Since hepatitis E virus (HEV) does not persist in infected hosts or in cultured cell lines, it has been difficult to know its spontaneous mutation rate. Recently, we identified an HEV isolate in ...stored serum from a patient having developed hepatitis E in 1995 (JSM-Sap95), nucleotide sequence of which showed a strong resemblance to those obtained from three patients who contracted hepatitis E in 2000 and 2002 (JKK-Sap00, JYW-Sap02, and JTS-Sap02). The remarkable nucleotide similarity together with the fact that all these patients were residents of the same city, Sapporo, prompted us to hypothesize that JKK-Sap00, JYW-Sap02 and JTS-Sap02 are descendants of JSM-Sap95. Then, the mutation rate of HEV was calculated to be 1.72, 1.41, or 1.40×10
−3 base substitutions per site per year, from JSM-Sap95 to JKK-Sap00, JYW-Sap02 or JTS-Sap02, respectively. Interestingly, these values were very similar to those (1.44×10
−3 to 1.92×10
−3) reported for hepatitis C virus. Because it remains possible that JSM-Sap95 is not the direct ancestor of the other three isolates but was merely a relative of the true ancestor, HEV mutation rate may be a little lower than 1.40×10
−3 base substitutions per site per year.
Hepatitis E virus (HEV) has been listed as one of the major agents that cause fulminant hepatitis in HEV-endemic areas, but not in non-endemic areas. Recently, however, we experienced two cases of ...fulminant hepatitis E in Hokkaido, Japan: case-1 was a 34-year-old woman and case-2, a 51-year-old man, neither having a history of travelling outside Japan or contact with travellers abroad or foreigners. HEV RNA was detected in their acute-phase serum and sequencing analyses indicated that they were infected with different strains of HEV: genotype III in case-1 and IV in case-2. Case-1 patient deceased after liver transplantation, while case-2 patient survived. Based on these cases, we suggest that HEV should be considered as an aetiologic agent for fulminant hepatitis, even in non-endemic areas.
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.
STUDY DESIGN AND METHODS: Nucleic acid testing was performed by real‐time reverse transcription–polymerase chain reaction targeting the open reading frame 2 region of HEV. Full‐length nucleotide sequences of HEV RNA were detected by direct sequencing.
RESULTS: Lookback study of a HEV‐positive donor revealed that the platelets (PLTs) donated from him 2 weeks previously contained HEV RNA and were transfused to a patient. Thirteen relatives including the donor were ascertained to enjoy grilled pork meats together in a barbecue restaurant 23 days before the donation. Thereafter, his father died of fulminant hepatitis E and the other 6 members showed serum markers of HEV infection. In the recipient, HEV was detected in serum on Day 22 and reached the peak of 7.2 log copies per mL on Day 44 followed by the steep increase of alanine aminotransferase. Immunoglobulin G anti‐HEV emerged on Day 67; subsequently, hepatitis was resolved. HEV RNA sequences from the donor and recipient were an identical, Japan‐indigenous strain of genotype 4. HEV RNA was detectable up to Day 97 in serum, Day 85 in feces, and Day 71 in saliva.
CONCLUSION: A transfusion‐transmitted hepatitis E case by blood from a donor infected via the zoonotic food‐borne route and the progress of HEV markers in the entire course are demonstrated. Further studies are needed to clarify the epidemiology and the transfusion‐related risks for HEV even in industrialized countries.
Background: Microwave or radiofrequency ablation therapy has been widely perfomed for hepatocellular carcinoma (HCC). Whereas ablation therapy is effective treatment, it cannot be perfomed easily, ...as is evident in several reports of severe complications. We treated surface‐type HCC under laparoscopy in avoidance of complications from March 1996. In the present study, we examined the efficacy and long‐term outcome of laparoscopic ablation therapy.
Patients and Methods: The patients were 47 cases (58 lesions) of HCC treated by laparoscopic ablation therapy under general anesthesia in our Center from March 1996 until March 2003.
