) and cirrhosis development and poor outcomes (decompensation, liver transplantation, and/or liver-related death) was assessed using Cox regression and its discriminating capacity with a receiver-operating characteristic curve. Results Most patients were female (n = 301, 70%), with a median age of 52 years. BLSM performed after a median of 2.18 (1.19-4.68) years had a median value of 6 kPa (4.5-8.5). At the time of BLSM, 332 (76%) patients had achieved a biochemical response and 57 (13%) had cirrhosis. During follow-up, eight patients (2%) presented with poor outcomes and 26 (7%) developed cirrhosis. BLSM was higher among patients with poor outcomes (13.5 kPa vs. 6 kPa; p <0.001) and was independently associated with cirrhosis development (hazard ratio 1.300; p <0.001), irrespective of the achievement of biochemical response. A cut-off of 8.5 kPa accurately predicted cirrhosis development and poor outcomes, with AUCs of 0.859 (95% CI 0.789-0.929) and 0.900 (95% CI 0.847-0.954), respectively. Conclusion BLSM could play a significant role in predicting AIH outcomes, potentially identifying a subgroup of patients at a high risk of progressing to cirrhosis and experiencing decompensation. Impact and implications The value of liver stiffness measurement as a predictor of outcomes in patients with autoimmune hepatitis (AIH) remains to be determined. In this large multicentre study, liver stiffness measurement was found to be an independent predictive factor of adverse clinical outcomes and cirrhosis development in AIH, irrespective of the achievement of biochemical response. A cut-off of 8.5 kPa accurately predicted cirrhosis development and poor outcomes in AIH.
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Affiliation(s)
- Ignasi Olivas
- Liver Unit, Hospital Clínic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d’Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Universitat de Barcelona, Barcelona, Spain
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER)
| | - Pinelopi Arvaniti
- Liver Unit, Hospital Clínic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d’Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Universitat de Barcelona, Barcelona, Spain
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Greece
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER)
| | - Stella Gabeta
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Greece
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER)
| | - Sonia Torres
- Liver Unit, Hospital Clínic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d’Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Universitat de Barcelona, Barcelona, Spain
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER)
| | - Maria Del Barrio
- Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases Group, Valdecilla Research Institute (IDIVAL), Marqués de Valdecilla University Hospital, Santander, Spain
| | - Alvaro Díaz-González
- Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases Group, Valdecilla Research Institute (IDIVAL), Marqués de Valdecilla University Hospital, Santander, Spain
| | - Paula Esteban
- Liver Unit, Internal Medicine Department, Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Mar Riveiro-Barciela
- Liver Unit, Internal Medicine Department, Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de investigación biomédica en red. Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
| | - Ezequiel Mauro
- Liver Unit, Hospital Clínic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d’Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Universitat de Barcelona, Barcelona, Spain
| | - Sergio Rodríguez-Tajes
- Liver Unit, Hospital Clínic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d’Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Universitat de Barcelona, Barcelona, Spain
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER)
- Centro de investigación biomédica en red. Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
| | - Kalliopi Zachou
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Greece
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER)
| | - George N. Dalekos
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Greece
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER)
| | - María-Carlota Londoño
- Liver Unit, Hospital Clínic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d’Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Universitat de Barcelona, Barcelona, Spain
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER)
- Centro de investigación biomédica en red. Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
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Belilos E, Strzepka J, Ritz E, Reau N, Aloman C. Characterizing outcomes in a large cohort of latinx patients with autoimmune hepatitis. Ann Hepatol 2024; 30:101570. [PMID: 39276991 DOI: 10.1016/j.aohep.2024.101570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Revised: 07/24/2024] [Accepted: 07/30/2024] [Indexed: 09/17/2024]
Abstract
INTRODUCTION AND OBJECTIVES This study aimed to characterize a large cohort of Latinx patients with autoimmune hepatitis (AIH) and analyze clinical outcomes, including biochemical remission, duration of steroid treatment, fibrosis regression, and incidence of clinical endpoints (hepatic decompensation, need for liver transplant, and death). MATERIALS AND METHODS This was a retrospective descriptive study of patients with biopsy proven AIH (2009-2019) at a single urban center. Demographics, medical comorbidities, histology, treatment course, biochemical markers, fibrosis using dynamic non-invasive testing (NIT), and clinical outcomes at three months and at one, two, and three years were analyzed. RESULTS 121 adult patients with biopsy-proven AIH were included: 43 Latinx (35.5%) and 78 non-Latinx (65.5%). Latinx patients were more likely to have metabolic dysfunction-associated steatotic liver disease (MASLD) (p = 0.004), and had higher Fibrosis-4 (FIB-4) (p = 0.0279) and AST-to-Platelet-Ratio-Index (APRI) (p = 0.005) at one year. Latinx patients took longer to reach biochemical remission than non-Hispanic Whites (p = 0.031) and longer to stop steroids than non-Hispanic Blacks (p = 0.016). There were no significant differences based on ethnicity in histological fibrosis stage at presentation or incidence of clinical endpoints. CONCLUSIONS MASLD overlap is highly prevalent in Latinx AIH patients. Longer time to biochemical remission and worse NITs support that this population may have slower fibrosis regression with standard of care AIH treatment. This may indicate differing response rates due to genetic polymorphisms affecting drug metabolism and immune response among Latinx individuals and is less likely related to AIH/MASLD overlap based on the findings of this study.
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Affiliation(s)
- Eleanor Belilos
- Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA.
| | - Jessica Strzepka
- Department of Internal Medicine, Division of Digestive Diseases and Nutrition, Rush University Medical Center, Chicago, IL, USA
| | - Ethan Ritz
- Department of Internal Medicine, Division of Digestive Diseases and Nutrition, Rush University Medical Center, Chicago, IL, USA
| | - Nancy Reau
- Department of Internal Medicine, Division of Digestive Diseases and Nutrition, Rush University Medical Center, Chicago, IL, USA
| | - Costica Aloman
- Department of Internal Medicine, New York Medical College, Westchester Medical Center, Vahalla, NY, USA
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Kim MN, Han JW, An J, Kim BK, Jin YJ, Kim SS, Lee M, Lee HA, Cho Y, Kim HY, Shin YR, Yu JH, Kim MY, Choi Y, Chon YE, Cho EJ, Lee EJ, Kim SG, Kim W, Jun DW, Kim SU. KASL clinical practice guidelines for noninvasive tests to assess liver fibrosis in chronic liver disease. Clin Mol Hepatol 2024; 30:S5-S105. [PMID: 39159947 PMCID: PMC11493350 DOI: 10.3350/cmh.2024.0506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 08/12/2024] [Accepted: 08/16/2024] [Indexed: 08/21/2024] Open
Affiliation(s)
- Mi Na Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Ji Won Han
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jihyun An
- Department of Gastroenterology and Hepatology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Young-Joo Jin
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
| | - Seung-seob Kim
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Minjong Lee
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Han Ah Lee
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
| | - Hee Yeon Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Yu Rim Shin
- Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Jung Hwan Yu
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
| | - Moon Young Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
| | - Young Eun Chon
- Department of Internal Medicine, Institute of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam, Korea
| | - Eun Ju Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Eun Joo Lee
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea
| | - Sang Gyune Kim
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Won Kim
- Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Dae Won Jun
- Department of Internal Medicine, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - on behalf of The Korean Association for the Study of the Liver (KASL)
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Gastroenterology and Hepatology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
- Department of Internal Medicine, Institute of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam, Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
- Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, Korea
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An J, Chon YE, Kim G, Kim MN, Kim HY, Lee HA, Yu JH, Choi M, Jun DW, Kim SU, Han JW, Jin YJ. Diagnostic accuracy of vibration-controlled transient elastography for staging liver fibrosis in autoimmune liver diseases: A systematic review and meta-analysis. Clin Mol Hepatol 2024; 30:S134-S146. [PMID: 39165158 PMCID: PMC11493360 DOI: 10.3350/cmh.2024.0586] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2024] [Revised: 08/17/2024] [Accepted: 08/20/2024] [Indexed: 08/22/2024] Open
Abstract
BACKGROUND/AIMS The assessment of liver fibrosis is crucial for managing autoimmune liver diseases such as primary biliary cholangitis (PBC), autoimmune hepatitis (AIH), and primary sclerosing cholangitis (PSC). However, data on the efficacy of noninvasive tests for these diseases are limited. This meta-analysis evaluated the diagnostic accuracy of vibration-controlled transient elastography (VCTE) for staging fibrosis in patients with autoimmune liver disease. METHODS Searches were conducted in PubMed, Embase, CINAHL, Web of Science, and Cochrane Library databases to assess the diagnostic accuracy of VCTE against histology as the reference standard in adult patients with autoimmune liver disease. The summary area under the curve (sAUC) and diagnostic odds ratio were calculated for significant fibrosis (SF), advanced fibrosis (AF), and cirrhosis, according to liver biopsy. RESULTS Fourteen articles were included, comprising 559 PBC patients from six studies, 388 AIH patients from five studies, and 151 PSC patients from three studies. VCTE demonstrated good performance for fibrosis staging in PBC, AIH, and PSC. In PBC, sAUCs of VCTE were 0.87, 0.89, and 0.99 for staging SF, AF, and cirrhosis, respectively. In AIH, the sAUCs were 0.88, 0.88, and 0.92, respectively, while in PSC, they were 0.88, 0.95, and 0.92, respectively. The cutoff values for AF were 7.5-17.9 kPa in PBC, 8.18-12.1 kPa in AIH, and 9.6 kPa in PSC. CONCLUSION VCTE shows high diagnostic accuracy for staging liver fibrosis in patients with autoimmune liver diseases. This non-invasive method serves as a valuable tool for the evaluation and monitoring of fibrosis in these lifelong diseases.
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Affiliation(s)
- Jihyun An
- Department of Gastroenterology and Hepatology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
| | - Young Eun Chon
- Department of Internal Medicine, Institute of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam, Korea
| | - Gunho Kim
- Hanyang University College of Medicine, Seoul, Korea
| | - Mi Na Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Hee Yeon Kim
- Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Han Ah Lee
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Jung Hwan Yu
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
| | - Miyoung Choi
- Division of Health Technology Assessment Research, National EvidenceBased Healthcare Collaborating Agency (NECA), Seoul, Korea
| | - Dae Won Jun
- Department of Gastroenterology, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Ji Won Han
- Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea
| | - Young-Joo Jin
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
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10
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Najafi N, Razavi A, Jafarpour H, Raei M, Azizi Z, Davoodi L, Abdollahi A, Frouzanian M. Evaluation of hepatic injury in chronic hepatitis B and C using APRI and FIB-4 indices compared to fibroscan results. Ann Med Surg (Lond) 2024; 86:3841-3846. [PMID: 38989210 PMCID: PMC11230742 DOI: 10.1097/ms9.0000000000002095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Accepted: 12/24/2023] [Indexed: 07/12/2024] Open
Abstract
Background Hepatitis B (HBV) and hepatitis C viruses (HCV) are significant causes of liver disease worldwide. Liver fibrosis (LF) is a complication of chronic liver damage caused by HBV and HCV due to our limited knowledge comparing the diagnostic performance of platelet to aspartate aminotransferase ratio index (APRI) and fibrosis-4 (FIB-4) index with fibroscan. Methods This study evaluated liver damage in HBV and HCV using APRI, FIB-4, and fibroscan indices. This retrospective cohort descriptive-analytical study was conducted on patients with HBV and HCV. This study uses laboratory results and imaging to investigate liver damage in chronic HBV and HCV patients. APRI and FIB-4 were computed based on laboratory results. Results A total of 185 patients (82 hepatitis B and 103 hepatitis C) were included in the study. Thirteen patients had liver cirrhosis. There was no statistically significant difference between the fibroscan results in the two groups (P=0.99). The HBV group's mean APRI and FIB-4 were lower than HCV, but no significant difference was observed (P>0.05). Our results in HBV and HCV patients showed that APRI and FIB-4 accomplished well anticipating cirrhosis with an area under the receiver operating characteristic curve (AUC) of 0.771-0.845 and 0.871-0.910, respectively. Conclusion Fibroscan is a powerful tool superior to APRI and FIB-4 in predicting LF and cirrhosis. Nevertheless, APRI and FIB-4 are inexpensive and non-invasive indicators with acceptable efficacy in predicting advanced fibrosis or cirrhosis. However, these two measures are not reliable in low-grade fibrosis.
