Patients with nonalcoholic steatohepatitis treated with colesevelam may experience a small increase in liver fat detectable only through MRI and spectroscopy, according to recent results.
In a placebo-controlled trial, researchers randomly assigned 50 patients with biopsy-proven nonalcoholic steatohepatitis (NASH) to receive either 3.75 g oral bile acid sequestrant colesevelam daily or placebo for 24 weeks. Participants underwent follow-up visits at weeks 4, 12 and 24, when they received blood tests, and their body weight and vital signs were documented. Proton-density-fat-fraction (PDFF) MRI and magnetic resonance spectroscopy (MRS) were used to measure liver fat at baseline and after therapy. Patients underwent liver biopsy upon completion of treatment, and an additional 8 weeks of follow-up was conducted to assess side effects.
“There are currently no FDA-approved treatments for NASH,” researcher Rohit Loomba, MD, MHSc, assistant professor of clinical medicine in the gastroenterology division at University of California at San Diego, told Healio.com. “Our study was conducted to assess rigorously the effects of this class of medication as a potential treatment for NASH.”
Mean liver fat increased among patients receiving colesevelam (14.2% to 17.0%, P=.01) with a mean difference of 5.6% compared with the placebo group, which experienced a mean liver fat decrease from 17.9% to 15.2% (P=.002). Cross-validation of the results with colocalized MRS indicated a difference in liver fat increase of 4.9% (P=.014) between the groups, and investigators found a strong correlation between the MRI-PDFF and MRS results (r2=0.96, P<.0001).
Analysis of posttreatment liver biopsy of 17 treated and 14 placebo patients did not indicate a difference in steatosis grade. Seven of the treated patients and two in the placebo group exhibited a 2-point improvement in nonalcoholic fatty liver disease activity score (P=.10).
No difference was observed in the incidence rate of adverse events between the two groups. Two patients in the treated group dropped out of the study, including one who had high triglycerides at baseline and one who experienced diffuse muscle ache considered unrelated to treatment.
“This is the first randomized, double blinded, placebo-controlled trial studying the effects of a bile acid sequestrant in patients with NASH,” Loomba said. “Colesevelam … causes liver fat increase in NASH patients, and this is measurable only by MRI-PDFF technique and not by liver biopsy. MRI-PDFF is a novel technique that should be used to quantify liver fat in future NASH clinical trials.”