Prognosis of Perinatally Acquired Hepatitis C Virus Infection
Prognosis of Perinatally Acquired Hepatitis C Virus Infection
Abstract & Commentary
Synopsis: A study of children with perinatally acquired hepatitis C infection followed for an average of 4.8 years showed persistent HCV infection in 81%, with liver disease that was mild. HCV genotype 3 was associated with a higher rate of loss of HCV RNA and normalization of ALT by 30 months of age.
Source: Resti M, et al. Clinical features and progression of perinatally acquired hepatitis C virus infection. J Med Virol. 2003;70:373-377.
A prospective-retrospective cohort study was conducted among children born to HCV-infected mothers in 5 European centers between 1990 and 1996. Seventy children with HCV RNA in the serum during the first year of life and/or with anti-HCV antibodies at 18 months of age were consecutively enrolled. Children initially tested between 6 and 12 months of age were all HCV-RNA positive. Three of 28 children (11%) first tested for HCV RNA at 3 months of age were negative but became viremic and had elevated ALT levels during subsequent months.
There was a wide range of ALT elevation during the first year of life. Overall, 65/70 (93%) developed ALT abnormalities, ranging from 1.2-21 times normal. Peak ALT values exceeding 5 times normal developed in 34%. Among 27 children with 3 or more ALT values obtained during the first year of life, the highest ALT value occurred during the first 6 months of life in 37% and during 6-12 months of life in 63%.
Sixty-two children were followed for an average of 4.8 ± 2.3 years (range, 24 months-11 years); follow-up for this study was terminated if therapy was initiated. During the follow-up, 12/62 children (19%) demonstrated loss of HCV RNA more than 6 months after initial testing, with sustained ALT normalization by 30 months of life. These children, compared to children with persistent viremia, were more likely to have an ALT peak greater than 5 times normal (66% vs 28%; P < .05) and to be infected with HCV genotype 3 (50% vs 17%). Chronic infection persisted in 50/62 children (81%) and was asymptomatic. Liver disease was mild in all 11 children who underwent a liver biopsy. Twenty-one mothers were coinfected with HIV; none were coinfected with hepatitis B. No correlation was found between outcome and mode of delivery (20% were delivered by cesarean section) or breast feeding (82% of children were formula fed).
Comment by Hal B. Jenson, MD, FAAP
This relatively large series of European children showed that the outcome of perinatally transmitted HCV infection is similar to HCV infection in adults, with resolution of viremia in approximately 20% of cases. In contrast, the children in this study who cleared the HCV infection lost viremia more than 6 months after their initial testing. These results also confirm the necessity of follow-up anti-HCV testing, at 18 months of life, since the HCV RNA determination was negative in 11% of children at 3 months of age. The ALT levels during the first year of life were highly variable, including levels that would be compatible with acute hepatitis, and were not useful as a predictor of outcome for individual patients. In this study, high ALT levels during the first year of life were associated with greater chances of sustained HCV RNA and normalization of ALT levels. Genotype 3 was also more common among children with clearance of HCV infection, although the small number of children limited statistically significant conclusions.
Perinatal transmission of hepatitis C is now the primary mode of HCV spread, because all blood and blood products are screened. The estimated rate of perinatal HCV transmission is approximately 5%. Most children with perinatal HCV infection remain asymptomatic, and liver histology shows minimal or mild hepatitis. The long-term prognosis of these children remains to be determined, which will require follow-up for at least 20-30 years of life. The role of antiviral treatment for perinatal HCV infection also remains unresolved.
Dr. Jenson is Chair, Department of Pediatrics, Director, Center of Pediatric Research, Eastern Virginia Medical School and Children's Hospital of the King's Daughters, Norfolk, VA.
A study of children with perinatally acquired hepatitis C infection followed for an average of 4.8 years showed persistent HCV infection in 81%, with liver disease that was mild. HCV genotype 3 was associated with a higher rate of loss of HCV RNA and normalization of ALT by 30 months of age.Subscribe Now for Access
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