People with HIV who were cured of hepatitis C were less
likely than HIV-negative people to develop hepatocellular carcinoma (HCC – liver
cancer) in the three-and-a-half years after completing hepatitis C treatment,
Spanish researchers report in the journal Clinical Infectious Diseases.
People with advanced liver fibrosis are at higher risk of
developing HCC. Since the introduction of direct-acting
antivirals, investigators have been following cohorts of people cured of
hepatitis C to check what effect clearing the infection has on the
subsequent risk of liver cancer.
Previous
studies have shown that curing hepatitis C resulted in a substantial
reduction in the risk of HCC, regardless of whether
treatment consisted of an interferon-based regimen or of direct-acting
antivirals.
Glossary
- 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’.
A
previous analysis of the Spanish GEHEP cohort showed that people with HIV and hepatitis C co-infection did not have a raised risk of HCC but the study did not compare risks between co-infected and monoinfected people. This
study was carried out because some
studies had suggested a raised risk of recurrence of HCC, a phenomenon subsequently disproved by larger analyses of
monoinfected people.
Spanish researchers have now published a larger analysis,
comparing the risk of developing HCC between HIV-positive and
HIV-negative people.
The study was a prospective cohort, recruiting people cured
of hepatitis C with a direct-acting antiviral regimen who had a liver stiffness
of 9.5 kPa or above prior to treatment (indicating advanced fibrosis). Participants
were recruited at 18 hospitals in Spain from October 2011 and were followed for
a median of 43 months.
The study recruited 1035 people, 64% with HIV and
hepatitis C co-infection. People living with HIV were significantly younger (52 vs 54 years,
p < 0.001) and more likely to be male (86% vs 72%, P < 0.001). People with HIV
were also more likely to be people who inject drugs (84% vs 36%).
The median liver stiffness was 15.1 kPA in the HIV-negative
group and 17.3kPA in the HIV-positive group, a non-significant difference.
People with HIV had significantly higher FIB-4 scores (1.94 vs 1.73, p = 0.005).
Fifty-seven per cent of those without HIV and 62% of those with HIV had
cirrhosis prior to starting treatment, almost all Child-Pugh class A (97%).
All people with HIV were on antiretroviral treatment at the
time of hepatitis C treatment.
Three per cent of monoinfected people and 1.2% of people with co-infection developed HCC (19 new cases, of which eight
occurred in people with HIV). People living with HIV were at more than 70%
lower risk of developing liver cancer in a multivariable analysis, although the
confidence intervals on this estimated reduction in risk were wide (aHR 0.27,
95% CI 0.08-0.90, p = 0.034). Two other methods of multivariable analysis that
adjusted for differences between HIV-positive and HIV-negative participants
showed a similar reduction in risk.
Other predictors of HCC were genotype 3 infection, higher
MELD score and greater liver stiffness after sustained virologic response.
There was no difference in the proportion of people who
developed decompensated cirrhosis (3%) nor in the speed that it developed (17
months).
Although follow-up was relatively short, more than
two-thirds of cases of HCC were diagnosed within two years of the completion of
hepatitis C treatment.
The study authors question whether antiretroviral treatment
containing tenofovir might inhibit the development of cancer in liver cells,
based on the observation that in people with hepatitis B, tenofovir stimulates
interferon beta production. As only eight people co-infected with HIV developed
HCC during the study, the numbers were too small to analyse risks according to
antiretroviral treatment.
The study authors say that further research is needed to identify
the reasons for the lower incidence of HCC in people with
HIV after hepatitis C is cured.