Background. Acute hepatitis C virus (HCV) infection is often asymptomatic; thus, its epidemiology and natural history are difficult to define.

Methods. Acute HCV infection was identified on the basis of HCV seroconversion within 1 year (n= 45), new anti-HCV seropositivity with clinical acute hepatitis (n = 21), or HCV strain sequencing after an iatrogenic exposure (n = 1). Risk factors were assessed with a baseline questionnaire, and participants were followed up prospectively with serial measurement of viral loads.

Results. Of 67 persons with acute HCV infection, most were asymptomatic (64%) and injection drug users (66%). Thirteen had an unknown mode of transmission; of these, 11 reported high-risk sexual behavior. Ten acquired acute HCV infection within 3 months of an iatrogenic exposure; 3 had confirmed iatrogenic infection, and 4 had no other risk factors identified. The spontaneous viral clearance rate after 6 months of infection was 18% (95% confidence interval, 11%–31%). The rate of viral clearance varied significantly by sex (34% vs. 3% for women vs. men;P<.001).

Conclusions. High-risk sexual or iatrogenic exposures may be important contemporary risk factors for HCV infection. The spontaneous viral clearance rate (18%) in this contemporary study was similar to that reported for past studies of transfusion-associated HCV infection. Women were more likely to clear acute HCV infection than men.