Hepatitis: Fujisawa T

Murray KF, Shah U, Mohan N, Heller S, González-Peralta RP, Kelly D, Chang MH, Mieli-Vergani G, Jara P, Fujisawa T, Anonymous00091. · Hepatobiliary Program, Seattle Children's Hospital and Regional Medical Center, Seattle, WA 98105, USA. · J Pediatr Gastroenterol Nutr. · Pubmed #18664880 No free full text.

This publication has no abstract.

Fujisawa T, Inui A, Sogo T, Komatsu H. · Department of Pediatrics, International University of Health and Welfare, Atami Hospital. · Nippon Rinsho. · Pubmed #15453335 No free full text.

This publication has no abstract.

Inui A, Fujisawa T, Sogo T, Komatsu H. · Department of Pediatrics, International University of Health and Welfare, Atami Hospital. · Nippon Rinsho. · Pubmed #15453313 No free full text.

This publication has no abstract.

Nakashima E, Fujisawa T, Kimura A, Kage M, Yamato Y, Maeda K, Kumagai M, Ushijima K, Yamashita Y, Matsuishi T. · Departments of Peditarics, Kurume University School of Medicine, Kurume, Japan. · J Gastroenterol Hepatol. · Pubmed #12653889 No free full text.

Abstract: BACKGROUND: We investigated the efficacy of natural interferon (IFN)-alpha treatment in 34 Japanese children with chronic hepatitis C. METHODS: Thirty-four children completed 6 months of therapy with natural IFN-alpha and were followed for 12 months or longer. We examined the serum hepatitis C virus (HCV) RNA titer and liver histology before, during, and after IFN treatment. RESULTS: At 6 months after the cessation of IFN-alpha treatment, 16 patients (47%) had normal serum alanine aminotransferase concentration and no detectable serum HCV RNA. There were no major side-effects, excluding some influenza-like symptoms during the IFN-alpha treatment. Most genotype 2a patients had a complete response (80%). Moreover, patients who had a low HCV RNA titer (<102 copies/mL) after 1 month of IFN-alpha treatment became complete responders at 6 months after the cessation of treatment. Histological improvement was observed in almost all patients after IFN-alpha treatment. CONCLUSION: Interferon-alpha treatment is safe and effective for children with chronic hepatitis C and has no serious side-effects. A HCV RNA concentration of <102 copies/mL after 1 month of IFN-alpha treatment and genotype 2a may be useful predictors of long-term IFN efficacy.

Shah U, Kelly D, Chang MH, Fujisawa T, Heller S, González-Peralta RP, Jara P, Mieli-Vergani G, Mohan N, Murray KF. · Harvard Medical School Dubai Center, Dubai Health Care City, Dubai, UAE. · J Pediatr Gastroenterol Nutr. · Pubmed #19322053 No free full text.

Abstract: Hepatitis B virus (HBV) infection is a worldwide problem and can cause acute liver failure, acute hepatitis, chronic hepatitis, liver cirrhosis, and liver cancer. In areas of high prevalence such as in Asia, Africa, southern Europe, and Latin America, the hepatitis B surface antigen positive rate ranges from 2% to 20%.In endemic areas, HBV infection occurs mainly during infancy and early childhood. Mother-to-infant transmission accounts for approximately half of the chronic HBV infections. In contrast to infection in adults, HBV infection during early childhood results in a much higher rate of persistent infection and long-term serious complications such as liver cirrhosis and HCC.Three phases of chronic hepatitis B have been identified: the immune-tolerant phase, the immune-active phase, and the inactive hepatitis B phase. These phases of infection are characterized by variations in viral replication, hepatic inflammation, spontaneous clearance, and response to antiviral therapy.The optimal goal of antiviral therapy for chronic HBV infection is to eradicate HBV and to prevent its related liver complications. However, due to the limited effect of available therapies in viral eradication, the goal of treatment is to reduce viral replication, to minimize liver injury, and to reduce infectivity. In this review the current recommendations for monitoring and treating chronic HBV infection in children are reviewed.

Komatsu H, Inui A, Sogo T, Hiejima E, Kudo N, Fujisawa T. · Department of Pediatrics, Yokohama Eastern Hospital, Yokohama. · Hepatol Res. · Pubmed #19260997 No free full text.

