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

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.

Clinical and histologic factors associated with discordance between steatosis grade derived from histology vs. MRI‐PDFF in NAFLD

“…To overcome such issues, several noninvasive methods have been developed with promising results 19,26,27 . For example, imaging‐based elastography techniques, such as vibration‐controlled transient elastography (VCTE), shear‐wave elastography, acoustic radiation force impulse elastography, and magnetic resonance elastography are available for non‐invasive assessment of hepatic fibrosis. 28,29 Another ultrasound‐based technique, controlled attenuation parameter (CAP), allows for the non‐invasive quantification of hepatic steatosis with considerable accuracy.…”

“…To overcome such issues, several noninvasive methods have been developed with promising results. 19,26,27 For example, imaging-based elastography techniques, such as vibration-controlled transient elastography (VCTE), shear-wave elastography, acoustic radiation force impulse elastography, and magnetic resonance elastography are available for non-invasive assessment of hepatic fibrosis. Abbreviations: ALT, alanine aminotransferase; aOR, adjusted odds ratio; AST, aspartate aminotransferase; CI, confidence interval; MRE, magnetic resonance; MRI, magnetic resonance imaging; PDFF, proton density fat fraction.…”

Screening for At-Risk Nonalcoholic Fatty Liver Disease in the Primary Care Setting

“…Conversely, LSM > 12 kPA has a high specificity for significant fibrosis (>80%). [55,58,59] In addition, VCTE is associated with risk of incident liver-related events and risk of events is very low in patients with LSM < 8 kPa [59,60].VCTE has higher accuracy in predicting LREs compared to FIB-4 and no significant difference compared to the more invasive liver biopsy [61]. Limitations of using VCTE are a higher rate of false positives for individuals with severe inflammation (elevated ALT) and right heart failure, and technical difficulty in patients with marked abdominal obesity.…”

“…Individuals with LSM < 8 kPa will have a low probability of advanced fibrosis, whereas the rest should be referred to a hepatologist for further evaluation, especially since in one study the median FIB-4 for bridging fibrosis and cirrhosis lies within the indeterminate range. [59] VCTE is largely not available in a community setting, but a number of academic medical centers including ours accept referrals from VCTE from community providers. We believe that while other modalities such as MRE are more accurate than VCTE and FIB-4, they are much more expensive and less widely available, though this may change in the future to allow them to be more often used in a community setting.…”

“…[55][56][57] Conversely, LSM greater than 12 kPa has a high specificity for significant fibrosis (> 80%). 55,58,59 In addition, VCTE is associated with risk of incident LREs and risk of events is very low in patients with LSM less than 8 kPa. 59,60 VCTE has higher accuracy in predicting LREs compared with FIB-4 and no significant difference compared with the more invasive liver biopsy.…”