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Affiliation(s)
- Narges Najafi
- Department of Infectious Diseases, School of Medicine, Antimicrobial Resistance Research Center, Communicable Diseases Research Institutes, Qaem Shahr Razi Hospital, Mazandaran University of Medical Sciences
| | - Alireza Razavi
- Student Research Committee, School of Medicine, Mazandaran University of Medical Sciences
| | - Hamed Jafarpour
- Student Research Committee, School of Medicine, Mazandaran University of Medical Sciences
| | - Maedeh Raei
- Gastrointestinal Cancer Research Center, Non-Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran
| | - Zahra Azizi
- Student Research Committee, School of Medicine, Mazandaran University of Medical Sciences
| | - Lotfollah Davoodi
- Department of Infectious Diseases, School of Medicine, Antimicrobial Resistance Research Center, Communicable Diseases Research Institutes, Qaem Shahr Razi Hospital, Mazandaran University of Medical Sciences
| | - Amirsaleh Abdollahi
- Student Research Committee, School of Medicine, Mazandaran University of Medical Sciences
| | - Mehran Frouzanian
- Student Research Committee, School of Medicine, Mazandaran University of Medical Sciences
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11
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Loomba R, Clark G, Teckman J, Ajmera V, Behling C, Brantly M, Brenner D, D'Armiento J, Fried MW, Iyer JS, Mandorfer M, Rockey DC, Tincopa M, Vuppalanchi R, Younossi Z, Krag A, Turner AM, Strnad P. Review article: New developments in biomarkers and clinical drug development in alpha-1 antitrypsin deficiency-related liver disease. Aliment Pharmacol Ther 2024; 59:1183-1195. [PMID: 38516814 DOI: 10.1111/apt.17967] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Revised: 01/04/2024] [Accepted: 03/12/2024] [Indexed: 03/23/2024]
Abstract
BACKGROUND Alpha-1 antitrypsin liver disease (AATLD) occurs in a subset of patients with alpha-1 antitrypsin deficiency. Risk factors for disease progression and specific pathophysiologic features are not well known and validated non-invasive assessments for disease severity are lacking. Currently, there are no approved treatments for AATLD. AIMS To outline existing understanding of AATLD and to identify knowledge gaps critical to improving clinical trial design and development of new treatments. METHODS This report was developed following a multi-stakeholder forum organised by the Alpha-1 Antitrypsin Deficiency Related Liver Disease Expert Panel in which experts presented an overview of the available literature on this topic. RESULTS AATLD results from a 'gain of toxic function' and primarily manifests in those with the homozygous Pi*ZZ genotype. Accumulation of misfolded 'Z' AAT protein in liver cells triggers intracellular hepatocyte injury which may ultimately lead to hepatic fibrosis. Male gender, age over 50 years, persistently elevated liver tests, concomitant hepatitis B or C virus infection, and metabolic syndrome, including obesity and type 2 diabetes mellitus, are known risk factors for adult AATLD. While the gold standard for assessing AATLD disease activity is liver histology, less invasive measures with low intra- and inter-observer variability are needed. Measurement of liver stiffness shows promise; validated thresholds for staging AATLD are in development. Such advances will help patients by enabling risk stratification and personalised surveillance, along with streamlining the development process for novel therapies. CONCLUSIONS This inaugural forum generated a list of recommendations to address unmet needs in the field of AATLD.
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Affiliation(s)
- Rohit Loomba
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, San Diego, California, USA
| | - Ginger Clark
- Department of Medicine, University of Florida, Gainesville, Florida, USA
| | - Jeff Teckman
- Pediatrics and Biochemistry, St. Louis University School of Medicine, Saint Louis, Missouri, USA
| | - Veeral Ajmera
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, San Diego, California, USA
| | - Cynthia Behling
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, San Diego, California, USA
- Pacific Rim Pathology Lab, San Diego, California, USA
| | - Mark Brantly
- Division of Pulmonary, Critical Care & Sleep Medicine, University of Florida College of Medicine, Gainesville, Florida, USA
| | - David Brenner
- Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA
| | - Jeanine D'Armiento
- Department of Medicine, Columbia University Medical Center, New York, New York, USA
| | | | | | - Mattias Mandorfer
- Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Don C Rockey
- Medical University of South Carolina, Charleston, South Carolina, USA
| | - Monica Tincopa
- University of California San Diego, San Diego, California, USA
| | - Raj Vuppalanchi
- Indiana University School of Medicine, Indianapolis, Indiana, USA
| | | | | | | | - Pavel Strnad
- University Hospital RWTH Aachen, Healthcare Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Aachen, Germany
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12
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Nawalerspanya S, Tantipisit J, Assawasuwannakit S, Kaewdech A, Chamroonkul N, Sripongpun P. Non-Invasive Serum Biomarkers for the Diagnosis of Cirrhosis in Patients with Autoimmune Hepatitis (AIH) and AIH-Primary Biliary Cholangitis Overlap Syndrome (AIH-PBC): Red Cell Distribution Width to Platelet Ratio (RPR) Yielded the Most Promising Result. Diagnostics (Basel) 2024; 14:265. [PMID: 38337781 PMCID: PMC10855432 DOI: 10.3390/diagnostics14030265] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Revised: 01/15/2024] [Accepted: 01/24/2024] [Indexed: 02/12/2024] Open
Abstract
Several serum biomarkers for fibrosis assessment have been proposed in various liver diseases, but in autoimmune hepatitis (AIH) or overlap with primary biliary cholangitis (PBC; AIH-PBC) patients, the data are scarce. This retrospective cross-sectional study was conducted to validate six non-invasive biomarkers in the diagnosis of cirrhosis (F4 fibrosis) in such patients. We included adult patients diagnosed with AIH or AIH-PBC overlap syndrome who underwent a liver biopsy between 2011 and 2021. Laboratory data were collected to calculate the following scores: red cell distribution width to platelet ratio (RPR), aspartate aminotransferase/platelet ratio index (APRI), Fibrosis-4 index (FIB-4), aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AAR), neutrophil-to-lymphocyte ratio (NLR), and lymphocyte-to-platelet ratio (LPR). A total of 139 patients were eligible (111 AIH and 28 AIH-PBC). The prevalence of cirrhosis was 35.3% (36% in AIH and 32.1% in AIH-PBC). The AUROCs of the RPR, FIB-4, APRI, AAR, LPR, and NLR in all patients were 0.742, 0.724, 0.650, 0.640, 0.609, and 0.585, respectively. RPR was significantly superior to APRI, NLR, and LPR. Moreover, RPR showed the highest AUROC (0.915) in the overlap AIH-PBC subgroup. In conclusion, RPR yielded the highest diagnostic accuracy to predict cirrhosis in AIH and AIH-PBC overlap syndrome patients, while FIB-4 was considerably optimal.
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Affiliation(s)
- Siwanon Nawalerspanya
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand; (S.N.); (S.A.); (A.K.); (N.C.)
- Department of Internal Medicine, Phaholponpayuhasena Hospital, Kanchanaburi 71000, Thailand
| | - Jarukit Tantipisit
- Department of Pathology, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand;
| | - Suraphon Assawasuwannakit
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand; (S.N.); (S.A.); (A.K.); (N.C.)
- Department of Medicine, Panyananthaphikkhu Chonprathan Medical Center, Srinakharinwirot University, Nonthaburi 11120, Thailand
| | - Apichat Kaewdech
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand; (S.N.); (S.A.); (A.K.); (N.C.)
| | - Naichaya Chamroonkul
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand; (S.N.); (S.A.); (A.K.); (N.C.)
| | - Pimsiri Sripongpun
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand; (S.N.); (S.A.); (A.K.); (N.C.)
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13
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Chen H, Shen Y, Wu SD, Zhu Q, Weng CZ, Zhang J, Wang MX, Jiang W. Diagnostic role of transient elastography in patients with autoimmune liver diseases: A systematic review and meta-analysis. World J Gastroenterol 2023; 29:5503-5525. [PMID: 37900994 PMCID: PMC10600811 DOI: 10.3748/wjg.v29.i39.5503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2023] [Revised: 09/09/2023] [Accepted: 10/11/2023] [Indexed: 10/19/2023] Open
Abstract
BACKGROUND Noninvasive methods have been developed to detect fibrosis in many liver diseases due to the limits of liver biopsy. However, previous studies have focused primarily on chronic viral hepatitis and nonalcoholic fatty liver disease. The diagnostic value of transient elastography for autoimmune liver diseases (AILDs) is worth studying. AIM To compare the diagnostic accuracy of imaging techniques with serum biomarkers of fibrosis in AILD. METHODS The PubMed, Cochrane Library and EMBASE databases were searched. Studies evaluating the efficacy of noninvasive methods in the diagnosis of AILDs [autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC)] were included. The summary area under the receiver operating characteristic curve (AUROC), diagnostic odds ratio, sensitivity and specificity were used to assess the accuracy of these noninvasive methods for staging fibrosis. RESULTS A total of 60 articles were included in this study, and the number of patients with AIH, PBC and PSC was 1594, 3126 and 501, respectively. The summary AUROC of transient elastography in the diagnosis of significant fibrosis, advanced fibrosis and cirrhosis in patients with AIH were 0.84, 0.88 and 0.90, respectively, while those in patients with PBC were 0.93, 0.93 and 0.91, respectively. The AUROC of cirrhosis for patients with PSC was 0.95. However, other noninvasive indices (aspartate aminotransferase to platelet ratio index, aspartate aminotransferase/alanine aminotransferase ratio, fibrosis-4 index) had corresponding AUROCs less than 0.80. CONCLUSION Transient elastography exerts better diagnostic accuracy in AILD patients, especially in PBC patients. The appropriate cutoff values for staging advanced fibrosis and cirrhosis ranged from 9.6 to 10.7 and 14.4 to 16.9 KPa for PBC patients.
