Treatment with tesamorelin, a synthetic growth hormone-releasing
hormone, reduced liver fat content and reduced the progression of liver fibrosis in people with HIV who had non-alcoholic
fatty liver disease (NAFLD), researchers report in the journal The Lancet HIV this month.
NAFLD – the accumulation of fat
in the liver – is a growing cause of liver disease in people living with HIV. Research
presented earlier this year at the International Liver Congress showed that the
prevalence of NAFLD more than doubled among people with HIV between 2006 and
2016 and accounted for 25% of cases of liver disease diagnosed in people living
with HIV receiving Medicare insurance. A study presented at the same conference
showed that almost a third of people living with HIV in cohorts in Italy and Canada
had NAFLD, and a quarter of these were at risk of progressing to advanced liver
The authors of the study published this week say that NAFLD
will soon become the greatest cause of liver-related ill health and deaths in
people living with HIV, as more people are cured of hepatitis C.
concentration of sugar in the blood.
Partial recovery from an illness, an alternative word for regression.
Abnormal fat deposits in the liver.
or pertaining to the internal organs.
The risk of developing NAFLD is higher in people who are obese,
especially if they have central fat accumulation.
NAFLD may lead to liver inflammation (NASH), scarring and
hardening of the liver (fibrosis) and to liver cancer. As people with HIV live
longer, conditions such as NAFLD are emerging as new health problems which
require monitoring and management.
Tesamorelin has been studied as a treatment for abdominal
fat accumulation, or lipodystrophy, in people living with HIV and is approved
for the reduction of visceral fat in people living with HIV in the United States.
It stimulates production of growth hormone, which is suppressed in people
living with HIV. The extent of growth hormone secretion inhibition corresponds
to central fat accumulation and weight gain.
By stimulating the production of growth hormone, tesamorelin
also promotes an increase in levels of insulin-line growth factor (IGF-1), which
promotes lipolysis (the breakdown of fats).
showed that tesamorelin reduced liver fat content over six months of follow-up
in people living with HIV.
To investigate the potential of tesamorelin as a treatment for
NAFLD in people living with HIV, investigators at Massachusetts General Hospital
and the US National Institutes of Health randomised 61 people living with HIV
who had hepatic steatosis (liver fat content of 5% or greater) to receive
either tesamorelin 2mg once daily or a placebo for 12 months, followed by
open-label tesamorelin treatment for all participants for six months.
The study excluded people who drank large amounts of
alcohol, people with poorly controlled diabetes, people with chronic hepatitis B
or C infection, and people with a variety of other liver conditions, including advanced
fibrosis or cirrhosis. The study also excluded people with active cancer (not
in remission), men with a history of prostate cancer and anyone receiving
treatment with systemic corticosteroids. The study also excluded anyone with a
CD4 count below 100 or a detectable viral load.
Tesamorelin was administered as a subcutaneous daily
injection and participants were trained in how to make up the powdered form of
the drug into an injectable form. Participants in the placebo group followed an
The study population was predominantly male (77% in the tesamorelin
group, 80% in the placebo group) and approximately two-thirds white.
The mean liver fat content was 12.9% in the tesamorelin group
and 14.7% in the placebo group.
Approximately one-third of participants had NASH and 48% of
the tesamorelin and 38% of the placebo group already has some degree of liver
fibrosis. 13.8% of the tesamorelin group and 6.9% of the placebo group has
stage 3 fibrosis.
The primary outcome of the study was the change in liver fat
fraction after 12 months of treatment. Intent-to-treat analysis showed that
hepatic fat fraction declined by 4.1% in the tesamorelin group but remained
unchanged in the placebo group (P = 0.018), a relative reduction of 37%
(p = 0.016).
Liver fat changes were not affected by race, antireroviral
use, statin use (32% of tesamorelin recipients and 46% of the placebo group
were taking a statin).
Just over a third of people in the tesamorelin group (35%)
experienced a reduction of hepatic fat below 5% by 12 months, so that they were
no longer classified as having NAFLD, compared to 4% of the placebo group
(p = 0.0069).
Tesamorelin recipients were significantly less likely to
experience progression of fibrosis (10% vs 37% in the placebo group, p = 0.044) and
there was an association between a higher level of liver inflammation (measured
by NAS score) and improvement in NAS score. Fibrosis was measured by biopsy at
baseline and after 12 months on treatment.
The investigators note that fibrosis stage is the most important
predictor of mortality in people with NAFLD and that preventing the progression
of fibrosis is an important criterion for judging the value of treatments for
There were no significant differences in liver enzymes,
fasting glucose, CD4 count, lipids or body weight between the two groups, except
for visceral adipose tissue, which fell significantly in the tesamorelin group.
There was no difference in adverse events between the two
groups, although two people in the tesamorelin group withdrew due to the
development of raised blood sugar (hyperglycaemia), a known side effect of the
drug. Tesamorelin was otherwise well tolerated and adherence to daily subcutaneous
injections was high (80% of all scheduled injections carried out in the
tesamorelin group and 87% in the placebo group), measured by returned vials of
The investigators say that further studies are needed to
find out if the effects on liver fat and fibrosis persist after discontinuation
of treatment, and when to initiate treatment with tesamorelin.