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Background: More than 45 cases of transfusion‐transmitted hepatitis E virus infection (TT‐HEV) have been reported in Japan. Therefore, in 2020, universal individual donation nucleic acid amplification testing (ID‐NAT) was implemented for HEV. Study Design and Methods: We characterized HEV NAT‐positive blood donors. The number of new HEV infections and the asymptomatic infection rate were estimated using the HEV NAT‐positive rate. HEV RNA quantitation, phylogenetic analysis, and antibody tests were performed, and the residual risk of TT‐HEV was assessed based on the lookback study results. Results: A total of 5,075,100 blood donations were screened with ID‐NAT during the first year of implementation, among which 2804 (0.055%; males: 0.060%, females: 0.043%) were NAT‐positive with regional differences. Approximately 270,000 new HEV infection cases were estimated to occur annually in Japan, with an asymptomatic infection rate of 99.9%. The median HEV RNA concentration, excluding cases below the limit of quantification, was 205 IU/mL. Among the 1113 cases where the genotype could be determined, HEV‐3 and HEV‐4 accounted for 98.8% (1100) and 1.2% (13), respectively. The maximum duration of HEV viremia, including the pre‐ and post‐ID‐NAT window periods, was estimated to be 88.2 days. Within the 3 years since ID‐NAT implementation, no confirmed cases of breakthrough TT‐HEV were observed. Discussion: Multiple indigenous HEV strains are prevalent in Japan, infecting a significant number of individuals. However, since the implementation of ID‐NAT, TT‐HEV has been prevented due to the test's high sensitivity. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is an emerging causative agent of acute hepatitis. To clarify the epidemiology of HEV and characterize the genetic diversity of the virus in Japan, nationwide enhanced surveillance and molecular characterization studies of HEV in Japan were undertaken from 2014 to 2021. In total, 2770 hepatitis E cases were reported, of which 88% were domestic cases, while only 4.1% represented cases following infection abroad. In addition, 57% of domestic infections occurred in males aged in their 40s–70s. For domestic cases, infection via pork meat consumption continued to be the most reported route. Analysis of the 324 sequences detected between 2016 and 2021 showed that the majority of domestic HEV strains belong to Genotype 3a (G3a) and G3b. In contrast, six of eight cases of G1 HEV reflected infection abroad. Our results suggest that HEV is circulating widely in Japan, with genotypes G3a and G3b being most prevalent. Continued surveillance is necessary to monitor future trends and changes in the epidemiology of HEV in Japan. [ABSTRACT FROM AUTHOR]

Aim: Both entecavir (ETV) and tenofovir alafenamide fumarate (TAF) are widely used to treat chronic hepatitis B (CHB) in Japan. However, it remains unclear whether the efficacy of TAF in decreasing the hepatitis B surface antigen (HBsAg) level, and its safety, are superior to those of ETV. This study aimed to report the long‐term effects and safety of 96‐week ETV and TAF treatment in patients with CHB. Methods: A prospective comparative observational study was undertaken on the following two groups: patients with CHB who received continuous ETV (n = 32) and patients with CHB who were switched from ETV to TAF upon request (n = 48). The HBsAg, urinary β2‐microglobulin (β2MG)/creatinine (Cr), urinary N‐acetyl‐β‐D‐glucosaminidase (NAG)/Cr, and serum alanine aminotransferase (ALT) levels, estimated glomerular filtration rate (eGFR), and bone mineral density (lumbar spine and femur) at 96 weeks were compared. Results: The two groups did not significantly differ with respect to mean age, male / female patient ratio, or rate of hepatitis B e antigen‐positive status. The mean changes in serum HBsAg level and eGFR at 96 weeks were not significantly different between the two groups. The β2MG/Cr and NAG/Cr levels at 96 weeks were similar between the two groups. Additionally, the bone mineral density of the lumbar spine and femur as well as the serum ALT did not significantly differ. Conclusions: When compared with patients who received continuous ETV, those who were introduced to TAF after ETV showed similar effects in terms of the decrease in HBsAg level and safety. [ABSTRACT FROM AUTHOR]

Aim: Studies regarding changes in antibodies to hepatitis E virus (HEV) after HEV infection in organ transplant patients are limited. This study aimed to clarify HEV infection trends in organ transplant patients who contracted HEV using data from a previous Japanese nationwide survey. Methods: This study was undertaken from 2012 to 2019. Among 4518 liver, heart, and kidney transplant patients, anti‐HEV immunoglobulin G (IgG) antibodies were positive in 164; data were collected from 106 of these patients, who consented to participate in the study. In total, 32 liver transplant patients, seven heart transplant patients, and 67 kidney transplant patients from 16 institutions in Japan were examined for IgG, IgM, and IgM antibodies to HEV and the presence of HEV RNA in the serum. The χ2‐test was used to determine the relationship between the early and late postinfection groups in patients with anti‐HEV IgG positive‐to‐negative conversion rates. The Mann–Whitney U‐test was used to compare clinical factors. Results: Anti‐HEV IgG positive‐to‐negative conversion occurred in 25 (23.6%) of 106 organ transplant patients. Of eight patients with hepatitis E who tested positive for HEV RNA, one (14.0%) had anti‐HEV IgG positive‐to‐negative conversion. Twenty‐four (24.5%) of 98 patients negative for HEV RNA had anti‐HEV IgG positive‐to‐negative conversion. Conclusions: This study revealed, for the first time, the changes in HEV antibodies in organ transplant patients. Loss of anti‐HEV IgG could often occur unexpectedly in organ transplant patients with previous HEV infection. [ABSTRACT FROM AUTHOR]