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Affiliation(s)
- Hong Chen
- Department of Gastroenterology and Hepatology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen 361015, Fujian Province, China
- Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200032, China
- Shanghai Institute of Liver Diseases, Fudan University Shanghai Medical College, Shanghai 200032, China
| | - Yue Shen
- Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200032, China
- Shanghai Institute of Liver Diseases, Fudan University Shanghai Medical College, Shanghai 200032, China
| | - Sheng-Di Wu
- Department of Gastroenterology and Hepatology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen 361015, Fujian Province, China
- Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200032, China
- Shanghai Institute of Liver Diseases, Fudan University Shanghai Medical College, Shanghai 200032, China
| | - Qin Zhu
- Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200032, China
- Shanghai Institute of Liver Diseases, Fudan University Shanghai Medical College, Shanghai 200032, China
| | - Cheng-Zhao Weng
- Department of Gastroenterology and Hepatology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen 361015, Fujian Province, China
| | - Jun Zhang
- Department of Gastroenterology and Hepatology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen 361015, Fujian Province, China
| | - Mei-Xia Wang
- Department of Gastroenterology and Hepatology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen 361015, Fujian Province, China
| | - Wei Jiang
- Department of Gastroenterology and Hepatology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen 361015, Fujian Province, China
- Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200032, China
- Shanghai Institute of Liver Diseases, Fudan University Shanghai Medical College, Shanghai 200032, China
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14
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Johnston JM, McMahon B, Townshend‐Bulson L, Plotnik J, Jain P, Judge M, Rhodes W, Homan C. Autoimmune hepatitis and overlap syndrome among Alaska Native people: Prevalence, clinical characteristics, and remission. JGH Open 2023; 7:545-552. [PMID: 37649864 PMCID: PMC10463022 DOI: 10.1002/jgh3.12946] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 06/22/2023] [Accepted: 07/05/2023] [Indexed: 09/01/2023]
Abstract
Background and Aim High autoimmune hepatitis (AIH) and overlap syndrome (OS) prevalence have been previously documented among Alaska Native people. The purpose of this project is to report changes in AIH/OS prevalence over time, clinical characteristics, and factors associated with biochemical remission. Methods We reviewed medical records for Alaska Native/American Indian (AN/AI) patients diagnosed with AIH/OS between 1984 and 2021. Point prevalence was calculated based on AIH/OS patients alive at the end of 2021 and at 5-year intervals from July 1, 2000, to July 1, 2020. Results We identified 189 AN/AI persons diagnosed with AIH or OS (157 AIH, 32 OS). Of these 189, 137 were alive at the end of 2021 for a point prevalence of 91.2 per 100 000 (95% confidence interval [CI]: 77.2-107.8)-75.9 (95% CI: 63.2-91.2) for AIH and 15.3 (95% CI: 10.2-23.0) for OS. Prevalence for both AIH and OS has risen steadily since 2000. Eighty-nine consented participants (62.7%) achieved biochemical remission with a median time from diagnosis to start of remission of 1.9 years (IQR 0.5-5.0 years). Consented patients with fatty liver were less likely to achieve remission, but their time to remission was shorter than for patients without fatty liver. Conclusion The AN/AI population in Alaska continues to have the highest reported prevalence of AIH/OS in the world, with prevalence rising steadily since 2000. High reported AIH/OS prevalence is likely due in part to strong referral networks for liver disease. Detection and treatment can lead to biochemical remission and improved health outcomes.
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Affiliation(s)
- Janet M. Johnston
- Liver Disease and Hepatitis ProgramAlaska Native Tribal Health ConsortiumAnchorageAlaskaUSA
| | - Brian McMahon
- Liver Disease and Hepatitis ProgramAlaska Native Tribal Health ConsortiumAnchorageAlaskaUSA
| | - Lisa Townshend‐Bulson
- Liver Disease and Hepatitis ProgramAlaska Native Tribal Health ConsortiumAnchorageAlaskaUSA
| | - Julia Plotnik
- Liver Disease and Hepatitis ProgramAlaska Native Tribal Health ConsortiumAnchorageAlaskaUSA
| | - Paarth Jain
- Liver Disease and Hepatitis ProgramAlaska Native Tribal Health ConsortiumAnchorageAlaskaUSA
| | - Meggan Judge
- Liver Disease and Hepatitis ProgramAlaska Native Tribal Health ConsortiumAnchorageAlaskaUSA
| | - Wileina Rhodes
- Liver Disease and Hepatitis ProgramAlaska Native Tribal Health ConsortiumAnchorageAlaskaUSA
| | - Chriss Homan
- Liver Disease and Hepatitis ProgramAlaska Native Tribal Health ConsortiumAnchorageAlaskaUSA
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15
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KASL clinical practice guidelines for management of autoimmune hepatitis 2022. Clin Mol Hepatol 2023; 29:542-592. [PMID: 37137334 PMCID: PMC10366804 DOI: 10.3350/cmh.2023.0087] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 03/27/2023] [Accepted: 04/03/2023] [Indexed: 05/05/2023] Open
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16
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Autoimmune Hepatitis and Fibrosis. J Clin Med 2023; 12:jcm12051979. [PMID: 36902767 PMCID: PMC10004701 DOI: 10.3390/jcm12051979] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Revised: 02/16/2023] [Accepted: 02/27/2023] [Indexed: 03/06/2023] Open
Abstract
Autoimmune hepatitis (AIH) is a chronic immune-inflammatory disease of the liver, generally considered a rare condition. The clinical manifestation is extremely varied and can range from paucisymptomatic forms to severe hepatitis. Chronic liver damage causes activation of hepatic and inflammatory cells leading to inflammation and oxidative stress through the production of mediators. This results in increased collagen production and extracellular matrix deposition leading to fibrosis and even cirrhosis. The gold standard for the diagnosis of fibrosis is liver biopsy; however, there are serum biomarkers, scoring systems, and radiological methods useful for diagnosis and staging. The goal of AIH treatment is to suppress fibrotic and inflammatory activities in the liver to prevent disease progression and achieve complete remission. Therapy involves the use of classic steroidal anti-inflammatory drugs and immunosuppressants, but in recent years scientific research has focused on several new alternative drugs for AIH that will be discussed in the review.
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Ahuja N, Singh J, Minz RW, Anand S, Das A, Taneja S. HLA and Non-HLA gene polymorphisms in autoimmune hepatitis patients of North Indian adults. Front Immunol 2023; 13:984083. [PMID: 36741403 PMCID: PMC9891307 DOI: 10.3389/fimmu.2022.984083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Accepted: 12/28/2022] [Indexed: 01/20/2023] Open
Abstract
Autoimmune hepatitis (AIH) is a chronic and progressive disease of the liver. This is a multifactorial autoimmune disease with both environmental factors and genetic factors playing a role in its pathogenesis. Certain environmental agents like viruses, drugs, etc., can trigger the disease in a genetically susceptible individual. The present study was aimed to explore the distribution of human leukocyte antigen (HLA)-DRB1, Protein tyrosine phosphatase non-receptor type 22 (PTPN22) and Cytotoxic T-Lymphocyte-associated protein 4 (CTLA-4) polymorphisms in North Indian adult AIH patients and their associations with clinical and pathological characteristics associated with the disease. A total of 147 subjects with 47 cases and 100 healthy controls were enrolled. Diagnosis of AIH was made by Revised International Autoimmune Hepatitis Group scoring system. HLA-DRB1 Typing was done by Luminex-based reverse Sequence-Specific Oligonucleotide Probing (SSOP). Single nucleotide variant (SNV) genotyping for CTLA-4 and PTPN22 was done by simple probe-based SNP arrays. Results indicated SLA positive AIH patients are poor responders to therapy. A significant predispositional association of HLA-DRB1*03 was observed in AIH patients from the North Indian population (p= 0.0001, OR=4.83 (2.30-10.15). The frequency of the GG genotype of CTLA-4 CT 60 was significantly increased in AIH patients compared to controls. Multinomial analysis showed that CTLA-4 CT 60 is an independent predictor for cases.
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Affiliation(s)
- Nishtha Ahuja
- Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Jagdeep Singh
- Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ranjana Walker Minz
- Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India,*Correspondence: Ranjana Walker Minz,
| | - Shashi Anand
- Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ashim Das
- Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Sunil Taneja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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18
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Chaidez A, Pan Z, Sundaram SS, Boster J, Lovell M, Sokol RJ, Mack CL. The discriminatory ability of FibroScan liver stiffness measurement, controlled attenuation parameter, and FibroScan-aspartate aminotransferase to predict severity of liver disease in children. Hepatol Commun 2022; 6:3015-3023. [PMID: 36069338 PMCID: PMC9592794 DOI: 10.1002/hep4.1983] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Accepted: 04/10/2022] [Indexed: 12/14/2022] Open
Abstract
Vibration controlled transient elastography (FibroScan) is used to predict the severity of liver fibrosis and steatosis. In pediatrics, few studies have been performed directly comparing liver histologic features with FibroScan liver stiffness measurements (LSMs) and controlled attenuation parameters (CAPs). The FibroScan-aspartate aminotransferase (FAST) score, which predicts liver disease severity in adult nonalcoholic fatty liver disease (NAFLD), has not been analyzed in children. The aims of this study were to determine if LSM and CAP correlated with liver histologic fibrosis stage and steatosis grade, respectively, and to determine the predictive capacity of FAST in pediatric NAFLD. Research participants (n = 216) included those with FibroScan within 90 days of a liver biopsy. The ability of LSM, CAP, and FAST to predict severity of liver disease was analyzed by Spearman correlation, linear regression, and receiver operating characteristic and C statistic. Significant correlations were identified between LSM and Ishak fibrosis stages, with the strongest correlation occurring in the non-NAFLD group (Spearman r = 0.47, p < 0.0001). LSM adequately predicted Ishak stages F0-2 versus F3-F6 (area under the receiver operating characteristic curve [AUROC], 0.73 for all; 0.77 for non-NAFLD). CAP strongly predicted histologic steatosis grade (r = 0.84; p < 0.0001; AUROC, 0.98). FAST had acceptable discriminatory ability for significant liver disease (AUROC, 0.75). A FAST cutoff ≥0.67 had a sensitivity of 89% but a specificity of only 62% at determining significant liver disease. This study encompasses one of the largest pediatric cohorts describing the accuracy of FibroScan LSM and CAP to predict liver histologic fibrosis stage and steatosis grade, respectively. In order to determine specific LSM, CAP, and FAST cut-off values for fibrosis stages, steatosis grades, and significant liver disease, respectively, a much larger cohort is necessary and will likely entail the need for multicentered studies.
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Affiliation(s)
- Alexander Chaidez
- Section of Pediatric Gastroenterology, Hepatology, and NutritionDepartment of PediatricsPediatric Liver CenterChildren's Hospital ColoradoUniversity of Colorado School of Medicine and Anschutz Medical CampusAuroraColoradoUSA
| | - Zhaoxing Pan
- Clinical and Translational Science InstituteUniversity of Colorado School of Medicine and Anschutz Medical CampusAuroraColoradoUSA
| | - Shikha S. Sundaram
- Section of Pediatric Gastroenterology, Hepatology, and NutritionDepartment of PediatricsPediatric Liver CenterChildren's Hospital ColoradoUniversity of Colorado School of Medicine and Anschutz Medical CampusAuroraColoradoUSA
| | - Julia Boster
- Section of Pediatric Gastroenterology, Hepatology, and NutritionDepartment of PediatricsPediatric Liver CenterChildren's Hospital ColoradoUniversity of Colorado School of Medicine and Anschutz Medical CampusAuroraColoradoUSA
| | - Mark Lovell
- Department of PathologyUniversity of Colorado School of Medicine and Anschutz Medical CampusAuroraColoradoUSA
| | - Ronald J. Sokol
- Section of Pediatric Gastroenterology, Hepatology, and NutritionDepartment of PediatricsPediatric Liver CenterChildren's Hospital ColoradoUniversity of Colorado School of Medicine and Anschutz Medical CampusAuroraColoradoUSA
| | - Cara L. Mack
- Section of Pediatric Gastroenterology, Hepatology, and NutritionDepartment of PediatricsPediatric Liver CenterChildren's Hospital ColoradoUniversity of Colorado School of Medicine and Anschutz Medical CampusAuroraColoradoUSA
- Department of PediatricsMedical College of WisconsinChildren's Hospital WisconsinMilwaukeeWisconsinUSA
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19
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Blood-Based Non-Invasive Tests of Hepatic Fibrosis in Autoimmune Hepatitis: Application among Selected Patients Leads to Higher Accuracy. GASTROENTEROLOGY INSIGHTS 2022. [DOI: 10.3390/gastroent13030029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Background. Assessment of liver fibrosis is essential to guide treatment in autoimmune hepatitis (AIH), but non-invasive tests (NITs) showed poor accuracy. Our study aims to evaluate the performance of NITs among different AIH presentations. Methods. Monocentric retrospective study among 122 AIH patients. NITs were compared to histological grading of liver fibrosis. We performed an accuracy analysis among acute (jaundice and/or transaminases > 10 times upper limit of normal) and non-acute patients. Results. A significant difference in the distribution of NIT values for each Ishak stage was found for spleen-diameter-to-platelet-count ratio (SD/PC) (p < 0.001), fibrosis-4-score (FIB-4) (p = 0.002), AST-to-ALT ratio (AAR) (p = 0.002), red-blood-cell-width-distribution-to-platelet-count ratio (RDW/PC) (p = 0.008) and AST-to-platelet-count ratio (APRI) (p = 0.029). The AUC for advanced fibrosis of SD/PC, FIB-4, RDW/PC, APRI and AAR were, respectively, 0.814, 0.770, 0.768, 0.708 and 0.694. The AUC of SD/PC, FIB-4 and APRI in non-acute subgroup were 0.902, 0.834 and 0.758, while in acute patients they were 0.754, 0.724 and 0.716. RDW/PC and AAR weren’t different among the two subgroups. Conclusions. For SD/PC, FIB-4 and APRI, diagnostic accuracy is higher in patients with non-acute presentation. In this context, SD/PC and FIB-4 showed an overall performance that could be of interest in clinical practice alongside other non-invasive techniques.
