Keiichi Itoh

Polyphyletic strains of hepatitis E virus are responsible for sporadic cases of acute hepatitis in Japan.

ABSTRACT Among 87 patients who were previously treated for acute hepatitis of unknown etiology between 1992 and 2001 at five hospitals in Japan, 11 (13%) patients were positive for immunoglobulin M-class antibodies to hepatitis E virus (HEV) by enzyme immunoassay and had detectable HEV RNA by reverse transcription-PCR with two independent sets of primers derived from well-conserved genomic areas in open reading frames 1 and 2. Clinical HEV infection was significantly associated with male sex (9 of 11 versus 29 of 76 patients [P < 0.01]) and older age (52 ± 11 [mean ± standard deviation] versus 41 ± 17 years [P < 0.05]), and its prevalence differed by geographic region (6 to 25%), with a higher rate in the northern part of Japan. At admission, the 11 patients with HEV-associated hepatitis had elevated alanine aminotransferase levels of 914 to 4,850 IU/liter, and all but 1 had elevated bilirubin levels of 1.5 to 24.0 mg/dl. The 11 HEV isolates were of genotype III or IV and were segregated into three groups with intergroup nucleotide differences of 9.5 to 22.0%. Phylogenetic analysis revealed that four isolates of genotype III were closely related to a Japanese isolate, while the other four isolates of the same genotype were nearest those from the United States. The remaining three isolates were close to known isolates of genotype IV in China and Taiwan but shared less than 88% identity with them. These results indicate that multiple genotypes of HEV cocirculate in Japan and contribute to the development of sporadic acute hepatitis, with the prevalence differing by age, sex, and geographic region.

Infection by an unenveloped DNA virus associated with non‐A to ‐G hepatitis in Japanese blood donors with or without elevated ALT levels

BACKGROUND: An unenveloped, single‐stranded DNA virus named TT virus has been found in association with elevated alanine aminotransferase (ALT) levels in recipients of transfusions and has been detected frequently in patients with acute or chronic hepatitis of non‐A to ‐G etiology in Japan. DNA of the TT virus was searched for in blood donors with or without elevated ALT levels.

Infection with hepatitis G virus and its strain variant, the GB agent (GBV-C), among blood donors in Japan

BACKGROUND: The purpose of the study was to survey the epidemiology of recently reported non‐A through ‐E hepatitis virus designated hepatitis G virus (HGV) and its strain variant, the GB agent (GBV‐C). STUDY DESIGN AND METHODS: Pilot samples from 2461 blood donors in Japan, randomly selected to form cohorts with different levels of alanine aminotransferase (ALT) and markers of hepatitis B virus or hepatitis C virus (HCV) infection, were tested for RNA of HGV/GBV‐C by reverse transcription‐polymerase chain reaction with nested primers deduced from the 5′‐noncoding region. RESULTS: HGV/GBV‐C RNA was detected in 23 (7.4%) of the 361 donors with anti‐HCV and HCV RNA. This detection is more frequent than that in donors without elevated ALT levels (< or = 45 U/L) or markers of HCV or hepatitis B virus infection (15/1303; 1.2%) (p < 0.001), donors with ALT values between 46 and 99 U per L (0/108) (p < 0.002), donors with ALT values > or = 100 U per L (5/361; 1.4%), and donors with anti‐HCV but without detectable HCV RNA (1/93; 1.1%) (p < 0.05). CONCLUSION: More than 1 percent of Japanese blood donors were infected with HGV/GBV‐C, and the prevalence was much higher in those with HCV RNA. Should persistent infection with HGV/GBV‐C induce any hepatotoxic sequelae, either alone or in concert with the other hepatitis viruses, screening of blood units for HGV/GBV‐C would deserve consideration.

An easy dipstick assay for anti-core antibodies to screen blood donors for hepatitis C virus viremia.

Department of Internal Medicine, Mataram General Hospital, Mataram, Indonesia; Indonesian Institute of Sciences, Bandung, Indonesia; Japanese Red Cross Yamaguchi Blood Center, Yamaguchi; Japanese Red Cross Hiroshima Blood Center, Hiroshima; ‘ Department of Medical Sciences, Toshiba General Hospital, Tokyo; Immunology Division, Jichi Medical School, Tochigi; Department of Hygiene, Hiroshima University School of Medicine, Hiroshima, Japan An Easy Dipstick Assay for Anti-Core Antibodies to Screen Blood Donors for Hepatitis C Virus Viremia

Cold activation of complement as a marker of hepatitis c viremia in sera from blood donors

Sera from 49,088 blood donors were tested for markers of hepatitis C virus (HCV) infection and decreased hemolytic activity after they had been stored at 4 degrees C for 24 h, a phenomenon known as the cold activation of complement. Antibody to HCV (anti-HCV) was detected in 315 (0.64%) units, of which 181 (57%) were positive for HCV RNA. The cold activation of complement was detected in 170 (0.35%) units, and HCV RNA was detected in 140 (82%) of them. Thus, the cold activation of complement was observed in 140 (77%) of 181 blood units with HCV RNA. The close association of HCV viremia with the cold activation of complement would be useful as a surrogate test in preventing post-transfusion HCV infection in developing areas where anti-HCV assays are not easily performed.

CHARACTERIZATION OF ANTI-HLA ANTIBODIES AFTER TRANSFUSION OF PLATELETS AND RED BLOOD CELLS ADMINISTERED USING LEUKOCYTE-REMOVAL FILTERS

We studied the characteristics of anti-human leukocyte antigen (HLA) antibodies developed after transfusion of platelets and red blood cells using leukocyte-removal filters in 14 patients with acute leukemia treated in our hospital from 1990 to 1992. A nonfilter group of 10 patients similarly multitransfused with acute leukemia treated from 1984 to 1986 were also studied. In the filter group, Class I anti-HLA antibodies were developed in 14% (2 of 14) of patients. The sera of these two patients showed the HLA specificities anti-B55+B56 and anti-A19, respectively. Refractoriness to platelet transfusion did not occur in these patients. In the nonfilter group, Class I anti-HLA antibodies developed in 20% (2 of 10) of patients.These sera contained multispecific anti-HLA antibodies. Both patients showed refractoriness to platelets transfusion. All four patients who developed anti-HLA antibodies had a history of pregnancy.

Cold activation of complement enhancing with the duration of storage in sera from blood donors with hepatitis C virus RNA

The cold activation of complement, determined by hemolytic activity of sera stored at low temperature, closely correlates with ongoing hepatitis C virus (HCV) injection. Of 53 189 blood units donated at a blood center in Japan, 187 (0.35%) were positive for antibody to HCV of which 65 (35% of the units with antibody) contained detectable HCV RNA. While sera from the 65 units with HCV RNA had been stored at 4°C, the cold activation of complement was observed in 43 (66%) at day 1, an additional 13 (20%) at day 4, and further in 4 (6%) at day 7. Thus, the cold activation was observed in 60 (92%) of 65 sera with HCV RNA during the storage at low temperature for 7 days. Cryoglobulins were detected only in 13 of the 43 sera which showed the cold activation at day 1, and the donors with cryoglobulinemia were older than the 52 viremic donors without it (mean ± S.D.: 47 ± 10 vs. 40 ± 11 years, P < 0.05). There were no differences in the distribution of HCV genotypes in sera which showed the cold activation at day 1; they were 24 (69%) of 35 sera with genotype II1b, 15 (68%) of 22 with III2a and 4 (50%) of 8 with IV2b. The results indicate that it would take up to a week before the cold activation is fully manifested in sera from persons infected with HCV.