The clinical and virologic features of hepatitis E virus (HEV) infection seem to vary among regions even in developed countries. However, we have little information on the diversity of HEV infection. Here, we investigated the characteristics of 26 patients in our hospital located in Tochigi prefecture, 90 km north of Tokyo, between 2000 and 2019. The reported number of patients with acute hepatitis E is increasing in Japan because measurement of IgA‐class anti‐HEV antibody was commercially available from 2011. In contrast, the numbers at our hospital were 1.5/y and 1.0/y in 2000 to 2011 and 2012 to 2019, respectively. This is attributed to the fact that we have been investigating HEV as a cause of unknown hepatitis before 2011. Among isolated HEV subgenotypes, including 3a, 3b, 4b, 4c, and 4d, all three patients with subgenotype 4c infection presented acute liver failure. Four HEV strains shared more than or equal to 99% identity within the 412‐nucleotide partial sequence, in which the time and place of HEV infection varied, except for one intrafamilial infection. In addition, some strains were similar to HEV strains isolated far from Tochigi prefecture. In conclusion, the number of patients with acute hepatitis E was not increasing at Jichi Medical University Hospital and some strains were found to circulate in Japan. Highlights: The numbers of patients with acute hepatitis E was not increasing at Jichi Medical University Hospital located in Tochigi prefecture, 90 km north of Tokyo.Among 5 subgenotypes noted in the present study, all 3 patients with subgenotype 4c infection presented acute liver failure.Several strains were similar to HEV strains isolated far from Tochigi prefectureHEV‐contaminated foods are likely to circulate around Japan. [ABSTRACT FROM AUTHOR]

Aim: Hepatitis E virus (HEV) can cause chronic infection in immunocompromised hosts. However, the dynamics of HEV during persistent infection is not well understood. To elucidate time course alterations in virus sequences and anti‐HEV antibodies during persistent infection, we analyzed the HEV sequences and titers of anti‐HEV antibodies from a chronic hepatitis E patient. Methods: Serum samples were obtained from a chronic hepatitis E patient under corticosteroid therapy for neurological disease. The titers of anti‐HEV antibodies (immunoglobulin A, immunoglobulin M, and immunoglobulin G) in serum samples were detected by enzyme immunoassay. The full or near‐full nucleotide sequences of HEV isolated from consecutive serum samples were identified and compared. Phylogenetic analysis was also performed. Results: Alterations of anti‐HEV antibodies from a chronic hepatitis E patient were different from those previously reported in acute hepatitis E patients. The virus sequence was unchanged in the period without treatment, but nucleotide mutations were observed after ribavirin treatment was started. In addition, the sequence of this strain had extremely high identity to that isolated from swine liver in Japan. Conclusions: Virus mutations in HEV emerged after ribavirin treatment was started. Sequence analysis may useful for deciding the treatment strategy for chronic hepatitis E patients who did not eliminate the virus with 3 months of RBV treatment and inferring the origin of the infection. This report provides insights into the chronicity of hepatitis E, and the impact of persistent infection and ribavirin treatment on the emergence of virus mutations. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the clinical and molecular characteristics of hepatitis E virus (HEV) infection in Mie Prefecture, Japan, from 2004 through 2018. Methods: The clinical information of hepatitis E cases was collected from 21 medical institutions in Mie Prefecture. The nucleotide sequences of infecting HEV strains were determined for cases with available serum samples. The origins or transmission routes were inferred from phylogenetic analyses of the nucleotide sequences. Results: Fifty‐three patients were diagnosed with HEV infection. The number of cases increased each year through 2012 and then decreased. Analyses of the clinical characteristics of the cases indicated that even mild cases were detected in the latter 10 years of the study. Nucleotide sequence analyses were undertaken on 38 of the 53 cases. The HEV subtype 3e (HEV‐3e) strains identified for 13 cases were closely related to a swine HEV‐3e strain that was isolated from the liver of a pig bred in Mie Prefecture. The number of cases infected with the indigenous Mie HEV‐3e strains increased until 2012 but have not been reported since 2014. In the latter half of the study, cases involving various HEV strains of different genotypes and subtypes emerged. Conclusions: The disappearance of indigenous Mie HEV‐3e strains appeared to be the primary cause for the decrease in hepatitis E cases in Mie Prefecture. The disappearance might have been associated with improved hygienic conditions on pig farms or the closure of contaminated farms. The results suggest that indigenous HEV strains can be eradicated by appropriate management. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) causes acute or chronic hepatitis in humans worldwide and can be transmitted via the fecal-oral route. Four HEV strains (HE-JA14-2173, HE-JA15-1335, HE-JA15-1920 and HE-JA16-0610) obtained from patients with imported (from Pakistan or India) or autochthonous acute hepatitis E in Japan were most closely related to the Nepalese and Mongolian genotype 1 HEV strains of unassigned subtype within the partial ORF2 sequence. To investigate whether a putative novel subtype (1g) of genotype 1 can be assigned, full-length genomic sequences were determined for the four HEV strains. They shared 95.4−99.2% nucleotide identity over the entire genome, and differed by 6.3−11.7% from the reported HEV strains of subtypes 1a−1f and by only 0.6−4.7% from a Mongolian genotype 1 HEV strain (MNE15-072) of unassigned subtype. A phylogenetic analysis showed that the four HEV strains obtained in the present study formed a cluster with MNE15-072, with a bootstrap value of 100%. Although the p-distance between subtypes 1a and 1f was 0.048−0.083, these five strains showed a higher nucleotide p-distance value of 0.068−0.138 with the genotype 1 HEV strains of subtypes 1a−1f. A BLAST search revealed the presence of candidate members of subtype 1g HEV in at least five other countries, including France, Israel, the Netherlands, Portugal, and the UK, sharing identities of 95.4−99.6% with the HE-JA16-0610 strain within the common sequence of 294−867 nucleotides. These results support the assignment of a new subtype 1g within genotype 1 and suggest a global distribution of subtype 1g strains. Subtype 1g strains found in Europe can be imported from Asia. Further studies are needed to confirm the global distribution of HEV subtype 1g. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is the causative agent of viral hepatitis E. In Japan, HEV genotype 3 (G3) and G4 are predominantly detected, while G1, mainly imported from countries in continental Asia, is rare. In the present study, we detected a G1 HEV strain in a patient who visited Japan from India. When PLC/PRF/5 cells (subclone 4-21) were inoculated with a stool suspension from this patient, accumulation of HEV RNA was observed in the spent culture medium, indicating that HEV had been successfully isolated from this specimen. A nearly complete HEV genome was obtained by RT-PCR amplification. Phylogenetic analyses revealed that the newly isolated HEV strain, designated 9HE36c, belongs to subtype 1g of HEV G1.