Abstract: Aim: In order to clarify the sources of chronic HBV (hepatitis B virus) infection in children after the implementation of an "at-risk" strategy in Japan, chronically infected children were assessed. In addition, chronically infected children born to HBsAg-negative mothers and their family members were assessed to identify the sources of HBV transmission. Methods: Fifty-seven children who tested HBsAg-positive after the initiation of a mother-to-child transmission prevention program were enrolled in this study. The full-genome HBV DNA sequence was analyzed to confirm the transmission sources. Results: Of the 57 patients, 37 (65%) were born to HBV carrier mothers. The remaining 20 (35%) patients were born to HBsAg-negative mothers. Fourteen of these patients had HBV carrier fathers, and 2 patients, who were siblings, did not have an HBV carrier father. The remaining 4 patients had no family members with HBV infection. Phylogenetic tree analysis confirmed that father-to-child transmission and sibling-to-sibling transmission occurred in 3 families and 1 family, respectively. Conclusion: Although vaccine failure of mother-to-child transmission was the major cause of chronic HBV infection in children, father-to-child transmission was the second most common mode of transmission. In addition, sibling-to-sibling transmission was found. Unless at-risk individuals and groups can be accurately identified to prevent horizontal transmission, the introduction of universal vaccination is essential for achieving the elimination of HBV infection in Japan.

Shiraki K, Ohto H, Inaba N, Fujisawa T, Tajiri H, Kanzaki S, Matsui A, Morishima T, Goto K, Kimura A, Hino S. · Department of Pediatrics, Tottori University Faculty of Medicine, Yonago, Tottori, Japan. · Pediatr Int. · Pubmed #18279227 No free full text.

This publication has no abstract.

Miyoshi Y, Tajiri H, Okaniwa M, Terasawa S, Fujisawa T, Iizuka T, Ozono K. · Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, Japan. · Pediatr Int. · Pubmed #18279197 No free full text.

Abstract: BACKGROUND: The clinical features of hepatitis C virus (HCV)-associated liver diseases, or the efficacy of interferon (IFN) therapy in children with Down syndrome (DS) remain to be elucidated. The purpose of the present paper was to survey the features of liver diseases in this subset of children and evaluate the efficacy of IFN treatment in those patients. METHODS: A questionnaire was sent to 41 members of the Japan Society of Pediatric Hepatology. Ten of them reported on 11 patients with DS who had concomitant chronic HCV infection, providing information on liver disease and the response to IFN treatment. RESULTS: Interferon therapy of 24 weeks duration using natural IFN-alpha was instituted in six of the 11 patients with DS, but none of the six patients cleared HCV-RNA from their serum. Among 12 age- and sex-matched control children who were treated with IFN using the same regimen against chronic HCV infection, half of them had a favorable response to IFN therapy with a sustained clearance of HCV-RNA from their serum. The major baseline features including alanine aminotransferase levels, HCV genotype and viral load were not apparently different between the six patients with DS and the 12 controls. CONCLUSIONS: IFN therapy for HCV infection in patients with DS may be unfavorable as compared with non-DS children.

Fujisawa T, Sogo T, Komatsu H, Inui A. · Children's Center for Health and Development, Yokohama City Tobu Hospital, Yokohama, Japan. · Hepatol Res. · Pubmed #17931209 No free full text.

Abstract: Autoimmune hepatitis (AIH) is a generally progressive inflammatory liver disease of unknown etiology that occurs in adults and children. Although the peak age of incidence is in prepubertal girls, AIH has been diagnosed as early 6 months of age. Two types of AIH are recognized according to the nature of the autoantibody detected in children at the time of diagnosis. The diagnosis of AIH is based on histological abnormalities, characteristic clinical and biochemical findings, and abnormal levels of serum globulin due almost exclusively to markedly increased immunoglobulin G including various autoantibodies. A genetic predisposition is suggested by the increase frequency of human leukocyte antigen (HLA) haplotypes HLA-B8/DR3, and allotypes DR3 and DR4. However, the incidence of these HLA types is different in each country.Proposed triggers of AIH that may initiate the inflammatory process include some viral infections and some drugs. There is much information about adults with AIH, however, little information on AIH in children, especially in Japanese children. To clarify the clinicohistological features of AIH in Japanese children, we analyzed the clinical, pathological features and response to treatment in 12 Japanese children with AIH. Furthermore, we discuss several problems for diagnosis and treatment for AIH in children.

