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Background & Objective: Hepatitis A is an enterically transmitted viral disease, highly prevalent in India and mainly presents as a paediatric sporadic disease. This study investigated an outbreak of viral hepatitis at Shimla, Himachal Pradesh, India, during January-March 2007., Methods: Eighty seven blood samples, 3 water samples and 2 sewage samples were collected. Serum samples were tested for IgM and IgG anti HAV and IgM and IgG anti HEV antibodies. Serum, sewage and water samples were tested for HAV-RNA by nested RT- PCR. Nearly complete full genome (excluding extreme 5' end) was amplified from one serum sample., Results: The hepatitis cases were mainly seen among children and young adults and 63.2 per cent (55/88) were positive for anti-HAV IgM. These cases were reported from the areas getting water supply from Ashwani Khud water supply system. This water purification system received water from a natural stream in which treated sewage water was let into 4 km upstream the collection point since one year. HAV-RNA present in serum, sewage and water samples showed 100 per cent sequence homology. Phylogenetic analysis based on 5' non coding (5' NC) and nearly complete genome showed the evidence of HAV genotype IIIA in all the samples., Interpretation & Conclusion: The aetiological agent of the present outbreak was hepatitis A virus which is emerging in an outbreak form in India, emphasizing a definite need for formulating vaccination/control strategies.

Open reading frame 2 proteins (ORF2) from swine (genotype 4, S-ORF2) and human (genotype 1, H-ORF2) hepatitis E virus (HEV) having 91.4% identity at amino acid level were expressed using baculovirus expression system. Comparison of ELISAs based on the two proteins yielded identical results when sequential serum samples from monkeys and pigs experimentally infected with genotypes 1 and 4 HEV, respectively, were tested. Samples from patients (n = 258) suffering from non-A, non-B hepatitis during outbreaks of the disease and 180 sera from apparently healthy children were screened by H-ORF2-, S-ORF2-based ELISAs and Genelabs ELISA, a widely used commercial test for HEV diagnosis. Specificity of all three tests in detecting IgM and IgG antibodies in healthy children was comparable. Excellent correlation was noted in detecting both IgM (98.7% concordance) and IgG (97.7% concordance) anti-HEV antibodies when H-ORF2 and S-ORF2 ELISAs were compared. When compared with Genelabs ELISA, both H-ORF2 and S-ORF2 ELISAs identified 34 and 18 additional positives, respectively, in IgM and IgG anti-HEV tests showing comparatively less sensitivity of the commercial assay. The concordance of Genelabs ELISA in IgM detection was 86.4% and 85.6%, respectively, with H-ORF2 and S-ORF2 ELISAs. The concordance between Genelabs ELISA and H-ORF2 decreased further to 73.6% when 129 human samples from recent HEV epidemics (2002-2004) were tested for IgM. Similar results were obtained when sequential samples from 11 hepatitis E patients were examined. Screening of serum samples from 137 sporadic non-A, non-B hepatitis cases further confirmed the superiority of the H-ORF2 and S-ORF2 ELISAs. All 36/137 HEV-RNA-positive samples from sporadic cases belonged to genotype 1 confirming absence/rarity of type 4 human infections. H-ORF2 and S-ORF2 antigens were swappable in ELISAs for detecting both genotypes 1 and 4 HEV infections.

Hepatitis E virus (HEV) is an emerging zoonotic pathogen that exhibits great host diversity. The primary means of transmission of the virus in low- and middle-income countries is contaminated water, often due to a lack of access to proper sanitation, which leads to faecal contamination of water sources. Environmental surveillance is an important tool that can be used to monitor virus circulation and as an early warning system for outbreaks. This study was conducted to determine the prevalence and genetic diversity of HEV in wastewater, surface water (rivers and standpipe/ablution water), and effluent from a piggery in South Africa. A total of 536 water samples were screened for HEV using real-time reverse transcription-polymerase chain reaction. Overall, 21.8% (117/536) of the wastewater, river, and ablution water samples tested positive for HEV, whereas 74.4% (29/39) of the samples from the piggery tested positive. Genotyping revealed sequences belonging to HEV genotypes 3 (98%, 53/54) and 4 (2%, 1/54), with subtypes 3c, 3f, and 4b being identified. [ABSTRACT FROM AUTHOR]

In contrast to countries reporting zoonotic spread of hepatitis E virus (HEV), distinct genotypes circulate in humans (genotype 1) and pigs (genotype 4) from India indicating rarity of such spread. Pigs were refractory to human HEV. As rhesus is an excellent animal model for human HEV, an attempt was made to infect rhesus monkeys with swine HEV. Experimental infection of both the rhesus monkeys with swine-HEV as evidenced by seroconversion to anti-HEV antibodies and presence of viraemia suggests possibility of human infections or differential susceptibility. Comparison of Open Reading Frame-2 and hypervariable regions of HEV genomes showed identity of swine and monkey-derived HEV.

