Liver stiffness thresholds to predict disease progression and clinical outcomes in bridging fibrosis and cirrhosis
Year: 2022
Type: article
Abstract: OBJECTIVE: In retrospective studies, liver stiffness (LS) by vibration-controlled transient elastography (VCTE) is associated with the risk of liver decompensation in patients with non-alcoholic steatohepatitis (NASH), but prospective data in biopsy-confirmed cohorts with advanced fibrosis are limited. We aimed to establish thresholds for LS by VCTE that predict progression to cirrhosis among patients with bridging fibrosis and hepatic decompensation among patients with cirrhosis due to NASH. DESIGN: We used data from four randomised placebo-controlled trials of selonsertib and simtuzumab in participants with advanced fibrosis (F3-F4). The trials were discontinued due to lack of efficacy. Liver fibrosis was staged centrally at baseline and week 48 (selonsertib study) or week 96 (simtuzumab study). Associations between LS by VCTE with disease progression were determined using Cox proportional hazards regression analysis. RESULTS: Progression to cirrhosis occurred in 16% (103/664) of participants with bridging fibrosis and adjudicated liver-related events occurred in 4% (27/734) of participants with baseline cirrhosis. The optimal baseline LS thresholds were ≥16.6 kPa for predicting progression to cirrhosis, and ≥30.7 kPa for predicting liver-related events. Baseline LS ≥16.6 kPa (adjusted HR 3.99; 95% CI 2.66 to 5.98, p<0.0001) and a ≥5 kPa (and ≥20%) increase (adjusted HR 1.98; 95% CI 1.20 to 3.26, p=0.008) were independent predictors of progression to cirrhosis in participants with bridging fibrosis, while baseline LS ≥30.7 kPa (adjusted HR 10.13, 95% CI 4.38 to 23.41, p<0.0001) predicted liver-related events in participants with cirrhosis. CONCLUSION: The LS thresholds identified in this study may be useful for risk stratification of NASH patients with advanced fibrosis.
Source: Gut
Authors: Rohit Loomba, Daniel Q. Huang, Arun J Sanyal, Quentin Mark Anstee, Michael Trauner, Eric J Lawitz, Dora Ding, Lily Ma, Catherine Jia, Andrew Billin, Ryan S Huss, Chuhan Chung, Zachary Goodman, Vincent Wai-Sun Wong, Takeshi Okanoue, Manuel Romero-Gómez, Manal F Abdelmalek, Andrew Muir, Nezam Afdhal, Jaime Bosch, Stephen Harrison, Zobair M Younossi, Robert P Myers
Institutions: University of California San Diego, National University of Singapore, National University Health System, Virginia Commonwealth University, Virginia Commonwealth University Medical Center, Newcastle University, Medical University of Vienna, The University of Texas at San Antonio Health Science Center, Texas Liver Institute, Gilead Sciences (United States), Inova Health System, Chinese University of Hong Kong, Saiseikai Suita Hospital, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Hospital Universitario de Valme, Duke University, Duke Medical Center, Duke Clinical Research Institute, Harvard University, University Hospital of Bern, University of Oxford, Pinnacle Clinical Research, Inova Fairfax Hospital
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: U.S. Department of Defense, Abbott Laboratories, Amgen, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, AstraZeneca, GlaxoSmithKline, Gilead Sciences, Celgene, Medpace, Regeneron Pharmaceuticals, European Federation of Pharmaceutical Industries and Associations, Arrowhead Pharmaceuticals, NGM Biopharmaceuticals, National Institute for Health and Care Research, European Commission, Eisai, Novo Nordisk, Shionogi, Servier, Genentech, Allergan, Novartis Pharma, Medical Research Council, National Medical Research Council, National Institute on Alcohol Abuse and Alcoholism, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Environmental Health Sciences, National Center for Advancing Translational Sciences, DOD Peer Reviewed Cancer Research Program
Awards: G1140353899, G1198267417, G1316440902, G1370780335, G1494183008, G1622551803, Liver Investigation: Testing Marker Utility in Steatohepatitis, G1820179381, G1893910623, G2323685147, G2928778974, G3331858215, G4119534169, Novel IL-23 inhibitor for the treatment of alcohol associated liver disease, G434337789, G4488924300, G641745218, NIHR Senior Investigator Award, G6467329045, ABBREVIATED MAGNETIC RESONANCE IMAGING AND BIOMARKER-BASED DETECTION OF EARLY LIVER CANCER, G7198334374, G745677937, G7501542120, G7562742651, G8150884884, G8166743225, San Diego Digestive Diseases Research Center, San Diego Cirrhosis Clinical Research Network, G969404240
OpenAlex ID: W4295074172