As a result of the study, investigators suggested expanding the indication for tesamorelin (Egrifta) to include people living with HIV who have been diagnosed with nonalcoholic fatty liver disease (NAFLD), a comorbidity in HIV.
The injectable hormone tesamorelin (Egrifta) reduces liver fat and prevents liver fibrosis in patients living with HIV, according to a new study published this week in The Lancet HIV.
Tesamorelin was approved by the FDA in 2010 to reduce excess abdominal fat in HIV patients with lipodystrophy—a complication characterized by an abnormal distribution of body fat initially associated with older classes of HIV medications.
As a result of the study, investigators suggested expanding the indication for tesamorelin to include people living with HIV who have been diagnosed with nonalcoholic fatty liver disease (NAFLD), a comorbidity in HIV. They also recommend additional research to determine if tesamorelin could contribute to long-term protection against serious liver disease in people without HIV.
NAFLD affects as many as 25% of people living with HIV in the developed world. It has no effective treatment, despite the fact that it is a risk factor for progressive liver disease and liver cancer. While liver disease is often associated with heavy alcohol use, NAFLD occurs when excess fat builds up in the liver without alcohol as a contributing factor.
The research was conducted by the National Institute of Allergy and Infectious Diseases (NIAID) and the National Cancer Institute, both parts of the National Institutes of Health, as well as by researchers at Massachusetts General Hospital.
“Many people living with HIV have overcome significant obstacles to live longer, healthier lives, though many still experience liver disease,” NIAID Director Anthony S. Fauci, MD, said in a statement. “It is encouraging that tesamorelin, a drug already approved to treat other complications of HIV, may be effective in addressing non-alcoholic fatty liver disease.”
The randomized, double-blind study enrolled 61 patients with HIV and hepatatic fat fraction (HFF) of 5% or more by proton magnetic resonance spectroscopy. The healthy range for HFF is less than 5%. Among the participants enrolled, 43% had at least mild fibrosis and 33% met the diagnostic criteria for a more severe subset of NAFLD called nonalcoholic steatohepatitis (NASH).
Participants were randomly assigned to receive either tesamorelin 2 mg once a day (n = 31) or placebo once a day for 12 months (n = 30), followed by a 6-month open label phase, when all participants received the active drug 2 mg a day. In addition, researchers provided nutritional counseling as well as training in self-administering the daily injections; measures of liver health in both groups were compared with baseline and 12 months.
Patients receiving tesamorelin had a greater reduction of HFF than did patients receiving placebo, with an absolute difference of −4.1% (95% CI; −7.6 to −0.7; P = .018), corresponding to a −37% (95% CI; −67 to −7; P = .016) relative reduction from baseline.
After 12 months, 35% of individuals receiving tesamorelin and 4% receiving placebo had a HFF of less than 5% (P = .0069). Changes in fasting glucose and glycated hemoglobin were not different between the groups at 12 months.
Patients receiving tesamorelin experienced more localized injection site complaints than those in the placebo group, but they were mild. Overall, tesamorelin was well-tolerated.
While nine participants receiving placebo experienced onset or worsening of fibrosis, only 2 participants in the tesamorelin group experienced the same. Additionally, levels of several blood markers associated with inflammation and liver damage—including the enzyme alanine aminotransferase—decreased more among those taking tesamorelin compared to those on a placebo, particularly among those with increased levels at the beginning of the study.
The most commonly reported side effects in previous clinical trials evaluating the drug included joint pain (arthralgia), skin redness and rash at the injection site (erythema and pruritis), stomach pain, swelling, and muscle pain (myalgia). Worsening blood sugar control occurred more often in trial participants treated with tesamorelin than with placebo.
Stanley T, Fourman LT, Feldpausch MN, et al. Effects of tesamorelin on non alcoholic fatty liver disease in HIV: a randomized, double-blind, multicenter trial [published online October 11, 2019]. Lancet HIV. doi: 10.1016/S2352-3018(19)30338-8.