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20
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Sutton H, Tayler R, Chalmers I, Cowieson J, Fraser K, Henderson P, Hansen R. The Epidemiology of Pediatric Autoimmune Hepatitis in Scotland: A National Cohort Study. JPGN REPORTS 2022; 3:e223. [PMID: 37168624 PMCID: PMC10158286 DOI: 10.1097/pg9.0000000000000223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 05/02/2022] [Indexed: 05/13/2023]
Abstract
Autoimmune hepatitis (AIH) is a rare, but potentially severe, cause of liver disease in children. We aimed to summarize how children with AIH in Scotland presented, were investigated and managed in addition to producing novel epidemiological data and outcomes. Methods All prevalent pediatric patients with AIH cared for in pediatric services between January 2013 and September 2018 were included. Individual patient data were obtained from electronic patient records in the 3-main academic pediatric centers in Scotland covering the entire population. Results Thirty-eight patients were included (25 female) with median follow-up of 33 months (range, 2-145 mo) and 136 total patient years. The incidence between 2014 and 2017 was 0.49/100 000/y (95% confidence interval, 0.29-0.78) and point prevalence between 2013 and 2018 was 1.75/100 000 (95% confidence interval, 1.42-2.13). Thirty-five (92%) patients were autoantibody positive, most commonly anti-nuclear antibody (63%) and anti-smooth muscle antibody (42%). Thirty-seven (97%) patients had induction therapy with oral corticosteroids, 30 (79%) required maintenance treatment with azathioprine, and 23 (61%) received ursodeoxycholic acid. There were 1.4 disease flares per 10 patient years and 3 patients required liver transplantation with an overall 5-year survival rate without the need for transplantation of 95%. Conclusions We calculated a novel incidence and prevalence rate for pediatric AIH in Scotland. Nearly all were invariably treated initially with corticosteroids with most placed-on azathioprine as maintenance therapy. Outcomes were generally favorable with low rates of disease flares and the need for transplantation being rare.
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Affiliation(s)
- Harry Sutton
- From the Department of Paediatric Gastroenterology, Royal Hospital for Children, Glasgow, United Kingdom
| | - Rachel Tayler
- From the Department of Paediatric Gastroenterology, Royal Hospital for Children, Glasgow, United Kingdom
| | - Iain Chalmers
- Department of Paediatric Gastroenterology, Royal Aberdeen Children’s Hospital, Aberdeen, United Kingdom
| | - Jennifer Cowieson
- From the Department of Paediatric Gastroenterology, Royal Hospital for Children, Glasgow, United Kingdom
| | - Karen Fraser
- From the Department of Paediatric Gastroenterology, Royal Hospital for Children, Glasgow, United Kingdom
| | - Paul Henderson
- Department of Paediatric Gastroenterology and Nutrition, Royal Hospital for Children and Young People, Edinburgh, United Kingdom
- Child Life and Health, University of Edinburgh, Edinburgh, United Kingdom
| | - Richard Hansen
- From the Department of Paediatric Gastroenterology, Royal Hospital for Children, Glasgow, United Kingdom
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21
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Dong B, Chen Y, Lyu G, Yang X. Aspartate Aminotransferase to Platelet Ratio Index and Fibrosis-4 Index for Detecting Liver Fibrosis in Patients With Autoimmune Hepatitis: A Meta-Analysis. Front Immunol 2022; 13:892454. [PMID: 35663945 PMCID: PMC9157437 DOI: 10.3389/fimmu.2022.892454] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Accepted: 04/21/2022] [Indexed: 11/13/2022] Open
Abstract
Background Aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) are the two most widely studied noninvasive markers of liver fibrosis. We aimed to assess the diagnostic accuracy of APRI and FIB-4 for liver fibrosis in patients with autoimmune hepatitis (AIH) using liver biopsy as the reference standard. Methods PubMed, EMBASE, Cochrane Library and Web of Science databases were searched for studies (published as of May 1st, 2021) that assessed the diagnostic performance of APRI and FIB-4 for liver fibrosis in AIH. The summary area under receiver operating characteristics curve (AUROC), sensitivity, specificity, diagnostic odds ratios were used to assess the diagnostic accuracy of APRI and FIB-4 for detecting liver fibrosis. Results Fourteen studies (including 1015 patients) were selected with 13 studies each evaluating the use of APRI and FIB-4 for detecting different stages of fibrosis in AIH. For prediction of significant fibrosis, advanced fibrosis, and cirrhosis, the summary AUROC value was 0.66 [95% confidence interval (CI): 0.61-0.70], 0.71 (95% CI: 0.67-0.75), and 0.75 (95% CI: 0.71-0.79) for APRI, and the summary AUROC value was 0.75 (95% CI: 0.71-0.79), 0.73 (95% CI: 0.69-0.77) and 0.79 (95% CI: 0.75-0.82) for FIB-4, respectively. The summary sensitivity and specificity for diagnosis of significant fibrosis, advanced fibrosis, and cirrhosis were 90% and 36%, 78% and 55%, and 77% and 61% for APRI, and 70% and 70%, 65% and 70%, and 78% and 65% for FIB-4, respectively. Conclusions APRI and FIB-4 showed suboptimal diagnostic performance for identifying liver fibrosis in AIH with mediocre sensitivity and specificity.
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Affiliation(s)
- Bingtian Dong
- Department of Ultrasound, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Yuping Chen
- Department of Endocrinology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Guorong Lyu
- Department of Ultrasound, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.,Department of Clinical Medicine, Quanzhou Medical College, Quanzhou, China
| | - Xiaocen Yang
- Department of Ultrasound, Chenggong Hospital, Xiamen University, Xiamen, China
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22
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Llovet LP, Gratacós-Ginès J, Téllez L, Gómez-Outomuro A, Navascués CA, Riveiro-Barciela M, Vinuesa R, Gómez-Camarero J, García-Retortillo M, Díaz-Fontenla F, Salcedo M, García-Eliz M, Horta D, Guerrero M, Rodríguez-Perálvarez M, Fernández-Rodriguez C, Albillos A, G-Abraldes J, Parés A, Londoño MC. Noninvasive Prediction of Outcomes in Autoimmune Hepatitis-Related Cirrhosis. Hepatol Commun 2022; 6:1392-1402. [PMID: 34989164 PMCID: PMC9134802 DOI: 10.1002/hep4.1889] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 12/02/2021] [Accepted: 12/06/2021] [Indexed: 12/19/2022] Open
Abstract
The value of noninvasive tools in the diagnosis of autoimmune hepatitis (AIH)-related cirrhosis and the prediction of clinical outcomes is largely unknown. We sought to evaluate (1) the utility of liver stiffness measurement (LSM) in the diagnosis of cirrhosis and (2) the performance of the Sixth Baveno Consensus on Portal Hypertension (Baveno VI), expanded Baveno VI, and the ANTICIPATE models in predicting the absence of varices needing treatment (VNT). A multicenter cohort of 132 patients with AIH-related cirrhosis was retrospectively analyzed. LSM and endoscopies performed at the time of cirrhosis diagnosis were recorded. Most of the patients were female (66%), with a median age of 54 years. Only 33%-49% of patients had a LSM above the cutoff points described for the diagnosis of AIH-related cirrhosis (12.5, 14, and 16 kPa). Patients with portal hypertension (PHT) had significantly higher LSM than those without PHT (15.7 vs. 11.7 kPa; P = 0.001), but 39%-52% of patients with PHT still had LSM below these limits. The time since AIH diagnosis negatively correlated with LSM, with longer time being significantly associated with a lower proportion of patients with LSM above these cutoffs. VNT was present in 12 endoscopies. The use of the Baveno VI, expanded Baveno VI criteria, and the ANTICIPATE model would have saved 46%-63% of endoscopies, but the latter underpredicted the risk of VNT. Conclusions: LSM cutoff points do not have a good discriminative capacity for the diagnosis of AIH-related cirrhosis, especially long-term after treatment initiation. Noninvasive tools are helpful to triage patients for endoscopy.
