Curing hepatitis C infection substantially reduces the risk of developing type 2 diabetes in people with HIV/hepatitis C virus (HCV) co-infection, but does not reduce the risk of cardiovascular disease, cancers or other non-AIDS events, a study of people with co-infection treated in Spain between 2000 and 2008 has shown. The findings are published online ahead of print in the journal Hepatology.
The study also found a trend towards a reduced risk of kidney failure in those cured of hepatitis C, although the trend did not reach statistical significance.
As well as causing liver damage, hepatitis C infection can lead to extrahepatic disease, including cryoglobulinemia, chronic kidney disease and renal failure, diabetes and B-cell non-Hodgkin lymphoma. Hepatitis C has also been implicated in the development of cardiovascular disease.
Curing hepatitis C infection has been shown to reduce the risk of diabetes, kidney failure and cardiovascular disease in people with mono-infection, but the extrahepatic effects of curing hepatitis C have not been established in people with HIV and hepatitis C co-infection.
Spanish researchers looked at this question by examining extrahepatic disease in people with HIV/HCV co-infection treated with interferon and ribavirin at 19 clinics in Spain between 2000 and 2008. People were eligible for hepatitis C treatment if they had CD4 cell counts above 200 cells/mm3 and were on stable antiretroviral therapy or were treatment-naïve with no active injection drug use. Severe concurrent extrahepatic disease including hypertension, cardiovascular disease, poorly controlled type 2 diabetes and severely reduced kidney function, were also criteria for treatment.
The cohort consisted of 1625 people, 75% male, with a median age of 40 years. Baseline liver biopsy was carried out in approximately 70% of people, of whom 38.6% had bridging fibrosis (F3 or F4), or cirrhosis.
The baseline prevalence of diabetes (2.9%) and chronic renal failure (0.2%) was low.
Most people received pegylated interferon (2a or 2b) (86.5%) rather than interferon alfa. All received ribavirin. Thirty-eight per cent of the cohort achieved a sustained virologic response, of which 2.5% were cured after retreatment.
After completion of treatment, participants were followed for a median of 5.4 years. 16.2% of non-responders and 11.8% of responders were lost to follow-up.
The analysis showed very substantial reductions in the risk of death (HR 0.36, 95% CI 0.24-0.54, p < 0.001), liver-related death (HR 0.13, 95% CI 0.06-0.28, p < 0.001) and new AIDS-defining events (HR 0.37 (95% CI 0.17-0.79, p = 0.01) in those cured of hepatitis C, in common with a number of previous studies looking at outcomes after treatment.
During the follow-up period the most frequent new non-liver, non-AIDS-related events were cancers (6.2%), type 2 diabetes (6%) cardiovascular event (5.6%), non-AIDS-related infections (sepsis) (5%), bone events including fractures and osteonecrosis (3.5%) and severe renal events (2%). Although the frequency of non-liver, non-AIDS events as a whole was not significantly lower in those who were cured, two types of events did occur less frequently in people who had been cured of hepatitis C.
Type 2 diabetes occurred in 3.7% of those cured, compared to 7.5% of non-responders (p = 0.002), (hazard ratio 0.57, 95% CI 0.35-0.93, p = 0.024).
Renal events – kidney failure, initiation of dialysis or kidney transplant – occurred in 0.1% of those cured compared to 2.7% of non-responders (p = 0.015). The reduction of risk was of borderline significance (HR 0.42, 95% CI 0.17-1.09, p = 0.074) in multivariate analysis.
The analysis also showed a trend towards a higher rate of cardiovascular events in people who were cured of hepatitis C (HR 1.57, 95% CI 0.99-2.50, p = 0.056).
The researchers say that their findings support an offer of treatment to anyone with HIV/HCV co-infection who has insulin resistance or type 2 diabetes, regardless of fibrosis stage, and that the decline in the risk of death, liver-related death, new AIDS-related events and liver-related events “argue for the prescription of HCV therapy regardless of liver fibrosis stage in coinfected patients.”
Berenguer J et al. Eradication of hepatitis C and non-liver-related non-AIDS-related events in HIV/HCV coinfection. Hepatology, advance online publication, January 2017.