Body and mind

Fewer people living with HIV have non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease among adults in high-income countries. One in four adults has NAFLD, and the disease is associated with an increased risk of cardiovascular disease and liver cancer. Previous research has suggested that people living with HIV are even more prone to NAFLD, but the most comprehensive research to date shows the exact opposite. The researchers’ theory is that biological causes cannot explain why fewer people living with HIV have NAFLD. Instead, they are more aware of their own health and more often seek healthcare in time.

When HIV and AIDS struck the world in the 1980s, being infected with HIV was closely linked to having immunodeficiency and a high risk of infections and their sequelae. As treatment for HIV has become more and more effective, HIV is considered a chronic disease, but the risk of sequelae remains greater than in the general population. One side-effect that has been widely disputed has been NAFLD. A major study now surprisingly reveals that people living with HIV have a lower prevalence of NAFLD than the general population.

“Previous studies have found a high prevalence of NAFLD among people living with HIV, but this has varied between 13% and 73%, depending on the method used and the subgroup of people living with HIV studied. In our study, with a comparable control group, people living with HIV had a considerably lower prevalence. We think this is because people living with HIV have more frequent health check-ups and often have a healthier lifestyle. The study also showed that tailoring HIV medication may be able to reduce the prevalence even further,” explains a main author, Ditte Marie Kirkegaard-Klitbo, MD, PhD student, Department of Infectious Diseases, Amager and Hvidovre Hospital.

Monitoring and health behaviour make a difference

The new study is part of the Copenhagen Co-Morbidity in HIV Infection Study and included 453 people living with HIV and a control group of 765 uninfected participants. None had previous or current viral hepatitis or excessive alcohol intake. Alcohol strongly contributes to building up excess fat in the liver, whereas NAFLD is often associated with lifestyle. Other risk factors can include medication, and people living with HIV take large amounts of medicine.

“Our study found that 9% of people living with HIV and 14% of the general population had NAFLD. Living with HIV was an independent factor for a lower prevalence of NAFLD than the general population even after controlling for overweight, physical activity and other factors we knew could affect developing NAFLD,” says Ditte Marie Kirkegaard-Klitbo.

However, other factors than people’s HIV status were associated with the prevalence of NAFLD. Women had a lower prevalence than men. Moderate alcohol intake and high physical activity were associated with a lower prevalence, but a high body mass index (BMI) was associated with a higher prevalence.

“We do not think that people living with HIV are protected by any biological factor. The lower prevalence of NAFLD probably results from such factors as people living with HIV more often getting health check-ups. This detects elevated cholesterol and diabetes earlier and treats these people earlier and, on average, these people live healthier because they know how important it is to stay healthy as a result of HIV infection,” explains Ditte Marie Kirkegaard-Klitbo.

May influence HIV treatment in the future

NAFLD is usually a condition that people can live with for many years with no or few symptoms other than fatigue or stomach pain. However, the long-term complications can include cirrhosis and cancer of the liver or oesophagus. About 20% of those with NAFLD develop non-alcoholic steatohepatitis.

“The control group in our study is the reason why the new results differ from previous results. Our study was more comprehensive because previous studies did not have a comparable control group. The control group was selected through collaboration with the Copenhagen General Population Study, so that it matched the group of people living with HIV by sex and age and all data were collected completely identically in the studies,” says Ditte Marie Kirkegaard-Klitbo.

The researchers thus directly compared blood tests and computed tomography scans of the liver from the large and diverse group of people living with HIV with a group of people who did not have HIV.

“The result that people living with HIV have a lower prevalence was surprising because all the other studies had shown otherwise. Conversely, we know that the main risk factors for NAFLD are type 2 diabetes and obesity and that lifestyle changes including dietary changes and exercise therefore play a crucial role,” explains Ditte Marie Kirkegaard-Klitbo.

However, the researchers still hope that their studies can lead to an even lower prevalence of NAFLD among people living with HIV, and the class of antiretroviral drugs called integrase inhibitors play a role. These are one of the three types of antiretroviral drugs, and they appear to be associated with an increased prevalence of NAFLD.

“Being exposed to an integrase inhibitor was associated with an increased prevalence of NAFLD. Other studies have shown that integrase inhibitors can result in weight gain over time. We should therefore pay close attention to identifying the people living with HIV who have an increased risk of NAFLD and consider replacing their integrase inhibitor with an alternative antiretroviral drug,” says Ditte Marie Kirkegaard-Klitbo.

Prevalence and risk factors of moderate to severe hepatic steatosis in HIV infection: the Copenhagen Co-Morbidity Liver Study” has been published in The Journal of Infectious Diseases. The Novo Nordisk Foundation has awarded grants to co-authors Thomas Benfield and Susanne Dam Nielsen for projects, including the Copenhagen Co-Morbidity in HIV Infection Study.

Ditte Marie Kirkegaard-Klitbo
MD, PhD Fellow
Non-alcoholic fatty liver disease (NAFLD) is highly prevalent with an estimated global prevalence of 25%. In people living with HIV (PLWHIV), NAFLD is even more frequent with an estimated prevalence of 35% and with a higher degree of inflammation and liver fibrosis compared to the background population. My research is part of the research consortium The Copenhagen Co-Morbidity (COCOMO) in HIV Infection Study, a prospective, longitudinal cohort study. The COCOMO Liver Study aims to determine i) the prevalence of NAFLD, ii) factors associated with NAFLD and iii) if HIV per se is independently associated with NAFLD severity in PLWHIV compared to the background population. We aim to thoroughly investigate a subgroup of individuals with signs of liver fibrosis or elevated liver enzymes to histologically characterize disease severity. Additionally, we aim to develop a clinical assessment tool to identify HIV positive individuals at risk of NAFLD.