Inui A, Komatsu H, Sogo T, Nagai T, Abe K, Fujisawa T. · Department of Pediatrics, Yokohama Sakae Kyosai Hospital, Katsura-cho 132, Sakae-ku, Yokohama, Kanagawa, Japan. · J Med Virol. · Pubmed #17457903 No free full text.

Abstract: The genotype distribution of hepatitis B virus (HBV) was investigated in 118 children in Japan. One hundred and sixteen children (98%) had chronic HBV infection, and the remainder had acute hepatitis. Genotyping of HBV was determined by PCR and sequencing analysis in the S gene. Genotype C (86%) was the most frequent, followed by genotype B (9%), D (2.5%), and A (1.0%). Transmission routes of HBV to children were from mothers in 91 patients (77%), fathers in 8 (6.5%), mother or father in 1 (1%), family members other than the parents in 5 (4%), and unknown in 13 (11.5%). The relationship between routes of HBV transmission and HBV genotypes was studied. Eighty-eight (97%) of 91 children of mother-to-infant transmission were genotype C, while 13 (49%) of 27 children of the routes other than the mother to infant transmission were genotype C. The number of children with genotype C who were infected from their mothers was significantly higher than those with genotype B, D, or A (P < 0.01). In conclusion, HBV genotypes influence not only clinical characteristics but also the mechanisms of inter-personal HBV transmission.

Michitaka K, Horiike N, Duong TN, Yagura M, Harada H, Shibayama T, Inui A, Fujisawa T, Matsuura K, Hiasa Y, Onji M. · Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan. · Intervirology. · Pubmed #17191017 No free full text.

Abstract: OBJECTIVE: Hepatitis B virus (HBV) genotypes B and C are predominant in Japan. Previously, we reported that approximately 9% of HBV carriers in the Ehime area of western Japan were infected with genotype D (HBV/D) and their sequences closely related. Recently, serum samples from 3 patients with chronic HBV/D infections living in Tokyo and the surrounding area became available for testing. The purpose of this study was to determine whether the HBV/D isolates from these different areas of Japan are closely related. METHODS: Of the 3 Tokyo area patients infected with HBV/D, 2 had chronic hepatitis, and 1 had hemophilia with a history of frequent coagulation factor injections. The complete HBV/D genome sequences of each were determined, and compared with those of subjects from the Ehime area. RESULTS: All 3 HBV/D sequences had a genomic length of 3,182 bases, and the hepatitis B surface antigen subtype was ayw3. Phylogenetic analysis revealed that the 1 of the HBV/D isolates was closely related to the isolates from Ehime Prefecture, while 1 was similar and 1 was clearly distinct. CONCLUSION: Our results indicate that HBV/D infections in Japan are heterogeneous.

Nakajima S, Umebayashi H, Kurosawa R, Imagawa T, Katakura S, Mori M, Aihara Y, Yokota S, Sogo T, Inui A, Fujisawa T, Hanzawa N. · Department of Pediatrics, Yokohama City University of Medicine, Yokohama, Japan. · Nihon Rinsho Meneki Gakkai Kaishi. · Pubmed #15997179 links to  free full text

Abstract: A 10-year-old girl with autoimmune hepatitis (AIH) was reported. She was admitted to our hospital because of cholestasis and elevation of liver enzymes for 2 months. Laboratory examination revealed that EBV-DNA copy number in the PBMNC (peripheral mononuclear cells) was 1.2 x 10(3) copies/microg of DNA, hypergammaglobulinemia, and positive antinuclear antibody, positive anti-smooth muscle antibody. The histology of her liver biopsy specimen revealed interface hepatitis, dense mononuclear cell infiltrates, mild fibrosis, and negative for EBV in situ hybridization assay indicating AIH and not EBV-associated hepatitis. She was treated firstly with methylprednisolone pulses, then will prednisolone p.o.+azathioprine p.o.. Intravenous cyclophosphamide pulse therapy was introduced because of her abnormal immune pathology. All abnormal laboratory parameters improved to normal levels within 2 months, and EBV-DNA copy number in the PBMNC became negative after 4 months. The histology of liver biopsy specimen was useful for the diagnosis of AIH in such a difficult case needed to be differentiated from EBV hepatitis.