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Affiliation(s)
- Laura-Patricia Llovet
- Liver UnitHospital Clínic BarcelonaIDIBAPSCIBEREHDUniversity of BarcelonaBarcelonaSpain
| | - Jordi Gratacós-Ginès
- Liver UnitHospital Clínic BarcelonaIDIBAPSCIBEREHDUniversity of BarcelonaBarcelonaSpain
| | - Luis Téllez
- Department of Gastroenterology and HepatologyHospital Universitario Ramón y CajalInstituto Ramón y Cajal de Investigación SanitariaCIBEREHDUniversidad de AlcaláMadridSpain
| | - Ana Gómez-Outomuro
- 16474Liver UnitDivision of Gastroenterology & HepatologyHospital Universitario Central de AsturiasOviedoSpain
| | - Carmen A Navascués
- 16474Liver UnitDivision of Gastroenterology & HepatologyHospital Universitario Central de AsturiasOviedoSpain
| | - Mar Riveiro-Barciela
- Liver UnitInternal Medicine DepartmentVall d'Hebron HospitalCIBEREHDBarcelonaSpain
| | - Raquel Vinuesa
- 16821Department of Hepatology and GastroenterologyHospital Universitario de BurgosBurgosSpain
| | - Judith Gómez-Camarero
- 16821Department of Hepatology and GastroenterologyHospital Universitario de BurgosBurgosSpain
| | - Montserrat García-Retortillo
- Liver SectionGastroenterology DepartmentDepartament der MedicinaHospital del MarUniversistat Autonoma de BarcelonaIMIMBarcelonaSpain
| | - Fernando Díaz-Fontenla
- Liver Unit and Digestive DepartmentHospital General Universitario Gregorio MarañónCIBEREHDMadridSpain
| | - Magdalena Salcedo
- Liver Unit and Digestive DepartmentHospital General Universitario Gregorio MarañónCIBEREHDMadridSpain
| | - María García-Eliz
- Liver Transplantation Unit and HepatologyHospital Universitario La FeCIBEREHDValenciaSpain
| | - Diana Horta
- Digestive Diseases UnitHospital Universitari Mutua TerrassaTerrassaSpain
| | - Marta Guerrero
- Department of Hepatology and Liver TransplantationIMIBICCIBEREHD, Hospital Universitario Reina SofíaCórdobaSpain
| | - Manuel Rodríguez-Perálvarez
- Department of Hepatology and Liver TransplantationIMIBICCIBEREHD, Hospital Universitario Reina SofíaCórdobaSpain
| | | | - Agustín Albillos
- Department of Gastroenterology and HepatologyHospital Universitario Ramón y CajalInstituto Ramón y Cajal de Investigación SanitariaCIBEREHDUniversidad de AlcaláMadridSpain
| | - Juan G-Abraldes
- Liver UnitDivision of GastroenterologyCEGIIRUniversity of AlbertaEdmontonABCanada
| | - Albert Parés
- Liver UnitHospital Clínic BarcelonaIDIBAPSCIBEREHDUniversity of BarcelonaBarcelonaSpain
| | - Maria-Carlota Londoño
- Liver UnitHospital Clínic BarcelonaIDIBAPSCIBEREHDUniversity of BarcelonaBarcelonaSpain
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23
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Wang Z, Zhou Y, Yu P, Liu Y, Mei M, Bian Z, Shao W, Lv J, Li X, Lu W, Xu L. Retrospective Evaluation of Non-Invasive Assessment Based on Routine Laboratory Markers for Assessing Advanced Liver Fibrosis in Chronic Hepatitis B Patients. Int J Gen Med 2022; 15:5159-5171. [PMID: 35642202 PMCID: PMC9148603 DOI: 10.2147/ijgm.s364216] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Accepted: 05/03/2022] [Indexed: 12/15/2022] Open
Abstract
Background At present, there is a lack of cheap, effective and convenient detection methods for hepatitis B-related liver fibrosis, especially in the developing area. Aim To evaluate the non-invasive methods for the significant and advanced fibrosis stage in chronic hepatitis B virus (HBV) patients in basic hospitals and to assess their diagnostic utility. Methods The study included 436 consecutive naive HBV individuals who had their livers biopsied. They were examined in one week using aspartate aminotransferase-to-aspartate aminotransferase ratio (AAR), age-platelet index (API), aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 (FIB-4), Forns, gamma-glutamyl transpeptidase-to-platelet ratio (GPR), S-index and transient elastography (TE). Scheuer scoring system was used to determine the histologic fibrosis grades (S0–S4). The diagnostic effectiveness was assessed using AUROCs and the DeLong test, both of which were based on statistical comparisons. Results For both substantial (≧S2) and advanced (≧S3) fibrosis phases, TE had good diagnostic performance in determining the hepatic fibrosis. Similar diagnostic performance was shown with Forns and S-index when it came to detecting fibrosis stages lower than S3. One model’s diagnostic value was not significantly improved by combining serum models. Correlation coefficients between clinical features and fibrosis phases were greatest for Forns (r = 0.397), S-index (r = 0.382) and TE (r = 0.535) when compared to other variables. Conclusion This investigation showed that Forns and S-index may be helpful strategies for detecting advanced fibrosis in HBV patients admitted to community hospitals.
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Affiliation(s)
- Zeyu Wang
- Department of Hepatobiliary Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060, People’s Republic of China
| | - Yonghe Zhou
- Ultrasound department, Tianjin Second People’s Hospital, Tianjin, 300192, People’s Republic of China
- Tianjin Research Institute of Liver Diseases, Tianjin, 300192, People’s Republic of China
| | - Pengzhi Yu
- Ultrasound department, Tianjin Second People’s Hospital, Tianjin, 300192, People’s Republic of China
- Tianjin Research Institute of Liver Diseases, Tianjin, 300192, People’s Republic of China
| | - Yonggang Liu
- Tianjin Research Institute of Liver Diseases, Tianjin, 300192, People’s Republic of China
- Pathology Department, Tianjin Second People’s Hospital, Tianjin, 300192, People’s Republic of China
| | - Mei Mei
- Department of Gastroenterology, Tianjin Haihe Hospital, Tianjin, 300350, People’s Republic of China
| | - Zhuo Bian
- Ultrasound department, Tianjin Second People’s Hospital, Tianjin, 300192, People’s Republic of China
| | - Wei Shao
- Ultrasound department, Tianjin Second People’s Hospital, Tianjin, 300192, People’s Republic of China
| | - Jinxia Lv
- Ultrasound department, Tianjin Second People’s Hospital, Tianjin, 300192, People’s Republic of China
| | - Xin Li
- Ultrasound department, Tianjin Second People’s Hospital, Tianjin, 300192, People’s Republic of China
| | - Wei Lu
- Department of Hepatobiliary Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060, People’s Republic of China
- Tianjin Research Institute of Liver Diseases, Tianjin, 300192, People’s Republic of China
- Department of Hepatology, Tianjin Second People’s Hospital, Tianjin, 300192, People’s Republic of China
- Correspondence: Wei Lu; Liang Xu, Email ;
| | - Liang Xu
- Tianjin Research Institute of Liver Diseases, Tianjin, 300192, People’s Republic of China
- Department of Hepatology, Tianjin Second People’s Hospital, Tianjin, 300192, People’s Republic of China
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24
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Manusov EG, Diego VP, Sheikh K, Laston S, Blangero J, Williams-Blangero S. Non-alcoholic Fatty Liver Disease and Depression: Evidence for Genotype × Environment Interaction in Mexican Americans. Front Psychiatry 2022; 13:936052. [PMID: 35845438 PMCID: PMC9283683 DOI: 10.3389/fpsyt.2022.936052] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Accepted: 06/13/2022] [Indexed: 11/17/2022] Open
Abstract
This study examines the impact of G × E interaction effects on non-alcoholic fatty liver disease (NAFLD) among Mexican Americans in the Rio Grande Valley (RGV) of South Texas. We examined potential G × E interaction using variance components models and likelihood-based statistical inference in the phenotypic expression of NAFLD, including hepatic steatosis and hepatic fibrosis (identified using vibration controlled transient elastography and controlled attenuation parameter measured by the FibroScan Device). We screened for depression using the Beck Depression Inventory-II (BDI-II). We identified significant G × E interactions for hepatic fibrosis × BDI-II. These findings provide evidence that genetic factors interact with depression to influence the expression of hepatic fibrosis.
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Affiliation(s)
- Eron Grant Manusov
- Department of Human Genetics, The University of Texas Rio Grande Valley, Brownsville, TX, United States.,School of Medicine, South Texas Diabetes and Obesity Institute, The University of Texas Rio Grande Valley, Brownsville, TX, United States
| | - Vincent P Diego
- Department of Human Genetics, The University of Texas Rio Grande Valley, Brownsville, TX, United States.,School of Medicine, South Texas Diabetes and Obesity Institute, The University of Texas Rio Grande Valley, Brownsville, TX, United States
| | - Khalid Sheikh
- School of Medicine, The University of Texas Rio Grande Valley, Edinburg, TX, United States
| | - Sandra Laston
- Department of Human Genetics, The University of Texas Rio Grande Valley, Brownsville, TX, United States.,School of Medicine, South Texas Diabetes and Obesity Institute, The University of Texas Rio Grande Valley, Brownsville, TX, United States
| | - John Blangero
- Department of Human Genetics, The University of Texas Rio Grande Valley, Brownsville, TX, United States.,School of Medicine, South Texas Diabetes and Obesity Institute, The University of Texas Rio Grande Valley, Brownsville, TX, United States
| | - Sarah Williams-Blangero
- Department of Human Genetics, The University of Texas Rio Grande Valley, Brownsville, TX, United States.,School of Medicine, South Texas Diabetes and Obesity Institute, The University of Texas Rio Grande Valley, Brownsville, TX, United States
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25
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Li Y, Yang Y, Li Y, Zhang P, Ge G, Jin J, Du T, Ma M, Na L, Ding L, Sheng H. Use of GP73 in the diagnosis of non-alcoholic steatohepatitis and the staging of hepatic fibrosis. J Int Med Res 2021; 49:3000605211055378. [PMID: 34772312 PMCID: PMC8593324 DOI: 10.1177/03000605211055378] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Accepted: 10/06/2021] [Indexed: 12/22/2022] Open
Abstract
OBJECTIVE To evaluate the utility of Golgi protein 73 (GP73) in the diagnosis of non-alcoholic steatohepatitis (NASH) and hepatic fibrosis (HF) staging. METHODS Ninety-one patients with non-alcoholic fatty liver disease (NAFLD) were allocated to NAFL (n = 46) and NASH (n = 45) groups according to their NAFLD activity score (NAS), and there were 30 healthy controls. Serum GP73 was measured by ELISA, GP73 protein expression was evaluated using immunohistochemistry, and FibroScan was used to determine liver hardness. RESULTS The serum GP73 concentrations of the NAFL and NASH groups were significantly higher than those of controls. GP73 expression in the liver of the patients gradually progressed from absent or low to moderate or high. Serum GP73 positively correlated with liver expression, and the serum and liver GP73 of the patients positively correlated with FibroScan value and HF stage. There was a strong positive correlation of the combination of alanine aminotransferase, gamma glutamyl transferase and GP73 with NASH. The combination of serum GP73 and FibroScan value was found to predict NASH (NAS > 4) and advanced HF (stage ≥2) in patients with NAFLD using receiver operating characteristic analysis. CONCLUSION Serum GP73 may be useful in the diagnosis of NASH and the staging of HF.
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Affiliation(s)
- Yadi Li
- Department of Clinical Medicine, Ningxia Medical University, Ningxia Medical University, Yinchuan, China
| | - Yan Yang
- Department of Infectious Diseases, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Yufang Li
- Department of Infectious Diseases, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Ping Zhang
- Department of Infectious Diseases, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Gaiying Ge
- Department of Clinical Medicine, Ningxia Medical University, Ningxia Medical University, Yinchuan, China
| | - Jing Jin
- Department of Clinical Medicine, Ningxia Medical University, Ningxia Medical University, Yinchuan, China
| | - Ting Du
- Department of Clinical Medicine, Ningxia Medical University, Ningxia Medical University, Yinchuan, China
| | - Maiyan Ma
- Department of Clinical Medicine, Ningxia Medical University, Ningxia Medical University, Yinchuan, China
| | - Li Na
- Biobank of General Hospital of Ningxia Medical University, Yinchuan, China
| | - Lu Ding
- Biobank of General Hospital of Ningxia Medical University, Yinchuan, China
| | - Huiping Sheng
- Department of Infectious Diseases, General Hospital of Ningxia Medical University, Yinchuan, China
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26
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Varchetta S, Mele D, D'Ambrosio R, Perbellini R, Lombardi A, Rojas A, Paolucci S, Baldanti F, Oliviero B, Mantovani S, Tinelli C, De Silvestri A, Romero Gomez M, Lampertico P, Mondelli MU. A new algorithm shows superior ability to discriminate liver fibrosis stages in chronic hepatitis C. J Viral Hepat 2021; 28:1443-1451. [PMID: 34228858 DOI: 10.1111/jvh.13570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 06/11/2021] [Accepted: 06/30/2021] [Indexed: 12/09/2022]
Abstract
Previous evidence suggests that sialic acid-binding Ig-like lectin 7 (Siglec-7) protein is significantly increased in patients with chronic hepatitis C virus (HCV) infection and directly correlates with clinical parameters of liver inflammation and fibrosis. The aim of this study was to determine the diagnostic value of Siglec-7 as a non-invasive tool to assess liver fibrosis in patients with chronic hepatitis C in a cross-sectional study. Serum levels of Siglec-7 were retrospectively tested in 1007 consecutive patients with chronic HCV infection recruited at three different European sites and data examined by the 'imperfect gold-standard' statistical analysis. Liver stiffness obtained by transient elastography (TE) was considered the standard reference. Liver fibrosis was staged according to published cut-offs of liver stiffness measurement by TE. Accuracy of detection of liver fibrosis stage was not increased by Siglec-7 alone. However, we developed a new index (SiGAP) including Siglec-7, γ-glutamyl transferase, age and platelet count which showed increased sensitivity and specificity in predicting fibrosis compared with APRI or FIB4 indices. The AUROC of SiGAP for the diagnosis of significant (≥F2) and advanced liver fibrosis (≥F3) showed significantly higher values than those of APRI and FIB-4. Siglec-7 may be useful as a complementary tool to assess liver fibrosis stage in patients with chronic hepatitis C when included in a specifically designed algorithm, which showed high level of accuracy in the detection of F2 and F3 fibrosis stage.
