Kanae Tada

Favorable response to lymphoblastoid interferon-alpha in children with chronic hepatitis C.

BACKGROUND/AIMS We investigated the efficacy of interferon therapy for the treatment of children with chronic hepatitis C virus infection. METHODS Twenty-four out of 26 children completed the 6-month treatment with lymphoblastoid interferon-alpha and were followed for 12 months or longer. Response to interferon therapy was defined by assaying for circulating HCV-RNA, using a nested PCR, at 6-month intervals after the end of the therapy. RESULTS At the end of treatment circulating HCV-RNA was undetectable in 18/24 patients and at 6 months in 12/24. Ten of these 12 primary responders have remained virus free for more than 2 years. One patient remained negative at 12 months. The remaining patient relapsed at 12 months. At 24 months 10 of 18 patients tested negative for HCV-RNA. Serum alanine aminotransferase was normal in 11/24 patients at the end of treatment, at 6 months 12/24 were normal, and at 12 months 11/12 were normal. In eight children with sustained response, repeated liver biopsies revealed a reduction in Knodells scores for inflammation in the hepatic lobules and in the portal areas. In three of them neither plus nor minus strand of HCV-RNA was detectable in the liver tissue. Responders had a significantly lower level of viremia than non-responders. Side effects of interferon including fever, hair loss, neutropenia, and thrombocytopenia were not serious enough to warrant cessation of interferon treatment. CONCLUSIONS Interferon therapy in children with chronic hepatitis C may be beneficial as evaluated by sustained loss of viremia as well as by primary response.

Three paediatric cases of primary sclerosing cholangitis treated with ursodeoxycholic acid and sulphasalazine

We present here three paediatric patients with primary sclerosing cholangitis. In case 1, the serum γ‐glutamyl transpeptidase was decreased only temporarily by ursodeoxycholic acid (UDCA) treatment and 34 months later, sulphasalazine was added because of microscopic colitis. The enzyme level decreased with dual therapy. Similarly, in case 3, first diagnosed as autoimmune hepatitis, the transpeptidase levels remained elevated for 18 months during treatment with UDCA, prednisolone and mizoribin. The enzyme decreased only after a diagnosis of primary sclerosing cholangitis complicated with ulcerative colitis was established and sulphasalazine was introduced. Case 2 also had Crohns colitis and was put on UDCA and sulphasalazine from the start. The enzyme level was normalized within 1 month and has remained normal for the following 5 years. Liver biopsies were analysed repeatedly in these three patients. In case 1, periductal fibrosis remained unchanged while being treated by UDCA. There appeared to be no progression in liver cirrhosis in case 3 while being treated by UDCA, prednisolone, and mizoribin. In case 2, who has been treated with both UDCA and sulphasalazine from the start, periductal fibrosis and portal fibrosis were remarkably improved 45 months later. We suggest that sulphasalazine in addition to UDCA might be a viable treatment for children with primary sclerosing cholangitis.

Cytomegalovirus Hepatitis Confirmed by In Situ Hybridization in 3 Immunocompetent Infants

We present 3 cases of immunocompetent infants with CMV infection who showed prolonged liver dysfunction. In all cases the CMV genome was detectable in hepatocytes using the in situ hybridization method. Combination therapy with ganciclovir (GCV) and hyperimmune gammaglobulin (HGG) was instituted in 2 cases and successfully suppressed the replication of CMV, with sustained improvement in liver function. In 1 of these cases, signals for CMV DNA were undetectable in the liver 12 months after termination of combination therapy. These results help to confirm the etiology of CMV for persistent hepatitis in immunocompetent infants using the in situ hybridization method and also show the efficacy of combination therapy with a virostatic agent, GCV, and an immune-modulating agent, HGG.

Follow-Up Study of Hypervariable Region Sequences of the Hepatitis C Virus (HCV) Genome in an Infant with Delayed Anti-HCV Antibody Responses

An infant born prematurely and infected with hepatitis C virus (HCV) one month after birth was followed for 4.5 years. The patient did not produce detectable anti‐HCV antibodies until two years after the onset of hepatitis. Before seroconversion, a single clone of HCV, as determined by quasispecies of the hypervariable region (HVR) of the HCV genome, was almost exclusively found in the serum. After seroconversion, however, another distinct lineage of HCV clones replaced it within half a year. As HCV infection persisted further in the presence of anti‐HCV antibodies, many derivatives of both sequence lineages emerged to exhibit the typical quasispecies feature of HVR sequences. Neither seroconversion nor the changes in HVR sequences influenced the serum aminotransferase titers.