Viral Clearance of HCV May Protect Against Re-infection

VANCOUVER, British Columbia, Nov. 3 -- Previous infection with hepatitis C virus (HCV) and spontaneous clearance of the virus appear to confer protection against re-infection, reported researchers here.

Among more than 3,500 inner-city residents, primarily injectable drug users, those who had been infected with HCV and had spontaneous virological clearance but were at high-risk for re-infection had half the rate of new HCV infections as similar people who had never been infected, reported Jason Grebely, M.D., and colleagues from the University of British Columbia here.

"Our data lend support to the hypothesis that previous exposure to HCV may be protective, possibly on an immunologic basis, despite repeated exposure to HCV," the authors wrote in the November issue of Hepatology.

There is evidence in both chimpanzees and in humans to suggest that previous infection with HCV may confer resistance to new infections.

To see whether this was true, the investigators conducted a large community-based cohort study of 3,553 residents of Vancouver's Downtown Eastside neighborhood. They looked at those who had been infected with HCV and had documented virological clearance, and compared their rates of re-infection with first-time infection rates in members of the same cohort.

They identified from among the cohort 926 HCV-uninfected, and 658 HCV-infected viremic participants at baseline. In all, 152 of the 658 viremic participants (23.1%) had spontaneous clearance of the virus over a median follow-up of 5.2 years (interquartile range 2.8-7.4).

The cohort members who cleared HCV were significantly more likely at baseline to have co-infection with HIV (P<0.001) and to use illegal drugs frequently (P<0.004) than those who were not infected at baseline.

The authors found that despite having the same risks of exposure to HCV, HCV infection rates were lower among those who had been previously infected compared with those who were never infected. Among previously infected participants, 14 of 152 (9.2%), had new infections. In contrast, 172 of 926 (18.6%) of those with no evidence of infection at baseline became infected with HCV during follow-up.

The incidence rate for new infections among previously infected cohort members was 1.8/100 person-years (95% confidence interval, 0.9-3.0/100). The incidence rate of new infections for previously uninfected cohort members was 8.1 (95% CI, 6.9-9.4/100).

When the authors performed a logistic regression analysis using previous HCV infection as a covariate with other potential confounding variables (such as age, gender, ethnicity, HIV infection, housing status, and use of illegal and injectable drugs), they saw that participants with previous HCV infection who cleared the virus had a 77% lower risk for infection compared with others experiencing first-time infections (adjusted odds ratio, 0.23; 95% CI, 0.10-0.51, P<0.001).

The authors noted that their finding could possibly be explained by the presence of genetic polymorphisms that favor viral clearance and resistance to infection among those who were infected with the virus previously.

Alternatively, previously infected participants may have changed some of their high-risk behaviors, such as needle sharing, after their first bout with HCV, they speculated.

"However, given the higher rate of HIV infection in those with previous clearance, it is more likely that those with HCV clearance remain at higher risk of acquiring HCV infection over time," they wrote.