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Affiliation(s)
- Stefania Varchetta
- Division of Clinical Immunology and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Dalila Mele
- Division of Clinical Immunology and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Roberta D'Ambrosio
- Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
| | - Riccardo Perbellini
- Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
| | - Andrea Lombardi
- Division of Clinical Immunology and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Angela Rojas
- SeLiver Group, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - Stefania Paolucci
- Molecular Virology Unit, Division of Microbiology and Virology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Fausto Baldanti
- Molecular Virology Unit, Division of Microbiology and Virology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.,Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy
| | - Barbara Oliviero
- Division of Clinical Immunology and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Stefania Mantovani
- Division of Clinical Immunology and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Carmine Tinelli
- Biostatistics Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | | | - Manuel Romero Gomez
- SeLiver Group, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.,UGC de Enfermedades Digestivas, Hospital Universitario Virgen del Rocío, Sevilla, Spain
| | - Pietro Lampertico
- Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.,Department of Pathophysiology and Transplantation, CRC "A.M. and A. Migliavacca" Centre for Liver Disease, University of Milan, Milan, Italy
| | - Mario U Mondelli
- Division of Clinical Immunology and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.,Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy
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Berzigotti A, Tsochatzis E, Boursier J, Castera L, Cazzagon N, Friedrich-Rust M, Petta S, Thiele M. EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis - 2021 update. J Hepatol 2021; 75:659-689. [PMID: 34166721 DOI: 10.1016/j.jhep.2021.05.025] [Citation(s) in RCA: 947] [Impact Index Per Article: 236.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 05/28/2021] [Indexed: 02/07/2023]
Abstract
Non-invasive tests are increasingly being used to improve the diagnosis and prognostication of chronic liver diseases across aetiologies. Herein, we provide the latest update to the EASL Clinical Practice Guidelines on the use of non-invasive tests for the evaluation of liver disease severity and prognosis, focusing on the topics for which relevant evidence has been published in the last 5 years.
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Wang G, Tanaka A, Zhao H, Jia J, Ma X, Harada K, Wang FS, Wei L, Wang Q, Sun Y, Hong Y, Rao H, Efe C, Lau G, Payawal D, Gani R, Lindor K, Jafri W, Omata M, Sarin SK. The Asian Pacific Association for the Study of the Liver clinical practice guidance: the diagnosis and management of patients with autoimmune hepatitis. Hepatol Int 2021; 15:223-257. [PMID: 33942203 PMCID: PMC8144150 DOI: 10.1007/s12072-021-10170-1] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Accepted: 02/27/2021] [Indexed: 02/06/2023]
Affiliation(s)
- Guiqiang Wang
- Peking University First Hospital, Beijing, China. .,Peking University International Hospital, Beijing, China.
| | | | - Hong Zhao
- Peking University First Hospital, Beijing, China.,Peking University International Hospital, Beijing, China
| | - Jidong Jia
- Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Xiong Ma
- Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Kenichi Harada
- Department of Human Pathology, Kanazawa University Graduate School of Medicine Kanazawa, Kanazawa, Japan
| | - Fu-Sheng Wang
- Fifth Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Lai Wei
- Beijing Tsinghua Changgung Hospital, Beijing, China
| | - Qixia Wang
- Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Ying Sun
- Fifth Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Yuan Hong
- Peking University First Hospital, Beijing, China
| | - Huiying Rao
- Peking University People's Hospital, Beijing, China
| | - Cumali Efe
- Department of Gastroenterology, Harran University, Şanlıurfa, Turkey
| | - George Lau
- Humanity and Health Medical Group, Hong Kong Special Administrative Region, China
| | - Diana Payawal
- Department of Hepatology, Cardinal Santos Medical Center, Manila, Philippines
| | - Rino Gani
- Department of Internal Medicine, Cipto Mangunkusumo Hospital, University of Indonesia, Jakarta, Indonesia
| | - Keith Lindor
- College of Health Solutions, Arizona State University, Phoenix, AZ, USA
| | | | - Masao Omata
- Department of Gastroenterology, Yamanashi Prefectural Central Hospital, Kofu-City, Yamanashi, Japan.,The University of Tokyo, Tokyo, Japan
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Nandi N, Fraquelli M. The role of elastography in viral hepatitis and autoimmune hepatitis. Minerva Gastroenterol (Torino) 2021; 67:141-150. [PMID: 34027931 DOI: 10.23736/s2724-5985.21.02788-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The prognosis of chronic liver diseases, which represent a major public health problem, is mainly linked to the extent and progression of liver fibrosis and the subsequent risk of developing cirrhosis and related complications, mainly hepatocellular carcinoma. During the past decade many noninvasive methods and in particular electrographic techniques, have been developed to reduce the need for liver biopsy in staging fibrosis and to overcome whenever possible its limitations, mainly: invasiveness, costs, low reproducibility and poor acceptance by patients. The aim of this review was to provide a comprehensive review of the role of elastography techniques in viral chronic liver diseases and autoimmune hepatitis, with the focus on the possible advantages and limitations of these techniques and on their diagnostic accuracy in predicting the stage of liver fibrosis.
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Affiliation(s)
- Nicoletta Nandi
- Unit of Gastroenterology and Endoscopy, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
| | - Mirella Fraquelli
- Unit of Gastroenterology and Endoscopy, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy -
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Tibuakuu M, Jjingo C, Kirk GD, Thomas DL, Gray R, Ssempijja V, Nalugoda F, Serwadda D, Ocama P, Opio CK, Kleiner DE, Quinn TC, Reynolds SJ. Elevated liver stiffness without histological evidence of liver fibrosis in rural Ugandans. J Viral Hepat 2020; 27:1022-1031. [PMID: 32388879 PMCID: PMC8919060 DOI: 10.1111/jvh.13320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Revised: 02/20/2020] [Accepted: 04/12/2020] [Indexed: 12/09/2022]
Abstract
Liver fibrosis may be assessed noninvasively with transient electrography (TE). Data on the performance of TE for detecting liver fibrosis in sub-Saharan Africa are limited. We evaluated the diagnostic accuracy of TE by performing liver biopsies on persons with liver fibrosis indicated by TE. We enrolled HIV-infected and HIV-uninfected participants with TE scores consistent with at least minimal disease (liver stiffness measurement [LSM]≥7.1 kPa). Biopsies were performed and staged using the Ishak scoring system. A concordant result was defined using accepted thresholds for significant fibrosis by TE (LSM ≥ 9.3 kPa) and liver biopsy (Ishak score ≥ 2). We used modified Poisson regression methods to quantify the univariate and adjusted prevalence risk ratios (PRR) of the association between covariates and the concordance status of TE and liver biopsy in defining the presence of liver fibrosis. Of 131 participants with valid liver biopsy and TE data, only 5 participants (3.8%) had Ishak score ≥ 2 of whom 4 had LSM ≥ 9.3 kPa (sensitivity = 80%); of the 126 (96.2%) with Ishak score < 2, 76 had LSM < 9.3 kPa (specificity = 61%). In multivariable analysis, discordance was associated with female gender (adjPRR = 1.80, 95%CI 1.1-2.9; P = .019), herbal medicine use (adjPRR 1.64, 95% CI = 1.0-2.5; P = .022), exposure to lake or river water (adjPRR 2.05, 95% CI = 1.1-3.7; P = .016), and current smoking (adjPRR 1.72, 95%CI 1.0-2.9; P = .045). These data suggest that TE among rural Ugandans has low specificity for detection of histologically confirmed liver fibrosis. Caution should be exercised when using this tool to confirm significant liver fibrosis.
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Affiliation(s)
- Martin Tibuakuu
- Department of Medicine, St. Luke’s Hospital, Chesterfield, Missouri
| | - Caroline Jjingo
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
| | - Gregory Dale Kirk
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland
| | - David Lee Thomas
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland
| | - Ronald Gray
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
- Rakai Health Sciences Program, Entebbe, Uganda
| | - Victor Ssempijja
- Clinical Research Directorate/Clinical Monitoring Research Program, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, Maryland
| | | | - David Serwadda
- Rakai Health Sciences Program, Entebbe, Uganda
- School of Public Health, Makerere University College of Health Sciences, Kampala, Uganda
| | - Ponsiano Ocama
- School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
| | | | | | - Thomas Charles Quinn
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland
| | - Steven James Reynolds
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland
- Rakai Health Sciences Program, Entebbe, Uganda
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31
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Ebid AHIM, Ahmed OA, Agwa SH, Abdel-Motaleb SM, Hagag RS. Impact of IL28B gene polymorphism on efficacy and safety of direct acting antivirals in hepatitis C Egyptian patients. Int J Clin Pharm 2020; 42:1207-1216. [PMID: 32712884 DOI: 10.1007/s11096-020-01085-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Accepted: 06/11/2020] [Indexed: 12/12/2022]
Abstract
Background Hepatitis C virus infection is one of the major causes of liver cirrhosis and hepatocellular carcinoma worldwide. IL28B gene polymorphism has a direct relation to the response of interferon-based regimens. However, the effect of IL28B gene polymorphism on efficacy of the new direct acting antivirals used in treatment of chronic hepatitis C Egyptian patients hasn't been studied yet. Objective This study aimed to investigate the frequency of IL28B genotypes and impact of its polymorphism on the efficacy and safety of two direct acting antiviral regimens. Setting Patients were recruited form faculty of Medicine Ain shams research institute, Cairo, Egypt. Methods Easy to treat chronic hepatitis C Egyptian patients were included in this prospective study. Patients were randomized into two groups, group 1 received sofosbuvir plus daclatasvir and group 2 received paritaprevir, ombitasvir and ritonavir plus ribavirin. Both treatment regimens were given for 3 months. Laboratory evaluation and IL28B rs 12979860 genotyping were performed at baseline. Follow ups were performed monthly. Fibrosis was assessed at baseline and after treatment. Main outcome measures The frequency of IL28B genotypes and their correlation with safety and efficacy of direct acting antiviral regimens. Results CT genotype was present in 52.42% of patients while CC and TT genotypes were present in 28.16% and 19.42% of patients, respectively. IL28B genotypes weren't correlated to sustained virologic response in both treatment groups. Baseline fibroscan scores didn't show any significant relations with IL28B genotypes. Aspartate aminotransferase/alanine aminotransferase ratio increased significantly at the end of treatment in group1. CC genotype had shown higher ratio values at the end of treatment in Group 2. Conclusion CT genotype is the predominant genotype in easy to treat HCV Egyptian patients. IL28B genotypes hasn't any predictive value on the efficacy or the safety of direct acting antiviral regimens.
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Affiliation(s)
| | - Ossama Ashraf Ahmed
- Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Sara Hassan Agwa
- Department of Clinical and Chemical Pathology at MASRI, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | | | - Radwa Samir Hagag
- Department of Pharmacy Practice, Faculty of Pharmacy, Egyptian Russian University, Badr City, Egypt.
