New Analysis Determines Factors Associated with NASH Disease Progression

Changes in fibrosis, but not nonalcoholic fatty liver disease (NAFLD) Activity Score (NAS), determine the progression of nonalcoholic steatohepatitis (NASH), according to the results of a recent analysis.

The analysis included data from 477 participants with NASH and advanced fibrosis involved in 2, phase 2b controlled trials that tested the efficacy of simtuzumab—the trials were stopped after 96 weeks, because the drug had no effect on disease progression. The patients in those 2 trials were combined for this analysis. Of the 477 subjects, 219 had bridging fibrosis and 258 had cirrhosis at the start of the trials.
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Liver biopsies were taken at baseline and 48 weeks and 96 weeks after the start of the trial and were assessed according to the NAS and Ishak classifications. Hepatic collagen was measured using morphometry, and enhanced liver fibrosis (ELF) scores were calculated.

A total of 47 of the 219 participants (21.5%) with bridging fibrosis at the start of the trials progressed to cirrhosis after a median of 24.9 months.

Baseline Ishak stage 4 and greater hepatic collagen and enhanced liver fibrosis (ELF) scores at baseline were associated with progression from bridging fibrosis to cirrhosis, but not baseline NAS scores. However, severe ballooning increased the risk of disease progression.

In addition, increases in Ishak stage, hepatic collagen, and ELF scores were associated with progression to cirrhosis during follow-up. Changes in NAS scores were not significant for evaluating disease progression, but worsening lobular inflammation was associated with progression to cirrhosis.

After a median 26.7 months, 49 participants with cirrhosis (19.0%) experienced clinical events, such as ascites, encephalopathy, and variceal hemorrhage.

Higher baseline hepatic collagen and ELF scores and a lack of improvement in Ishak stage were factors associated with disease progression.

While lobular inflammation was associated with increased risk for progression, changes in NAS did not show significant associations with disease progression.

“In patients with advanced fibrosis due to NASH, the primary determinant of disease progression is fibrosis and its change over time,” the researchers concluded.

—Melissa Weiss

Reference:

Sanyal A, Harrison S, Ratziu V, et al. Changes in fibrosis, but not the NAFLD Activity Score (NAS), are associated with disease progression in patients with nonalcoholic steatohepatitis (NASH) and advanced fibrosis. Presented at: International Liver Congress; April 19-23, 2017; Amsterdam, Netherlands. Abstract GS-004. https://www.ilc-congress.eu/wp-content/uploads/2017/04/ebooks/abstract_book/21friday/2017EASL_Friday.pdf.