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Abstract Details
Liver stiffness thresholds to predict disease progression and clinical outcomes in bridging fibrosis and cirrhosis
1Division of Epidemiology, Department of Family Medicine and Public Health, University of California at San Diego, University of California at San Diego, San Diego, California, USA roloomba@ucsd.edu.
2NAFLD Research Center, University of California San Diego, La Jolla, California, USA.
3Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
4Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore.
5Division of Gastroenterology, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA.
6Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
7Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
8Texas Liver Institute, UT Health San Antonio, San Antonio, Texas, USA.
9Gilead Sciences Inc, Foster City, California, USA.
10Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia, USA.
11Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, China.
12Hepatology Center, Saiseikai Suita Hospital, Suita, Japan.
13Unit for The Clinical Management of Digestive Diseases and CIBERehd, Hospital Universitario de Valme, Sevilla, Spain.
14Duke University, Durham, North Carolina, USA.
15Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina, USA.
16Division of Gastroenterology and Hepatology, Beth Israel Medical Center, Harvard University Medical School, Boston, Massachusetts, USA.
18Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
19Pinnacle Clinical Research, San Antonio, Texas, USA.
20Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, Virginia, USA.
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.