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32
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Mack CL, Adams D, Assis DN, Kerkar N, Manns MP, Mayo MJ, Vierling JM, Alsawas M, Murad MH, Czaja AJ. Diagnosis and Management of Autoimmune Hepatitis in Adults and Children: 2019 Practice Guidance and Guidelines From the American Association for the Study of Liver Diseases. Hepatology 2020; 72:671-722. [PMID: 31863477 DOI: 10.1002/hep.31065] [Citation(s) in RCA: 515] [Impact Index Per Article: 103.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Accepted: 11/25/2019] [Indexed: 02/06/2023]
Affiliation(s)
- Cara L Mack
- Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO
| | - David Adams
- Centre for Liver Research, University of Birmingham, Birmingham, UK
| | - David N Assis
- Department of Internal Medicine, Yale School of Medicine, New Haven, CT
| | - Nanda Kerkar
- Golisano Children's Hospital at Strong, University of Rochester Medical Center, New York, NY
| | - Michael P Manns
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Marlyn J Mayo
- Division of Digestive and Liver Diseases, University of Texas SW Medical Center, Dallas, TX
| | - John M Vierling
- Medicine and Surgery, Baylor College of Medicine, Houston, TX
| | | | - Mohammad H Murad
- Mayo Knowledge and Encounter Research Unit, Mayo Clinic College of Medicine, Rochester, MN
| | - Albert J Czaja
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN
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33
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Patel K, Sebastiani G. Limitations of non-invasive tests for assessment of liver fibrosis. JHEP Rep 2020; 2:100067. [PMID: 32118201 PMCID: PMC7047178 DOI: 10.1016/j.jhepr.2020.100067] [Citation(s) in RCA: 160] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Revised: 01/05/2020] [Accepted: 01/08/2020] [Indexed: 02/07/2023] Open
Abstract
The diagnostic assessment of liver injury is an important step in the management of patients with chronic liver disease (CLD). Although liver biopsy is the reference standard for the assessment of necroinflammation and fibrosis, the inherent limitations of an invasive procedure, and need for repeat sampling, have led to the development of several non-invasive tests (NITs) as alternatives to liver biopsy. Such non-invasive approaches mostly include biological (serum biomarker algorithms) or physical (imaging assessment of tissue stiffness) assessments. However, currently available NITs have several limitations, such as variability, inadequate accuracy and risk factors for error, while the development of a newer generation of biomarkers for fibrosis may be limited by the sampling error inherent to the reference standard. Many of the current NITs were initially developed to diagnose significant fibrosis in chronic hepatitis C, subsequently refined for the diagnosis of advanced fibrosis in patients with non-alcoholic fatty liver disease, and further adapted for prognostication in CLD. An important consideration is that despite their increased use in clinical practice, these NITs were not designed to reflect the dynamic process of fibrogenesis, differentiate between adjacent disease stages, diagnose non-alcoholic steatohepatitis, or follow longitudinal changes in fibrosis or disease activity caused by natural history or therapeutic intervention. Understanding the strengths and limitations of these NITs will allow for more judicious interpretation in the clinical context, where NITs should be viewed as complementary to, rather than as a replacement for, liver biopsy.
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Key Words
- AGA, American Gastroenterology Association
- ALT, alanine aminotransferase
- APRI, AST-platelet ratio index
- AST, aspartate aminotransferase
- AUC, area under the curve
- BMI, body mass index
- Biomarkers
- CAP, controlled attenuation parameter
- CHB, chronic hepatitis B
- CHC, chronic hepatitis C
- CLD, chronic liver disease
- CPA, collagen proportionate area
- DAA, direct-acting antiviral
- ELF, enhanced liver fibrosis
- Elastography
- FIB-4, fibrosis-4
- FLIP, fatty liver inhibition of progression
- HCC, hepatocellular carcinoma
- IFN, interferon
- LSM, liver stiffness measure
- Liver biopsy
- MR, magnetic resonance
- MRE, magnetic resonance elastography
- NAFLD, non-alcoholic fatty liver disease
- NFS, NAFLD fibrosis score
- NITs, non-invasive tests
- Non-alcoholic fatty liver disease
- SVR, sustained virologic response
- US, ultrasound
- VCTE, vibration-controlled transient elastography
- Viral hepatitis
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Affiliation(s)
- Keyur Patel
- Division of Gastroenterology, University Health Network Toronto, Toronto General Hospital, Toronto, ON, Canada
- Corresponding author. Address: Division of Gastroenterology, University of Toronto Health Network, Toronto General Hospital, 200 Elizabeth Street, 9EN, Toronto, ON M5G 2C4.
| | - Giada Sebastiani
- Division of Gastroenterology and Hepatology, McGill University Health Center, Montreal, QC, Canada
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34
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Shiha GES, Mousa N. Transient Elastography in Chronic Liver Diseases. LIVER DISEASES 2020:545-552. [DOI: 10.1007/978-3-030-24432-3_48] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/30/2024]
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35
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Huang D, Lin T, Wang S, Cheng L, Xie L, Lu Y, Chen M, Zhu L, Shi J. The liver fibrosis index is superior to the APRI and FIB-4 for predicting liver fibrosis in chronic hepatitis B patients in China. BMC Infect Dis 2019; 19:878. [PMID: 31640590 PMCID: PMC6805580 DOI: 10.1186/s12879-019-4459-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2018] [Accepted: 09/10/2019] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND The purpose of this study was to prospectively investigate the value of real-time ultrasound elastography (RTE) for the diagnosis of liver fibrosis (LF) in patients with chronic hepatitis B (CHB), to correlate the elastography findings with the histologic stage of LF and to compare RTE findings with those from noninvasive tests of LF calculated using laboratory blood parameters. METHODS Liver biopsies, laboratory blood testing, and RTE were performed in 91 patients with CHB. The LF index (LFI) was calculated using a multiple linear regression equation involving 11 parameters, which represented the degree of LF. The higher the LFI is, the greater the degree of LF. RESULTS The mean aspartate aminotransferase-to-platelet ratio index (APRI) and the mean fibrosis index based on four factors (FIB-4) were significantly different for the 5 stages of LF, respectively. The APRI (r = 0.43, P = 0.006), FIB-4 (r = 0.51, P = 0.012) and LFI (r = 0.562, P = 0.004) were correlated with the stages of LF. For discriminating stage F0 from F1, only the LFI had significant power (P = 0.026) for predicting stage F1. For discriminating stage F4 from F3, only the LFI had statistically significant power (P = 0.024) in predicting stage F4. The areas under the receiver operating characteristic curves (AUCs) of the LFI for diagnosing significant, advanced LF and liver cirrhosis were significantly higher than those of the APRI and FIB-4, and the LFI had better sensitivity and specificity. CONCLUSIONS The LFI calculated by RTE is reliable for the assessment of LF in patients with CHB and has better discrimination power than the APRI and FIB-4.
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Affiliation(s)
- Dedong Huang
- Department of Infectious Diseases, the 903rd Hospital of PLA, Hangzhou, China
| | - Taofa Lin
- Department of Infectious Diseases, the 900th Hospital of PLA, No.156 North Road West 2nd Ring Road, Fuzhou, 350013, China
| | - Shaoyang Wang
- Department of Infectious Diseases, the 900th Hospital of PLA, No.156 North Road West 2nd Ring Road, Fuzhou, 350013, China. .,Clinical educational Institute of the 900th Hospital of PLA affiliated Fujian Medical University, No.156 North Road West 2nd Ring Road, Fuzhou, 350013, China.
| | - Lieyun Cheng
- Department of ultrasound, the 900th Hospital of PLA, Fuzhou, China
| | - Liping Xie
- Department of Infectious Diseases, the 900th Hospital of PLA, No.156 North Road West 2nd Ring Road, Fuzhou, 350013, China
| | - Youguang Lu
- Department of Infectious Diseases, the 900th Hospital of PLA, No.156 North Road West 2nd Ring Road, Fuzhou, 350013, China
| | - Muxing Chen
- Department of Infectious Diseases, the 900th Hospital of PLA, No.156 North Road West 2nd Ring Road, Fuzhou, 350013, China
| | - Lingling Zhu
- Department of Infectious Diseases, the 900th Hospital of PLA, No.156 North Road West 2nd Ring Road, Fuzhou, 350013, China
| | - Jie Shi
- Department of Infectious Diseases, the 903rd Hospital of PLA, Hangzhou, China
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36
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Transient elastography reliably estimates liver fibrosis in autoimmune hepatitis. Clin Exp Hepatol 2019; 5:244-249. [PMID: 31598562 PMCID: PMC6781822 DOI: 10.5114/ceh.2019.87639] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2019] [Accepted: 05/19/2019] [Indexed: 02/08/2023] Open
Abstract
Aim of the study Autoimmune hepatitis (AIH) may result in liver fibrosis and cirrhosis. While the gold standard for staging fibrosis is biopsy, transient elastography (TE) represents a non-invasive alternative. TE has been validated in several chronic liver diseases, but no data exist to establish an association between histologic fibrosis on biopsy and TE liver stiffness measurements among a United States cohort of AIH patients. Material and methods We conducted a retrospective cohort study of 53 AIH patients who received TE assessment and liver biopsy. Histologic fibrosis was classified as advanced (F3-F4) or mild/moderate (F0-F2). Liver stiffness by TE was measured in kilopascals (kPa). We performed a score test for trend to test the association between histologic fibrosis stage and increasing TE kPa categories. Analyses incorporated probe type (medium or extra-large) and body mass index (BMI). Linear regression was used to generate predicted associations between median kPa and histologic fibrosis score with the medium probe. Results The cohort was primarily female (83%) with median age 56.3 years. Increasing kPa category was associated with worsening fibrosis stage when using the medium probe (p = 0.04), but not the extra-large probe (p = 0.40). BMI, however, differed between these groups (median 25.8 vs. 33.1, respectively, p < 0.001). In adjusted linear regression, increasing median kPa corresponded well to worsening fibrosis stage (p = 0.003). Conclusions In a United States AIH cohort, increasing TE kPa measurements are associated with worsening histologic fibrosis staging. While medium probe performance was superior to the extra-large probe, significant variation in BMI between groups may explain this difference.
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37
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Agbim U, Asrani SK. Non-invasive assessment of liver fibrosis and prognosis: an update on serum and elastography markers. Expert Rev Gastroenterol Hepatol 2019; 13:361-374. [PMID: 30791772 DOI: 10.1080/17474124.2019.1579641] [Citation(s) in RCA: 87] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Non-invasive assessment of fibrosis is increasingly utilized in clinical practice to diagnose hepatic fibrosis. Non-invasive assessment of liver fibrosis relies on biologic and/or physical properties to assess tissue fibrosis. Serum markers estimate fibrosis by incorporating markers reflecting hepatic function (indirect markers) and/or markers measuring extracellular matrix degradation/fibrogenesis (direct markers). Radiology based techniques relay the mechanical properties and stiffness of a tissue, with increased stiffness associated with more advanced fibrosis. Areas covered: In this comprehensive review, the recent literature discussing serum markers and elastography-based techniques will be covered. These modalities are also explored in the setting of various liver diseases. Expert opinion: The etiology of liver disease and clinical context should be taken into consideration when non-invasive markers are incorporated in clinical practice. Non-invasive assessment of fibrosis has been most extensively utilized in hepatitis C, followed by hepatitis B and nonalcoholic fatty liver disease, but its role remains less developed in other etiologies of liver disease such as alcohol-associated liver disease and autoimmune liver disease. The role of non-invasive markers in predicting progression or regression of fibrosis, development of liver-related events and survival needs to be further explored.
