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A woman in her late 70 s was diagnosed with liver injury at a health examination. Despite treatment with ursodeoxycholic acid at a nearby hospital, her transaminase levels elevated in two peaks. She was transferred to our hospital 77 days after the health examination. She weighed 42 kg and had a low body mass index of 19.8 kg/m

Hepatitis E virus (HEV) causes acute or chronic hepatitis in humans. Pigs are the primary reservoir for zoonotic HEV genotypes 3 and 4 worldwide. This study investigated the infection dynamics and genomic mutations of HEV in domestic pigs on a farrow-to-finish pig farm in Japan between 2012 and 2021. A high prevalence of anti-HEV IgG antibodies was noted among pigs on this farm in 2012, when the survey started, and persisted for at least nine years. During 2012–2021, HEV RNA was detected in both serum and fecal samples, indicating active viral replication. Environmental samples, including slurry samples in manure pits, feces on the floor, floor and wall swabs in pens, and dust samples, also tested positive for HEV RNA, suggesting potential sources of infection within the farm environment. Indeed, pigs raised in HEV-contaminated houses had a higher rate of HEV infection than those in an HEV-free house. All 104 HEV strains belonged to subgenotype 3b, showing a gradual decrease in nucleotide identities over time. The 2012 (swEJM1201802S) and 2021 (swEJM2100729F) HEV strains shared 97.9% sequence identity over the entire genome. Importantly, the swEJM2100729F strain efficiently propagated in human hepatoma cells, demonstrating its infectivity. These findings contribute to our understanding of the prevalence, transmission dynamics, and genetic characteristics of HEV in domestic pigs, emphasizing the potential risks associated with HEV infections and are crucial for developing effective strategies to mitigate the risk of HEV infection in both animals and humans.

Objectives: Infections with hepatitis B, C, and D virus (HBV, HCV, and HDV) are a major public health problem and lead to serious complications such as cirrhosis and hepatocellular carcinoma. We aimed to determine the seroprevalence of hepatitis B surface antigen (HBsAg), anti-HCV, anti-HDV immunoglobulin G, alpha-fetoprotein (AFP), and dual and triple hepatitis virus infections in Mongolia.Methods: A total of 2313 participants from urban and rural regions were randomly recruited for this cross-sectional study. A questionnaire was used to identify the risk factors for hepatitis virus infections, and the seromarkers were measured using immunoassay kits.Results: Among all participants, the prevalence of HBV, HCV, and HDV was 15.6%, 36.6%, and 14.3%, respectively. The infection rates were significantly higher in females and participants with a lower education level, rural residence, older age, and a history of blood transfusion. HBV and HCV co-infection was found in 120 (5.2%) participants and HBV, HCV, and HDV triple infection was detected in 67 (2.9%) participants. The prevalence of elevated AFP was 2.7%, 5.5%, and 2.6% higher in participants who were seropositive for HBsAg (p=0.01), anti-HCV (pp=0.022), respectively. Elevated AFP was more prevalent in participants co-infected with HBV and HCV (5.8%, p=0.023), HBV and HDV (6.0%, p

Hepatitis E virus (HEV) is a major cause of acute viral hepatitis globally. Genotype 1 HEV (HEV-1) is responsible for multiple outbreaks in developing countries, causing high mortality rates in pregnant women. However, studies on HEV-1 have been hindered by its poor replication in cultured cells. The JE04-1601S strain recovered from a Japanese patient with fulminant hepatitis E who contracted HEV-1 while traveling to India was serially passaged 12 times in human cell lines. The cell-culture-generated viruses (passage 12; p12) grew efficiently in human cell lines, but the replication was not fully supported in porcine cells. A full-length cDNA clone was constructed using JE04-1601S_p12 as a template. It was able to produce an infectious virus, and viral protein expression was detectable in the transfected PLC/PRF/5 cells and culture supernatants. Consistently, HEV-1 growth was also not fully supported in the cell culture of cDNA-derived JE04-1601S_p12 progenies, potentially recapitulating the narrow tropism of HEV-1 observed in vivo. The availability of an efficient cell culture system for HEV-1 and its infectious cDNA clone will be useful for studying HEV species tropism and mechanisms underlying severe hepatitis in HEV-1-infected pregnant women as well as for discovering and developing safer treatment options for this condition.

