Researchers found that an injectable hormone called tesamorelin decreases liver fat and prevented liver fibrosis in this patient population.
Non-alcoholic fatty liver disease (NAFLD) affects about a quarter of people with HIV. There are no effective treatments, and NAFLD carries a risk for progressive liver disease and liver cancer. However, researchers at the National Institutes of Health (NIH) and Massachusetts General Hospital (MGH) in Boston published research that found an injectable hormone called tesamorelin decreases liver fat and prevented liver fibrosis in this patient population.
The researchers, led by Colleen M. Hadigan, senior research physician in NIAID’s Laboratory of Immunoregulation, and Steven K. Grinspoon, chief of the Metabolism Unit at MGH, conducted research on whether tesamorelin could decrease liver fat in men and women with HIV and with NAFLD. In the research group, 43% of the patients had at least mild fibrosis, or scarring, of the liver. About a third, 33%, met the diagnostic criteria for nonalcoholic steatohepatitis (NASH), a more severe subpopulation of NAFLD.
In the study, 31 patients were randomized to receive daily 2mg injections of tesamorelin and 30 were given placebo injections. All patients received nutritional counseling and were trained in how to give themselves the injections. The researchers than evaluated liver health in both groups at the beginning of the trial and at the 12-month mark. They published the results in the journal The Lancet.
Liver health was evaluated by hepatic fat fraction (HFF), which is the ratio of fat to other tissue in the liver. In a healthy person, HFF is less than 5%. In the study, 35% of the patients receiving tesamorelin hit a normal level of HFF, while only 4% of those receiving the placebo injections did. The drug was well-tolerated and decreased the patients’ HFF by an absolute different of 4.1%, which corresponds to a 37% relative decrease from the beginning of the trial.
Nine patients who received the placebo had onset or worsening of fibrosis, while only two receiving tesamorelin did. Other blood markers were also analyzed, including the enzyme alanine aminotransferase (ALT), which decreased more among patients receiving tesamorelin compared to the placebo group.
“Our hope is that this intervention may help people living with HIV, as well as benefit HIV-negative people with liver abnormalities,” said Hadigan. “Further research may inform us of the potential long-term benefits of this approach and develop formulations that can benefit everyone with liver disease, regardless of HIV status.”
Thera Technologies’ Egrift (tesamorelin) was approved by the U.S. Food and Drug Administration (FDA) in 2010 to decrease excess abdominal fat in HIV patients with lipodystrophy. This lipodystrophy is marked by an abnormal body distribution and it was initially linked to older classes of HIV drugs.
In earlier clinical trials of Egrifta, side effects including joint pain, skin redness and rash, stomach pain, swelling, and muscle pain. Also, patients receiving Egrifta appeared to have more difficulty managing blood glucose levels.
“Because tesamorelin proved effective in treating abnormal fat build-up in the abdomens of people in the context of HIV and related medication use, we hypothesized that the drug might also reduce fat that accrues in the liver and causes damage in a similar population,” said Grinspoon.
