Kosuke Kozaiwa

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.

Three Cases with TT Virus Infection and Idiopathic Neonatal Hepatitis

We present three cases of infants with idiopathic neonatal hepatitis showing diffuse intrahepatic fatty degeneration. Prolonged cholestasis has improved immediately upon intravenous administration of a high-dose gammaglobulin treatment in all three patients. The TT virus (TTV) genome was detectable in the serum of two patients, in the duodenal fluid of one and in the liver of all three. By analyzing sequence homology, we observed that the respective TTV isolated from serum, duodenal fluid and liver tissue were completely identical in cases 2 and 3. These findings suggest that TTV infection was one of the contributing factors for neonatal cholestasis in these patients. TTV was isolated from the serum of two out of the three mothers. The viruses were either completely or almost identical in sequence to those isolated from their respective infants, suggesting that they had been transmitted from mother to infant in these 2 cases. The patients presented here, whose livers were infected with the TTV and showed a favorable response to gammaglobulin therapy, may represent a subset of idiopathic neonatal hepatitis patients.

A 13C-urea breath test in children with helicobacter pylori infection: assessment of eradication therapy and follow-up after treatment.

Purpose. Our aim was to evaluate the usefulness of the 13C-urea breath test (UBT) for the diagnosis of Helicobacter pylori infection, for assessment of the efficacy of eradication therapy, and for post-treatment follow-up in children. Methods. Seventy-two patients who underwent endoscopy for symptoms related to the upper gastrointestinal tract were examined by rapid urease test, histology, and culture. The patients were also studied with serology and UBT. Results. Forty-seven of the 72 patients were diagnosed with H. pylori infection, based on the results of biopsy-based tests and serology. As an initial diagnostic test to detect H. pylori infection, the sensitivity of the UBT was 95%, which was comparable with that of histology (94%), rapid urease test (96%), and serology (91%) and was greater than that of culture (79%). The specificity of the UBT was 100%, which was comparable with that of the other four tests. The efficacy of eradication therapy was assessed by biopsy-based tests and the UBT in 24 H. pylori-positive patients. For this purpose, the sensitivities of UBT and histology were 100%, while the sensitivities of culture and the rapid urease test were 88%. The specificity was 100% for all of these tests. Eleven patients were assessed by biopsy-based tests and UBT after more than 6 months of post-treatment follow-up. There were no discordances between the results of the UBT and those of the biopsy-based tests in any of the patients. Conclusions. The UBT may be useful for detecting H. pylori infection in children with upper gastrointestinal tract symptoms, for assessment of the efficacy of eradication therapy, and for the follow-up evaluation of patients after the therapy.

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.

A simplified 13C-urea breath test in children with Helicobacter pylori infection: Assessment of eradication therapy and follow-up after treatment

Our aim was to evaluate the usefulness of the 13C-urea breath test (UBT) for the diagnosis of Helicobacter pylori infection, for assessment of the efficacy of eradication therapy, and for post-treatment follow-up in children. Methods. Seventy-two patients who underwent endoscopy for symptoms related to the upper gastrointestinal tract were examined by rapid urease test, histology, and culture. The patients were also studied with serology and UBT. Results. Forty-seven of the 72 patients were diagnosed with H. pylori infection, based on the results of biopsy-based tests and serology. As an initial diagnostic test to detect H. pylori infection, the sensitivity of the UBT was 95%, which was comparable with that of histology (94%), rapid urease test (96%), and serology (91%) and was greater than that of culture (79%). The specificity of the UBT was 100%, which was comparable with that of the other four tests. The efficacy of eradication therapy was assessed by biopsy-based tests and the UBT in 24 H. pylori-positive patients. For this purpose, the sensitivities of UBT and histology were 100%, while the sensitivities of culture and the rapid urease test were 88%. The specificity was 100% for all of these tests. Eleven patients were assessed by biopsy-based tests and UBT after more than 6 months of post-treatment follow-up. There were no discordances between the results of the UBT and those of the biopsy-based tests in any of the patients. Conclusions. The UBT may be useful for detecting H. pylori infection in children with upper gastrointestinal tract symptoms, for assessment of the efficacy of eradication therapy, and for the follow-up evaluation of patients after the therapy.

Poor prognosis of mediastinal non-Hodgkin's lymphoma with an immature phenotype of CD2+, CD7 (or CD5)+, CD3−, CD4−, and CD8−

Nine children with mediastinal non‐Hodgkins lymphoma (NHL) were treated according to our new regimen which is characterized by intensified therapy with high‐dose cytosine arabinoside (HDCA). After induction therapy with a combination of five drugs, such as vincristine, doxorubicin, cyclophosphamide, 1‐asparaginase, and prednisolone, intermediate dosages of methotrexate (MTX) (1 g/m2) and HDCA (1.5 g/m2 × 12 doses) were administered. All but one patient (88.9%) achieved complete remission and then received this intensified therapy. With a median follow‐up period of 25.5 months, five patients are still in complete remission, but three patients have relapsed. From the phenotypic point of view, these relapsed patients showed only very immature T‐cell differentiation antigens such as CD2 and CD7 (or CD5). These results suggest that HDCA as intensified therapy for children with mediastinal NHL seems to be effective. However, for patients with an immature phenotype of T‐lineage cells, more sophisticated regimens should be prepared.

Mass Protection Program of Perinatal Hepatitis B Virus Infection in Japan and Impact of an Optional Booster Vaccination on Its Efficacy

We assessed the efficacy of a government‐sponsored mass protection program in Osaka, Japan, for perinatal HBV infection in infants born to HBeAg positive HBV carrier mothers. We also evaluated the impact of optional follow‐up procedures in such infants, including an evaluation of anti‐HBs response and a booster dose of HBV vaccine for poor responders. The results demonstrated that this mass protection program protected 94.4% of the infants from perinatal HBV infection in the Osaka area. However, the proportion of infants with an unprotective level of anti‐HBs was higher in the standard group than in the follow‐up group both at 1.0 and 1.5 years of age, which was also the case for HBV events. Furthermore, the present study showed that a booster dose of vaccine in poor responders was very effective in promoting an anti‐HBs response. In conclusion, we recommend that a follow‐up blood test to confirm a response of anti‐HBs to HBV vaccine should be performed at 4–8 weeks after the third injection of HBV vaccine in infants born to HBeAg positive HBV carrier mothers. We also recommend that a booster injection of HBV vaccine should be immediately given to poor responding infants who otherwise are at a considerable risk of developing HBV infection in late infancy.