Liver fat changes unreliable for some histological predictions

Changes in liver fat can predict changes in steatosis but not other liver histological parameters like improvements in nonalcoholic fatty liver disease activity score or resolution of nonalcoholic steatohepatitis without worsening of fibrosis, according to data published in Journal of Hepatology.

“The clinical implication of our findings is that MRI-based imaging may not be as reliable as previously believed to guide about the clinical efficacy of a given intervention in patients with NASH,” Fernando Bril, MD, from the University of Florida, and colleagues wrote.

The study comprised 121 patients with NASH who participated in one of three randomized control trials designed to evaluate response to Actos (pioglitazone, Takeda Pharmaceuticals). The degree of steatosis at baseline as measured by either MRI-proton density fat fraction (MRI-PDFF) or proton magnetic resonance spectroscopy (¹H-MRS).

The researchers divided patients based on relative change of intrahepatic triglyceride (IHTG) content after therapy (no change or increase; reduction of 1% to 30%; reduction of 31% to 50%; reduction of 51% to 70%; and reduction of more than 70%).

Results showed no difference in NASH resolution between patients with an IHTG reduction of more than 30% vs. those with less reduction in either the treated or placebo groups. Reduction by 2 points in NAFLD activity score and no worsening of fibrosis rates were also similar.

There was no difference in resolution of NASH or reduction of NAFLD activity score without worsening of fibrosis between patients who achieved “normal” IHTG content of less than 5.56% compared with those with a higher content percentage.

Additionally, the researchers observed no correlations between IHTG reduction and histological parameters including lobular inflammation, hepatocyte ballooning, and fibrosis.

Relative changes in IHTG content after follow-up correlated with changes in plasma alanine aminotransferase (r = 0.23; P = .008); however, improvements of plasma ALT were of similar magnitude in both patients with steatosis resolution and those who did not achieve resolution.

“The most straightforward implication of these findings is that the use of MRI-PDFF or ¹H-MRS cannot be considered as useful as currently believed to assess histological response to treatment. In addition, it calls for a paradigm shift about individual histological parameters improving in tandem,” Bril and colleagues concluded. “Until [further] studies become available, randomized controlled trials using IHTG as a surrogate endpoint for broader histological response should be interpreted with caution.” – by Talitha Bennett

Disclosures: Bril reports no relevant financial disclosures. Please see the full study for all other authors’ relevant financial disclosures.