scarlet1967 wrote: Some details from this study so they are explaining the proteomic (studying proteins) and transcriptomic (studying molecules expressed from the genes) effect of tesamorelin a dual approach for the treatment of NAFL/NASH. Nothing new but they sum it up nicely and tied some loose ends (totality of data). I like the fact that they mentioned innovative treatment few times.
“Tesamorelin suppressed key angiogenic (blood vessel growth), fibrogenic (promoting the development of fibers) and pro-inflammatory mediators. CSF1 (gene), a regulator of monocyte (white blood cell that fight infections) recruitment and activation, may serve as an innovative therapeutic target for NAFLD in HIV.
Notably, compared to the general population, NAFLD has a more aggressive clinical course with a high frequency of nonalcoholic steatohepatitis (NASH) and fibrosis, and an accelerated rate of fibrosis progression among PLWH.
Within the tesamorelin-treated arm, reductions in plasma VEGFA (gene) and CSF1 correlated with a decline in NAS score. Furthermore, among tesamorelin-treated participants, reductions in TGFB1 (gene) and CSF1were associated with a decline in gene-level fibrosis score.
Notably, among tesamorelin-treated participants, decreases in plasma levels of VEGFA and CSF1 correlated with a reduction in NAS score, whereas declines in TGFB1 and CSF1 were associated with a decrease in fibrosis-related gene score.
Human and animal studies have shown hepatic upregulation of TGFB1 expression with NASH and fibrosis. Moreover, in a NASH mouse model, hepatocyte (liver cells)-specific TGFB receptor type II deficiency reduced hepatic steatosis, inflammation, hepatic stellate cell activation, and collagen deposition17. Given the role of TGFB1 in NAFLD, the decline in this growth factor with tesamorelin may contribute to its attenuation of NAFLD, and particularly fibrosis, progression in PLWH.
Taken together, in this focused proteomic analysis guided by a whole transcriptomic approach, we 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. The current study extends our knowledge of the biologic actions of GH axis augmentation to encompass systemic changes in key angiogenic, fibrogenic, and pro-inflammatory factors that may underlie a tesamorelin response. Notably, among these proteins, CSF1 is a key regulator of monocyte recruitment and activation that has not been previously well studied in the context of NAFLD, but may serve as an innovative therapeutic target in this regard. Lastly, our data indicate that VEGFA, TGFB1, and CSF1 are candidate biomarkers for a tesamorelin response among PLWH with NAFLD, which should be explored in future studies.”