Various small focus spot applicators are being investigated for hyperthermia therapy, which requires microwave concentration to heat tumors in the human body. Dielectric lens antenna is frequency independent and has strong focusing capability to achieve a very small focusing spot. In this paper, lenses with diameters of 30, 50 and 70 cm were designed to evaluate the size of the focal spot in the human body model. The electromagnetic simulator, FEKO was used to generate rays and near-field focusing data of dielectric lenses at a frequency of 2.45 GHz. The simulated focal spot sizes agreed well with the theoretical values. An analytical investigation into the power at the focal spot was conducted using the proposed power relations of the focused lens novel equation. The theoretical propagation loss is used to represent the power density degradation at the focal spot caused by microwave absorption by the human body. The simulation results of the focused lens in the human body indicated that the 30 cm lens achieved a larger focal spot with a greater focusing power, 0.714 mW compared to the 70 cm lens, which achieved a smaller focal spot but a lower focusing power, which was 0.393 mW.

Hepatitis E virus (HEV) is increasingly recognized as the leading cause of acute hepatitis. Although HEV infections are mostly self-limiting, a chronic course can develop especially in those with immunocompromised state. Ribavirin is currently used to treat such patients. According to various reports on chronic HEV infections, a sustained virological response (SVR) was achieved in approximately 80% of patients receiving ribavirin monotherapy. To increase the SVR rate, drug combination might be a viable strategy, which we attempted in the current study. Ritonavir was identified in our previous drug screening while searching for candidate novel anti-HEV drugs. It demonstrated potent inhibition of HEV growth in cultured cells. In the present study, ritonavir blocked HEV internalization as shown through time-of-addition and immunofluorescence assays. Its combination with ribavirin significantly increased the efficiency of inhibiting HEV growth compared to that shown by ribavirin monotherapy, even in PLC/PRF/5 cells with robust HEV production, and resulted in viral clearance. Similar efficiency was seen for HEV genotypes 3 and 4, the main causes of chronic infection. The present findings provide insight concerning the advantage of combination therapy using drugs blocking different steps in the HEV life cycle (internalization and RNA replication) as a potential novel treatment strategy for chronic hepatitis E.

Hepatitis B, C, and D virus infections are a major public health problem, and Mongolia has one of the highest prevalences of dual and triple infections in the world. We aimed to determine the seroprevalence of hepatitis infection and dual or triple hepatitis infections among 10–64-year-olds. A questionnaire was used to identify risk factors for hepatitis infection, and seromarkers were measured by the fully automated immunologic analyzer HISCL-5000. Among a total of 10,040 participants, 8.1% of the population aged 10–64 was infected with HBV, 9.4% with HCV, and 0.4% with HBV and HCV, and the prevalence of the disease varied by age, sex, and the area of residence. Young people were particularly unaware of their hepatitis infection status. A small proportion of children aged 10 to 19 years and the majority of adults younger than 30 years were unaware of their HBV and HCV infection. Men were also more likely to be unaware of their HBV and HCV infection status than women. The results suggested that the prevalence of infection in the general population is high and that most people are unaware that they are infected or have become chronic carriers. Identifying mono-, co-, or triple-infection status is critical to prevent the rapid progression of liver disease among the Mongolian population.

A 59-year-old woman who had been diagnosed with cirrhotic primary biliary cholangitis (PBC) 5 years earlier was admitted for severe jaundice (total bilirubin: 30.1 mg/dL). We suspected that her cirrhotic PBC had deteriorated acutely for some reason. Her general condition deteriorated quickly, and she passed away on day 18 of admission. Hepatitis E virus (HEV)-IgA antibodies were positive, and Genotype 3b HEV involvement was confirmed from a blood sample taken on admission. Histopathological findings revealed cirrhosis and submassive loss and necrosis of hepatocytes. Clinicians should consider the possibility of acute HEV infection as a trigger for acute PBC exacerbation.

