Metreleptin therapy for nonalcoholic steatohepatitis: Open-label therapy interventions in two different clinical settings

Summary Background Recombinant leptin therapy reverses nonalcoholic steatohepatitis (NASH) in leptin-deficient lipodystrophy. We inquired if leptin therapy would improve NASH in more common forms of this heterogeneous condition. Methods Nine male patients with relative leptin deficiency (level, Findings Of 9 participants recruited in the relative leptin deficiency treatment study, 7 completed 12 months of therapy. Mean global NASH scores were reduced from 8 ± 3 to 5 ± 2 (range, from 1 to 6; p = 0.004). In the partial lipodystrophy study, 19 of 22 subjects completed 12 months of treatment and 18 completed a second liver biopsy. Global NASH scores also reduced significantly from 6 ± 2 to 5 ± 2 (range, from −2 to 4; p = 0.008). In both studies, the predominant changes were in steatosis and hepatic injury scores. Conclusions Our findings show that patients with NASH associated with both relative leptin deficiency and partial lipodystrophy have reductions in hepatic steatosis and injury in response to exogenous leptin therapy. Moreover, leptin deficiency may have regulatory effects in mediating fat deposition and ensuing injury in the liver. Funding NIH grants R03 DK074488 (E.A.O.) and R01 DK088114 (E.A.O. and H.S.C.).