The full-length genomic sequence of an Indian swine hepatitis E virus (HEV) isolate (IND-SW-00-01) recovered from feces of a pig experimentally infected with swine HEV pool from western India was determined. The genome consisted of 7,240 nucleotides, excluding the poly (A) tail of at least 22 residues and contained three open reading frames (ORFs), ORF-1 encoding 1,707 amino acids, ORF-2 encoding 674 amino acids and ORF-3 encoding 114 amino acids. Comparative full-length genome sequence and phylogenetic analyses suggested that the Indian swine HEV represents a distinct variant among the genotype 4 isolates with a divergence of 15-16.6%. Analyses based on ORF-1, 2 and 3 as well as partial ORF-2 (227 nucleotides) yielded similar results. As compared to type 4 HEV isolates, 26 unique amino acid substitutions were recorded, 16 in ORF-1, 8 in ORF-2 and 2 in ORF-3. IND-SW-00-01 showed insertion of 'C' at 5159 position while all other type 4 isolates have insertion of 'U' at the same position. Whether these changes contribute towards observed absence of type 4 HEV infections in Indian patients needs to be determined.

Hepatitis E is endemic in India. It was recently noted that although all the Indian human hepatitis E virus (HEV) isolates (1976-2001) were placed in genotype I, the swine HEV recovered from western India (2000) belonged to genotype IV. This was in contrast to reports from the United States and Taiwan wherein both human and swine HEV belonged to the same genotype, i.e., genotypes III and IV, respectively. In order to validate these findings further, we retrospectively examined serum samples collected from pigs from southern India. Sequential serum samples from 45 (1985-1987) and 12 (1999) pigs from Karnataka state, south India, were screened for the presence of HEV RNA (nested PCR) and IgG-anti-HEV (ELISA). PCR products (Open Reading Frame-2 region) were sequenced and subjected to phylogenetic analysis. In this study, 42/45 (1985-1987) and 12/12 (1999) pigs showed seroconversion to IgG anti-HEV antibodies, with a mean age at seroconversion of 4.8 +/- 1.6 months. Four samples collected in 1999 and two samples collected during 1985 were HEV RNA positive. All swine HEV sequences clustered with genotype IV, demonstrating that swine HEV was prevalent among south Indian pigs for at least for 16 years and, similar to western India, belonged to genotype IV. Thus, genotype I and IV HEV continue to circulate in humans and pigs, respectively, from India. Whether swine HEV infects humans remains to be determined., (Copyright 2003 Wiley-Liss, Inc.)

Objective: To determine and compare the etiology of sporadic acute and fulminant viral hepatitis in two groups of patients 16 years apart., Methods: Serologic diagnostic tests for hepatitis A, B, C, D and E, and cytomegalovirus infection were carried out in 276 patients during 1994-1997 (Group A) and 206 patients during 1978-1981 (Group B)., Results: Among children, hepatitis A virus was the major etiologic agent (81.6% in Group A and 51.4% in Group B), followed by hepatitis E virus (12.2%, 46.4%) and hepatitis B virus (5.4%, none). Among adults, hepatitis E virus was the main causative agent (42.4% in Group A and 71.2% in Group B) followed by HBV (28%, 25.5%) and hepatitis A virus (10.6%, 3.5%). Delta hepatitis was found only in Group A. No viral cause was found in 25% of patients in Group A and 13.5% patients in Group B., Conclusions: Hepatitis E virus is a major cause of sporadic acute and fulminant hepatitis. There has been an increase in hepatitis A in adults who developed fulminant hepatic failure. Our data points to the emergence of hepatitis A in adults and emergence of delta virus infection. Hepatitis C virus was unimportant in causing sporadic hepatitis.

Background/aims: Hepatitis E is endemic in India. Earlier, we showed prevalence of IgG antibodies to hepatitis E virus (IgG-anti-HEV) in different animal species and inability of at least one human hepatitis E virus (HEV) strain to infect pigs. In the US where hepatitis E is not endemic in humans, zoonotic spread of HEV was suspected as swine and human HEV were closely related and cross-species infection was documented. The present study attempts to identify and partially characterize swine HEV from India., Methods: Serum samples from 284 pigs were screened for the presence of HEV-RNA (nested polymerase chain reaction; PCR) and IgG-anti-HEV (enzyme-linked immunosorbent assay; ELISA). PCR products (Open Reading Frame-2 region) were sequenced and subjected to phylogenetic analysis. Two sero-negative pigs were inoculated with swine HEV-positive serum pool., Results: ELISA and PCR positivity were 42.9 and 4.6%, respectively. All Indian swine HEV sequences clustered with genotype IV. Pigs could be experimentally infected with swine HEV., Conclusions: Swine HEV circulates in Indian pigs. In contrast to US and Taiwan wherein both human and swine HEV isolates belong to same genotype, Indian human HEV isolates belong to genotype I whereas genotype IV circulates in swine. Though experimental infection with Indian swine HEV was possible, at least one human HEV strain could not infect pigs.