In Japan, hepatitis E had long been considered to be a rare liver disease which can be accidentally imported from endemic countries in Asia and Africa, where the sanitation conditions are suboptimal. However, since the identification of the first autochthonous hepatitis E case and hepatitis E viremic domestic pigs in Japan in 2001, our understanding of hepatitis E virus ( HEV) infection in this country has been changing markedly. This has largely been due to the development of serological and gene-based diagnostic assays, the accumulation of molecular epidemiological findings on HEV infection in humans and animals (as potential reservoirs for HEV in humans) and the recognition of the importance of zoonotic food-borne and other routes of transmission of HEV, including blood-borne transmission. Although it is now evident that autochthonous hepatitis E in Japan is far more common than was previously thought, clinical and subclinical HEV infections indigenous to Japan remain underdiagnosed and their prevalence is still underestimated due to the presence of unknown transmission routes and a low awareness of the infection status by many physicians in Japan. This review focuses on the features of HEV infection in humans and animals, as definitive or potential reservoirs for HEV, in Japan, and updates the current knowledge on the routes of transmission, including zoonotic routes, which are important for the maintenance and spread of HEV in Japan. [ABSTRACT FROM AUTHOR]

Putative animal reservoirs and environmental samples were studied to investigate potential routes of transmission for indigenous hepatitis E virus (HEV) infection in Hokkaido, Japan. A total of 468 liver samples and 954 environmental samples were collected from 2003 to 2011 for this study. Four swine livers (1 %) were positive for HEV RNA; two strains belonged to genotype 3 and the other two strains were genotype 4. Genotype 3 HEV was detected in a sewage sample and a seawater sample. HEV strains derived from swine liver, seawater and raw sewage samples shared 93-100 % sequence similarity with human HEV strains. [ABSTRACT FROM AUTHOR]

Aim: In developed countries including Japan, the transmission route of indigenous hepatitis E virus (HEV) infection is obscure. Accordingly, public health implications of indigenous HEV infection have not been well addressed. The aim of this study was to clarify the route of transmission of a small outbreak of acute hepatitis E and assess the public health implications of indigenous zoonotic HEV transmission. Methods: Three patients with non-A, B and C acute hepatitis, two of whom presented in a critical condition, were assessed for HEV infection using polymerase chain reaction and their route of infection; the genome sequences of the infecting HEV were also analyzed. A phylogenetic tree based on the full, or near full, HEV RNA sequences were constructed by neighbor-joining method. Results: All three patients ingested grilled pork meat and entrails at the same barbecue restaurant in Abashiri, Hokkaido, Japan. When comparing partial to entire, or nearly entire, nucleotide sequences of HEV detected in these patients, they were 99.9-100% identical to each other. These genotype 4 isolates had great resemblance to the genome sequences of the isolates from the mini-outbreak in 2004 in Kitami, a city adjacent to Abashiri. These Kitami/Abashiri strains were segregated into a single cluster on the phylogenetic tree of HEV genotype 4 indigenous to Japan. Conclusion: Indigenous HEV transmission via a zoonotic food-borne route has been demonstrated in Kitami and Abashiri via pork meat and entrails contaminated with virulent HEV strains. Because a similar outbreak can recur in the future, infection sources and distribution routes should be clarified rapidly for public health. [ABSTRACT FROM AUTHOR]

Background Since previous studies have investigated the population dynamics of Japan-indigenous genotype 3 hepatitis E virus ( HEV) using virus sequences, more nucleotide sequences have been determined, and new techniques have been developed for such analysis. Aims To prevent future hepatitis E epidemic in Japan, this study aimed to elucidate the cause of past HEV expansion. Methods The epidemic history of Japan-indigenous genotype 3 HEV was determined using the coalescent analysis framework. Bayesian skyline plot ( BSP) and Bayesian estimate of phylogeny with relaxed molecular clock models were calculated using Markov chain Monte Carlo sampling. Results Japan-indigenous strains consist of New World strains (subtype 3a), Japanese strains (3b) and European strains (3e). The oldest lineage, 3b, appeared around 1929. Lineages 3a and 3e appeared around 1960. BSPs indicated similar radical population growth of the 3a and 3b lineages from 1960 to 1980. Conclusions Population dynamics of the three lineages shared some common characteristics, but had distinguishing features. The appearance of 3a and 3e lineages coincides with the increase of large-race pig importation from Europe and the USA after 1960. The epidemic phase of 3a and 3b strains from 1960 to 1980 could be related to increased opportunity for HEV infection arising from large-scale pig breeding since 1960. Our observations revealed new findings concerning the close relationship between the epidemic history of Japan-indigenous genotype 3 HEV and the improvement of the Japanese pig industry. Infection control in pig farms should be an effective method of preventing HEV infection in humans. [ABSTRACT FROM AUTHOR]

To investigate the nationwide prevalence of hepatitis E virus (HEV) infection and to characterize HEV genomes among Japanese wild boars ( Sus scrofa leucomystax), 578 boars captured in 25 prefectures from 2003 to 2010 were studied. Anti-HEV IgG was detected in 8.1%, and HEV RNA in 3.3% of boars. Among the 19 boar HEV isolates obtained from infected boars, 14 isolates (74%) were classified as genotype 3, 4 isolates (21%) as genotype 4, and the remaining isolate (wbJOY_06) was distantly related to all known HEV isolates of genotypes 1-4, differing by 18.4-25.0% and 18.0-24.3% within the 412-nucleotide sequence of ORF1 and ORF2, respectively. A genotype 4 boar HEV isolate (wbJGF_08-1) obtained herein shared 98.6% identity over the entire genome with a human HEV isolate obtained from a patient who developed acute hepatitis after consuming undercooked wild boar meat, suggesting that wild boars are also reservoirs for genotype 4 HEV in humans. [ABSTRACT FROM AUTHOR]

