Tesamorelin has demonstrated extraordinary benefits for liver health, particularly in addressing non-alcoholic fatty liver disease (NAFLD). Nonalcoholic fatty liver disease (NAFLD) is a substantial cause of comorbidity in people living with HIV (PLWH), without proven pharmacologic treatments in this population. Researchers assessed the effects of tesamorelin on liver fat and histology in PLWH with NAFLD.
Tesamorelin (N=26) reduced HFF compared to placebo (N=28), with an absolute effect size of −4.1% (95% CI −7.6, −0.7, P=0.02), corresponding to a −37% (CI −67, −7, P=0.02) relative reduction.
The data demonstrate that tesamorelin, currently FDA approved for reduction of abdominal fat accumulation in PLWH, robustly decreases liver fat, while also preventing fibrosis progression, in association with improvement in indices of liver inflammation among PLWH with NAFLD.
In a recent randomized placebo-controlled trial, researchers 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.
In a recent clinical trial in HIV patients with NAFLD, tesamorelin reduced liver fat content and prevented liver inflammation and fibrosis progression.
Growth hormone increases lipolysis and suppresses de novo lipogenesis in the liver. Tesamorelin, a growth hormone-releasing hormone analogue, increases endogenous pulsatile growth hormone production and reduces visceral fat in people with HIV.
Using gene set enrichment analysis, researchers 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.
In an unbiased analysis of the MSigDB hallmark gene sets, researchers found that tesamorelin led to hepatic upregulation of oxidative phosphorylation genes compared with placebo over 1 year. Furthermore, among tesamorelin-treated participants, enhanced expression of these genes related to oxidative phosphorylation was associated with decreased fibrosis-related gene score and degree of hepatic fat reduction. Moreover, increases in oxidative phosphorylation were related to increased IGF-1 transcription, providing evidence linking augmented GH signaling to increased oxidative phosphorylation.
Tesamorelin downregulated hepatic gene sets involved in inflammation, tissue repair, and cell division. In a focused proteomic analysis guided by a whole transcriptomic approach, researchers identified VEGFA, TGFB1, and CSF1 as novel proteins whose circulating levels were reduced by tesamorelin in association with a decline in NAFLD severity among PLWH with NAFLD.
Tesamorelin suppressed key angiogenic, fibrogenic, and pro-inflammatory mediators. CSF1, a regulator of monocyte recruitment and activation, may serve as an innovative therapeutic target for NAFLD in HIV.
Tesamorelin is given subcutaneously and has major effects on glucose and lipid metabolism, but has not been linked to serum aminotransferase elevations during therapy or to instances of clinically apparent acute liver injury.
Tesamorelin has been associated with decreased liver fat content, potentially improving liver health. This makes Tesamorelin a uniquely valuable therapeutic option for individuals concerned about liver health.
