hepatitis C reinfection

a recent article from the Netherlands looking at hepatitis C (HCV) infection and reinfection in HIV positive MSM (men who have sex with men) sheds some light on the murky subject of HCV virology (See hep c reinfection clin inf dz 2014 in dropbox, orClinical Infectious Diseases 2014;59(12):1678–85).  it has been known that anti-HCV antibody titers can decline in both acute and chronic HCV infection and can even lead to seroreversion (ie, negative blood test for anti-HCV antibody). in this study, 63 people, who were followed a median of 4 years with HCV testing at least annually, seroconverted from negative anti-HCV Ab to positive. these men denied injection drug use and "phylogenetic analyses of circulating HCV strains have revealed the presence of multiple MSM-specific clusters". the researchers differentiated HCV reinfection (either infection with a different genotype than the initial infection, or at least looking for changes in certain genetic sequences from the initial infection within the same genotype) vs relapse (resurgence of HCV RNA in the blood with the same viral strain).  baseline: median age at primary HCV infection was 42, 62% were genotype 1a, baseline CD4 count was 495 and nadir 260. results:

--in those who developed an acute HCV infection, median time from first positive viral load (HCV RNA test) to positive antibody (anti-HCV Ab) was 74 days (no different from the timeframe found in non-HIV infected individuals)

--in the 36 who cleared the HCV RNA (5 cleared HCV spontaneously, 31 by treatment), there was a significant decline in the quantitative anti-HCV Ab levels 

--in the 31 who developed a sustained virologic response (SVR) to HCV treatment, 8 developed non-detectable anti-HCV Ab, with a cumulative incidence of such seroreversion being 37% within 3 years of seroconversion.

--18 of these seroreverters became reinfected with HCV (a total of 21 reinfections) during follow-up, with an increase in anti-HCV Ab (the peak anti-HCV titers were significantly higher with reinfections)

--1 treated patient had 3 reinfections, which showed large increases of anti-HCV titer with each newly positive HCV RNA test.

--in 17 of 63 people (27%), no anti-HCV Ab could be detected 4 months after infection, and ALT levels only showed reinfection in 72% (ie, one needs to check the HCV RNA to reliably detect a reinfection)

for a recent review of the complex and not completely understood immunologic response to hepatitis C, see http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3497039/​ .

so, i bring up this study for a few reasons.  

    --HCV​ infection is so common (2-3% of people globally, and certainly lots in our health center)

    --this study provides a snapshot of the epidemiology of acute HCV infections in a high risk group, since these people had annual hepatitis C measurements, as well as with any signs of hepatitis (the study did not include those with chronic HCV)

    --it is important to note that HIV-infected patients, though relatively frequently coinfected with HCV, do have in differences in the immunology of their HCV. for example, patients with HIV, especially advanced (not represented in above study), are more likely to have a false negative anti-HCV antibody with hep C infection (ie, if clinical hepatitis is suspected, you should routinely check a viral load and not just the antibody or rely on an ALT elevation in those with HIV. the same holds for those with recent exposure who are immunocompetent)

    --people who either spontaneously clear the HCV infection, or respond well to therapy, remain susceptible to reinfection (ie, neither a robust neutralizing antibody response associated with spontaneous viral clearance, nor vigorous HCV-specific T-cell responses seem to confer reliable long-term immunity from reinfection)

    ​--at least in HIV-positive MSM, it seems that sexual transmission of HCV is pretty common (the data on heterosexual HCV-discordant couples is: a very low rate of sexual transmission, though this does slowly increase with number of years of sexual exposure)

    --it seems useful to follow quantitative anti-HCV Ab levels as a means to diagnosis HCVreinfection (our lab currently does not report levels, but it should...)