Background and Objectives In previous studies, we reported the transmission of hepatitis E virus (HEV) by transfusion, and the frequent detection of HEV markers in Japanese blood donors with elevated ALT levels. For the current study, we carried out a nationwide survey of the prevalence of IgG anti-HEV in qualified blood donors throughout Japan. Materials and Methods The 12 600 samples from qualified blood donors were collected from seven blood centres (1800 per centre) representing nearly all regions of Japan. Samples were from age- and sex-matched blood donors who tested negative for all the current blood screening tests. The samples were screened using the in-house IgG anti-HEV ELISA. Sequentially, the positive samples were tested by the commercial IgG anti-HEV ELISA. Results Of 12 600 samples, 431 (3·4%) were regarded as positive for IgG anti-HEV. The prevalence of IgG anti-HEV was higher in eastern Japan (5·6%) than in western Japan (1·8%) ( P < 0·001), and was also age-dependent and higher in men (3·9%) than in women (2·9%) ( P = 0·002). Conclusion The spread of the domestic infection of HEV was observed in qualified blood donors in Japan. A higher prevalence of IgG anti-HEV was observed in male donors, older donors and in donors residing in eastern Japan. Further studies are necessary to clarify the potential risk of transfusion-transmission of HEV in Japan. [ABSTRACT FROM AUTHOR]

The epidemiology of acute viral hepatitis (AVH) is dynamic and affected by many factors including hygiene, socioeconomic status and vaccination coverage. A total of 4,302 cases of AVH were sequentially enrolled in this nationwide study between 1980 and 2008. Of the cases of AVH, acute hepatitis A (AHA) accounted for 1,583 (36.8%), acute hepatitis B (AHB) for 1,197 (27.8%), acute hepatitis C (AHC) for 359 (8.3%), and non-A, non-B and non-C (non-ABC) for 1,163 (27.0%). Between 1980 and 1995, the proportions of AHA, AHB, AHC and non-ABC were approximately 40, 25, 10 and 25%; between 1996 and 2003, they were approximately 30, 30, 10 and 30%, and this shifted to approximately 10, 40, 10 and 40% in the last 5 years. The number of AHB caused by genotype A, which is not indigenous to Japan, was 6.0% between 1991 and 1996 but has been markedly increasing since 2000, to reach 52% in 2008. Autochthonous acute hepatitis E (AHE) accounted for 10–15% of non-ABC hepatitis after 2002. The etiology of AVH in Japan has been drastically changing. A marked increase of AHB genotype A and constant occurrence of autochthonous AHE require attention, and necessary measures should be taken. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

There have been reports from several countries that hepatitis E virus (HEV) infection is frequently associated with Guillain-Barré syndrome (GBS). This study aimed to determine the frequency of HEV infection associated with GBS in Japanese patients, and to clarify the clinical characteristics of these patients. Sera obtained from 63 patients with GBS or Miller Fisher syndrome (MFS) and 60 control subjects were examined for both HEV-IgM and HEV-IgG. Of the 63 patients, three were positive for both HEV-IgM and elevated hepatic enzymes: Two had GBS, and one had MFS. No control subjects were positive for HEV-IgM. Our study demonstrated that 4.8 % of patients with GBS or MFS from our institution had associated acute HEV infection. There were no clinical differences between GBS with HEV infection and other GBS cases. To our knowledge, this is the first survey in Japan of HEV-associated GBS or MFS. [ABSTRACT FROM AUTHOR]

Abstract: The emergence of fluoroquinolone-resistant strains of Salmonella enterica subspecies enterica serovar Choleraesuis is an important concern in several countries, including Japan. We examined the intracellular concentration of enrofloxacin in S. Choleraesuis to determine the existence of a relationship with the emergence of quinolone resistance. The intracellular concentration of enrofloxacin was significantly lower in nalidixic acid-resistant isolates compared with nalidixic acid-susceptible isolates. In the presence of carbonyl cyanide m-chlorophenylhydrazone, the intracellular concentration of enrofloxacin increased in all isolates, with no significant difference in the intracellular concentration between nalidixic acid-susceptible and -resistant isolates. The frequency of emergence of fluoroquinolone-resistant mutants was higher in susceptible isolates with a low intracellular concentration of enrofloxacin. The results presented suggest that a decrease in the intracellular concentration of enrofloxacin is related to active efflux pumps and contributes to the emergence of fluoroquinolone resistance. [Copyright &y& Elsevier]

In this study, 520 serum samples from Yezo-deer in the Hidaka district, Hokkaido, Japan were examined by enzyme-linked immunosorbent assay to investigate whether the animals were infected with hepatitis E virus (HEV). The distribution of optical density values showed a bimodal pattern and 181 samples (34.8%) were deemed to be antibody-positive against HEV. At least five (2.8%) of the positive sera gave specific bands by Western blot analysis. An age-dependent increase in prevalence of the antibodies was found among the animals. These findings indicate that Yezo-deer are a possible host for HEV infection. To avoid the risk of becoming HEV infected, the consumption of raw Yezo-deer meat must be prohibited. [ABSTRACT FROM AUTHOR]

Recent studies have shown that indigenous hepatitis E virus (HEV) strains cause hepatitis E in industrialized countries. We aimed to clarify the characteristics of HEV infection in sporadic hepatitis patients during the last decade in Miyagi, northeast Japan. We analyzed 94 serum samples obtained from acute or fulminant hepatitis patients of non-A, non-B, and non-C etiology between 1999 and 2008. Antibody to HEV (anti-HEV) was assayed, and patients who were positive for IgM- and/or IgA-class anti-HEV were diagnosed with hepatitis E. HEV RNA was tested in these patients, and phylogenetic analysis was performed. The occurrence of hepatitis E was compared with that of hepatitis A. Eight acute hepatitis patients (8.5%) were diagnosed with hepatitis E, and HEV RNA was detectable in seven patients. Five isolates of HEV were segregated into genotype 3 and the remaining two isolates into genotype 4. The year of the occurrence of hepatitis E was distributed almost equally from 1999 to 2008, whereas the cases of acute hepatitis A ( n = 16) have decreased markedly in the last several years. In 2004–2008, the occurrence of hepatitis E was greater than that of hepatitis A (five cases vs. one case). As for seasonality, hepatitis E occurred more frequently from September to December than hepatitis A (five cases vs. four cases), although less frequently from January to April (one case vs. seven cases). The occurrence of hepatitis E has not decreased during the last decade in northeast Japan, in contrast to hepatitis A. [ABSTRACT FROM AUTHOR]

