Hepatitis C virus (HCV) infection has become the most common cause of community-acquired and post-transfusion non-A, non-B hepatitis. A majority of those persons subsequently develop long-term liver disease that may lead to hepatocellular cancer. Interferon is becoming the standard treatment in patients with long-term HCV infection, but only a minority show a long-term response to therapy. Perinatal transmission of HCV infection can occur, but the consequences are not clearly quantified. A network of European health care centers was recently established to clarify issues about vertically acquired HCV infection. This study describes the natural history of perinatal HCV infection through a retrospective analysis of prospectively collected data from the health care centers that are a part of this network.
The study followed 104 children born to mothers who were known to be infected with HCV. The children were seen within the first two weeks of birth. Excluded were children with human immunodeficiency virus (HIV) infection, hepatitis B co-infection or a history of blood transfusion. The diagnosis was confirmed by the persistence of HCV-specific antibody beyond 18 months of age and/or the detection of HCV-RNA in serum by polymerase chain reaction (PCR) test on at least two separate occasions. These two criteria are consistent with Centers for Disease Control and Prevention guidelines. The children were followed clinically and with laboratory monitoring every three to six months for the first two years of life, then every six to 12 months thereafter. Of note, most of the mothers of these children were co-infected with HIV.
The children were followed for a mean duration of 49 months (range: six to 153 months). PCR analyses for detection of HCV-RNA in serum were conducted in all children. Based on the presence or absence of viremia over time, three groups of children were identified. Three patterns among the children were observed. The first group included 54 children in whom persistent viral HCV-RNA was present in all samples tested. The second group included 44 children in whom serum HCV-RNA was below detection levels by PCR. The third group included six children in whom HCV-RNA was undetectable, but who showed persistent HCV-specific antibody beyond 18 months of age.
Clinical signs of infection or illness were observed in only four children. Two children were found to have hepatomegaly; one child had atopic dermatitis, and one child developed type 1 diabetes (formerly known as insulin-dependent diabetes mellitus). None of the children exhibited problems with growth or a reduction in quality of life.
Serum alanine aminotransferase (ALT) levels were recorded for 90 of the 104 children. The mean serum ALT levels were highest during the first two years of life and declined substantially thereafter. Most of the infected children showed transient or persistent increases in ALT activity with significant ALT concentration variations in individual patients after two years.
In 20 children, a liver biopsy was performed, with the most common reasons being persistent elevation of serum ALT or HCV-RNA levels. The histologic features varied and included steatosis and portal lymphoid agregates. None of the 20 children had severe liver damage, but three children showed a certain degree of fibrosis. No apparent correlation was seen between HCV-RNA and serum ALT levels and degree of histologic abnormalities.
Four children received treatment with interferon, and one child with intermittent viremia was treated with interferon for 12 months. During treatment, serum ALT levels were normal, but they relapsed when treatment stopped. One child who was PCR-negative at months 3, 6 and 10, was PCR-positive when tested a day after treatment was stopped. Two other children remained HCV-RNA negative: one at 25 months and one at 52 months after discontinuing treatment.
The authors conclude that most children who acquire HCV infection through vertical transmission have a high rate of long-term infection. The figure in this cohort of children was approximately 90 percent. However, the degree of liver injury appears to be less severe in these children than in adults. The authors believe that this observation supports the theory that hepatocellular injury from HCV infection is immune-mediated and not a result of the direct cytopathic effects of the virus.