Liver stiffness thresholds to predict disease progression and clinical outcomes in bridging fibrosis and cirrhosis

Author:

Loomba RohitORCID,Huang Daniel Q.ORCID,Sanyal Arun J,Anstee Quentin Mark,Trauner MichaelORCID,Lawitz Eric J,Ding Dora,Ma Lily,Jia Catherine,Billin Andrew,Huss Ryan S,Chung Chuhan,Goodman Zachary,Wong Vincent Wai-SunORCID,Okanoue Takeshi,Romero-Gómez Manuel,Abdelmalek Manal F,Muir Andrew,Afdhal Nezam,Bosch Jaime,Harrison Stephen,Younossi Zobair MORCID,Myers Robert P

Abstract

ObjectiveIn 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.DesignWe 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.ResultsProgression 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.ConclusionThe LS thresholds identified in this study may be useful for risk stratification of NASH patients with advanced fibrosis.

Funder

Gilead Sciences, Inc

National Center for Advancing Translational Sciences

NIEHS

DOD PRCRP

NIAAA

National Heart, Lung, and Blood Institute

National Institute of Diabetes and Digestive and Kidney Diseases

Publisher

BMJ

Subject

Gastroenterology

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