The article offers information on hepatitis E Virus (HEV) which replicates in hepatocyte culture of human beings and macaques. It states that HEV infection is self-limiting with low death rate though higher that hepatitis a virus (HAV) infection. It is transmitted by the faecal-oral route and is excreted in through faeces for 3-4 weeks. It highlights that in Japan, the only country to report sporadic cases of HEV, HEVspecific antibodies have been found in 7.1 percent studies on blood donors.

The article presents research which investigated the prevalence of hepatitis E virus (HEV) infection in wild boars and pigs in Gunma Prefecture, Japan. The main focus of the research was the serologic and genetic examination of anti-HEV IgG. The article provides details on the serologic analysis and RNA extraction. The results showed that anti-HEV IgG was in 4.5% of the wild boars tested and in approximately 75% of the pigs. The research suggests that consumption of the liver and meat from infected animals may be a risk for HEV infection in humans.

Background and Aim: The aim of this study was to investigate the prevalence of hepatitis E virus (HEV) infection in the general population of Japan by determining presence of the antibody to HEV (anti-HEV). Methods: The prevalence of HEV infection was determined by positivity of serum antibody to HEV (anti-HEV). Results: On retrospective analysis, a significant decrease in anti-HEV prevalence was found in Okinawa healthy residents from 1995 (15.8%) to 2005 (5.5%) ( P < 0.0001). In 2005, the anti-HEV prevalence was significantly higher in Okinawa wild boar hunters (25.3%) than in the residents (male 7.7% and female 4.1%) ( P < 0.0001). A significant difference was found in the history of consumption of undercooked or raw boar meat between anti-HEV positive and negative hunters (100% vs 64.3%) ( P = 0.0018). Conclusions: In conclusion, the anti-HEV prevalence has decreased in the residents of this area, but HEV infection has continued at a high rate in the hunters through the custom of eating undercooked or raw boar meat. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although we reported two cases of transfusion-transmitted hepatitis E in Japan, the prevalence of hepatitis E virus (HEV) in Japanese blood donors is not very clear. STUDY DESIGN AND METHODS: Blood samples of donors who were deferred from donation because of elevated alanine aminotransferase (ALT) levels were collected from all Japanese Red Cross Blood Centers and subjected to HEV tests. RESULTS: Among the 41 donors with elevated ALT levels higher than 500 IU per L in Hokkaido, HEV RNA was detected in 8 (19.5%) samples. In 1389 donor samples with ALT levels of higher than 200 IU per L in nationwide Japan, the numbers of positive HEV RNA, immunoglobulin M (IgM) anti-HEV, and immunoglobulin G (IgG) anti-HEV samples were 15 (1.1%), 14 (1.0%), and 45 (3.2%), respectively. Although RNA-positive donors were predominantly male and found in any geographic area of Japan, they tended to be higher in number in eastern Japan including Hokkaido and lower in number in western Japan. Of the 23 HEV-positive samples, 19 were Genotype 3 and 4 were Genotype 4. DNA sequences of the 9 isolates showed more than 98.5 percent homology with the known swine HEV isolates. In 1062 donor samples with ALT levels of 61 to 199 IU per L, the percentages of IgM and IgG anti-HEV–positive samples were 0.1 and 2.7 percent, respectively, although there was no HEV RNA–positive sample. CONCLUSION: HEV markers (HEV RNA and anti-HEV) were detected in donors with elevated ALT levels who were widely distributed over Japan. The prevalence and incidence were higher in eastern Japan than in western Japan. [ABSTRACT FROM AUTHOR]

Objective: We investigated the prevalence of antibody against hepatitis E virus (HEV) in Japanese patients with hemophilia. Methods: IgG antibody against HEV was measured in serum of 80 Japanese patients with hemophilia by enzyme-linked immunosorbent assay. The prevalence of HEV antibody was compared with the reported prevalence of HEV antibody in Japanese patients undergoing hemodialysis and in Japanese healthy blood donors. Characteristics of patients and coinfection with other transfusion-transmissible viruses were compared in patients with and without HEV antibody. Results: Anti-HEV IgG antibody was detected in 13 of 80 patients (16.3%). The prevalence was far higher than that reported in Japanese blood donors (3.7%) and was higher than that in Japanese patients undergoing hemodialysis (9.4%). The patients with HEV antibody were significantly older than those without. HEV antibody was not detected in patients <20 years of age and in patients who had received only virus-inactivated coagulation factors. No association was observed between positivity for anti-HEV antibody and severity of hemophilia or coinfection with other parenterally transmissible viruses. Conclusion: Our results suggest that the parenteral transmission of HEV may have occurred in Japanese patients with hemophilia via non-virus-inactivated coagulation factors. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Hepatitis E is rare in Japan but is occurring more frequently than previously thought. To investigate whether de novo subclinical infection of hepatitis E virus (HEV) has recently increased in Japan, HEV RNA was assayed in serum samples obtained from 4019 Japanese voluntary blood donors with alanine aminotransferase (ALT) of ≥61 IU/l, who are likely to have ongoing HEV infection, during 1991–2006. The overall rates of IgG-class antibody to HEV (anti-HEV IgG), anti-HEV IgM/IgA and HEV RNA among 3185 donors in 2004–2006 were comparable with those among 594 donors in 1998 (5.3 vs. 5.2%, 0.2 vs. 0.5%, and 0.2 vs. 0.3%, respectively). Among blood donors with ALT ≥ 201 IU/l in three groups according to the year of blood collection (1991–1995 [ n = 156], 1996–1999 [ n = 116] and 2004–2006 [ n = 61]), there were no appreciable differences in the prevalence of anti-HEV IgG (5.8, 4.3, and 6.6%, respectively), anti-HEV IgM/IgA (1.9, 3.4, and 3.3%, respectively) and HEV RNA (1.3, 3.4, and 3.3%, respectively). The eleven HEV isolates obtained in the present study differed from each other by 1.7–22.8% in the ORF2 sequence and segregated into genotype 3 or 4. The occurrence rate of subclinical infection with divergent HEV strains has essentially remained unchanged during 1991–2006 in Japan. [ABSTRACT FROM AUTHOR]

