One of the known comorbidities of HIV is non-alcoholic fatty liver disease (NAFLD), a condition characterized by excess fat in the liver in the absence of significant alcohol consumption. People with NAFLD often suffer from hepatic fibrosis , or scar tissue, which can impair liver function and lead to liver failure.
Antiretroviral therapy (ART) has been implicated in the development of excess abdominal fat , or lipodystrophy, which is itself a risk factor. Recognizing the threat that HIV and its treatment can pose to the liver, scientists tested a hormone analogue known as tesamorelin and found that it reduced liver fat and prevented the progression of fibrosis in a population of people living with HIV.
A team of researchers from the National Institutes of Health (NIH) and Massachusetts General Hospital in Boston recruited 61 people to participate in the study. All were adults, and none were heavy drinkers. Each had a hepatic fat fraction (the percentage of the liver composed of fatty tissue) of at least 5%, above average. Participants were randomly assigned in a 1:1 ratio to receive the standard 2 mg daily dose of tesamorelin or a placebo daily. After one year of receiving tesamorelin or a placebo, all participants received tesamorelin for six months.
Researchers found that 35% of participants taking tesamorelin were able to reduce their liver fat fraction to the normal range, while only 4% of those in the placebo group achieved the same. Only two people in the tesamorelin arm of the study saw their fibrosis progress, while nine in the placebo group experienced this outcome. The study team also observed that certain blood markers for liver damage and inflammation decreased more in the tesamorelin group.
Although newer ART regimens do not cause lipodystrophy, patients who took older antiretroviral drugs may still experience its effects. “Patients who have received older antiretrovirals and have lipodystrophy often continue to have this condition for years and are known as so-called inherited patients, with residual lipodystrophy despite a switch to more HIV-friendly regimens, for reasons that are unclear,” Steven Grinspoon, MD, chief of the metabolism unit at Massachusetts General Hospital and author of the study, told Contagion® . “The prevalence of NAFLD in HIV is high, and no one expects it to decrease anytime soon, so there is a great need for therapeutic treatment.”
Tesamorelin proved equally effective in men and women, working more efficiently in those with more fat to lose. While the hormone was specifically developed to help people with HIV suffering from NAFLD, others may benefit, Grinspoon said: “[It is not approved by the U.S. Food and Drug Administration (FDA) for use in patients who do not have HIV. Analogous studies are being conducted to determine whether it reduces liver fat in patients without HIV.”]
Grinspoon said tesamorelin is not recommended for people with uncontrolled diabetes or active cancers, though she added that negative effects such as increased glucose levels or higher rates of malignancy have not been demonstrated. “This precaution is seen with all growth hormone-boosting products, just to be safe,” she said.
In 2010, the FDA approved the use of tesamorelin in people with HIV who have lipodystrophy, and Grinspoon would like to see it prescribed more widely. “It’s certainly even more compelling now to use this drug in HIV patients with significant abdominal fat accumulation, many of whom are likely to have fat in their liver, which we’ve now shown to be reduced,” he said. “So, there are two benefits. We’re working on larger studies to confirm our findings, but the results are compelling and robust, and very exciting.”
Co-author Colleen Hadigan, MD, MPH, senior research physician at the National Institute of Allergy and Infectious Diseases' Laboratory of Immune Regulation, part of the NIH, agreed. "I think this opens an opportunity to rethink prescribing practices," she told Contagion® , emphasizing that physicians don't need to test for fatty liver in a patient with HIV and abdominal fat before recommending tesamorelin. "This could be additional clinical information to justify adding another medication."
By Laurie Saloman, In: https://www.contagionlive.com/news/tesamorelin-promising-in-people-with-hiv-and-nafld