Having HIV almost doubles the risk of liver fibrosis, according to European research published in the online edition of the Journal of Infectious Diseases.
Investigators in Denmark and the Netherlands compared rates of liver
fibrosis between people living with HIV and people without HIV.
Importantly, none of the participants had hepatitis B or hepatitis C. All were aged between 50 and 70 years and liver
fibrosis was present in 12% of people with HIV and 7% of the HIV-negative
comparison group. Risk factors for fibrosis among people with HIV
included increasing age, higher body mass index (BMI), disturbed liver
function and treatment with didanosine, an obsolete anti-HIV drug.
“Our results are comparable with previous studies, where the
prevalence of liver fibrosis has been reported to range from 8% to 18%
in adult people with HIV without viral hepatitis,” comment the study
authors. The study has clear implications for the care of people with
HIV, showing the importance of regular monitoring of liver function. The
association with higher BMI also suggests that people with HIV can
reduce their fibrosis risk by losing excess weight.
Abnormal fat deposits in the liver.
Improvements in treatment and care mean that most people with HIV now
have a realistic chance of living well into old age. This makes the
prevention and treatment of chronic illnesses associated with older age a
priority of routine HIV care. Liver disease is currently the second
most important cause of serious illness and death in people with HIV.
This is largely due to co-infection with hepatitis B and/or hepatitis C. However, it is
also important to understand rates of liver disease and its risk factors
among ageing HIV-positive people who don’t have viral hepatitis.
Liver fibrosis – or hardening of the liver – is a key
marker of liver disease and can lead to cirrhosis and other serious
outcomes, including death. Prompt detection of fibrosis means that
people can be offered appropriate treatment and make lifestyle changes
to reduce the risk of disease progression.
With all this in mind, a team of Danish and Dutch researchers led by
Dr Ditte Marie Kirkegaard-Klitbo of Copenhagen University Hospital
undertook a cross-sectional observational study involving HIV-positive
individuals and a comparison group of HIV-negative people. Their aim was
to determine the prevalence of liver fibrosis and its risk factors
among people living with HIV.
The 342 HIV-positive participants received care in Denmark, whereas
the 2190 HIV-negative participants in the comparison group lived in the
Netherlands. Recruitment was restricted to people aged 50 to 70 years –
an important aspect of the study design given the ageing of the
HIV-positive community. None of the participants in either study group
had hepatitis B or hepatitis C.
Liver fibrosis was assessed using a technique called
transient elastography. This involves placing a probe on the skin above
the liver. The probe sends out a series of pulses that detect liver
stiffness, a marker of fibrosis. A reading of 7.6kPa is consistent with
the presence of significant liver fibrosis.
Information on other aspects of the participants’ health was obtained
from their clinical notes. Assessment for hepatic steatosis – fatty
liver disease – was conducted using either CT scanning or ultrasound.
The baseline characteristics of the two study groups differed in
several important respects. For instance, the HIV-positive group was
younger (median age 57 vs 63 years), more likely to be male (87% vs.48%) and less likely to be Caucasian (78% vs 97%) than the HIV-negative
There was also a higher prevalence of some known risk
factors for liver disease among the study participants with HIV. These
included abdominal obesity, elevated ALT and AST readings (key measures
of liver function) and blood lipids. On the other hand, the comparator
group were more likely to have a high BMI, be overweight or obese, and
Almost all the HIV-positive participants (98%) were taking antiretroviral therapy and
97% had an undetectable viral load. The median time since HIV diagnosis
was 19 years. Over three-quarters (77%) had a CD4 cell count above 500.
Liver fibrosis was present in 12% of people with HIV and 7% of the
comparison group. This was a statistically significant difference (p
Prevalence was higher in the HIV-positive group than HIV-negative
group for mild (5% vs 3.6%), moderate (5% vs 2.5%) and severe fibrosis
(2% vs 1%). In each case, the difference between the HIV and non-HIV
group was statistically significant (p < 0.01).
The study investigated a range of possible risk factors for liver
fibrosis, including certain anti-HIV drugs. The only drug that was found
to have an association with liver fibrosis was didanosine (aOR = 2.26,
95% CI, 1.01-5.06). This now-obsolete drug was widely used in the late
1990s and early 2000s and was later found to cause liver toxicity. But
the association with didanosine fell just short of statistical
significance when the investigators limited their analysis to people who
had been diagnosed with HIV for 20 years or longer. This suggests a
role for longer duration of HIV infection in fibrosis risk. If left
untreated, HIV can cause damage to liver cells.
The final analysis showed that fibrosis risk among people with HIV
was associated with increasing age (each decade, aOR = 3.34; 95% CI,
1.81-6.18), elevated ALTs (aOR = 1.25; 95% CI, 1.05-1.49) and higher BMI
(each 1kg/m2 increase, aOR = 1.17; 95% CI, 1.05-1.29).
After adjusting for these risk factors and differences between the
groups, the investigators calculated that the HIV-positive group still
had almost twice the odds of having fibrosis compared to the comparator
group (aOR = 1.84, 95% CI, 1.17-2.88, p < 0.001). This finding
suggests that HIV itself may play a role in the development of liver
fibrosis, although further research is needed to understand how this
Overall, the research underlines the importance of monitoring the
liver health of people with HIV, especially older individuals who have a
history of treatment with potentially liver-toxic anti-HIV drugs.
Paying attention to diet, exercise and losing excess body weight may
also help reduce fibrosis risk.