Hepatitis E virus (HEV) is a quasi-enveloped virus with a single-stranded positive-sense RNA genome belonging to the family Hepeviridae. Studies of the molecular aspects of HEV and drug screening have benefited from the discovery of bioluminescent reporter genes. However, the stability of large foreign genes is difficult to maintain after insertion into the viral genome. Currently, ribavirin is used to treat HEV-infected patients who require antiviral therapy. This has several major drawbacks. Thus, the development of novel anti-HEV drugs is of great importance. We developed a system consisting of recombinant infectious HEV harboring a small luciferase gene (nanoKAZ) in the hypervariable region (HVR) of the open reading frame 1 (ORF1) (HEV-nanoKAZ). It replicated efficiently in cultured cells, was genetically stable, and had morphological characteristics similar to those of the parental virus. Both membrane-associated (eHEV-nanoKAZ) and membrane-unassociated (neHEV-nanoKAZ) particles were infectious. HEV particles circulating in the bloodstream and attaching to hepatocytes in HEV-infected patients are membrane-associated; thus, eHEV-nanoKAZ was applied in drug screening. The eHEV-nanoKAZ system covers at least the inhibitor of HEV entry and inhibitor of HEV RNA replication. Four drugs with anti-HEV activity were identified. Their effectiveness in cultured cells was confirmed in naive and HEV-producing PLC/PRF/5 cells. Two hit drugs (azithromycin and ritonavir) strongly inhibited HEV production in culture supernatants, as well as intracellular expression of ORF2 protein, and may therefore be candidate novel anti-HEV drugs. The HEV-nanoKAZ system was developed and applied in drug screening and is expected to be useful for investigating the HEV life cycle. IMPORTANCE Bioluminescent reporter viruses are essential tools in molecular virological research. They have been widely used to investigate viral life cycles and in the development of antiviral drugs. For drug screening, the use of a bioluminescent reporter virus helps shorten the time required to perform the assay. A system, consisting of recombinant infectious HEV harboring the nanoKAZ gene in the HVR of ORF1 (HEV-nanoKAZ), was developed in this study and was successfully applied to drug screening in which four hit drugs with anti-HEV activity were identified. The results of this study provide evidence supporting the use of this system in more variable HEV studies. In addition, both forms of viral particles (eHEV-nanoKAZ and neHEV-nanoKAZ) are infectious, which will enable their application in HEV studies requiring both forms of viral particles, such as in the investigation of unknown HEV receptors and the elucidation of host factors important for HEV entry.

A case of subclinical hepatitis E virus (HEV) infection was detected by nucleic acid amplification test on blood donation. The patient was followed-up until day 220 after the blood donation but showed no symptoms throughout the observation period. Aspartate aminotransferase and alanine aminotransferase levels reached the maximum values on day 37 with a slight increase but remained in normal ranges from day 67 to 220. The quantity of HEV RNA at the initial examination on day 13 was 1.1 × 10

Rat hepatitis E virus (HEV-C1) in the Orthohepevirus C species has been reported to cause zoonotic infection and hepatitis in humans. HEV-C1 strains have been detected from wild rats in many countries in Europe, Asia, and North America. However, in Japan, no HEV-C1 strains have been identified. In the present study, 5 (1.2%) of 428 wild rats (Rattus norvegicus or R. rattus) were positive for anti-HEV-C1 IgG. Although all 428 rat sera were negative for HEV-C1 RNA, it was detectable in 20 (19.8%) of 101 rat fecal samples collected on a swine farm, where HEV (genotype 3b, HEV-3b) was prevalent and wild rats were present. In addition, HEV-C1 RNA was detectable in the intestinal contents and liver tissues of 7 (18.9%) of 37 additional rats captured on the same farm. The HEV-C1 strain (ratEJM1703495L) obtained in this study shared only 75.8-84.7% identity with reported HEV-C1 strains over the entire genome but propagated efficiently in cultured cells. HEV-3b strains were detected in the rats' intestinal contents, with 97.3-99.5% identity to those in pigs on the same farm, but were undetectable in rat liver tissues, suggesting that wild rats do not support the replication of HEV-3b of swine origin.

