Shunji Mishiro

Transmission of Hepatitis C Virus from Mothers to Infants

Background Although there are case reports of vertical transmission of hepatitis C virus (HCV), it remains uncertain to what extent infected mothers transmit this virus to their infants. Methods We investigated the transmission of HCV from infected mothers to their babies by analyzing HCV RNA in the blood. Three independent studies were performed. First, 7698 parturient women were tested for anti-HCV antibodies; 53 were positive. Their 54 infants (including one set of twins) were followed prospectively for at least six months and tested for HCV infection. Second, the babies of six women with known HCV disease were prospectively studied. Third, the families of three HCV-infected infants were examined retrospectively. Results Of the 53 antibody-positive mothers, 31 were also positive for serum HCV RNA. Three of the 54 babies born to these mothers (5.6 percent) became positive for HCV RNA during the follow-up period. None of the babies of the 22 women who were antibody-positive but HCV RNA-negative became po...

Influence of the genotypes of hepatitis C virus on the severity of recurrent liver disease after liver transplantation.

BACKGROUND/AIMS Several genotypes of hepatitis C virus (HCV) have been identified by phylogenetic analysis, but their clinical relevance remains elusive. Liver transplantation for HCV-related cirrhosis offers a unique opportunity for prospective studies of this issue. METHODS Sixty anti-HCV-positive liver recipients with precise virological and histological assessments were included. HCV genotype was determined with both type-specific capsid primers and a line probe genotyping assay. RESULTS HCV genotype 1b was the predominant type before transplantation (40 of 60 patients); after liver transplantation, acute and chronic active hepatitis developed more frequently in these patients than in patients infected by other genotypes (31 of 40 and 24 of 40 vs. 8 of 20 and 4 of 20 patients). Actuarial rates of acute hepatitis and chronic active hepatitis were 77% and 59%, respectively, 3 years after transplantation in patients infected by type 1b and 40% (P = 0.008) and 22% (P = 0.004) in those infected by other types. There was no statistical relation between the level of HCV viremia and HCV genotypes both before and after transplantation. In contrast, after transplantation, serum HCV RNA values were significantly increased in patients who developed hepatitis after transplantation. CONCLUSIONS This study provides direct evidence that HCV 1b is associated with more aggressive recurrent liver disease than other genotypes.

Very high prevalence of TT virus (TTV) infection in general population of Japan revealed by a new set of PCR primers

Clear evidence for TT virus (TTV) to be a hepatitis virus remains unseen despite its origination from a hepatitis patient. Epidemiological studies on TTV have been limited more or less by the prematurity of the diagnostic systems. We sought after PCR systems that could detect TTV DNA more efficiently than those reported previously, and found that a PCR with new primers designated T801 and T935 was 10–100 times more sensitive than that with published primers NG061 and NG063. To our surprise, TTV DNA was identified by the new PCR system with T801/T935 in 92% of 100 individuals who visited our hospital for health screening, compared to 23% with NG061/NG063. Liver function test values were comparable between TTV DNA-negative and positive individuals, but mean age was younger in the former than in the latter: 29.7±6.9 versus 41.4±14.7 years (P<0.05). Our results suggest that asymptomatic carriers of TTV are very common in general population of adults in Japan.

Transfusion-transmitted hepatitis E caused by apparently indigenous hepatitis E virus strain in Hokkaido, Japan

BACKGROUND:  In industrialized countries, sporadic cases of hepatitis E have been reported in individuals who have never been in an endemic area. Hepatitis E virus (HEV) infection commonly occurs via the fecal‐oral route but a potential risk of transfusion transmission route has been suggested.

Non-A, non-B hepatitis specific antibodies directed at host-derived epitope: implication for an autoimmune process

A cDNA clone (GOR47-1) bearing an epitope with an aminoacid sequence GRRGQKAKSNPNRPL (GOR epitope) was isolated from the plasma of a laboratory chimpanzee infected with human non-A, non-B hepatitis (NANBH) agent. The epitope was not encoded by reported sequences of hepatitis C virus (HCV) but instead was coded for by a host cellular sequence. An enzyme-linked immunosorbent assay (ELISA) was developed for antibodies to the GOR epitope (anti-GOR). A patient with acute NANBH produced both IgM and IgG classes of anti-GOR in the acute phase of the illness, with concentrations of IgG class anti-GOR rising when anti-HCV became detectable. Anti-GOR was detected in serum from 59 (81%) of 73 patients with chronic NANBH, 40 (65%) of 62 with NANB liver cirrhosis, and 25 (63%) of 40 NANB patients with primary hepatocellular carcinoma, but in only less than 10% of patients with chronic liver diseases due to hepatitis B virus, alcohol, or an autoimmune disorder, and in only 2% of voluntary blood donors. Circulating HCV-RNA was detected by polymerase chain reaction (PCR) in most patients seropositive for anti-GOR but negative for anti-HCV. Detection of anti-GOR would therefore help in the diagnosis of NANBH and in reducing the occurrence of post-transfusion hepatitis.