Komatsu H, Inui A, Sogo T, Fujisawa T, Egawa H, Tanaka K. · Department of Pediatrics, National Defense Medical College, Saitama, Japan. · Transpl Infect Dis. · Pubmed #15984949 No free full text.

Abstract: Hepatic vein stenosis is a vascular complication that can lead to graft loss after liver transplantation. Although ascites frequently occurs as a symptom of hepatic vein stenosis, the development of severe hypogammaglobulinemia associated with hepatic vein stenosis has not been reported in the literature. An 8-year-old boy underwent living-related liver transplantation (LRLT) because of Wilson disease with chronic hepatic failure. Because de novo autoimmune hepatitis was diagnosed 1 year after LRLT, azathioprine, and prednisolone were added to the baseline immunosuppression of tacrolimus. The patient developed ascites with severe hypogammaglobulinemia (immunoglobulin G [IgG], 288 mg/dL) 2 years after LRLT. Ultrasonography and angiography disclosed stenosis of the hepatic vein. The ascites completely resolved after percutaneous balloon angioplasty. Despite serum IgG trough levels of >500 mg/dL maintained by the addition of immunoglobulin, cytomegalovirus reactivation and sepsis occurred. Serum IgG levels should be monitored to prevent opportunistic infections when hepatic vein stenosis is diagnosed after LRLT.

Inui A, Sogo T, Komatsu H, Miyakawa H, Fujisawa T. · Department of Pediatrics, International University of Health and Welfare, Atami Hospital, Japan. · Liver Transpl. · Pubmed #15838910 links to  free full text

Abstract: Graft dysfunction mimicking autoimmune hepatitis rarely develops after liver transplantation for nonautoimmune disease. The mechanism(s) and causes of de novo autoimmune hepatitis are unknown. We examined autoantibodies serially in a patient with de novo autoimmune hepatitis and in patients without de novo autoimmune hepatitis after liver transplantation. Anticytokeratin 8/18 antibodies were detected in the first patient's sera after the onset of de novo autoimmune hepatitis, whereas other patients without de novo autoimmune hepatitis were seronegative throughout the follow-up period even with acute cellular rejection or other cause of liver dysfunction. In conclusion, the changes in cytokeratin 8/18 in hepatocytes might be one of the sources of pathogenesis of de novo autoimmune hepatitis after liver transplantation.

Komatsu H, Inui A, Sogo T, Kuroda K, Tanaka T, Fujisawa T. · Department of Pediatrics, National Defense Medical College, Saitama, Japan. · J Med Virol. · Pubmed #15368510 No free full text.

Abstract: The TT virus (TTV) was isolated recently from the serum of a patient with post-transfusion hepatitis. TTV infection is widespread in the general population, and its prevalence increases continuously with age. The pathogenic role of TTV in liver disease remains controversial, and the source of transmission is still unclear. We investigated the pathogenicity and epidemiology of TTV infection in infants born to TTV DNA-positive mothers. Enrolled in this study were 22 mother-child pairs testing negative for antibodies to hepatitis B, hepatitis C, and the human immunodeficiency viruses (HIVs). The children were followed for 30 months after birth. Serum TTV DNA was detected by N22-PCR, and the PCR products were cloned and sequenced. The prevalence of TTV infection in children increased with age. Of the 22 children, 13 (59%) became positive for TTV DNA during the follow-up period. Of these 13 children, 6 (46%) had elevated levels of serum alanine aminotransferase (ALT), although the elevations were transient and mild. TTV viremia was not associated significantly with the abnormal ALT levels. Children with TTV viremia developed neither severe liver disease nor fulminant hepatitis. Phylogenetic analysis showed that, in 11 (85%) of the 13 pairs, the mother and child had the same genotype at the first PCR-positive time point. Among those 11 mother-child pairs, 6 (55%) had identical TTV nucleotide sequences. However, the genotype of predominant clones changed in 5 (50%) of 10 children who were positive for TTV DNA at two or more time points during the follow-up period. In conclusion, this study did not provide evidence that TTV infection is related to liver disease in children. Although the main source of TTV infection in children is presumed to be their mothers, transmitted via non-parenteral routes in the course of daily contact, intrafamilial carriers may also be sources of TTV infection.

