Maud Lemoine of Imperial College London presented findings from a
study of the association between metabolic syndrome and liver fibrosis
in HIV-positive people without viral hepatitis (known as HIV
monoinfection). Metabolic syndrome
is a cluster of factors associated with elevated cardiovascular risk,
including abdominal obesity, high blood pressure, abnormal blood lipid
levels and high blood glucose, a sign of insulin resistance and type 2
diabetes.
The METAFIB study, conducted at a single centre in France, looked at
nearly 500 HIV-positive people without hepatitis B or C virus (HBV or
HCV) co-infection who said they did not drink heavily and did not have
other causes of chronic liver disease.
Fibrosis was assessed using transient elastography (FibroScan),
a non-invasive method of measuring liver 'stiffness' using
sound waves; a stiffer liver indicates more extensive fibrosis.
Among participants with valid liver stiffness results, 203 people
with metabolic syndrome were matched by age and sex with 202 people who
did not. Nearly 90% were men and the average age was 53 years.
Participants had been HIV-positive for around 17 years on average, most
were on ART with undetectable viral load and the mean CD4 count was over
600 cells/mm3. People with metabolic syndrome had a higher
body mass index, were more likely to be obese and more likely to have
insulin resistance (49 vs 9%) or type 2 diabetes (15 vs 1%).
The researchers found that participants with metabolic syndrome were
significantly more likely to have liver fibrosis compared to those
without it. A quarter of people with metabolic syndrome had moderate
fibrosis (stage F2), compared with about 7% of those without. Advanced
fibrosis (stage F3) was seen in about 15% of those with and 3% of those
without metabolic syndrome, and for cirrhosis the proportions were about
8% and 1%, respectively.
People with moderate or worse fibrosis had significantly higher
levels of inflammatory markers than those with absent or mild fibrosis
(stage F0 or F1), including C-reactive protein, interleukin 6, leptin
and adiponectin (two hormones produced by adipose or fat tissue) and a
marker linked to macrophage activation (a type of immune system white
blood cell). This was also the case when comparing people with and
without cirrhosis.
After adjusting for other factors, participants with metabolic
syndrome were about twice as likely to have at least stage F2 fibrosis,
about four times more likely to have at least stage F3 fibrosis and
about eight times more likely to have cirrhosis. Those with obese people
were about three times more likely to have stage F2 or F3 fibrosis and
about four times more likely to have cirrhosis. Liver enzyme (ALT and
AST) levels, HIV-related factors and type of ART did not predict
fibrosis status.
"HIV-monoinfected patients with metabolic syndrome are at risk of
liver fibrosis and should be systematically screened for liver fibrosis
irrespective of transaminases levels or HIV parameters," the
investigators concluded.
"Mass fat measured by [body mass index] and circulating level of
leptin is strongly associated with liver fibrosis independently of HIV
parameters and ART exposure," they added.
They suggested that adipose tissue, insulin resistance and macrophage
activation "are probably key players" in the development of liver
fibrosis in HIV-positive people without viral hepatitis.