Histopathology of the Liver in Children With Chronic Hepatitis C Viral Infection

Abstract

Although the epidemiology, natural history, and pathological aspects of chronic hepatitis C are well-defined in the adult population, little is known about the characteristics of chronic hepatitis C infection in children. Reports on the histological features and progression of hepatitis C in children are scarce, and consist primarily of multicenter studies in Japanese and European children. Given the geographic variations in viral genotype and the association of pathology with genotype, whether the Japanese and European studies can be extended to the North American populations is unclear. We report the histopathology of the liver in 40 children with chronic hepatitis C infection treated in a single North American institution. The children included 19 males and 21 females ranging in age from 2.0 to 18.6 years at the time of liver biopsy (mean ؎ SD: 11.4 ؎ 4.3 years). Our findings indicate that the characteristic histopathological lesions of chronic hepatitis C infection, including sinusoidal lymphocytosis, steatosis, portal lymphoid aggregates/follicles, and bile duct epithelial damage, occur with approximately the same frequencies in children as have been reported in adults. Necroinflammatory activity was generally mild. Portal fibrosis was present in 78% of the specimens, including fibrous portal expansion (26%), bridging fibrosis (22%), bridging fibrosis with architectural distortion (22%), and cirrhosis (8%). Centrilobular pericellular fibrosis, which has not been previously reported in the context of chronic hepatitis C infection in adults or children, was also a prominent feature in our series, occurring with a similar frequency as steatosis or portal lymphoid aggregates/follicles. Our data suggest that in spite of mild histological necroinflammatory activity in general, the stage of fibrosis in children can be severe in spite of relatively short duration of infection. (HEPATOLOGY 1998;28:1416-1423.)Hepatitis C virus (HCV) infects nearly 4 million people in the United States, and is now the leading cause of liver transplantation in adults. Although it is likely that some of these adults acquired the infection during childhood, the number of children infected with HCV is unknown. In spite of extensive epidemiological data, natural history, and detailed characterization of the morphological features of chronic hepatitis C infection in adults, [1][2][3][4][5][6][7][8][9] little is known about the epidemiology, histology, and progression of chronic HCV infection in children. Available studies consist primarily of clinically oriented reports from Japan and Europe. [10][11][12][13][14][15][16][17] Given the geographic variations in HCV genotypes, 18,19 and the potential effect of genotype on pathology, 20-26 whether the Japanese and European findings can be extrapolated to the infected American children is unclear.The only series of pediatric hepatitis C patients reported with special emphasis on the liver pathology is that of a multicenter study of Japanese children. 27 Surprisingly, the stage of fibrosis in thi...

Interferon alfa-2b in combination with ribavirin for the treatment of chronic hepatitis C in children: Efficacy, safety, and pharmacokinetics

“…Based on our current understanding of the pathobiology of HCV, it is reasonable to assume that the virus behaves in the same manner in children as in adults. Although childhood HCV infection is generally associated with mild liver damage, it has been associated with significant liver disease, [1][2][3][4] including chronic hepatitis, cirrhosis, and hepatocellular carcinoma, in this population. Our studies demonstrate that interferon alfa-2b in combination with oral ribavirin is effective and reasonably safe for the treatment of childhood chronic hepatitis C. Infection with HCV genotypes 2 or 3, and lower level of serum HCV RNA at baseline in HCV genotype 1, are associated with higher virological response rates.…”

“…Although our understanding about the natural history and pathobiology of HCV infection in children is incomplete, it has been associated with significant liver disease, including chronic hepatitis, cirrhosis, and hepatocellular carcinoma in this population. [1][2][3][4] Approximately 10% to 20% of adults 5 and 36% of children 6 treated with interferon alone achieve long-term virological remission. The addition of ribavirin to interferon-based regimens markedly improves virological responses in adults.…”

Children with hepatitis C

“…In contrast, in a series from the United States, overall histological activity (using the Scheuer and METAVIR scoring systems) was generally mild, but portal fibrosis was much more frequent, described in 78% of 40 children. 41 The degree of fibrosis was rated as mild in 26%, moderate in 22%, severe in 22%, and as cirrhosis in 8% of children. Two children with cirrhosis were young adolescents who had acquired HCV infection perinatally.…”

Pathology of chronic hepatitis C in children: Liver biopsy findings in the Peds-C Trial

“…2,3 By contrast, relatively few children with chronic hepatitis C undergo liver biopsy, and there are only a few published series describing the range of histopathology in a significant number of patients. [4][5][6][7][8][9][10] In general, these have found that children tend to have milder disease than adults, with less inflammation, steatosis, and fibrosis, but with some variation between series collected in different parts of the world.…”