Factors Associated with Histologic Response in Adult Patients with Nonalcoholic Steatohepatitis.

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FLINT Trial; FXR agonist; NAFLD; OCA


BACKGROUND AND AIMS: Nonalcoholic steatohepatitis (NASH) is a leading cause of liver transplantation and many trials are underway to evaluate potential therapies. The farnesoid X receptor ligand obeticholic acid in NASH treatment trial evaluated the effects of obeticholic acid vs placebo on histologic response (defined as decrease in nonalcoholic fatty liver disease activity score [NAS] by ≥2, with no worsening of fibrosis); 45% of patients had a histologic response to obeticholic acid (25 mg) and 21% had a response to placebo (P

METHODS: We used a logistic regression model with a stepwise selection procedure to identify baseline and early on-treatment factors associated with a histologic response at 72 weeks. Baseline demographics, liver histology, medical history, concomitant medications, cardiometabolic parameters, and serum biochemistry as well as the changes over the course of the trial (at weeks 12 and 24) were evaluated as potential predictors of a histologic response. The model was cross-validated by a jackknife method and performance was evaluated with the area under the receiver operating characteristic curve (AUROC).

RESULTS: The logistic regression model found obeticholic acid treatment, baseline NAS>5, baseline triglycerides≤154 mg/dL, baseline international normalized ratio≤1, baseline aspartate aminotransferase≤49 U/L, and a decrease in alanine aminotransferase at week 24 by 17 U/L or more, to be significantly associated with histologic response (AUROC, 0.83; 95% CI, 0.77-0.89; P<.0001).

CONCLUSIONS: In a secondary analysis of data from a clinical trial of obeticholic acid in patients with NASH, we identified routine clinical and laboratory paramenters during the first 24 weeks of treatment (such as baseline NAS, triglyceride levels, and a decrease in alanine aminotransferase) to significantly associate with histologic markers of response.

Clinical Institute

Digestive Health