Study summary · research use only
Effects of tesamorelin on hepatic transcriptomic signatures in HIV-associated NAFLD
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This study analyzed liver biopsy specimens from a previously reported randomized placebo-controlled trial of tesamorelin, a growth hormone-releasing hormone analog, in human patients with HIV-associated nonalcoholic fatty liver disease (NAFLD), to identify hepatic gene pathways modulated by the drug versus placebo. Using gene set enrichment analysis, tesamorelin was associated with increased hepatic expression of gene sets involved in oxidative phosphorylation and decreased expression of gene sets involved in inflammation, tissue repair, and cell division, along with reciprocal changes in gene sets linked to favorable versus poor hepatocellular carcinoma prognosis. Among tesamorelin-treated participants, these expression changes correlated with an improved fibrosis-related gene score. The authors describe the findings as informing understanding of pulsatile growth hormone action and providing a mechanistic basis for tesamorelin's previously observed liver effects.
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a common comorbidity among people living with HIV that has a more aggressive course than NAFLD among the general population. In a recent randomized placebo-controlled trial, we demonstrated that the growth hormone-releasing hormone analog tesamorelin reduced liver fat and prevented fibrosis progression in HIV-associated NAFLD over 1 year. As such, tesamorelin is the first strategy that has shown to be effective against NAFLD among the population with HIV. The current study leveraged paired liver biopsy specimens from this trial to identify hepatic gene pathways that are differentially modulated by tesamorelin versus placebo. Using gene set enrichment analysis, we found that tesamorelin increased hepatic expression of hallmark gene sets involved in oxidative phosphorylation and decreased hepatic expression of gene sets contributing to inflammation, tissue repair, and cell division. Tesamorelin also reciprocally up- and downregulated curated gene sets associated with favorable and poor hepatocellular carcinoma prognosis, respectively. Notably, among tesamorelin-treated participants, these changes in hepatic expression correlated with improved fibrosis-related gene score. Our findings inform our knowledge of the biology of pulsatile growth hormone action and provide a mechanistic basis for the observed clinical effects of tesamorelin on the liver.
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