Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial
Stanley TL, Fourman LT, Feldpausch MN, Purdy J, Zheng I, Pan CS, Aepfelbacher J, Buckless C, +11 more
Lancet HIV (2019) · n=61
12-month randomized trial in HIV-associated NAFLD — tesamorelin reduced liver fat 37% on average, drove a third of treated participants below the 5% steatosis threshold, and prevented fibrosis progression on biopsy.
This is the Lancet HIV multicenter trial that elevated tesamorelin from a visceral-fat drug to a NAFLD drug with biopsy-grade fibrosis evidence. Investigators at Massachusetts General Hospital and the NIH randomized 61 antiretroviral-treated adults with HIV-associated nonalcoholic fatty liver disease (defined by hepatic fat fraction >5% on proton MR spectroscopy) to tesamorelin 2 mg subcutaneously daily or matching placebo for 12 months, with an optional 6-month open-label extension. The primary endpoint was change in hepatic fat fraction at 12 months. Tesamorelin produced an absolute 4.1% reduction in hepatic fat fraction versus placebo (95% CI -7.6 to -0.7; P=0.018), corresponding to a 37% relative reduction from baseline (P=0.016). Among tesamorelin recipients, 35% achieved hepatic fat fraction below the 5% steatosis threshold versus 4% on placebo (P=0.0069). The clinically most striking finding came from paired liver biopsies: fibrosis progressed in 10.5% of tesamorelin recipients versus 37.5% of placebo recipients (P=0.04) — the first prospective evidence that a GHRH-axis intervention can stall the hepatic fibrosis trajectory in NAFLD. C-reactive protein fell on tesamorelin (-4.7 mg/L effect; P=0.04), consistent with reduced hepatic inflammation, and fasting glucose and HbA1c did not differ significantly between groups across the 12-month period. Localized injection-site complaints were more frequent in the tesamorelin group; two participants discontinued for hyperglycemia.
The trial was conducted in HIV-positive adults with HIV-associated NAFLD; generalizability to broader non-HIV NAFLD/NASH populations is not formally established and is the central limitation for off-label biohacker interpretation. Sample size is modest (n=61) and the fibrosis-progression endpoint is reported in the subset with paired biopsies, not the full intent-to-treat population, which lowers the statistical robustness of that specific finding even though the effect size is striking. The biopsy histology readouts are conducted by a single expert pathologist (Kleiner of the NIH NAFLD network); inter-rater variability is not formally addressed. The hyperglycemia signal — two discontinuations in the tesamorelin arm — is consistent with the known GH-axis insulin-resistance concern and is one of the more important safety considerations for off-label long-duration use. Industry disclosure: Steven Grinspoon serves on the Theratechnologies scientific advisory board and holds a patent application for tesamorelin in hepatic disease; this is properly disclosed in the paper, and the trial was NIH-funded rather than industry-funded, which strengthens but does not eliminate the disclosure concern. The trial does not establish that tesamorelin reduces hard clinical outcomes (cirrhosis, hepatocellular carcinoma, liver-related mortality) — only that it improves the proximal liver-fat and fibrosis-progression endpoints over 12 months.
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