The epidemiology of hepatitis A virus (HAV) and hepatitis E virus (HEV) was assessed among age-stratified urban high socioeconomic, lower middle socioeconomic status and rural populations from western India in 1998. When compared with previous surveys, a clear shift from high to intermediate endemicity of HAV was evident only for higher socioeconomic population (1982-98), raising the possibility of outbreaks of hepatitis A in this category. A decrease in anti-HAV positivity was noted in rural children aged 6-10 years. Lower circulation of HEV was noted among < 25-year-old urban higher socioeconomic and rural individuals. For both viruses, the lower middle socioeconomic populations were comparable in 1982 and 1998. Socioeconomic status and family size (odds ratio = 23 and 1.6, respectively) were independently associated with anti-HAV positivity. Age, lower middle socioeconomic status and well water were significant independent variables for HEV infection (odds ratio = 5.7, 2.4 and 1.9, respectively). Hence, vaccination policy for hepatitis A needs to be reviewed.

Prevalence of IgG antibodies to hepatitis E virus (IgG-anti-HEV) was determined among different animal species from India. Seropositivity varied from 4.4% to 6.9% in cattle, 54.6-74.4% in pigs and 2.1-21.5% in rodents. Of the 44 dogs screened, 10 were positive (22.7%). None of the 250 goat sera tested were found to be anti-HEV positive. Among rodents, over 50% serum samples collected in 1985 from Bandicota bengalensis were positive for anti-HEV antibodies. No evidence of HEV infection was obtained following experimental inoculation of an Indian strain (AKL-90) of HEV into anti-HEV negative pigs and goats. The results document varied prevalence of anti-HEV antibodies in different animal species from India and of inability of Indian pigs and goats to support replication of at least one human strain of HEV.

Objectives: To determine the prevalence of hepatitis G virus (HGV) infection in western India and to carry out phylogenetic analysis of HGV isolates., Methods: Reverse transcription-polymerase chain reaction (RT-PCR) assay was used to detect HGV RNA in serum samples obtained from paid plasma donors, patients with hemophilia and voluntary blood donors. Nine Indian and one Kenyan HGV RNA-positive samples were sequenced in the 5' non-coding region (5'-NCR). Phylogenetic analysis based on the comparison of a 101 nucleotide fragment from a large number of HGV isolates from 22 countries (including Indian and Kenyan sequences obtained during the present study) was carried out., Results: HGV RNA positivity rates among paid plasma donors from a commercial plasmapheresis unit (7/43, 16.3%) and patients with hemophilia (5/44, 11.4%) were significantly higher than that in voluntary blood donors (0/51; p=0.003 and 0.019, respectively). Among patients with acute non-A to E hepatitis and fulminant hepatic failure, 1 of 50 and 1 of 28 were HGV RNA-positive, whereas 6 of 49 (12%) patients with chronic liver disease had circulating HGV RNA. All Indian isolates belonged to genotype 2, whereas the Kenyan isolate formed a distinct branch within genotype 1 consisting of African isolates., Conclusion: Our results suggest existence of parenteral transmission of HGV in the Indian population. HGV was not an important cause of acute non-A to E hepatitis or fulminant hepatic failure among the patients investigated. Genotype 2 seems to be the most prevalent genotype in western India.

Background and Objectives: Of 200 volunteer blood donors we had screened earlier for hepatitis E virus (HEV) RNA, using reverse-transcription polymerase chain reaction, 3 were positive, raising the possibility of transfusion-associated hepatitis E in areas endemic for this virus. This retrospective study was to reassess the extent of post-transfusion hepatitis E among transfusion recipients, investigated in 1982., Materials and Methods: We re-evaluated 56 recipients followed biweekly for 3 months after transfusion. The controls were 51 normal, healthy persons who gave blood at a 2-month interval, as well as 412 blood donors from whom blood was taken once in 1982., Results: Of the 56 transfusion recipients, 19 were positive for IgG antibodies against HEV (anti-HEV) in the pretransfusion sample. Two of the 37 IgG anti-HEV-negative recipients seroconverted to IgM and IgG anti-HEV 5 and 4 weeks after transfusion, 1 with raised serum alanine aminotransferase levels. None showed symptoms of hepatitis. Attempts to detect HEV RNA in transfused blood, from aliquot units stored at -20 degrees C for over 17 years, were not successful. Of the controls, 17 out of 51 were IgG anti-HEV positive in the initial sample itself. None of the 34 IgG anti-HEV-negative controls seroconverted during the 2-month follow-up. Of the blood donors, 154 out of 412 were IgG anti-HEV positive. None of the 412 donors had circulating IgM anti-HEV antibodies. A significantly higher (p<0.03) proportion of susceptible transfusion recipients were IgM anti-HEV positive as compared with susceptible blood donors., Conclusion: The results suggest that, in countries where HEV is endemic, the transmission of hepatitis E may be associated with blood transfusion.