We examined 976 sika deer serum samples, 159 liver tissue samples and 88 stool samples collected from 16 prefectures in Japan, and performed ELISA and RT-PCR assays to detect antibodies to HEV and HEV RNA, respectively. Although 25 (2.6%) of 976 samples were positive for anti-HEV IgG, the antibody titers were very low. The OD values ranged between 0.018 and 0.486, forming a single distribution rather than a bimodal distribution, suggesting that the antibody detected in this study was not induced by HEV infection, or that deer have low sensitivity to HEV. HEV RNA was not detected in these samples, also suggesting that deer may not play a role as an HEV reservoir. [ABSTRACT FROM AUTHOR]

There have been several emerging animal diseases and food-borne infection problems occurring in Japan over the last 5 years. We describe brief pictures of these epidemics and our control activities. As acute contagious and/or emerging animal diseases, the foot and mouth disease (FMD) outbreak caused by the Pan-Asian topotype of the type O virus occurred in March 2000 after 92 years of FMD-free status. In 2004, four cases of the highly pathogenic avian influenza (HPAI), which was the first outbreak after 79 years, and caused by the H5N1 subtype, were identified. As part of the responses against these outbreaks, all the animals in the affected farms were destroyed, and movement control areas were established around the infected premises, and a nation-wide intensive survey for FMD and HPAI was performed. As for food-borne or feed-borne infections, the first bovine spongiform encephalopathy (BSE) was identified in September 2001 and 19 more cases have been reported until June 2005. A large outbreak of food-borne infection caused by low-fat milk contaminated with enterotoxin A produced by Staphylococcus aureus, involving more than 13,000 patients, occurred in 2000. In 2003, people who consumed uncooked liver and meat from wild boar and deer developed clinical signs of hepatitis caused by the hepatitis E virus. Pork is also suspected as natural source of virus transmission. Early detection of the first cases and rapid action in preventing and controlling the spread of infections are very important combined with proper risk communication about correct information of the diseases. [ABSTRACT FROM AUTHOR]

Abstract: Hepatitis E virus (HEV), a single-strand RNA virus, has been recovered not only from human beings but also from various species of animals. Here we report our results suggesting that mongoose should be added to the list of reservoir animals of HEV. Of 100 mongooses we examined in Okinawa, Japan, 21 were thought to be positive for anti-HEV antibodies, among which one was definitely positive for HEV RNA. Full-genome sequencing of the HEV isolate revealed that it segregates to a unique subgroup within genotype III. Interestingly, this mongoose strain was closely related to a swine isolate previously reported from Okinawa, implicating the possibility of interspecies transmission between these animals. [Copyright &y& Elsevier]

Tanaka H, Yoshino H, Kobayashi E, Takahashi M, Okamoto H. Molecular investigation of hepatitis E virus infection in domestic and miniature pigs used for medical experiments.Xenotransplantation 2004.© Blackwell Munksgaard, 2004Hepatitis E virus (HEV) infection is highly prevalent among domestic pigs in Japan. It has been reported that pig handlers such as farmers and veterinarians are at increased risk of contracting HEV infection. Pigs are regarded as the most acceptable candidate animals for xenotransplantation and, recently, they are being used as experimental animals.We investigated the prevalence of IgG class antibodies to swine HEV (anti-HEV) and HEV RNA among 152 2-month-old domestic pigs and 38 miniature pigs of 4 to 10 months of age that had been brought to our center for medical experiments from five swine farms (A–E) in Japan. Serum samples were tested for anti-HEV by in-house enzyme immunoassay, and for HEV RNA by reverse transcription-polymerase chain reaction using primers targeting the open reading frame 2 (ORF2) region.One percent (one of 84), 6% (one of 16), and 38% (20 of 52) of the domestic pigs from farms A, B and C, respectively, had detectable HEV RNA, and the 22 HEV isolates recovered from the viremic pigs were 89.8 to 100% identical to each other in the 412-nucleotide sequence of ORF2 and segregated into three clusters within genotype 3. Although one pig from farm A had detectable HEV RNA reproducibly, the HEV isolate recovered from this pig was up to 100% similar to those recovered from pigs from farm C, and the sera from all 84 pigs from farm A were negative for anti-HEV. These results suggested that farm A is free from HEV infection. As the viremic pig from farm A had been raised for 1 month in a barn at our center before serum sampling, it is most likely that the pig acquired HEV infection in the barn at our center where HEV-viremic pigs from farm C had been reared for several days approximately 3 months earlier. The 38 miniature pigs from farms D and E were negative for both anti-HEV and HEV RNA. In an attempt to further investigate the prevalence of HEV infection, pigs that were being raised in four swine farms (farms A, C, D, and E) were tested for anti-HEV. Although 96 (86%) of the 112 pigs from farm C were positive for anti-HEV, none of the 48 pigs in farm A and 138 miniature pigs in farms D and E was positive for anti-HEV.These results suggest that three of the five swine farms tested were free from HEV, and that periodic testing for anti-HEV and HEV RNA of pigs used as experimental animals and pigs raised in swine farms from which pigs are purchased, is useful for providing HEV-free pigs to researchers who are engaged in studies using pigs. [ABSTRACT FROM AUTHOR]

