People with HIV and hepatitis C are no longer at higher risk
of end-stage liver disease than people with hepatitis C alone, and
the trend is probably associated with the improved effectiveness of
antiretroviral treatment, a French study has reported in the journal Hepatology.
The study also found that people with HIV and hepatitis C virus (HCV)
co-infection do not have a raised risk of liver cancer compared to people with HCV alone.
Past studies have shown that people with HIV and HCV
experience much faster progression of liver fibrosis to cirrhosis and end-stage
liver disease than people with HCV alone. This accelerated rate of disease
progression is due to dampened immune responses to HCV in people with HIV, together
with much higher levels of HCV replication and liver inflammation. Older
antiretroviral drugs may also have contributed to liver damage.
A protein made in the liver, needed to maintain a balance of the fluids in the body. In a blood test, lower than normal levels of albumin and total protein may indicate liver damage or disease. If there is not enough albumin, fluid may accumulate in the abdomen (ascites).
- decompensated cirrhosis
The later stage of
cirrhosis, during which the liver cannot perform some vital functions and
complications occur. See also ‘cirrhosis’ and ‘compensated cirrhosis’.
- hepatocellular carcinoma (HCC)
Liver cancer. A long-term complication of chronic inflammation of the liver or cirrhosis.
The most recent meta-analysis, published in 2009,
took data from 29 studies and calculated that people with HIV/HCV co-infection
were five times more likely to develop decompensated cirrhosis and
three and a half times more likely to die than their counterparts with HCV
Most of those studies were carried out prior to the
widespread uptake of early antiretroviral treatment, however, and prior to the
availability of direct-acting antiviral treatment to cure hepatitis C.
French researchers wanted to know whether the prognosis of
people with HIV/HCV co-infection has changed as treatment patterns for HIV and
HCV have changed.
Using data from the HEPAVIH and CirVir cohorts, they
investigated rates of decompensated cirrhosis, liver cancer and death in people
with HIV and HCV compared to HCV alone.
Liver cancer and decompensated cirrhosis – the onset of
end-stage liver disease when the liver ceases to compensate for damage caused
by HCV – were chosen as endpoints in this study because they are unambiguous
clinical events. Previous studies assessing the impact of HIV on HCV disease
progression have used varying measures of fibrosis and cirrhosis, creating
difficulties in comparing between studies and patients.
The study population consisted of people with early-stage
(Child-Pugh A) cirrhosis confirmed by biopsy. The HepaVIH cohort contributed
175 people with HIV/HCV co-infection and cirrhosis and the CirVir cohort
contributed 1253 people with hepatitis C and cirrhosis. People also with hepatitis B co-infection were not included in this analysis, nor were people with a
prior history of liver complications.
The cohorts were followed for just under five years in the
case of the HCV cohort and four and a half years for the co-infected cohort,
from the date of inclusion in the cohort to which they belonged or biopsy-proven
diagnosis of cirrhosis, whichever was later.
At baseline those with co-infection were younger (47 years vs
56 years, p < 0.001), more likely to have genotype 3 infection (25% vs 15%,
p < 0.001) and were more likely to be current alcohol users (40 vs 25%,
P < 0.001). 19.9% per cent of the HCV cohort and 16.6% of the co-infected
cohort had already been cured of hepatitis C at baseline.
Almost all people with co-infection (92%) were already on
antiretroviral treatment at baseline and 80% had an undetectable viral load.
At the end of the follow-up period the investigators found:
- No difference in cure rate between the two
cohorts (47% HIV vs 52% HCV).
- No significant difference between cohorts in the
incidence of hepatocellular carcinoma (HCC) (liver cancer) (14% HCV vs 7.4% HIV),
although liver cancer was more severe at diagnosis in people with co-infection despite
comparable frequency of monitoring for HCC.
- No difference in the proportion who suffered at
least one episode of decompensation (liver decompensation can be reversed)
(16.4% HCV vs 10.9% HIV).
- No difference in the interval between baseline
and first occurrence of decompensation.
- No difference in the death rate between the two
cohorts (13% in each) although people with HIV died a median of ten years
younger, had a higher risk of death overall and a higher risk of non-liver-related
death (SHR = 2.44, 95% CI 1.18-5.07, p = 0.016).
Multivariate analysis showed that decompensation or death
were each associated with a lack of hepatitis C cure or greater severity of
cirrhosis, as measured by platelets < 100,000/mm3 and albumin
< 35 g/L. Death was also associated with older age.
It was not possible to analyse the effect of antiretroviral
treatment on the study outcomes within the HIV cohort because the proportion of
people already receiving treatment at baseline was so high, but the study
authors argue that their results indicate that antiretroviral treatment has
altered the course of hepatitis C co-infection in people living with HIV.
They also argue that the abandonment of drugs such as
stavudine and didanosine has reduced the incidence of liver damage in people
living with HIV.
They caution that despite these improvements, liver cancer
remains more aggressive in people with co-infection, underscoring the importance of
curing hepatitis C in people living with HIV.