Egrifta improves liver health in people living with HIV
Egrifta (tesamorelin), a growth hormone releasing factor analogue, turns off genes that promote inflammation and scar tissue build-up in people living with HIV who have non-alcoholic fatty liver disease (NAFLD) , thereby improving the health of their liver and potentially reducing the risk of liver cancer, according to a recent study.
“These data demonstrate for the first time how tesamorelin reduces the accumulation of fat in the liver and improves the expression of hepatic genes that reflect an overall return to liver health in people living with HIV-associated NAFLD / NASH “Steven Grinspoon, MD, of Massachusetts General Hospital, said in a Press release of Theratechnologies.
NAFLD and its most severe form, non-alcoholic steatohepatitis (NASH), are increasing causes of advanced liver disease. The buildup of fat in the liver triggers inflammation, which over time can lead to liver fibrosis (build-up of scar tissue), cirrhosis, and liver cancer. NAFLD is common in people living with HIV and appears to progress more rapidly in this population. In the absence of currently approved effective medical therapies, management relies on lifestyle changes such as weight loss and exercise.
Egrifta, a self-administered once-daily injectable medicine, mimics a natural hormone produced in the brain that triggers the release of growth hormone, which both builds muscle and breaks down fat. It was approved in 2010 as a treatment to reduce excess abdominal fat in HIV-positive people with lipodystrophy.
Research has shown that Egrifta may also reduce liver fat in HIV-positive people with NAFLD, although it is not yet approved for this indication. In a phase II trial by the Grinspoon team published in 2019, Egrifta decreased the accumulation of fat in the liver and prevented the progression of fibrosis compared to placebo in people with HIV-associated NAFLD.
Now, a substudy from this trial has shed light on how the drug reduces liver fat and fibrosis. As described in JCI Insight, Grinspoon and colleagues evaluated the effect of Egrifta on genetic pathways in liver biopsy samples from HIV-positive people with NAFLD who participated in the study.
By comparing matched liver biopsy samples taken at the start of the trial and after a year of treatment, the researchers found that Egrifta increased gene expression related to oxidative phosphorylation, the process by which nutrients are broken down to provide energy to cellular power plants called mitochondria. .
“Mitochondrial insufficiency may promote the accumulation of hepatic fat and the generation of toxic lipid metabolites, increasing oxidative stress, cell death, inflammation and fibrosis, which are key events in the progression of NAFLD”, wrote the study authors.
In addition, Egrifta resulted in decreased expression of genes related to inflammation, tissue repair and cell division. These changes in gene expression were correlated with an improvement in fibrosis and a decrease in biomarkers related to inflammation.
Excessive cell growth as the liver tries to repair tissue damage is responsible for the buildup of scar tissue and can trigger hepatocellular carcinoma (HCC), the most common type of liver cancer. The substudy showed that Egrifta up-regulates genes associated with a favorable prognosis for HCC while down-regulating those associated with poor outcome.
“Our results inform our knowledge of the biology of growth hormone action on the liver and provide a mechanistic basis for the observed clinical effects of tesamorelin on the liver,” the study authors concluded.
“Given that the HIV population is at high risk for NAFLD and increased rates of fibrosis progression, there is a critical need for dedicated studies among this group of patients,” they wrote. “Our results may also provide information for other populations with NAFLD, and thus provide a strong rationale for further studies.”
Click here to learn more about HIV-related lipodystrophy.