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
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.
Abnormal fat deposits in the liver.
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 participants 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
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 or 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 co-infected people, it becomes even more
important to identify and control other forms of liver injury such as [fatty
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 co-infected people, say Naga Chalasani of Indiana University
and Tinsay Woreta of Johns Hopkins School of Medicine in an accompanying
editorial. They say that longer-term comparative studies would enable greater
understanding fatty liver disease in this population.