living with HIV who have non-alcoholic fatty liver disease (NAFLD)
often have liver fibrosis and are at risk for fibrosis worsening,
researchers reported earlier this month at the Conference on Retroviruses and Opportunistic Infections (CROI 2020).
The research was presented virtually after the in-person
meeting in Boston was cancelled due to the coronavirus crisis.
NAFLD and its more severe form, non-alcoholic steatohepatitis (NASH),
are responsible for a growing proportion of advanced liver disease as
obesity rates rise worldwide. Research presented
at last year's International Liver Congress showed that the prevalence
of NAFLD more than doubled between 2006 and 2016 among people with HIV
receiving Medicare insurance in the United States. Another study showed
that almost a third of HIV-positive people in Italy and Canada had
The accumulation of fat in the liver triggers inflammation, which
over time can lead to fibrosis (build-up of scar tissue), cirrhosis and
liver cancer. There are currently no approved therapies for NAFLD or
NASH, and management relies on lifestyle changes such as weight loss and
Improvement in a tumour. Also, a mathematical model that allows us to measure the degree to which one of more factors influence an outcome.
Abnormal fat deposits in the liver.
or pertaining to the internal organs.
Dr Lindsay Fourman of Massachusetts General Hospital in
Boston presented findings from a study of liver fibrosis among
HIV-positive people with NAFLD in a clinical trial of tesamorelin (Egrifta).
Fibrosis severity is the strongest predictor of mortality in people
with HIV-associated NAFLD, the researchers noted as background.
Tesamorelin is a synthetic growth hormone-releasing hormone. It
stimulates the production of growth hormone, which promotes the
breakdown of fat. It is approved in the US as a treatment for abdominal
fat accumulation (lipodystrophy) in people living with HIV; it is not
approved in Europe.
The study included 61 participants. About 80% were men and two-thirds
were white. They had had HIV for a median of 16 years and current CD4
counts were high, with the median exceeding 700 cells/mm3.
People with chronic hepatitis B or C, heavy alcohol consumption, poorly
controlled diabetes or cirrhosis were excluded. NAFLD was defined as
having liver fat content of 5% or greater.
The participants were randomly assigned to receive
tesamorelin or a placebo, given by self-administered daily injections
for 12 months. They underwent liver biopsies at baseline and again at 12
months. Visceral fat (internal fat surrounding the abdominal organs)
and subcutaneous fat (fat lying under the skin) were measured using MRI
scans, while liver fat content was assessed by magnetic resonance
As reported recently in The Lancet HIV,
the study showed that tesmorelin reduced liver fat content and slowed
the progression of liver fibrosis in people with HIV and NAFLD.
Fourman's CROI study analysed the biopsy samples collected in the
trial to identify predictors of fibrosis presence and progression.
Samples were available for 58 people assigned to tesamorelin and 24
At study entry, a third of the participants had NASH and
43% already had some degree of liver fibrosis. Of these, 36% had mild
fibrosis (stage F1), 40% had moderate fibrosis (stage F2) and 24% had
advanced fibrosis (stage F3).
The presence of fibrosis was associated
with more visceral fat, but
not with subcutaneous fat or body mass index (BMI). People with fibrosis
had higher NAFLD activity scores – a composite measure made up of
steatosis (fat accumulation), inflammation and 'ballooning' (swelling)
of liver cells – as well as higher ALT and AST liver enzyme levels
(biomarkers of liver inflammation). However, the amount of liver fat did
not differ significantly between those with and without fibrosis.
Looking at the placebo group – reflecting the natural course of liver
disease progression when not treated with tesamorelin – 38% experienced
fibrosis progression over 12 months, 13% showed regression and 50%
remained stable. More than half of those with fibrosis progression had
no evidence of fibrosis at baseline. People with worse fibrosis at
baseline were most likely to see improvement.
Higher visceral fat content at baseline was the only
significant predictor of fibrosis progression. Liver fat content, NAFLD
activity score and BMI at baseline were not significantly link to
progression. Age, sex, duration of HIV and CD4 count were not associated
with either presence of fibrosis at baseline or fibrosis progression.
"We demonstrated a high prevalence and progression
rate of biopsy-proven liver fibrosis" in people with HIV and NAFLD, the
This fibrosis progression rate was more than six times higher than
rates previously seen in the general HIV-negative population, they
"Visceral adiposity was found to be a novel clinical predictor of
accelerated hepatic disease, which suggests that therapies to reduce
visceral fat may be particularly effective in HIV-associated NAFLD,"
lead investigator Dr Steve Grinspoon of Harvard Medical School and
Massachusetts General Hospital said in a press release from Theratechnologies, the company that makes tesamorelin.