Of 200 voluntary blood donors screened for hepatitis E virus (HEV) RNA, employing the reverse transcription-polymerase chain reaction (RT-PCR), three were found to be positive (1.5%). None of the HEV RNA-positive blood donors had any symptoms at the time of blood donation or during subsequent follow-up. One donor was positive for immunoglobulin M (IgM) antibodies to HEV, with a raised serum alanine aminotransferase (ALT) level, whereas the other two donors were negative for both immunoglobulin G (IgG) and IgM antibodies to HEV. Follow-up blood samples collected 2-5 months later from HEV RNA-positive blood donors demonstrated the presence of IgG anti-HEV antibodies. Overall seroprevalence of IgG anti-HEV was 18.6%. Retrospective studies on samples collected from commercial blood donors and haemophiliacs revealed IgG anti-HEV positivity to be 24. 6% (46/191) and 24.4% (22/90) and statistically not different (P>0. 1) from the prevalence among voluntary blood donors and an age-matched normal population, respectively. However, a highly significant proportion of the paid plasma donors, with a high prevalence of IgG antibodies to human immunodeficiency virus and hepatitis C virus, were positive for IgG antibodies to HEV (54/71, 76%, P<0.001), indicating a possible role of blood-derived HEV in the transmission of the virus among plasma donors. These results demonstrate the possible risk of transfusion-associated hepatitis E in hyperendemic areas.

Background/aims: The aims of this study were to examine the decline of IgG anti-HEV antibodies over a period of 7 years in rhesus monkeys experimentally infected with hepatitis E virus, and to assess the protectivity of these antibodies by challenging the monkeys with a heterologous isolate of hepatitis E virus, 5 years after the primary inoculation., Methods: Nine rhesus monkeys (six non-pregnant and three pregnant at the time of hepatitis E virus inoculation) were followed serologically and biochemically for 7 years post-inoculation. Based on regression analysis, estimated time for IgG anti-HEV titers to reach 1:100 or 1:50 was calculated. Three of the monkeys inoculated initially with AKL-90 isolate and challenged 2 years later with PUN-85 isolate of hepatitis E virus were rechallenged with KOL-91 isolate of the virus, 5 years post-primary inoculation. Evidence of viral replication was assessed by measuring serum alanine aminotransferase levels, excretion of the virus in feces or bile (reverse-transcription polymerase chain reaction) and rise in IgG anti-HEV titers (ELISA)., Results: None of the challenged monkeys showed evidence of disease. In contrast to extensive replication of the virus in anti-HEV-negative control monkeys, limited replication was noted in one of the challenged monkeys. The estimated time for the titers to reach 1:100 or 1:50 varied from 3.15 to 44.9 years (19.4+/-11.6 years) and 6.9 to 84.3 years (35.4+/-21.3 years), respectively. Decline in titers was independent of the pregnancy status at the time of infection or reexposure of the monkeys to HEV CONCLUSION: The results show persistence of IgG anti-HEV antibodies for a long time and protectivity of low titered antibodies against reinfection, leading to disease even after intravenous exposure to a heterologous isolate of hepatitis E virus.

Out of the 15 hepatitis E (HEV) epidemics that occurred during the years 1976-1995 in the Gujarat and Maharashtra states of India, 45.78% (76/166) stool samples showed the presence of HEV RNA. HEV RNA was found significantly more often in samples that were transported in liquid nitrogen (50.9%) compared with samples that were transported in wet ice (37.0%) (P < 0.05). Stool samples collected within 7 days after the onset of the disease (59.2%) were more often positive for HEV RNA when compared with samples that were collected 7-20 days after the onset of the disease (28.5%) (P < 0.01). It has been observed in experimentally infected Rhesus monkeys that they excrete HEV throughout the incubation period and for a variable length of time after the elevation of serum ALT levels. A similar situation is found in humans.

The aim of this study was to determine if rhesus monkeys infected with one isolate of hepatitis E virus (HEV) were immune to subsequent challenge with other isolates of the virus. Three epidemic and one sporadic Indian HEV isolates were employed in the study. The interval between primary inoculation and challenge varied from 1 year and 6 months to 2 years and 9 months. Evidence of HEV infection was ascertained by rise in serum alanine transaminase (ALT) levels and/or seroconversion to antibodies to HEV (anti-HEV), and the presence of HEV-RNA in the bile or faeces of the infected monkeys. No evidence for multiplication of virus in monkeys challenged with different HEV isolates was obtained. These results show that immunity generated by one isolate of HEV protects against different isolates of hepatitis E virus.

Non-A, non-B (NANB) hepatitis viruses are now classified as hepatitis E (enterically transmitted) and hepatitis C (parenterally transmitted). India experiences a large number of epidemics of the enteric disease every year. In addition, about 70% of the sporadic cases among adults are also due to NANB hepatitis. With the availability of an immunoblot assay for the detection of anti-HEV-IgM and the polymerase chain reaction (PCR) for the detection of HCV-RNA, serum samples from epidemic and sporadic NANB patients were screened for these markers. We found that a large number of cases from the epidemics were HEV, though a few remained undiagnosed, while of the sporadic cases only a few could be diagnosed as HCV or HEV; a large proportion remained undiagnosed.

