HIV-positive people with fatty liver disease are at high risk for fibrosis

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People living with HIV who have non-alcoholic fatty liver disease (NAFLD) often have liver fibrosis and are at risk for fibrosis worsening, researchers reported last week at the Conference on Retroviruses and Opportunistic Infections (CROI 2020). The research was presented virtually last week 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 NAFLD.

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 exercise.



Thickening and scarring of connective tissue. Often refers to fibrosis of the liver, which can be caused by an inflammatory reaction to long-term hepatitis infection. See also ‘cirrhosis’, which is more severe scarring.

non-alcoholic fatty liver disease (NAFLD)

Non-alcoholic fatty liver disease (NAFLD) is a very common disorder and refers to a group of conditions where there is accumulation of excess fat in the liver of people who drink little or no alcohol. The most common form of NAFLD is a non-serious condition called fatty liver, by which fat accumulates in the liver cells. A small group of people with NAFLD may have a more serious condition named non-alcoholic steatohepatitis (NASH).


Pertaining to the internal organs. Visceral fat is fat tissue that is located deep in the abdomen and around internal organs.


non-alcoholic steatohepatitis (NASH)

In NASH, fat accumulation is associated with liver cell inflammation and different degrees of scarring. NASH is a potentially serious condition that may lead to severe liver scarring and cirrhosis. It sometimes affects older people living with HIV.

body mass index (BMI)

Body mass index, or BMI, is a measure of body size. It combines a person's weight with their height. The BMI gives an idea of whether a person has the correct weight for their height. Below 18.5 is considered underweight; between 18.5 and 25 is normal; between 25 and 30 is overweight; and over 30 is obese. Many BMI calculators can be found on the internet.

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 spectroscopy.

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 placebo recipients.

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 researchers concluded.

This fibrosis progression rate was more than six times higher than rates previously seen in the general HIV-negative population, they noted.

"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.


Fourman L et al. Clinical predictors of liver fibrosis presence & progression in HIV-associated NAFLD. Conference on Retroviruses and Opportunistic Infections, abstract 128, March  2020.

View the abstract on the conference website.

Watch the webcast on the conference website.

Update: Following the conference presentation, this study was published in a peer-reviewed journal:

Fourman L et al. Clinical Predictors of Liver Fibrosis Presence and Progression in HIV-Associated NAFLD. Clinical Infectious Diseases, published online ahead of print, April 2020.

DOI: 10.1093/cid/ciaa382