Results: The surface‐type HCC to which the therapy was applicable accounted for approximately 15% of all cases. The overall 5‐year survival rate was 62%. Hepatic reserve and rate of intrahepatic recurrences in the remnant liver after curative treatment were the limiting factors on the survival rate. There was no serious complication in the treatment. It was well tolerated and brought about good quality of life.
Conclusion: Laparoscopic ablation therapy was considered to be an easy and effective approach, and its utility was also recognized in the avoidance of the problems of percutaneous treatment, such as bleeding or damage to the adjacent organs.
We developed a new enzyme-linked immunosorbent assay (ELISA) for the detection of antimitochondrial antibody (AMA)-M2 in sera from patients with primary biliary cirrhosis (PBC), using 2-oxo-acid ...dehydrogenase complex (2-OADC) purified from porcine myocardium as the antigen source. The immunoreactivity was tested in a total of 354 sera, including 63 sera from patients with PBC by our ELISA. In the sera, indirect immunofluorescence for AMA, former ELISA for anti-pyruvate dehydrogenase complex (PDC) and immunoblot assay were performed, respectively. Of the 63 sera from patients with PBC, 51 sera (81.0%) were positive for anti-M2 in the new ELISA. Thirty-eight of the 63 sera (60.3%) were positive for anti-PDC in the former ELISA; the difference was significant between them (
P=0.011). None of the 291 control sera from healthy volunteers showed reactivity against 2-OADC in the new ELISA. Moreover, in comparison with the results of immunoblot analysis, sensitivity and specificity in our ELISA to the sera from patients with PBC were 100 and 92.3%, respectively. Our results indicate that the new ELISA for anti-M2 using 2-OADC is simple, rapid and sensitive enough for the detection of AMA specific to PBC.
Background : Microwave or radiofrequency ablation therapy has been widely perfomed for hepatocellular carcinoma (HCC). Whereas ablation therapy is effective treatment, it cannot be perfomed easily, ...as is evident in several reports of severe complications. We treated surface-type HCC under laparoscopy in avoidance of complications from March 1996. In the present study, we examined the efficacy and long term outcome of laparoscopic ablation therapy. Patients and Methods : The patients were 47 cases (58 lesions) of HCC treated by laparos-copic ablation therapy under general anesthesia in our Center from March 1996 until March 2003. Results : The surface-type HCC to which the therapy was applicable accounted for approx-imately 15% of all cases. The overall 5-year survival rate was 62%. Hepatic reserve and rate of intrahepatic recurrences in the remnant liver after curative treatment were the limiting factors on the survival rate. There was no serious complication in the treatment. It was well tolerated and brought about good quality of life. Conclusion : Laparoscopic ablation therapy was considered to be an easy and effective approach, and its utility was also recognized in the avoidance of the problems of percutaneous treatment, such as bleeding or damage to the adjacent organs.
Ranges of variation and conservation in sequence need to be defined for detecting and genotyping hepatitis E virus (HEV).
Six HEV isolates from Japanese patients were sequenced over the entire genome ...and compared phylogenetically along with 16 reported HEV isolates, including two from pigs.
Three of the six HEV isolates were of genotype III, and the remaining three were of genotype IV. Local clusterings of Japanese HEV isolates were observed in the phylogenetic analyses, including a swine HEV isolate reported previously (swJ570). All six HEV isolates possessed three open reading frames (ORFs). The ORF3 in the three isolates of genotype III were in a different reading frame, while that in the three isolates of genotype IV were in the same reading frame as ORF1. A stretch of 46-96 nucleotides was identified, point mutations and deletions in which were specific for the four genotypes (I-IV). A polymerase chain reaction method was developed with 9 nested universal primers, deduced from conserved regions in the 5'-terminal sequences of the 22 HEV genomes.
Conserved and genotype-specific variation in HEV sequences, identified in the comparison of 22 full-length genomes, would be useful in designing primers for sensitive detection and specific genotyping of HEV RNA.
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