Ten non-pregnant female monkeys and four pregnant monkeys (all Macaca mulatta) in the last third of their gestation period were infected intravenously with the stool sample of a patient with hepatitis E virus infection (immuno-electronmicroscopy positive for hepatitis E virus). Four more non-pregnant monkeys were inoculated with a lower dose (less number of virus particles by IEM) of a stool sample collected on a different day from the same patient. The average incubation period as evidenced by the rise of serum alanine transferase in the non-pregnant monkeys, was 36.4 +/- 4.9 days. The dose of the virus did not affect the incubation period. Two of the pregnant monkeys had incubation periods of 9 and 13 days respectively. They delivered healthy babies on 40th and 53rd day respectively after inoculation. At the age of 11 months, both babies were negative for anti-HEV antibodies. One monkey which delivered a healthy baby on the 2nd day after inoculation had incubation period of 36 days. The baby of this monkey was anti-HEV positive at the age of 11 months. The incubation period was 41 days in the fourth monkey which delivered a macerated foetus on the 36th day after infection. No fatality was recorded in the infected monkeys. Bile samples collected from all monkeys showed strong signals in nested polymerase chain reaction (PCR). It seems that the incubation period in pregnant monkeys was determined by the state of pregnancy.

Animal models are one of the most important tools in the study of human hepatitis E virus (HEV) infection. They are particularly important in light of the major limitations of the cell culture system for HEV. Besides nonhuman primates, which are extremely valuable because of their susceptibility to HEV genotypes 1-4, animals like swine, rabbit, and humanized mice are also potential models for studies of pathogenesis, cross-species infection, and the molecular biology of HEV. Identification of a useful animal model for human HEV infection studies is crucial to further investigations into this ubiquitous yet poorly understood virus and facilitate the development of antiviral therapeutics and vaccines., (© 2023. The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.)

The hepatitis E has been increasingly recognized as an underestimated global disease burden in recent years. Subpopulations with more serious infection associated damage or death include pregnant women, patients with basic liver diseases, and elderly persons. Vaccine would be the most effective means for prevention of HEV infection. The lack of an efficient cell culture system for HEV makes the development of classic inactive or attenuated vaccine infeasible. Hence, the recombinant vaccine approaches are explored deeply. The neutralizing sites are located almost exclusively in the capsid protein, pORF2, of the virion. Based on pORF2, many vaccine candidates showed potential of protecting primate animals, two of them were tested in human and evidenced to be well-tolerated in adults and highly efficacious in preventing hepatitis E. The world's first hepatitis E vaccine, Hecolin ® (HEV 239 vaccine), was licensed in China and launched in 2012., (© 2023. The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.)

Hepatitis E virus (HEV) usually causes acute self-limiting hepatitis but sometimes leads to chronic infection in immunocompromised persons. HEV is not directly cytopathic. Immunologically mediated events after HEV infection are believed to play important roles in the pathogenesis and clearance of infection. The anti-HEV antibody responses have been largely clarified since the determination of major antigenic determinant of HEV, which is located in the C-terminal portion of ORF2. This major antigenic determinant also forms the conformational neutralization epitopes. Robust anti-HEV immunoglobulin M (IgM) and IgG responses usually develop 3-4 weeks after infection in experimentally infected nonhuman primates. In humans, potent specific IgM and IgG responses occur in the very early phase of the disease and are critical in eliminating the virus, in concert with the innate and adaptive T-cell immune responses. Testing anti-HEV IgM is valuable in the diagnosis of acute hepatitis E. The long-term persistence and protection of anti-HEV IgG provide the basis for estimating the prevalence of HEV infection and for the development of a hepatitis E vaccine. Although human HEV has four genotypes, all the viral strains are considered to belong to a single serotype. It is becoming increasingly clear that the innate and adaptive T-cell immune responses play critical roles in the clearance of the virus. Potent and multispecific CD4+ and CD8+ T cell responses to the ORF2 protein occur in patients with acute hepatitis E, and weaker HEV-specific CD4+ and CD8+ T cell responses appear to be associated with chronic hepatitis E in immunocompromised individuals., (© 2023. The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.)

To assess the risk of hepatitis B infection among dental personnel, serum samples were collected from dentists of Pune and students, staff, auxiliary staff and class D staff of a dental college in Bombay. Dentists (32.02%), dental auxiliary staff (35.89%), clinical assistants and post-graduate students (19.56%) were found to have significantly higher prevalence of HBV infection as compared to undergraduate dental students (3.94%). The prevalence of HBV infection was high among the dentists as compared to voluntary donors. A positive linear association was observed in the positivity of HBV seromarkers with increasing age and number of years spent by the workers in the dental environment. The rate of increase in HBV seropositivity with age was higher (P less than 0.05) among dental personnel when compared to voluntary donors. Vaccination against hepatitis B is recommended for all the dental students before they start their clinical phase and for susceptible dentists and dental auxillary staff.

