Hepatitis C
treatment that leads to sustained virological response (SVR) – generally
regarded as a cure – was associated with a reduced risk of liver-related death
and improved overall survival in an analysis of 3500 people with HIV and
hepatitis C virus (HCV) co-infection, according to a presentation at the 15th
European AIDS Conference last month in Barcelona, Spain. A related study found
that while some liver-related events are declining over time, liver cancer remains
a risk for people with co-infection.
Over years or decades, chronic HCV infection can lead to serious liver
disease including cirrhosis, hepatocellular carcinoma (HCC, a type of liver
cancer) and end-stage liver failure necessitating a liver transplant. Research
has shown that people living with HIV who have HCV co-infection experience more
rapid liver disease progression, on average, than those with hepatitis C alone.
Lars Peters of Rigshospitalet in Copenhagen, Denmark, and fellow
investigators with the COHERE Hepatitis Subgroup looked at the long-term
risk of all-cause,
liver-related and non-liver-related death among people with HIV and HCV
co-infection, and its relation to hepatitis C treatment response, in a
large
multi-cohort study.
Glossary
- sustained virological response (SVR)
Undetectable hepatitis C RNA after treatment has come to an end. Usually SVR refers to RNA remaining undetectable for 24 weeks (six months) after ending treatment and is considered to be a cure. SVR4 and SVR12 refer to RNA remaining undetectable for 4 and 12 weeks respectively.
Prior research has shown that sustained response to hepatitis C
treatment is associated with reduced mortality among HIV-negative people with
HCV, Peters noted as background. The survival benefit of treatment for people
with co-infection could be greater due to their accelerated fibrosis progression,
or less because they are more likely to die of other ‘competing’ causes.
COHERE (Collaboration of Observational HIV Epidemiological Research in
Europe), part of the EuroCoord network of HIV cohort studies, is comprised of
33 prospective cohorts from across Europe; this analysis included data from 18
of these cohorts.
The analysis included all COHERE participants with HIV and HCV
co-infection who had ever started interferon-based hepatitis C therapy and were
followed for at least 96 weeks. (Interferon-free therapy using direct-acting
antiviral agents is too recent to have played a role in this study.)
Overall, nearly 80% were men, the median age at hepatitis C treatment
initiation was 42 years and 60% had a history of injecting drugs. Most were on
antiretroviral therapy (ART) and the median CD4 cell count was 426 cells/mm3.
Just 4% were triply infected with hepatitis B virus (HBV). Over half (56%) had
HCV genotype 1.
Participants were classified into three groups:
- Responders: received interferon/ribavirin for at least
24 weeks and latest HCV RNA test was negative (undetectable).
- Non-responders: received interferon/ribavirin for less
than 24 weeks (presumed ineffective) or latest HCV RNA test was positive
(detectable).
- Unknown response: received interferon/ribavirin for at
least 24 weeks but missing HCV RNA data.
Among the 3500 people with co-infection who started hepatitis C
treatment, 28.5% were responders, 45.3% were non-responders and 26.2% had
unknown response.
Compared to non-responders, the responders started interferon-based
therapy later (2007 vs 2005), were less likely to inject drugs (47% vs 65%) and
were more likely to have hepatitis B (5.1% vs 3.6%). Responders had a higher
median CD4 count (461 vs 405 cells/mm3) and were less likely to have
been diagnosed with AIDS.
Responders were also less likely than non-responders to have HCV
genotype 1 (50% vs 62%), which does not respond as well to interferon. Median
APRI scores – a biomarker index used to estimate liver fibrosis – were 0.8 for non-responders
and 0.9 for responders at the start of treatment, suggesting moderate to
advanced fibrosis; a score over 1.5 suggests cirrhosis.
The researchers assessed survival times starting from week 96 after treatment
initiation until death or last follow-up visit. A total of 213 participants (6.1%) died
during a median 3.8 years of follow-up.
The rate of death due to all causes was about half as high for treatment
responders as for non-responders: 6.79 vs 12.31 deaths per 1000 person-years
(7.8 for unknown response). Non-responders had a significantly higher risk of
all-cause mortality after adjusting for demographics, HIV-related and
HCV-related factors.
Liver-related mortality showed an even greater advantage for responders.
Liver-related death rates were 0.73 and 4.17 per 1000 person-years for
responders and non-responders, respectively (1.9 for unknown responders). Non-responders
were 4.5 times more likely to die of liver-related causes, Peters said. Again,
non-responders had a higher risk of liver-related death after adjusting for various
factors.
Liver-related deaths accounted for 10.8% of all deaths among responders,
35.4% among non-responders and 24.5% among those with unknown response. After
liver-related deaths were excluded, non-responders had a 16% higher risk of
death due to non-liver related causes – not a significant difference.
Among the four treatment responders who nonetheless died of
liver-related causes, one had evidence of HCV reinfection, suggesting active
infection despite having been cured once. None of the responders died from
hepatocellular carcinoma.
“HIV/HCV co-infected patients with a favourable virological response to
HCV treatment had reduced incidence of liver-related death and improved overall
survival,” the researchers concluded.
A limitation of this study is the lack of follow-up HCV RNA measurements
for all participants, but Peters said this would tend to underestimate rather
than exaggerate the survival benefit of successful treatment.