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Successful hepatitis C treatment lowers risk of death for people with HIV and HCV co-infection
Liz Highleyman, 2015-10-28 12:20:00

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 week 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.

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.

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