Enterically transmitted waterborne hepatitis E (HE) caused due to hepatitis E virus (HEV) prevails as a significant public health problem endemic to India. Due to short-term viremia/fecal excretion and poor in vitro transmissibility of HEV, HE diagnosis depends on detection of specific IgM antibodies in serum. Present study evaluated performances of two in-house and six commercial IgM detection enzyme-linked immunosorbent assays (ELISAs) using sera collected from volunteers/acute hepatitis patients (n = 716). The in-house ELISAs were based on complete and truncated open reading frame 2 (ORF2) proteins containing neutralizing epitope/s region of genotype 1 HEV (ORF2p, 1-660 amino acid (a.a.) and T1NEp, 458-607 a.a., respectively). The commercial ELISAs included Wantai (China), MP Diagnostics (MPD) (Singapore), DIA.PRO Diagnostics (Italy), MBS (Italy), abia (Germany), and ImmunoVision (USA). T1NE ELISA showed 97.0% positive percent agreement (PPA), 99.4% negative percent agreement (NPA), and 98.6% concordance (κ = 0.97, P = 0.0000) with ORF2 ELISA. ORF2, T1NE, Wantai, and MPD ELISAs agreed on results for 88% of sera tested. Two percent sera showed reactivity in each combination of three and two of aforementioned four ELISAs. Remaining 8% sera were single ELISA reactive. PPA and NPA value ranges were 76.3-99.0% and 84.8-99.5%, respectively. Pairwise concordances between all the eight ELISAs ranged from 88.0 to 100% (κ: 0.74-1.00). Both the in-house ELISAs agreed better with Wantai over MPD ELISA. In conclusion, both ORF2 and T1NE ELISAs were equally efficient in diagnosing HEV infections. T1NEp proved to be an excellent tool in HE sero-diagnosis and is worth exploring in development of simple rapid tests. KEY POINTS: • In-house ELISA based on bacterially expressed neutralizing epitope/s region protein • In-house ELISA based on complete ORF2 protein expressed in insect cells • Comparison of two in-house and six commercial anti-HEV IgM antibody detection ELISAs., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Hepatitis E virus (HEV) is a major cause of enterotropic viral hepatitis, a major public health problem in many developing countries. In Central African Republic (CAR), HEV genotypes 1, 2, and 3 have been found to have an impact on human health. However, data on HEV in animal reservoirs are still lacking for CAR. Here, we investigated the presence of HEV in farmed pigs and goats in Bangui, the capital city of CAR, using molecular methods. Methodology: In a prospective study, fecal samples from 61 pigs and 39 goats from farms in five districts (2nd, 4th, 6th, 7th, 8th) of Bangui were collected and tested for HEV RNA by real-time RT-PCR. The samples were further analyzed by nested-PCR and sequenced to determine the genotype and subtype to which the virus belong. Results: In total, 22/100 (22.0%) feces samples were successfully amplified for HEV RNA by real time RT-PCR. All positive samples were from pigs (22/61; 36.1%), while all goat samples were negative (0/39). Twelve HEV RNA samples (12/22 or 54.5%) were successfully amplified by nested RT-PCR, and subsequently sequenced. Phylogenetic analysis revealed that the obtained sequences clustered with subtype 3h and were genetically related to the human HEV sequences from CAR. Conclusion: This study confirms that pigs constitute an HEV reservoir, with genotype 3 being the major circulating strain. Further studies are needed to investigate other local reservoirs and to improve knowledge of the molecular epidemiology of HEV in CAR. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is the leading cause of acute viral hepatitis globally, with zoonotic potential, and pigs are considered the major reservoir. To determine the seroprevalence of HEV infection in pigs reared in backyard conditions in the northeastern region of India, blood samples were collected from 400 pigs from five northeastern states (80 samples from each state) and tested for IgG antibodies against HEV using an ELISA assay. Questionnaires on farm characteristics and management practices were completed, and risk factors associated with HEV were studied using univariate and multivariate analysis. The apparent seroprevalence of HEV infection was 51% (46.1–55.9, 95% CI), with a true prevalence of 52.98% (47.22–58.75, 95% CI). The risk factors significantly associated with higher HEV seropositivity were as follows: lack of disinfection (OR 4.65), feeding swill (restaurant and bakery waste) (OR 2.55), failure to follow the all-in-all-out production system (OR 3.47), and medium holding size (OR 9.83), which refers to mixed rearing of younger and older age groups. This study demonstrates that HEV is widespread among pigs reared in northeastern India. The risk factor analysis conducted in this study provides valuable insights into the prevalence of HEV in the region. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) genotype 3 infections in Germany are mainly transmitted zoonotically through the consumption of swine meat. Furthermore, there is evidence that pets might come into contact with HEV, but the relevance of companion animals as possible sources of HEV transmission in Germany still needs to be defined. A monitoring study was therefore carried out on dogs, cats, and horses from Germany. In total 365 serum samples from pets (124 dogs, 119 cats, and 122 horses) were tested for HEV by PCR and for anti-HEV antibodies by a commercial ELISA. The HEV seroprevalence determined by the sero-assay varied significantly between dogs (10%), cats (6%), and horses (2%). Liver injury-related enzymes, alanine transaminase (ALT), and aspartate transaminase (AST) showed no differences between HEV-positive or negative animals. None of the pet serum samples tested positive for PCR. This serological study suggests that dogs and cats are significantly exposed to HEV in Germany, while horses are of minor relevance. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is a prevalent pathogen responsible for acute viral hepatitis, HEV genotypes 3 and 4 infections causing zoonotic infections. Currently, the nucleotide similarity analysis between humans and pigs for HEV genotype 4 is limited. In this study, stool samples from an HEV-infected patient who is a pig farmer and from pigs were collected to obtain the near full-length genome of HEV, phylogenetic trees were constructed for genotyping, and similarity of HEV sequences was analyzed. The results showed that HEV-RNA was detected in the stool samples from the patient and six pigs (6/30, 20.0%). Both HEV subtype in the patient and pigs was 4b. Additionally, similarity analysis showed that the range was 99.875%-99.944% between the patient and pigs at the nucleotide level. Four isolates of amino acid sequences (ORFs 1-3) from pigs were 100% identical to the patient. Phylogenetic tree and similarity analysis of an additional nine HEV sequences isolated from other patients in this region showed that the HEV sequence from the pig farmer had the closest relationship with the pigs from his farm rather than other sources of infection in this region. This study provides indirect evidences for HEV subtype 4b can be transmitted from pigs to humans at the nucleotide level. Further research is needed to explore the characteristics of different HEV subtypes., (© 2024 Wiley Periodicals LLC.)

