Middle-aged people with HIV and no hepatitis co-infection have a twofold increase in the risk of liver fibrosis

By | January 26, 2021

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 virus (HBV) or hepatitis C virus (HCV). All were aged between 50 and 70 years and liver fibrosis was present in 12% of people with HIV and 7% of 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.

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 HBV and/or HCV. 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.



Thickening and scarring of connective tissue. Often refers to fibrosis of the liver. See also ‘cirrhosis’, which is more severe scarring.

adjusted odds ratio (AOR)

Comparing one group with another, expresses differences in the odds of something happening. An odds ratio above 1 means something is more likely to happen in the group of interest; an odds ratio below 1 means it is less likely to happen. Similar to ‘relative risk’. 

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.

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hepatitis B virus (HBV)

The hepatitis B virus can be spread through sexual contact, sharing of contaminated needles and syringes, needlestick injuries and during childbirth. Hepatitis B infection may be either short-lived and rapidly cleared in less than six months by the immune system (acute infection) or lifelong (chronic). The infection can lead to serious illnesses such as cirrhosis and liver cancer. A vaccine is available to prevent the infection.

statistical significance

Statistical tests are used to judge whether the results of a study could be due to chance and would not be confirmed if the study was repeated. If result is probably not due to chance, the results are ‘statistically significant’. 

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 HBV or HCV.

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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 comparison group.

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 have diabetes.

Almost all the HIV-positive participants (98%) were taking ART 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 < 0.01).

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 might occur.

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.

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