Long-Term Course of Hepatitis C Viral Infections in Children
ABSTRACTs & COMMENTARY
Synopsis: Fourteen percent of German children who had undergone cardiac surgery before implementation of donor screening of blood donors were positive for antibodies against hepatitis C virus (HCV) and 55% of these antibody-positive children had circulating HCV. Liver function tests and liver biopsy of these children showed a small number of patients with significant liver disease. Children with hemophilia exhibited a high circulating HCV load but had less severe liver histopathology compared to children who had acquired HCV either from blood transfusions or vertically.
Sources: Vogt M, et al. Prevalence and clinical outcome of hepatitis C infection in children who underwent cardiac surgery before the implementation of blood-donor screening. N Engl J Med 1999;341:866-870; Zellos A, et al. High viral load and mild liver injury in children with hemophilia compared with other children with chronic hepatitis C virus infection. J Pediatr Gastroenterol Nutr 1999;29:418-423.
German children who underwent cardiac surgery before 1991, when routine blood donor screening for hepatitis C was introduced, were studied for hepatitis C virus (HCV). Sixty-seven of 458 patients (14.6%) had antibodies against HCV. The positive rate in normal age-matched controls was only 0.7%. At a mean follow-up time of 19.8 years, 37 of 67 antibody-positive patients (55%) had detectable HCV RNA in their blood. Only one of the HCV RNA-positive patients had elevated alanine aminotransferase (ALT). Seventeen of 37 patients had liver biopsy. Three of these had histologic signs of progressive liver damage, and these three patients had additional risk factors.
Zellos and associates evaluated whether the mode of transmission of HCV infection had an effect on subsequent liver injury and circulating viral load of children with HCV infections.
Thirty-nine children who had positive enzyme-linked immunoassay (ELISA) immune tests for HCV antibodies were divided into three groups reflecting their route of infection: blood transfusions, hemophilia factor replacement therapy, and vertical transmission from mother to infant. Serum HCV viral load was approximately five times higher in the hemophiliacs than in the other groups. Surprisingly, however, the degree of histologic liver injury (including inflammation and fibrosis) was significantly less severe in the hemophiliac boys compared to the other groups.
Group 1 consisted of nine children, 13.3 ± 0.9 years of age, who had a history of whole blood or red blood cell (RBC) transfusions. Group 2 consisted of 19 hemophiliac boys, 11.6 ± 0.8 years of age. Group 3 consisted of 10 children, aged 4.7 ± 1.1 years old, who presumably had vertically acquired HCV resulting from maternal to neonate transmission. Liver function tests (serum ALT), HCV viral load determined by polymerase chain reaction assay that measures the number of circulating viral copies per mL of blood, HCV genotype, and liver histology were assessed in all of these children and the results in the three groups were compared.
Despite a considerably shortened duration of infection, the children in group 3 with vertically acquired HCV infections had liver injury comparable to those in group 1. Genotype of the HCV infection did not influence either the level of viremia or histologic liver injury. Vogt and colleagues and Zellos et al conclude that children with hemophilia had higher levels of circulating HCV, but paradoxically had less evidence of hepatic damage than children who had acquired HCV by blood transfusions or vertical transmission at birth. Host resistance factors may have an important influence in the pathogenesis and expression of this disease.
Comment by Howard A. Pearson, MD, FAAP
There are few data on the prevalence and clinical outcome of HCV infections in children. These two papers examine this issue from somewhat different perspectives. In adults who have chronic HCV infections, the severity of subsequent hepatocellular disease may be influenced by the mode of transmission of the virus to the patient. This has not been studied in children. The report of Zellos et al showing a marked difference in the prevalence of persistent viremia in hemophiliac boys who were infected by virus contaminated Factor VIII but less severe hepatocellular damage compared to infections resulting from blood transfusions or vertical transmission suggest the possibility that host immune responses may affect the clinical expression of this disease. The finding of such a large group of HCV-infected hemophiliac boys is distressing, following as it does the 1980-1985 infection of about 70% of these boys with HIV that has virtually wiped out a generation of them. The present replacement therapies for hemophilia A are increasingly produced in vitro by recombinant DNA technologies and should be free of virus.
Vogt et al show that although there was a substantial risk of acquiring HCV infection from nonscreened blood transfusions, after about 20 years the virus had spontaneously cleared in many patients, and the clinical course in those still infected appeared more benign than would be expected in persons infected in adult life.
Even today, when extensive testing of blood has essentially eliminated most of the diseases that are now known to be transmissible, such as HIV and hepatitis A, B, and C, there could well be currently unknown viruses that are lurking or could enter the blood supply in the future. Only when these viruses and the diseases that they produce are recognized and appropriate testing is developed to detect them, there is at least a theoretical risk of repetition of the hepatitis C and HIV disasters of the last 25 years. As a hematologist, I would be the last person to argue against the appropriate use of blood products. However, transfusion of blood products has at least a theoretical risk of transmitting serious and even fatal diseases and they should not be administered for trivial or unnecessary indications. (Dr. Pearson is Professor of Pediatrics, Yale University School of Medicine.)
True statements about hepatitis C viral infections in children who had undergone cardiac surgery in infancy before implementation of donor screening include all of the following except:
a. infections occurred in more than half of these children.
b. there was a high prevalence of detectable HCV in their blood one to three decades later.
c. infections caused severe, long-term hepatocellular disase.
d. the course was considerably less severe than observed in patients infected as adults.
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