Background: Hepatitis-E virus (HEV) is an emerging infectious threat to blood safety. The enormity of the transmission of HEV and its clinical consequence are issues currently under debate. This study aimed to evaluate the prevalence of HEV-RNA in blood donors in western India., Materials and Methods: We screened 13 050 blood donors for HEV using HEV-RNA screening of 10 mini-pools using RealStar HEV RT-PCR Kit (95% limit of detection (LOD): 4.7 IU/ml). Furthermore, all HEV-RNA-positive donors were investigated for the presence of IgM/IgG antibody along with liver function tests., Results: Of the 13 050 blood donations, 7 (0.53%) were found to be HEV-RNA positive, and the prevalence of HEV nucleic acid testing yield cases among blood donors was 1 in 1864. All seven HEV-RNA-positive samples were tested with anti-HEV IgM and anti-HEV IgG antibodies; this resulted in two (28.5%) positive anti-HEV IgM and two (28.5%) positive anti-HEV IgG antibodies. Hepatic activity was measured, with two of seven HEV-RNA-positive donors demonstrating abnormal serum glutamic oxaloacetic transaminase (SGOT) andserum glutamic pyruvic transaminase (SGPT). Two HEV-RNA-positive blood donors who had abnormal SGOT and SGPT were found to have a high HEV viral load. Furthermore, we were able to follow up two HEV-RNA donors, and both were HEV-RNA positive and had anti-HEV IgM and anti-HEV IgG antibodies; moreover, their liver function tests were also abnormal. One of the HEV-RNA donors with high viral load did show hepatitis-E-like virus on electron microscopy., Conclusion: Our studies indicate that there is a significant risk of blood-borne transmission of HEV. This finding may help to provide a direction towards the safety of blood transfusions in clinical settings in countries like India, which fall under the endemic category for HEV infection., (© 2021 British Blood Transfusion Society.)

Hepatitis E, a public health concern in developing countries, frequently presents in epidemic, as well as in sporadic forms. This study investigated an outbreak of viral hepatitis at Yavatmal, Maharashtra, India in March 2019. Blood samples from 10 patients were received at Indian Council of Medical Research-National Institute of Virology, Pune to test for the presence of enterically transmitted hepatitis viruses. Subsequently, 49 suspected cases were screened for anti-hepatitis E virus (HEV)/hepatitis A virus (HAV) immunoglobulin M and immunoglobulin G (IgG) antibodies, alanine amino-transferase levels and HEV RNA. Water samples were screened for HEV and HAV RNA followed by phylogenetic analysis. Overall 32 of 49 (65.3%) suspected cases had recent acute HEV infection, while dual infection with HAV was noted in one case (2.04%). Forty-eight of 49 suspected cases were positive for anti-HAV IgG antibodies indicative of previously acquired immunity against HAV. Water samples had evidence of HEV contamination as detected by reverse transcription-polymerase chain reaction. Sequencing of HEV RNA from both patients (n = 2) and water samples (n = 5) indicated HEV genotype 1 to be the etiological agent of this outbreak. Serological and molecular evidence confirmed HEV as the etiology. Mixing of contaminated drain water with the domestic water supply may have triggered this outbreak. Subsequent changing of the defaulted water pipelines and its segregation from drain pipelines by the health authorities resulted in progressive decline of this outbreak. Despite the limitations, periodic surveillance of HEV exposure pattern and reporting of small outbreaks would supplement to the global disease burden data of hepatitis E., (© 2020 Wiley Periodicals LLC.)

