LAUSR

Sustained weight loss improves liver histology in non‐alcoholic fatty liver disease. This post hoc analysis of four phase III, 56‐week, randomized controlled trials investigated if extended‐release naltrexone and bupropion (NB) affects alanine aminotransferase (ALT) and Fibrosis‐4 (FIB‐4) index in adults with overweight or obesity. Two thousand and seventy‐three subjects (NB = 1310; placebo = 763; 79.0% female; 81.6% Caucasian) had baseline mean weight 101 kg, body mass index 36.2 kg/m2, ALT 26.9 IU/L and FIB‐4 0.79. At 56 weeks, NB‐treated subjects experienced more weight loss than placebo (8.7 vs. 3.2 kg, respectively, P < .0001). Weight loss, independent of treatment, was associated with improved ALT and FIB‐4 (P < .0001). There was a significant independent effect of NB on change from baseline for FIB‐4 (P < .0001), but not for ALT (P = .54). Categorical ALT response (from above to within normal ranges: 10‐40 IU/L for men; 7‐35 IU/L for women) and achievement of 25% and 50% reduction in ALT were greater for NB versus placebo, and independently affected by weight loss (P < .0001), but not treatment. NB‐associated weight loss may improve liver health by normalizing ALT values for those with high baseline levels.