Despite
effective antiretroviral therapy, people co-infected with HIV and hepatitis C
remain at higher risk for decompensated liver disease and other liver-related
complications than those with hepatitis C alone, according to
findings presented on Wednesday at the 19th International AIDS Conference (AIDS 2012) in
Washington DC.
Prior studies
have indicated that HIV positive people with hepatitis C virus (HCV) have more
rapid liver disease progression than HCV-monoinfected individuals. Combination
antiretroviral therapy (ART) appears to slow liver disease progression, but
late-stage clinical outcomes in the combination ART era are not fully
understood.
Vincent Lo Re
from the University of Pennsylvania and colleagues conducted a retrospective cohort
study comparing 4280 HIV/HCV ART-treated co-infected patients and 6079 HCV-monoinfected
patients matched for age and race/ethnicity in the Veterans Aging Cohort Study
Virtual Cohort between 1997 and 2010.
Glossary
- ascites
An accumulation of fluid in the abdomen; may be caused by liver damage, especially cirrhosis.
- encephalopathy
-
A disease or infection affecting the brain.
- steatosis
Abnormal fat deposits in the liver.
- varices
Stretched veins which may burst and cause severe bleeding; a complication of cirrhosis.
Almost all participants
were men and about two-thirds were black. All had detectable HCV viral load and
had not previously been treated for hepatitis C. Just over one-quarter were
heavy alcohol drinkers. Co-infected people had been on combination ART for at
least one year. About 45% had pre-ART CD4 cell counts of 200 cells/mm3
or less.
The researchers
analysed occurrence of clinical conditions related to liver decompensation
including ascites (fluid accumulation in the abdomen), bacterial peritonitis
(inflammation of the abdominal lining) and bleeding varices (swollen veins in
the oesophagus). Hepatic encephalopathy and jaundice were not included.
They also
looked at hepatocellular carcinoma and death from any cause. Follow-up
continued for a median of seven years for the co-infected group and ten years
for the monoinfected group.
Co-infected
people on combination ART had a significantly higher rate of liver
decompensation than those with hepatitis C alone (6.3 vs 5.0%, respectively), for an adjusted
hazard ratio (HR) of 1.83, or nearly twice the risk. The median age at which
decompensation occurred was similar for both groups, however.
At the time of the first decompensation episode,
frequencies of both ascites and peritonitis were similar in the co-infected and
monoinfected groups, but bleeding varices were about twice as common in the monoinfected
group.
The two groups had
similar rates of hepatocellular carcinoma (1.2 vs 0.9%, respectively), for an
adjusted HR of 1.69. Co-infected people had a small but statistically
significant increase in risk for all severe liver events taken together.
Co-infected
people had significantly higher mortality than people with hepatitis C alone (32.9
vs 15.4%, respectively). The co-infected group was less
likely to have liver-related causes of death (7.8 vs 20.1% of all deaths,
respectively), due to competing causes of death in the co-infected group.
Looking at
co-infected people with low or undetectable HIV viral load, hazard ratios fell
slightly (to 1.71 for <1,000 copies/mL and 1.73 for <400 copies/mL), but rates of liver decompensation
still remained higher in co-infected compared with mono-infected patients.
Lo
Re explained that when stratifying according to pre-ART CD4 cell count, hazard
ratios were lower for people with 350-499 or 200-349 cells/mm3 than for those with
less than 200 cells/mm3.
"Despite ART,
HIV/HCV [co-infected] patients had higher risk of hepatic decompensation that HCV
monoinfected patients," the researchers concluded.
Lo Re suggested
that poorer outcomes among HIV/HCV co-infected people may be related to greater immune activation,
steatosis (fatty liver) or apoptosis (programmed cell death), with more study
needed to determine the precise mechanisms.
It
is incumbent upon providers to assess risk factors, develop ways to detect the
subgroups of patients at highest risk for rapid progression, and to prioritise such
individuals for hepatitis C treatment and trials of new agents, he added.