Le TA et al. – Colesevelam increases liver fat in patients with nonalcoholic steatohepatitis (NASH) as assessed by magnetic–resonance–imaging (MRI) as well as MR spectroscopy (MRS) without significant changes seen on histology. Thus, MRI and MRS may be better than histology to detect longitudinal changes in hepatic fat in NASH. Underlying mechanisms and whether the small MR detected increase in liver fat has clinical consequences is not known.

• Fifty patients with biopsy-proven NASH were randomly assigned to either colesevelam 3.75 gram/day orally or placebo for 24 weeks.
• The primary outcome was change in liver fat as measured by MRI PDFF in co-localized regions of interest within each of the nine liver segments.

• Compared with placebo, colesevelam increased liver fat by MRI PDFF in all nine segments of the liver with a mean difference of 5.6% (p=0.002).
• The authors cross-validated the MRI-PDFF determined fat content with that assessed by co-localized MRS; the latter showed a mean difference of 4.9% (p=0.014) in liver fat between the colesevelam and the placebo-arms.
• MRI PDFF correlated strongly with MRS determined hepatic fat content (r2=0.96, P<0.0001).
• Liver biopsy assessment of steatosis, cellular injury and lobular inflammation did not detect any effect of treatment.