Inui A, Fujisawa T, Sogo T, Komatsu H, Isozaki A, Sekine I. · Department of Pediatrics, National Defense Medical College, Saitama, Japan. · J Gastroenterol Hepatol. · Pubmed #12084037 No free full text.

Abstract: The risk of vertical transmission of hepatitis C virus (HCV) from mother to infant has been well documented, but the exact mode of transmission is still unclear. In a set of monochorionic diamniotic monozygous twins, only the second baby was infected with HCV from the mother who was positive for serum HCV-RNA. The babies had an uncomplicated vaginal delivery 3 min apart and they were both bottle fed from the outset. The second baby developed clinical hepatitis that persisted to 30 months follow up. The intrauterine environment should have been identical for these twins, and therefore, the maternal HCV factors, including viral load are not the sole determining factors for mother-to-infant transmission of HCV.

Komatsu H, Fujisawa T, Sogo T, Isozaki A, Inui A, Sekine I, Kobata M, Ogawa Y. · Department of Pediatrics, National Defense Medical College, Saitama, Japan. · J Med Virol. · Pubmed #11748655 No free full text.

Abstract: The occurrence of acute hepatitis after failure of immunoprophylaxis in cases of mother-to-infant transmission of hepatitis B virus (HBV) is uncommon. Because immunoprophylaxis failure is caused by the emergence of an "a" determinant escape mutant, the infants usually become HBV carriers. To evaluate whether mutations in the S gene coding for the surface protein that contains the "a" determinant are associated with acute hepatitis after immunoprophylaxis failure, HBV DNA of an infant in with acute hepatitis developed with seroconversion to anti-HBs antibodies at 12 months of age despite administration of anti-hepatitis B immunoglobulin and hepatitis B vaccine was analyzed. The S gene from HBV DNA isolated from the serum of the infant at 12, 19, and 27 months of age was cloned and sequenced. Mutations affecting amino acid residues in the first loop within the "a" determinant (codons 124-147) were found at 12 months of age. Moreover, a novel deletion mutant, with a 1-bp deletion at nucleotide 449 of the S gene, was found at 19 and 27 months of age. This deletion resulted in a frame shift and it introduced a stop codon (TAG) at codon 176. Because the open reading frame of the S gene is completely overlapped by the polymerase gene, mutations in the S gene may affect the polymerase gene. Based on this case, this study suggests that the observed frame-shift mutation in the S gene might affect the polymerase protein and induce prompt suppression of viral replication.

Komatsu H, Inui A, Morinishi Y, Sogo T, Fujisawa T. · Department of Pediatrics, National Defense Medical College, 3-2, Namiki, Tokorozawa, Saitama 359-8513, Japan. · J Med Virol. · Pubmed #11596078 No free full text.

Abstract: It is well known that fulminant hepatitis B can occur in infants born to hepatitis B e antigen (HBeAg)-negative hepatitis B virus (HBV) carrier mothers, whereas fulminant hepatitis and severe hepatitis are uncommon in infants born to HBeAg-positive mothers. We have encountered an infant with severe acute hepatitis B born to a HBeAg-positive mother. The aim of this study was to determine whether HBV variants contribute to the pathogenesis of fulminant hepatitis and severe hepatitis in an infant born to an HBeAg-positive mother. The nucleotide sequence of HBV genomes from the infant and his HBeAg-positive carrier mother was analyzed. All HBV isolated from the infant and his mother were subtype adr. The sequences of the cloned HBV genomes, each including a part of the X and precore/core regions, isolated from the infant were almost identical (homology of 99.1-99.9%) to those from his mother. There was no mutation in any of the 17 clones examined at nucleotides 1762 and 1764 in the core promoter, which is reported to be associated with fulminant hepatitis. A point mutation at nucleotide 1758 in the second AT-rich region of the basic core promoter was present in all clones. None of the clones had a point mutation at nucleotide 1896 of the precore region. In this study, no specific HBV variants contributing to the development of neonatal severe hepatitis were found. There is a possibility that host factors rather than viral factors play an important role in some cases of severe neonatal hepatitis B.

