Study summary · research use only
Delineating tesamorelin response pathways in HIV-associated NAFLD using a targeted proteomic and transcriptomic approach
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This study analyzed plasma samples from a prior randomized-controlled human trial of tesamorelin in HIV-associated NAFLD, using a targeted proteomic assessment of 9 plasma proteins corresponding to genes identified in earlier transcriptomic analysis. Compared with placebo, tesamorelin was associated with reductions in vascular endothelial growth factor A (VEGFA, P = 0.02), transforming growth factor beta 1 (TGFB1, P = 0.05), and macrophage colony stimulating factor 1 (CSF1, P = 0.004). Among tesamorelin-treated participants, reductions in VEGFA (r = 0.62) and CSF1 (r = 0.50) correlated with a decline in NAFLD activity score, and decreases in TGFB1 (r = 0.61) and CSF1 (r = 0.64) were associated with a reduced gene-level fibrosis score. The authors describe CSF1 as a possible target for further research in HIV-associated NAFLD.
Abstract
NAFLD is a leading comorbidity in HIV with an exaggerated course compared to the general population. Tesamorelin has been demonstrated to reduce liver fat and prevent fibrosis progression in HIV-associated NAFLD. We further showed that tesamorelin downregulated hepatic gene sets involved in inflammation, tissue repair, and cell division. Nonetheless, effects of tesamorelin on individual plasma proteins pertaining to these pathways are not known. Leveraging our prior randomized-controlled trial and transcriptomic approach, we performed a focused assessment of 9 plasma proteins corresponding to top leading edge genes within differentially modulated gene sets. Tesamorelin led to significant reductions in vascular endothelial growth factor A (VEGFA, log2-fold change - 0.20 ± 0.35 vs. 0.05 ± 0.34, P = 0.02), transforming growth factor beta 1 (TGFB1, - 0.35 ± 0.56 vs. - 0.05 ± 0.43, P = 0.05), and macrophage colony stimulating factor 1 (CSF1, - 0.17 ± 0.21 vs. 0.02 ± 0.20, P = 0.004) versus placebo. Among tesamorelin-treated participants, reductions in plasma VEGFA (r = 0.62, P = 0.006) and CSF1 (r = 0.50, P = 0.04) correlated with a decline in NAFLD activity score. Decreases in TGFB1 (r = 0.61, P = 0.009) and CSF1 (r = 0.64, P = 0.006) were associated with reduced gene-level fibrosis score. 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. Clinical Trials Registry Number: NCT02196831.
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