Background. Recently, chronic hepatitis E has been reported in solid organ transplant (SOT) recipients in European countries. Previously, we clarified the prevalence of hepatitis E virus (HEV) infection in Japanese liver transplant recipients and identified 2 chronic hepatitis E patients infected by blood transfusion. However, the rate of HEV infection in recipients of SOTs other than liver in Japan remains unclear, so we conducted a nationwide survey to clarify the prevalence of chronic HEV infection in Japanese heart and kidney transplant recipients. Methods. A total of 99 heart and 2526 kidney transplant recipients in 17 hospitals in Japan were examined for the presence of the IgG class of anti-HEV antibodies as well as for serum HEV RNA. Results. The prevalence of anti-HEV IgG among heart and kidney transplant recipients was 7.07% (7/99) and 4.08% (103/2526), respectively. One heart transplant patient (1.01%) and 11 kidney transplant patients (0.44%) were found to be positive for HEV RNA. The HEV isolates from all viremic patients were typed as genotype 3. Four patients developed chronic hepatitis E after transplantation. Three patients were treated with ribavirin; their liver enzymes normalized, and HEV RNA became negative immediately. Sustained virologic response was achieved in all cases. Conclusions. This is the first nationwide survey of HEV infection in Japanese heart and kidney transplant recipients. The prevalence of anti-HEV IgG and HEV RNA in heart and kidney transplant recipients in Japan was lower than that in European countries. Of note, 42% of viremic transplant patients developed chronic hepatitis.

A 66-year-old man, who had undergone plasma exchange 30 years previously in Egypt for the treatment of falciparum malaria, was referred to our hospital for treatment of chronic hepatitis C (HCV). An analysis of the 655-nucleotide 5'-untranslated region-core region sequence revealed infection with HCV subtype 1g. A phylogenetic analysis of the full-length HCV genome confirmed that the patient's HCV was subtype 1g, which was the first case identified in Japan. Although his HCV possessed several naturally occurring resistance-associated substitutions in the nonstructural (NS) 3 and NS5A regions, he was successfully treated by combination therapy with glecaprevir/pibrentasvir.

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.

A 76-year-old woman with spontaneous reactivation of hepatitis B virus (HBV) without any immunosuppressants who had been successfully treated with tenofovir alafenamide fumarate (TAF) was reported. The patient was admitted to our hospital because of acute exacerbation of the liver function and jaundice. She had been found to have chronic HBV infection with a normal liver function and had been treated for lifestyle-related diseases, such as diabetes mellitus, dyslipidemia and hypertension, for over 10 years at a local clinic. At admission, her serum HBV DNA was high (7.3 log IU/mL), and anti-hepatitis B core protein immunoglobulin M was slightly elevated (1.47 S/CO). Due to the absence of known risk factors for HBV reactivation, the reactivation was regarded as "spontaneous". After the initiation of the nucleotide analog TAF, her liver function gradually improved with a decrease in the HBV DNA load. Her HBV genome was typed as subgenotype B1 and possessed a frameshift mutation due to an insertion of T after nucleotide (nt) 1817 and G to A mutations at nt 1896 and nt 1899 (G1896A/G1899A) in the precore region as well as serine to glutamine substitution of amino acid 21 in the core protein. In addition to these viral mutations, aging and complications of lifestyle-related diseases in the present case may have been responsible for the spontaneous HBV reactivation. Careful observation and management of aged HBV carriers with underlying diseases are needed even when persistent HBV infection is free from symptoms and liver dysfunction and no immunosuppressive conditions are involved.

A 65-year-old man presented with acute liver failure and grade IV coma caused by hepatitis B virus (HBV) infection in 2017. The patient died on day 12 from the disease onset. The HBV isolated from the patient was genotype/subgenotype B/B1 and had multiple genomic mutations. The patient's wife was hepatitis B surface antigen (HBsAg)-positive when she delivered her first daughter in 1979. The HBV isolates of the patient and the wife shared 100% similarity over the entire genome. Because the patient's HBsAg value had been negative one year earlier, we considered the source of HBV transmission to be his wife.

The impedance expansion method (IEM) is a circuit modeling technique for electrically very small devices based on the method of moments. In the authors’ previous work, a circuit model of a wireless power transfer system was developed using the modal IEM, which utilizes the IEM and eigenmode analysis, wherein the currents on the coils were expanded into thin-wire basis functions. However, surface basis functions are required to apply the modal IEM to arbitrarily shaped conductors. In this letter, the problems arising when the surface basis functions are applied to the modal IEM are pointed out, and the cause of these problems is clarified. Then, the resolvability of these problems is demonstrated using the loop-star basis functions.