Fujisawa T, Horiike N, Michitaka K, Onji M. · The Third Department of Internal Medicine, Ehime University School of Medicine, Japan. · J Gastroenterol Hepatol. · Pubmed #10921417 No free full text.

Abstract: BACKGROUND: A relationship between the pretreatment RNA titre of GB virus C/hepatitis G virus (GBV-C/HGV) and the effectiveness of interferon (IFN) therapy has been reported previously. However, the influence of changes in the amino acid sequence of the NS5A region of GBV-C/HGV on the effectiveness of IFN therapy has not been examined, although this influence has been explored in patients with chronic hepatitis caused by hepatitis C virus. We examined the relationship between changes in the amino-acid sequence of the NS5A region and the effectiveness of IFN therapy. METHODS: The subjects were 10 patients with chronic hepatitis C coinfected with GBV-C/HGV and treated with IFN. The pretreatment level of GBV-C/HGV-RNA (copies/mL) in their sera was measured by real-time detection polymerase chain reaction (PCR) assay. At 6 months after cessation of therapy, four of 10 patients had become negative for GBV-C/HGV-RNA (CR, complete response) and six patients were still positive for GBV-C/HGV-RNA (NR, non-response). We determined the nucleotide sequence of the NS5A region (amino acid residues 1865-2279; NS5A1865-2279) of pretreatment GBVC/HGV-RNA by direct sequencing. RESULTS: The pretreatment GBV-C/HGV-RNA level of CR patients (7.8 x 10(4) - 6.2 x 10(5), mean 3.30 x 10(5)) was significantly lower than that of NR patients (6.3 x 10(7) - 7.2 x 10(8), mean 3.55 x 10(8); P< 0.01). The number of amino acid substitutions in NS5A1865-2279 was five to seven (mean 5.8 +/- 1.0) in CR patients, and four to eight (mean 6.8 +/- 1.6) in NR patients, a difference that is not significant. Moreover, there were no amino acid substitutions or sites of substitution in NS5A1865-2279 that were specific to either group. CONCLUSIONS: The effectiveness of IFN therapy for GBV-C/HGV is strongly related to the pretreatment GBV-C/HGV-RNA level, but is not related to changes in NS5A1865-2279.

Fujisawa T, Komatsu H, Inui A, Sogo T, Miyagawa Y, Fujitsuka S, Sekine I, Kosugi T, Inui M. · Department of Pediatrics, National Defense Medical College, Saitama, Tokorozawa City, Japan. · J Pediatr Gastroenterol Nutr. · Pubmed #10697141 No free full text.

Abstract: BACKGROUND: It has not yet been defined whether children with chronic hepatitis B are likely to develop severe liver disease in the future. The purpose of this study was to evaluate the evolution of chronic hepatitis B acquired in childhood. METHOD: Fifty-two children in the age range of 0 to 15 years who were positive for hepatitis B surface antigen and hepatitis B e antigen in serum for at least 6 months were enrolled in this study. In the majority of the 52 children, hepatitis B virus infection was acquired by perinatal transmission. All 52 showed abnormal liver function test findings for more than 6 months before enrollment, and the subjects were followed up longitudinally for 3 to 22 years (mean, 11 years). They are now more than 15 years of age (15-27 years old). RESULTS: During the follow-up period, 26 (50%) children had spontaneous seroconversion to anti-hepatitis B e. Serum levels of alanine aminotransferase normalized in these 26 children. In one child of these children, hepatocellular carcinoma developed at the age of 21 years, 16 years after seroconversion, although his liver function profiles remained normal. The other 26 children remained hepatitis B e antigen positive, most with unchanged biochemical features. Sixteen (62%) children among these 26 children were treated with interferon-alpha. Eleven (69%) children had seroconversion to anti-hepatitis B e within the first year after the cessation of therapy. Hepatocellular carcinoma developed in 1 of these 11 children at the age of 16 years, 6 years after interferon therapy. Thus, hepatocellular carcinoma developed in two children in an anti-hepatitis B e positive phase. CONCLUSION: All children carrying hepatitis B surface antigen should be observed carefully to monitor the possible development of hepatocellular carcinoma, especially in the antihepatitis B e-positive phase after spontaneous seroconversion or even after interferon treatment.