Background. We compared acute hepatitis E (AH-E) and acute hepatitis A (AH-A) to investigate the epidemiology, clinical features, and prognosis of AH-E caused by an indigenous hepatitis E virus (HEV) in Japan. Methods. We enrolled 58 patients diagnosed with AH-A or AH-E (32 men and 26 women; age, 20–72 years) from December 1997 to October 2002. Phylogenetic analysis of the partial 412-nucleotide sequence of open reading frame (ORF) 2 was performed in patients with AH-E. Results. Regarding the geographic distribution of the HEV genotype, genotype III was principally distributed in Honshu Island, and genotype IV in Hokkaido Island (P = 0.0034). The phylogenetic analysis of the ORF2 region revealed that there were significant geographic differences in the distribution of the HEV strains in Japan, with some strains being widespread and some, localized. In comparison with AH-A patients, those with AH-E were older (56.1 ± 10.6 vs 45.9 ± 10.8 years; P = 0.0017). The proportion of males among patients with AH-E was significantly higher (P = 0.0001). Pyrexia was often observed in AH-A, and malaise in AH-E. Laboratory data indicate that AH-E induces a weak immunological reaction, whereas jaundice appears earlier in AH-E than in AH-A. One patient with AH-E died of acute hepatic failure, but none of those with AH-A died during the study period. Conclusions. Our results suggest that there are geographical differences between HEV strains in Japan, and that AH-E is more common in males and older patients than AH-A. Laboratory data indicate a weak immunological reaction and early appearance of jaundice in AH-E. [ABSTRACT FROM AUTHOR]

Recent studies indicate that hepatitis E virus (HEV) infection occurs not only in developing countries but also in industrialized nations. However, the characteristics of domestic infections of hepatitis E in Japan are not fully understood. We analyzed serum samples from 34 patients who were seen at a city hospital in Sendai, Japan, between January 1997 and December 2002, and who had been given the diagnosis of sporadic acute hepatitis of non-A, non-B, non-C etiology. Among these 34 patients, 3 (9%; all men; aged 54, 59, and 61 years) were positive for both IgG and IgM anti-HEV antibodies and for HEV RNA. The HEV isolates (HE-JAS1 and HE-JAS3) obtained from case 1 and case 3, respectively, segregated into genotype III; they had the highest nucleotide sequence identity, of 99.5% and 99.0%, with HE-JA7 and HE-JA8, respectively, both of which had been isolated in Iwate, a neighboring prefecture of Sendai. In contrast, the remaining HEV isolate (HE-JAS2), obtained from case 2, segregated into genotype IV; it had the highest nucleotide sequence identity, of 99.8% and 99.3%, with JKK-Sap and HE-JA3, respectively, both of which had been isolated in Hokkaido, Japan, although case 2 had never been to Hokkaido. Our three patients with hepatitis E had not traveled abroad in the preceding 1 year, had had no contact with pigs, and no history of blood transfusion. These results indicate that HEV should be considered as an etiological agent of acute hepatitis of non-A, non-B, non-C etiology in Japan. The risk factor(s) for acquiring domestic HEV infection in Japan needs to be clarified in future studies. [ABSTRACT FROM AUTHOR]

Recently studies have reported the possibility that an indigenous hepatitis E virus (HEV) exists in Japan, but the epidemiological features of HEV in Japan are inadequate to make a judgment. In order to search the present state of HEV infection in Japan, we used ELISA to test 1033 sera from residents living in Tokyo and the Tokyo suburbs, for the presence of the antibody against HEV. The positive rate of anti-HEV IgG was 15.4% in all liver disease patients (68 of 440), 3% (6/200) in healthy individuals and 0.4% in infants (1/246), respectively (P<0.01). Anti-HEV IgG was seen in 17.6% (35/199) of liver disease patients of unknown etiology; 29.4% (5/17) of fulminant hepatitis, 17% of acute hepatitis (15/88) and 16% of chronic hepatitis (15/94). Anti-HEV IgG co-existed with hepatitis B virus and hepatitis C virus in 23.6% (21/89) and 7.9% (12/152), respectively. Furthermore, the prevalence of anti-HEV IgG was significantly higher in hemodialysis patients (18/60: 30%) and hospital workers (8/87: 9.2%) than in the healthy population (P<0.01). Anti-HEV IgM was detected in 0.1% of all samples tested (1/1033). The prevalence of anti-HEV IgG increased with age. No individuals with HEV antibody had a recent history of visiting countries where hepatitis E is endemic. These results indicate that generally 15.4% of Japanese patients with liver diseases had a history of HEV infection in the past. The routes of transmission of HEV require clarification in Japan. [Copyright &y& Elsevier]

Sporadic cases of hepatitis E have been reported in industrialized countries, including Japan. The source of hepatitis E virus (HEV) in these patients is unknown, although zoonotic transmission has been suggested. To investigate whether or not rodents might be a reservoir of HEV, we conducted an epidemiological survey for the antibody to a recombinant capsid protein of HEV using serum samples from wild rodents in Japan. One hundred and fourteen of 362 (31.5%) Norway rats (Rattus norvegicus) and 12 of 90 (13.3%) black rats (Rattus rattus) were positive for anti-HEV IgG. In contrast, all of the sera from 55 mice were negative for anti-HEV IgG. The rate of antibody positivity increased with weight among Norway rats. Seropositive rats were found in all five districts surveyed in this study, but the prevalence of anti-HEV IgG in wild rats differed among these prefectures. Despite the fact that Japan is a non-endemic country of hepatitis E, widespread infection of HEV was observed among wild rats in Japan. Our results suggested that HEV or a closely related virus is circulating among wild rats in Japan. [Copyright &y& Elsevier]

We encountered a patient with sporadic acute hepatitis E who had not traveled to areas endemic for hepatitis E virus (HEV) infection and may have been infected in Japan. The patient was a 47-year-old male who had no history of blood transfusion or contact with travelers to hepatitis E-endemic regions or unspecified individuals. The disease presented with general malaise, fever, and brown urine as chief complaints in April 2002. Various hepatitis virus markers were negative, but IgM class antibodies to hepatitis E virus (anti-HEV) and HEV RNA were positive, and the patient was diagnosed with acute hepatitis E. The entire nucleotide sequence (7240 bases) of HEV (HE-JK4) isolated from this patient was determined and compared with known HEV strains. HE-JK4 belonged to genotype IV and exhibited higher similarities to genotype IV HEV strains previously isolated in Japan than to those isolated in China, Taiwan, and Vietnam. The patient''s family members living with him were negative for anti-HEV IgG and IgM, but their pet cat was anti-HEV IgG-positive. This finding suggests a potential route of infection of sporadic cases of hepatitis E in Japan. Since the presence of HEV indigenous to Japan is predicted, HEV infection should be considered in the diagnosis of acute hepatitis of unknown cause, even for patients who have not traveled abroad. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

