Around one in three people with HIV and hepatitis B had fatty liver disease and one in ten had liver damage, US researchers from the Hepatitis B Research Network report in Clinical Infectious Diseases.
They express concern about the additional harm that fatty liver disease may cause in people already at higher risk for fibrosis (liver damage).
Non-alcoholic fatty liver disease is caused by the accumulation of fat in the liver. In people with HIV, older antiretroviral drugs that caused high triglyceride levels may have led to fat accumulation in the liver. Insulin resistance caused by HIV or antiretroviral drugs – especially older protease inhibitors – can also cause fat to build up in the liver. High body mass index, high cholesterol levels and high blood pressure are also risk factors for fatty liver disease.
Liver fat accumulation can lead to inflammation of liver cells (steatohepatitis) and damage to liver tissue (fibrosis). Eventually a small proportion of people will develop cirrhosis of the liver, in which liver function declines sharply. Until this point, liver damage causes no clinical symptoms and can only be detected by liver enzyme tests.
It is unclear if the prevalence of fatty liver disease is higher in people with HIV than the general population. US studies show that about one in four adults in the general population and one in three people with HIV has fatty liver disease.
Little is known about fatty liver disease in people with HIV co-infected with hepatitis B. The prevalence of hepatitis B co-infection in people living with HIV varies widely, from around 11% in the Swiss HIV Cohort to around 20% in west Africa.
To investigate fatty liver disease and its role in liver damage in people co-infected with hepatitis B and HIV, and to determine if HIV may accelerate liver damage, the Hepatitis B Research Network carried out a study of liver biopsies to assess the prevalence of fatty liver disease and fibrosis in an established cohort of people with HIV and hepatitis B. They also monitored liver enzyme measurements on a longitudinal basis, to assess whether liver fat accumulation led to liver enzyme elevations.
One hundred and fourteen people had liver biopsies available for evaluation. Study participant were predominantly male (93%), just over half were non-Hispanic Black (51%), all except one were on antiretroviral therapy and all but three were taking treatment for hepatitis B, either as part of antiretroviral therapy (tenofovir, emtricitabine or lamivudine, 80%) or the anti-hepatitis B drug entecavir (15%). Thirty-five per cent had HBV DNA levels above 20 IU/ml and 56% remained HB e antigen positive, a marker of active HBV replication.
The study population had a high prevalence of metabolic syndrome (35%), obesity (27%) or overweight (32%) and insulin resistance (21%) or diabetes (14%).
Twenty-three participants (20%) had steatosis (liver fat accumulation) and a further eleven (9.7%) had steatohepatitis (liver fat accumulation, inflammation and ballooning of liver cells with fat).
Twenty-three per cent had advanced liver fibrosis (Ishak fibrosis score 3 or above) and a further 13% had significant fibrosis (stage 2). Twenty-one per cent had hepatic activity index (HAI) scores of 5 or above, indicating moderate inflammation and ballooning of liver cells. Only four participants had scores of 9 or above, indicating more extensive inflammation and liver damage.
Multivariable analysis showed that the risk of fatty liver was much greater in non-Hispanic White and other races compared to non-Hispanic Black participants. Non-Hispanic White people had eight times greater odds of fatty liver disease and other races 16 times greater odds of fatty liver disease compared to non-Hispanic Black participants.
Fatty liver disease risk was also higher when ALT or AST was higher, and high blood pressure greatly increased the odds of fatty liver disease (aOR 10.93), as did elevated lipid levels (aOR 4.36) and a family history of diabetes (aOR 5.38).
Liver enzyme levels over time (over a median of three years of follow-up) were higher in people with steatohepatitis. After adjusting for HBV DNA level, steatohepatitis was associated with 1.93 times higher ALT during the follow-up period compared to no steatohepatitis (p < 0.01).
“These findings suggest that in those HBV-HIV persons with low HBV viral levels, fatty liver disease should be considered when ALT levels are persistently elevated,” the authors conclude. They say that as liver injury is already more severe in coinfected people,” it becomes even more important to identify and control other forms of liver injury such as fatty liver disease.
The lack of a comparison group of people with HIV alone, or hepatitis B alone, makes it difficult to tell whether either infection is exacerbating fatty liver disease in coinfected people, say Dr Naga Chalasani of Indiana University and Dr Tinsay Woreta of Johns Hopkins School of Medicine in an accompanying editorial. They say that longer-term comparative studies would enable greater understanding of fatty liver disease in this population.
Khalili M et al. Fatty liver disease in a prospective North American cohort of adults with HIV and hepatitis B coinfection. Clinical Infectious Diseases, 1 September 2020.
Woreta T, Chalasani N. Fatty liver disease in HIV-HBV coinfection: a cause for concern. Clinical Infectious Diseases, 1 September 2020.