Fujisawa T, Inui A, Komatsu H, Ohkawa T, Sogo T, Miyagawa Y. · Department of Pediatrics, National Defense Medical College, Saitama, Japan. · Pediatr Int. · Pubmed #10618877 No free full text.

Abstract: BACKGROUND: In adults, hepatitis B virus (HBV) with a G to A point mutation at nucleotide 83 in the precore region (mutant HBV 83), is commonly found in HB e antibody positive HBV carriers. It has been reported that this mutant is not able to produce HB e antigen. The exact prevalence of mutant HBV 83 in patients with chronic HBV infection is not fully understood, especially in children. METHODS: To investigate the role of mutant HBV 83 in children with chronic HBV infection, sera were tested for the presence of mutant HBV 83 using a mutation site-specific assay. RESULTS: Mutant HBV 83 was detected in 15 of 22 children (68%). Seven children were followed longitudinally, of which three were asymptomatic carriers and the other four had chronic hepatitis B on entry. There was no clear relationship between the disease activity and the presence of mutant HBV 83. CONCLUSIONS: It was concluded that mutant HBV 83 is commonly present in children with chronic HBV infection and this mutant is not necessarily associated with activation of hepatitis.

Hoshiyama A, Kimura A, Fujisawa T, Kage M, Kato H. · Department of Pediatrics and Child Health, Kurume University School of Medicine. Kurume, Japan. · Pediatrics. · Pubmed #10617705 No free full text.

Abstract: OBJECTIVE: To characterize the clinical and histologic features of chronic hepatitis C virus (HCV) infection after blood transfusion in Japanese children. STUDY DESIGN: We studied 231 children with a history of blood product transfusion. Patients were divided into two groups: 116 patients with a history of malignant disease (group 1), 115 patients who had undergone open heart surgery (group 2). We examined changes in serum alanine aminotransferase (ALT) activity and HCV markers, and patients' clinical course. Moreover, in 38 patients in whom the time of HCV infection could be defined, we examined liver histology. RESULTS: The proportions of patients in each group who were anti-HCV-positive were 35 out of 116 (30%) and 20 out of 115 (17%), respectively. Of the anti-HCV-positive patients, the proportions of HCV RNA-positive patients in each group were 30 out of 35 (86%) and 12 out of 20 (60%), respectively. Levels of ALT activity in patients with HCV infection varied widely for several years after blood transfusion; thereafter ALT activity fell to <100 IU/L in 2 groups. Serum ALT activity in patients who were HCV RNA-negative became normal. With regard to liver histology, there were no differences in the grade of necroinflammation or stage of fibrosis in patients with different durations of infection or when patients were analyzed according to the presence or absence of malignant disease. Patients mostly had grade 2-4 inflammation and stage 1-2 fibrosis. Thus, chronic hepatitis C was a morphologically mild disease in most children in this study. CONCLUSIONS: Sixty percent to 80% of children with HCV infection in this study developed chronic hepatitis C. However, examination of liver histology findings in children with chronic hepatitis C showed only mild changes.

Nakashima S, Kurozumi H, Imagawa T, Miyamae T, Ito S, Inui A, Fujisawa T, Yokota S. · Department of Pediatrics of Yokohama City University. · Ryumachi. · Pubmed #10536482 No free full text.

Abstract: A 6 year-old boy with autoimmune hepatitis accompanied with cirrhosis was reported. He was admitted to our hospital because of abdominal distention, high fever, and diarrhea. Laboratory examination revealed abnormalities in hepatic function, cholestasis, anemia, thrombocytopenia, hypoalbuminemia, hypocomplementemia, and low concentration of coagulation factors. Abdominal MRI, and asialoglycoprotein receptor-mediated liver scintigraphy strongly indicated liver cirrhosis. Viral hepatitis, Wilson's disease, and antitrypsin deficiency were excluded serologically. Instead, hypergammaglobulinemia, and positive antinuclear antibody suggested autoimmune hepatitis, and the survey of anti-mitochondrial antibody, anti-smooth muscle antibody, and anti-LKM-1 antibody was negative, indicating type I autoimmune hepatitis. Finally, the histology of liver biopsy specimen indicating the destruction of hepatic lobular architecture, dense mononuclear cell infiltrates, and severe fibrosis confirmed the diagnosis. He was treated firstly with methylprednisolone pulses, and then prednisolone p.o. + azathioprine p.o. All of the abnormal laboratory parameters improved to normal levels, indicating that the immunosuppressive therapy will be effective for the severe AIH with cirrhosis.

