Reuters Health Information (2013-03-08): Leptin helpful in non-alcoholic steatohepatitis
Drug & Device Development
Leptin helpful in non-alcoholic steatohepatitis
Last Updated: 2013-03-08 13:26:21 -0400 (Reuters Health)
NEW YORK (Reuters Health) - Recombinant human methionyl leptin (metreleptin) appears highly effective for non-alcoholic steatohepatitis (NASH) in lipodystrophy patients with hypoleptinemia, a new paper says.
NASH is common not just in obesity but also in lipodystrophy syndromes. But "unlike obese patients, individuals with lipodystrophy are deficient in the hormone leptin, and thus leptin replacement with metreleptin is a promising therapy for the metabolic complications of lipodystrophy," senior author Dr. Philip Gorden told Reuters Health by email.
Dr. Gorden of the National Institutes of Health, Bethesda, Maryland, and colleagues reported on an open-label prospective study of leptin therapy in patients with inherited and acquired lipodystrophy, online February 22 in The Journal of Hepatology.
Patients were recruited worldwide. All 50 had liver biopsies at baseline and 27 did so following leptin replacement.
At baseline, 88% of patients met criteria for NASH. This proportion had fallen to 33% after an average 25.8 months of treatment. Steatosis mean score fell from 1.8 to 0.9. Ballooning injury scores were reduced from 1.2 to 0.4.
The authors report that nonalcoholic fatty liver disease scores also fell by a significant 42%, with the decrease "paralleled by significant reductions in metabolic parameters, including triglycerides, fasting glucose, hemoglobin A1c and transaminases."
Although the researchers were unable to show an improvement in fibrosis, those patients remained stable. "Importantly", say the investigators, "there was no worsening of fibrosis while on leptin therapy.
Given the lack of a control group and the small numbers, the authors say they can't establish a definite causative relationship between the improvement and metreleptin therapy. The improvements in NASH scores may have been spontaneous, they say.
However, they note, unlike patients with obesity-associated nonalcoholic fatty liver disease, "lipodystrophic patients cannot substantially alter the course of their disease by lifestyle modification without metreleptin therapy."
"The present paper," Dr. Gorden concluded, "demonstrates that therapy with metreleptin not only improves diabetes and lipids, but also significantly improves non-alcoholic steatohepatitis in these patients."
J Hepatol 2013.