Medical researchers from the US National Institutes of Health and the Massachusetts General Hospital (MGH) in Boston report that the injectable hormone tesamorelin
) reduces liver fat and prevents liver fibrosis
(scarring) in people living with HIV.
Dr Anthony S. Fauci,NIAID Director (NIAID is one of the entities under the NIH) commented in a phone interview with Thailand Medical
News “Many people living with HIV
have overcome significant obstacles to live longer, healthier lives, though many still experience liver disease
.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 findings were published in October in the The Lancet HIV
or Non-alcoholic fatty liver disease
frequently occurs alongside HIV,
affecting as many as 28% of people living with HIV
in the developed world. No effective treatments currently exist to treat the condition, which is a risk factor for progressive liver disease
and liver cancer.
Medical researchers led by Colleen M. Hadigan, M.D., senior research physician in NIAID’s Laboratory of Immunoregulation, and Steven K. Grinspoon, M.D., Chief of the Metabolism Unit at MGH, tested whether tesamorelin
could decrease liver fat in men and women living with both HIV and NAFLD.
Of 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)
. Thirty-one participants were randomized to receive daily 2-mg injections of tesamorelin
, and 30 were randomized to receive identical-looking injections containing a placebo. Researchers then compared measures of liver health in both groups at baseline and 12 months.
After 12 months, participants receiving tesamorelin
had better liver health than those receiving placebo, as defined by reduction in hepatic fat fraction (HFF) ie the r
atio of fat to other tissue in the liver. The healthy range for HFF is less than 5%. Thirty-five percent of study participants receiving tesamorelin
achieved a normal HFF, while only 4% of those on placebo reached that range with nutritional advice alone. Overall, tesamorelin
was well-tolerated and reduced participants’ HFF by an absolute difference of 4.1% (corresponding to a 37% relative reduction from the beginning of the study). While nine participants receiving placebo experienced onset or worsening of fibrosis, only two 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 (ALT),decreased more among those taking tesamorelin
compared to those on a placebo, particularly among those with increased levels at the beginning of the study.
Considering these positive results, investigators suggest expanding the indication for tesamorelin t
o include people living with HIV
who have been diagnosed with NAFLD
. They also recommend additional research to determine if tesamorelin could contribute to long-term protection against serious liver disease in people without HIV.
Dr Colleen M. Hadigan further commented to Thailand Medical
News via phone, “Our hope is that this intervention may help people living with HIV
, as well as benefit HIV
-negative people with liver abnormalities.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
) was approved in 2010 by the US FDA 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. The most commonly reported side effects in previous clinical trials evaluating Egrifta
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 Egrifta
than with placebo.
proved effective in treating abnormal fat build-up in the abdomens of people in the context of HIV
and related medication use, the researchers hypothesized that the drug might also reduce fat that accrues in the liver and causes damage in a similar population.
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. This condition may progress to liver damage, cirrhosis or cancer that could be life-threatening and necessitate liver transplantation.
Previous studies have found that vitamin E supplements, weight loss and other lifestyle changes can improve outcomes among HIV
-negative people with NASH
. However, treatment options for NASH
are often not tested in people with HIV
and none are available for this group. Obesity and type 2 diabetes raise the risk of developing NAFLD
regardless of HIV
status, and people with HIV
are at increased risk of NAFLD
because some HIV
medications and HIV
itself are associated with gaining abdominal fat and may contribute to liver fat build-up.
Individuals living with HIV
are advised to have routine liver screenings and if signs of NAFLD
or liver fibrosis are developing to consult their doctors about starting Tesamorelin
Reference: “Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial” by Takara L Stanley, MD; Lindsay T Fourman, MD; Meghan N Feldpausch, ANP; Julia Purdy, CRNP; Isabel Zheng, BS; Chelsea S Pan, BA; Julia Aepfelbacher, BS; Colleen Buckless, MS; Andrew Tsao, BS; Anela Kellogg, MSN; Karen Branch, RN; Hang Lee, PhD; Chia-Ying Liu, MD; Kathleen E Corey, MD; Raymond T Chung, MD; Martin Torriani, MD; Prof David E Kleiner, MD; Colleen M Hadigan, MD and Prof Steven K Grinspoon, MD, 11 October 2019, The Lancet HIV. DOI: 10.1016/S2352-3018(19)30338-8