Komatsu H, Fujisawa T, Inui A, Sogo T, Morinishi Y, Miyagawa Y, Inui M. · Department of Pediatrics, National Defense Medical College, Saitama, Japan. · J Med Virol. · Pubmed #10459149 No free full text.

Abstract: The role of GB virus-C/hepatitis G virus (GBV-C/HGV), a recently identified member of the Flaviviridae family, in children with liver disease is not well understood. The aims of this study were to evaluate the prevalence of GBV-C/HGV and to clarify its pathogenic role in young patients with chronic hepatitis C. Sixty-four Japanese children and adolescents with chronic hepatitis C virus (HCV) infection, with a mean age of 9.8 years, were evaluated retrospectively. Twenty-one (32.8%) of the 64 patients were positive for serum GBV-C/HGV RNA. Only 1 (1.6%) of the 64 patients was positive for antibody against the envelope protein E2 of GBV-C/HGV (anti-E2) and GBV-C/HGV. None of them was positive for anti-E2 alone. There was no significant difference in clinical, virological, or histological characteristics between GBV-C/HGV-positive and GBV-C/HGV-negative patients, except for underlying malignant disease. There was no evidence that GBV-C/HGV might affect the response of HCV to interferon therapy in young patients with chronic hepatitis C. The prevalence of GBV-C/HGV infection in young patients with chronic hepatitis C is similar to that in adult patients with chronic hepatitis C, but E2-seroconversion is observed infrequently. Underlying malignant disease is a risk factor for GBV-C/HGV viremia. GBV-C/HGV does not seem to affect the clinical course of young patients with chronic hepatitis C.

Fujisawa T, Kumagai T, Akamatsu T, Kiyosawa K, Matsunaga Y. · Second Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan. · Am J Gastroenterol. · Pubmed #10445533 No free full text.

Abstract: OBJECTIVE: The age groups most susceptible to infection and the mode of transmission of Helicobacter pylori (H. pylori) are not yet clear. To contribute to a better understanding of this disease, this study was undertaken to evaluate changes in the seroepidemiological pattern of H. pylori in a group of Japanese people over the last 20 yr sampled in 1974, 1984, and 1994 in comparison with that of the hepatitis A virus (HAV), which was used as a marker of the fecal-oral route of transmission. METHODS: A total of 1015 serum samples were obtained from the National Institute of Infectious Diseases in Tokyo. All of these samples were from healthy persons aged 0-89 yr (442 male and 573 female; median age 35.6 yr), living in seven prefectures in the central part of Japan in 1974, 1984, and 1994. All serum samples were assayed for H. pylori IgG by means of enzyme-linked immunosorbent assay (ELISA). Further, anti-HAV antibodies were assayed by blocking ELISA in the same samples. We investigated the prevalence of H. pylori and HAV for all ages, and the positive rate of H. pylori for infants and children separately. RESULTS: The overall prevalence of H. pylori antibodies was 72.7% (CI 95%, 68.0-77.3) in 1974, 54.6% (CI 95%, 49.1-60.0) in 1984 and 39.3% (CI 95%, 34.1-44.4) in 1994. That of HAV was 57.7% (CI 95%, 52.5-62.8) in 1974, 41.7% (CI 95%, 36.3-47.0) in 1984, and 23.4% (CI 95%, 18.9-27.8) in 1994. The prevalence of both H. pylori and HAV was found to increase with age, whereas there have been clear cohort shifts in the seroepidemiological patterns of both infections over the last 20 yr in Japan. This study shows that there is a slight similarity in the concordance of positive and negative populations between H. pylori and HAV. However, it was very difficult to determine the concordance between H. pylori and HAV infection in this study. CONCLUSIONS: Our data strongly suggest that the highest infection rates for both H. pylori and HAV occur among infants and children in Japan. This study provides evidence that H. pylori and HAV may share a common mode of transmission but that changes in environmental conditions make this very difficult if not impossible to prove with seroepidemiological data.