The recent discovery of a presumably Japan-indigenous hepatitis E virus (HEV) strain (JRA1) spurred analysis of additional isolates from 7 cases of acute sporadic hepatitis E infection. Comparison of a 326-nucleotide region from open-reading frame 1 indicated that 1, 3, and 3 isolates segregated to genotypes I, III, and IV, respectively. Six patients had not traveled abroad recently. One patient had traveled to Hawaii 1 month before becoming ill, and the nucleotide sequence of the HEV isolate infecting her resembled those of US isolates (89%-91% nucleotide identity). However, the isolate was even more homologous to 2 other Japanese isolates (95 %-97 % nucleotide identity), suggesting that it is more likely a domestic, rather than an imported, strain. Three genotype IV isolates from Japan also had a higher homology to each other (100 % amino acid identity) than to 2 Chinese isolates (97%-98% amino acid identity). These findings suggest that HEV strains of at least 3 different genotypes have already made inroads and are spreading in Japan. [ABSTRACT FROM AUTHOR]

• Wild sika deer (n = 405) in Japan (1997–2020) were analyzed for HEV infection. • Anti-HEV IgG was detectable in 4.3% of deer, while HEV RNA was detected in 1 deer. • The HEV strain in deer differed by 8.7–9.0% from those in boars in the same habitat. • Spillover HEV infection from wild boars to deer was not supported in our study. • A low but nonnegligible zoonotic risk of HEV infection in wild deer was suggested. Hepatitis E virus (HEV) is a zoonotic agent mainly transmitted through the consumption of uncooked or undercooked meat products derived from infected animals. In Japan, domestic pigs and wild boars are the major animal reservoirs, and whether or not deer are an HEV reservoir remains controversial. We analyzed 395 serum and 199 liver samples from 405 sika deer (Cervus nippon) caught in the wild between 1997 and 2020 in 11 prefectures of Japan for markers of HEV infection. Overall, 17 deer had anti-HEV IgG (4.3%), while 1 (0.2%) had HEV RNA (genotype 3b), indicating the occurrence of ongoing HEV infection in wild deer in Japan. An analysis of the complete HEV genome (deJOI_14) recovered from a viremic deer in Oita Prefecture revealed only 88.8% identity with the first HEV strain in sika deer (JDEER-Hyo03L) in Japan, being closest (96.3%) to the HEV obtained from a hepatitis patient living in the same prefecture. Of note, the deJOI_14 strain was 8.7–9.0% different from the wild boar HEV strains obtained in the same habitat and the same year, suggesting that difference in infected HEV strains between boar and deer may be explained by the limited possibility of close contact with each other, although boars are a known source of HEV infection. Increased numbers of hepatitis E cases after consumption of raw or undercooked meat products of wild deer have been reported in Japan. These results suggest a low but nonnegligible zoonotic risk of HEV infection in wild deer in this country. [ABSTRACT FROM AUTHOR]

Abstract  We encountered a 14-year-old Bangladeshi boy who developed acute hepatitis E in Japan. He showed improvement without the development of fulminant hepatitis. His hepatitis E virus (HEV) genotype was I, which causes epidemics mainly in South Asia. He developed this disease more than 6 months after coming to Japan. Considering the latent period, it was suspected that he had been infected with HEV in Japan, although the HEV virus is presumed not to be indigenous to Japan. [ABSTRACT FROM AUTHOR]

The author comments on the detection of hepatitis E virus (HEV) in wild boar in western Japan. He discusses the isolation of an HEV strain of genotype 3 from a Japanese patient with acute hepatitis in 2001. Moreover, he asserts that the consumption of boar meat puts individuals at a high risk of developing hepatitis E infection in western Japan.

The article focuses on the study "Hepatitis E Virus Transmission From Wild Boar Meat," conducted by Tetsuya Ishibashi, Tatsuo Miyamura et al. The study investigated a case of hepatitis E acquired after persons ate wild boar meat. The Genotype 3 hepatitis E virus (HEV) RNA was detected in both patient serum and wild boar meat. Deer, pig, and wild boar are suspected sources of foodborne zoonotic transmission of HEV in Japan.

Hepatitis E virus (HEV) is a common cause of acute hepatitis. Four major genotypes of HEV have been studied, with genotype 4 being the predominant genotype across Asia. We herein describe the case of a 50-year-old man with a history of human immunodeficiency virus (HIV) infection who was admitted with acute transaminitis. Serum anti-HEV-IgA and HEV-RNA were detected at the time of presentation and further testing revealed HEV genotype 4. To the best of our knowledge, this represents the first clinical case report of acute symptomatic HEV genotype 4 infection in an HIV-positive patient in Japan.

This article focuses on epidemiological and clinical features of hepatitis E in Japan. Hepatitis E virus (HEV) is the causative agent of acute hepatitis E, which is now recognized as the major cause of enterically transmitted non-A, non-B hepatitis in many developing countries in Asia and Africa, where the disease usually occurs as epidemics. HEV is transmitted primarily via a fecal-oral route. In these areas, epidemics and the spread of HEV, the etiological agent of hepatitis E, are predominantly caused by contaminated water, due to inadequate sanitation practices; the highest incidence of HEV infections occurs in young adults, and the mortality rate of HEV-infected pregnant women is approximately 20%.

Presents a letter to the editor commenting on a reported occurrence of severe hepatitis E virus infection after ingestion of uncooked meat. Case studies on Japanese patients; Diagnosis and treatment; Notoriety of the Japanese for their eating habits.