Three broad modalities in the natural history of vertically acquired hepatitis C virus infection

Abstract

Background: Little is known about the natural history of vertically acquired hepatitis C virus (HCV) infection.

Methods: We performed a large, multicenter, prospective study of children born to HCV-infected women in Europe. Children were considered to be infected on the basis of > or = 2 polymerase chain reaction (PCR) test results positive for HCV RNA and/or test results positive for anti-HCV antibody > 18 months after birth.

Results: Two hundred sixty-six children with vertical HCV infection were followed up until a median of 4.2 years of age (range, 3.2 months to 15.9 years of age). Twenty-six children were coinfected with human immunodeficiency virus. Hepatomegaly, the only clinical sign reported, was found in 10% of children and was significantly associated with a high proportion of abnormal alanine transaminase (ALT) levels (adjusted odds ratio [OR], 4.17; 95% confidence interval [CI], 1.67-10.42; P = .002). An estimated 21%-25% of children may have cleared the virus (i.e., had 2 consecutive PCR test results negative for HCV RNA, normal ALT levels, and no clinical signs) at a median age of 14.9 months. A high proportion of positive PCR test results obtained in the first year of life was associated with a lower likelihood of clearance (OR, 9.77; 95% CI, 2.92-32.67; P < .0001) and persistent viremia in children > 1 year old (adjusted OR, 2.92; 95% CI, 1.09-7.80; P = .03).

Conclusions: We confirm the low prevalence of HCV-related clinical signs and symptoms among vertically infected children in the first 10-15 years of life. Approximately 20% of children appear to clear the infection, 50% have evidence of chronic asymptomatic infection, and 30% have evidence of chronic active infection. Although viremia and abnormal ALT levels were associated with hepatomegaly, further investigation is necessary before these markers can be used in the clinical management of HCV infection in children.