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Affiliation(s)
- Uchenna Agbim
- a Division of Transplant Surgery, Department of Surgery , University of Tennessee Health Science Center , Memphis , TN , USA
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Ferraioli G, Wong VWS, Castera L, Berzigotti A, Sporea I, Dietrich CF, Choi BI, Wilson SR, Kudo M, Barr RG. Liver Ultrasound Elastography: An Update to the World Federation for Ultrasound in Medicine and Biology Guidelines and Recommendations. ULTRASOUND IN MEDICINE & BIOLOGY 2018; 44:2419-2440. [PMID: 30209008 DOI: 10.1016/j.ultrasmedbio.2018.07.008] [Citation(s) in RCA: 322] [Impact Index Per Article: 46.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/01/2018] [Revised: 07/02/2018] [Accepted: 07/13/2018] [Indexed: 06/08/2023]
Abstract
The World Federation for Ultrasound in Medicine and Biology has produced these guidelines for the use of elastography techniques in liver diseases. For each available technique, the reproducibility, results and limitations are analyzed, and recommendations are given. This set of guidelines updates the first version, published in 2015. Since the prior guidelines, there have been several advances in technology. The recommendations are based on the international published literature, and the strength of each recommendation is judged according to the Oxford Centre for Evidence-Based Medicine. The document has a clinical perspective and is aimed at assessing the usefulness of elastography in the management of liver diseases.
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Affiliation(s)
- Giovanna Ferraioli
- Ultrasound Unit, Department of Clinical Sciences and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, School of Medicine, University of Pavia, Pavia, Italy
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong
| | - Laurent Castera
- Service d'Hepatologie, Hopital Beaujon, Clichy, Assistance Publique-Hopitaux de Paris, INSERM UMR 1149 CRI, Universite Denis Diderot Paris-VII, Paris, France
| | - Annalisa Berzigotti
- Swiss Liver Center, Hepatology, University Clinic for Visceral Surgery and Medicine, Inselspital, University of Bern, Switzerland
| | - Ioan Sporea
- Department of Gastroenterology and Hepatology, University of Medicine and Pharmacy, Timisoara, Romania
| | | | - Byung Ihn Choi
- Department of Radiology, Seoul National University Hospital, Seoul, South Korea
| | - Stephanie R Wilson
- Department of Diagnostic Imaging, Foothills Medical Centre, University of Calgary, Calgary, Alberta, Canada
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University School of Medicine, Osaka Sayama, Japan
| | - Richard G Barr
- Department of Radiology, Northeastern Ohio Medical University and Southwoods Imaging, Youngstown, Ohio, USA.
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Systematic review: diagnostic accuracy of non-invasive tests for staging liver fibrosis in autoimmune hepatitis. Hepatol Int 2018; 13:91-101. [PMID: 30443702 DOI: 10.1007/s12072-018-9907-5] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Accepted: 10/22/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Non-invasive fibrosis assessment has been highly recommended in many liver diseases. However, comparative diagnostic accuracy of laboratory markers, ultrasound and magnetic resonance elastography (MRE) for fibrosis in autoimmune hepatitis (AIH) patients has not been established. METHODS Medline, Embase and Cochrane Library were searched. Primary outcome was significant fibrosis (SF), advanced fibrosis (AF) and cirrhosis, defined as Metavir stage F ≥ 2, F ≥ 3 and F = 4 according to liver biopsy. Hierarchical summary receiver operating characteristic curve (ROC) model was used to evaluate diagnostic accuracy of non-invasive methods. Summary area under ROC (AUROC) and diagnostic odds ratio (DOR) with 95% confidence interval (CI) were calculated. The Grading of Recommendations Assessment, Development and Evaluation system was used to assess quality of evidence. RESULTS Overall, 16 studies with 861 patients were included, comparing aspartate aminotransferase to platelet ratio index (APRI), fibrosis-4 index (FIB-4), aspartate aminotransferase/alanine aminotransferase ratio, transient elastography (TE), acoustic radiation force impulse, shear wave elastography and MRE versus liver biopsy. Among all non-invasive markers, TE had good performance for fibrosis staging. Summary AUROCs and DORs of TE were 0.90 (95% CI 0.87, 0.92) and 23.7, 0.91 (95% CI 0.89, 0.93) and 31.6, 0.89 (95% CI 0.86, 0.92) and 80.5 for staging SF, AF and cirrhosis, whereas APRI and FIB-4 showed poor performance for detecting AF (DOR, 4.6 and 4.7) and cirrhosis (DOR, 5.5 and 12.9). CONCLUSIONS TE performs well to stage liver fibrosis in patients with AIH, compared with other laboratory non-invasive indexes. Nevertheless, diagnostic accuracy of APRI and FIB-4 is poor.
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Regenboog M, van Dussen L, Verheij J, Weinreb NJ, Santosa D, Vom Dahl S, Häussinger D, Müller MN, Canbay A, Rigoldi M, Piperno A, Dinur T, Zimran A, Mistry PK, Salah KY, Belmatoug N, Kuter DJ, Hollak CEM. Hepatocellular carcinoma in Gaucher disease: an international case series. J Inherit Metab Dis 2018; 41:819-827. [PMID: 29423829 PMCID: PMC6133179 DOI: 10.1007/s10545-018-0142-y] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2017] [Revised: 01/07/2018] [Accepted: 01/11/2018] [Indexed: 02/07/2023]
Abstract
Gaucher disease (GD) is associated with an increased risk for malignancies. Next to hematological malignancies, the development of solid tumors in several organs has been described. The liver is one of the major storage sites involved in GD pathogenesis, and is also affected by liver-specific complications. In this case series, we describe 16 GD type 1 (GD1) patients from eight different referral centers around the world who developed hepatocellular carcinoma (HCC). Potential factors contributing to the increased HCC risk in GD patients are studied. Eleven patients had undergone a splenectomy in the past. Liver cirrhosis, one of the main risk factors for the development of HCC, was present in nine out of 14 patients for whom data was available. Three out of seven examined patients showed a transferrin saturation > 45%. In these three patients the presence of iron overload after histopathological examination of the liver was shown. Chronic hepatitis C infection was present in three of 14 examined cases. We summarized all findings and made a comparison to the literature. We recommend that GD patients, especially those with prior splenectomy or iron overload, be evaluated for signs of liver fibrosis and if found to be monitored for HCC development.
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Affiliation(s)
- Martine Regenboog
- Department of Internal Medicine, division of Endocrinology & Metabolism, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
| | - Laura van Dussen
- Department of Internal Medicine, division of Endocrinology & Metabolism, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
| | - Joanne Verheij
- Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands
| | - Neal J Weinreb
- Department of Human Genetics and Medicine, University of Miami, Miller School of Medicine, Miller, FL, USA
| | - David Santosa
- Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine University, Düsseldorf, Germany
| | - Stephan Vom Dahl
- Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine University, Düsseldorf, Germany
| | - Dieter Häussinger
- Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine University, Düsseldorf, Germany
| | - Meike N Müller
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany
| | - Ali Canbay
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany
| | - Miriam Rigoldi
- Medical Genetics, University of Milano-Bicocca and ASST-Monza, S. Gerardo Hospital, Monza, Italy
| | - Alberto Piperno
- Medical Genetics, University of Milano-Bicocca and ASST-Monza, S. Gerardo Hospital, Monza, Italy
| | - Tama Dinur
- Gaucher Clinic, Shaare Zedek Medical Center, Jerusalem, Israel
| | - Ari Zimran
- Gaucher Clinic, Shaare Zedek Medical Center, Jerusalem, Israel
| | - Pramod K Mistry
- Department of Internal Medicine, Yale University School of Medicine, New Haven, USA
| | - Karima Yousfi Salah
- Department of Internal Medicine, Referral Center for Lysosomal Diseases, University Hospital Paris Nord Val de Seine, site Beaujon, Clichy, France
| | - Nadia Belmatoug
- Department of Internal Medicine, Referral Center for Lysosomal Diseases, University Hospital Paris Nord Val de Seine, site Beaujon, Clichy, France
| | - David J Kuter
- Department of Hematology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Carla E M Hollak
- Department of Internal Medicine, division of Endocrinology & Metabolism, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
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Dong H, Xu C, Zhou W, Liao Y, Cao J, Li Z, Hu B. The combination of 5 serum markers compared to FibroScan to predict significant liver fibrosis in patients with chronic hepatitis B virus. Clin Chim Acta 2018; 483:145-150. [PMID: 29709450 DOI: 10.1016/j.cca.2018.04.036] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2018] [Revised: 04/24/2018] [Accepted: 04/26/2018] [Indexed: 12/17/2022]
Abstract
BACKGROUND We evaluated the performance of serum hyaluronan (HA), procollagen type III N-terminal peptide (PIIINP), type IV collagen (IVC), laminin (LN), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), compared to transient elastography (FibroScan) in predicting significant liver fibrosis. METHODS We therefore determined 4 serum fibrosis markers, FibroScan and liver biopsy in 70 consecutive adult patients with chronic hepatitis B. According to a modified Scheuer scoring system, significant fibrosis was defined as fibrosis stage ≥S2. We compared serum fibrosis markers to histological staging and FibroScan results using Spearman correlation analysis and area under receiver operating characteristic (ROC) curves (AUROCs). RESULTS Of the 212 patients who had the results of FibroScans and four serum fibrosis markers for HBV, 70 had concurrent liver biopsy. Significant liver fibrosis was found in 24/70 patients. The serum levels of HA, PIIINP, IVC, LN, ALT, AST was all positively correlated with fibrosis stage of Liver biopsy. The coefficients with stages were respectively 0.468, 0.392, 0.538, 0.213, 0.350, 0.375. There was a significant difference between mild fibrosis (<S2) and significant fibrosis (≥S2), excluding LN, in the levels of these 5 serum makers (P < .05). AUROC for FibroScans and HA, PIIINP, IVC, LN, ALT, AST to correctly allocate patients to histological fibrosis stage ≥ S2 was 0.866, 0.784, 0.738, 0.827, 0.630, 0.713 and 0.728 respectively. Since LN shows the worst performance of the others. We decided to check the performance of the combination of HA, PIIINP, CIV, ALT, AST, excluding LN, to distinguish fibrosis stages. The index of the histological fibrosis stage ≥ S2, combining the 5 serum markers, significantly improved diagnostic performance (AUROC = 0.861) compared to the use of 5 serum markers alone in all HBV patients. CONCLUSION The combination of the 5 serum markers and FibroScan performed equally well in predicting significant fibrosis. The combination of the 5 serum markers is a reliable noninvasive method to predict significant liver fibrosis in patients with CHB. So, it provide another choice rather than FibroScan in predicting significant liver fibrosis.
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Affiliation(s)
- Huimin Dong
- Department of Laboratory Medicine, Third Affiliated Hospital, Sun Yat-sen University, PR China
| | - Changzhi Xu
- Department of Laboratory Medicine, Third Affiliated Hospital, Sun Yat-sen University, PR China
| | - Wenying Zhou
- Department of Laboratory Medicine, Third Affiliated Hospital, Sun Yat-sen University, PR China
| | - Yuan Liao
- Department of Laboratory Medicine, Third Affiliated Hospital, Sun Yat-sen University, PR China
| | - Junyan Cao
- Department of Laboratory Medicine, Third Affiliated Hospital, Sun Yat-sen University, PR China
| | - Zhaoxia Li
- Department of Laboratory Medicine, Third Affiliated Hospital, Sun Yat-sen University, PR China.
| | - Bo Hu
- Department of Laboratory Medicine, Third Affiliated Hospital, Sun Yat-sen University, PR China.
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