A case of transfusion‐transmitted hepatitis E caused by blood from a donor infected with hepatitis E virus via zoonotic food‐borne route

BACKGROUND: Five cases of transfusion transmission of hepatitis E virus (HEV) have been reported so far. The infection routes of the causative donors remain unclear, however. Also, the progress of virus markers in the entire course of HEV infection has not been well documented.

Mutations within the S Gene of Hepatitis B Virus Transmitted from Mothers to Babies Immunized with Hepatitis B Immune Globulin and Vaccine

ABSTRACT: A variant of hepatitis B virus (HBV) having a specific mutation within the S gene has been found to infect vaccinees. To know whether similar variants were involved in Japan, we analyzed two cases of maternal transmission of HBV in infants immunized with hepatitis B immune globulin and hepatitis B vaccine. DNA clones of HBV S genes were propagated from patients and family members and sequenced. In one family, the DNA clones from the baby patient had a Gly-to-Arg mutation at the 145th codon of the S gene, whereas those from her mother had no such mutations. In the other family, all the DNA clones obtained from the two infected children had the 145th codon intact, but they had a missense mutation at the 126 th codon of the S gene, causing an amino acid substitution of Asn for Thr or Ile. This same mutation was observed in 12 of 17 clones of DNA obtained from their mother. In comparison with the wild type HBV-derived hepatitis B surface antigen, the two types of S gene mutations, either at the 145th or the 126th codon, were associated with a significant decrease in the antigenicity of some determinants on the hepatitis B surface antigen, measured by MAb. Amino acid substitution at these sites, therefore, would have induced the escape from conventional vaccines that were S gene products of wild type HBV and also from hepatitis B immune globulin, whose main components were probably also antibodies against the S gene products expressed by wild type HBV.

Identification of a new human DNA virus (TTV-like mini virus, TLMV) intermediately related to TT virus and chicken anemia virus

Summary. TT virus (TTV) is the only known human virus with single-stranded circular DNA, with a possible but yet unclear relationship to chicken anemia virus (CAV) of the family Circoviridae. Here we report a new human virus resembling TTV and CAV, designated TTV-like mini virus (TLMV). This non-enveloped virus was smaller (>30 nm) but had a similar density (1. 31–1.34 g/ml in CsCl) to TTV, when a TLMV/TTV-coinfected plasma was analyzed. Full-length sequencing revealed that the TLMV genome was a circular DNA comprising 2860 nt (isolate CBD231); significantly shorter than TTV (TA278, 3852 nt) but longer than CAV (CAECUX1, 2319 nt). A strand-specific hybridization assay using oligonucleotide-coated beads suggested TLMV was negative-stranded, like TTV and CAV. In genomic organization, TLMV was similar to both TTV and CAV. The untranslated region of TLMV resembled CAV in that both had direct repeats, whereas the sequence homology was more evident between TLMV and TTV. The predicted ORF1 protein of TLMV was rich in R/W/F residues at its amino terminus; the richness in W was shared by TTV, F by CAV, and R by both. ORF2 proteins of the three viruses had a common motif, WX7HX3CXCX5H. Thus, TLMV is an intermediate between the remotely related TTV and CAV. Since CAV differs much from other circoviruses, it may better be classified together with TTV and TLMV under a new family: we would coin the Paracircoviridae.

Persistent infection of hepatitis E virus transmitted by blood transfusion in a patient with T-cell lymphoma.

Aim:  With advent of reverse‐transcription (RT)/polymerase chain reaction (PCR) for detection of the hepatitis E viral genome, we carried out retrospective examinations.

Identification of a Single Nucleotide Polymorphism in the MxA Gene Promoter (G/T at nt –88) Correlated with the Response of Hepatitis C Patients to Interferon

The interferon (IFN)-inducible MxA protein is known to play an important role in the host defense against certain viruses. We aimed to see if any genetic polymorphism in the promoter region of the MxA gene is associated with the IFN responsiveness of hepatitis C virus (HCV)-infected patients. Initially we sequenced the promoter region of the MxA gene in 12 subjects and found a polymorphic site. We then constructed a specific PCR-RFLP system for this site and subjected 63 samples from chronic hepatitis C patients who were nonresponders (NR) to IFN therapy to it, 52 with sustained response (SR), and 42 healthy controls. Subjects were all Japanese, and unrelated. A single nucleotide polymorphism (SNP) was identified in the MxA promoter region: G/T alleles at nt position –88. Interestingly, this SNP was involved in a genetic element highly homologous to the IFN-stimulated response element consensus sequence, and the G-to-T change there makes this homology a little greater. The rate of G·G homozygosity was 31% in the SR patients, significantly lower than in the NR patients (62%, p = 0.0009), while that of healthy controls was between the two groups (48%). Differences in HCV genotypes did not influence this result. Based on these findings, we propose that the SNP of the MxA promoter at nt –88 identified in this study affects the expression of MxA protein, and may thus be associated with the response of HCV patients to IFN.