Acute liver disease (ALD) or chronic liver diseases (CLD) are the two major comorbidities observed in patients with diabetes mellitus (DM) and metabolic syndrome (MS). It is well known that, aetiology of liver disease such as hemochromatosis, nonalcoholic fatty liver disease (NAFLD), hepatitis C virus (HCV) and non-alcoholic steatohepatitis (NASH) are frequently associated with DM. However, in many studies there is no direct relationships between MS and cirrhosis, acute hepatic failure, end-stage liver disease, hence, we tried to investigate the association between diabetes mellitus and metabolic syndrome (DM/MS) group Vs. non-diabetes and non-metabolic syndrome having ALD and CLD, which might further explore the feasibility of using DM and MS as a prognostic indicator in such patients. Consecutive, age and sex matched ALD (n=31) and CLD (n=62) patients of above 18 years age were included in this study. Patients were categorized into two groups of having diabetes and metabolic syndrome; whose anthropometric, clinical and biochemical details were documented. Further, clinical reports were analyzed to assess the immediate and short-term consequences. Among ALD patients, FBG, HbAlc, ALT values were found significantly higher in DM/MS group (P<0.05). Time to resolution of injury (bilirubin normalization) was found to be significantly higher in DM/MS group (p<0.05). Among CLD patients, high PPBG, HbAlc, TG, LDL, VLDL values were observed in DM/MS group (p<0.05) compared to the nonDM/nonMS group. Higher number of deaths occurred in DM/MS group (n= 6; 28%) in comparison to non DM / non MS group (n=3; 7%)(P>0.05). Overall, patients having DM/MS had high risk of liver disease, mortality and more length of stay in hospital. Patients with DM/MS are at a higher risk of developing severe hepatitis. There is a great impact of DM/MS on development and prognosis of acute as well as chronic liver disease, so, every DM patient must be screened and evaluated for liver injury and its complications. [ABSTRACT FROM AUTHOR]

Background: Hepatitis E virus (HEV) infection is a common cause of acute hepatitis worldwide and causes approximately 30% case fatality rate among pregnant women. Pregnancy serum (PS), which contains a high concentration of estradiol, facilitates HEV replication in vitro through the suppression of the PI3K–AKT–mTOR and cAMPK–PKA–CREB signaling pathways. However, the proteomics of the complex host responses to HEV infection, especially how PS facilitates viral replication, remains unclear. Methods: In this study, the differences in the proteomics of HEV-infected HepG2 cells supplemented with fetal bovine serum (FBS) from those of HEV-infected HepG2 cells supplemented with serum from women in their third trimester of pregnancy were quantified by using isobaric tags for relative and absolute quantification technology. Results: A total of 1511 proteins were identified, among which 548 were defined as differentially expressed proteins (DEPs). HEV-infected cells supplemented with PS exhibited the most significant changes at the protein level. A total of 328 DEPs, including 66 up-regulated and 262 down-regulated proteins, were identified in HEV-infected cells supplemented with FBS, whereas 264 DEPs, including 201 up-regulated and 63 down-regulated proteins, were found in HEV-infected cells supplemented with PS. Subsequently, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that in HEV-infected cells, PS supplementation adjusted more host genes and signaling pathways than FBS supplementation. The DEPs involved in virus–host interaction participated in complex interactions, especially a large number of immune-related protein emerged in HEV-infected cells supplemented with PS. Three significant or interesting proteins, including filamin-A, thioredoxin, and cytochrome c, in HEV-infected cells were functionally verified. Conclusions: The results of this study provide new and comprehensive insight for exploring virus–host interactions and will benefit future studies on the pathogenesis of HEV in pregnant women. [ABSTRACT FROM AUTHOR]

Access to Hepatitis B Virus (HBV) testing for people in low-resource settings has long been challenging due to the gold standard, enzyme immunoassay, being prohibitively expensive, and requiring specialised skills and facilities that are not readily available, particularly in remote and isolated laboratories. Routine pathology data in tandem with cutting-edge machine learning shows promising diagnostic potential. In this study, recursive partitioning ("trees") and Support Vector Machines (SVMs) were applied to interrogate patient dataset (n = 916) that comprised results for Hepatitis B Surface Antigen (HBsAg) and routine clinical chemistry and haematology blood tests. These algorithms were used to develop a predictive diagnostic model of HBV infection. Our SVM-based diagnostic model of infection (accuracy = 85.4%, sensitivity = 91%, specificity = 72.6%, precision = 88.2%, F1-score = 0.89, Area Under the Receiver Operating Curve, AUC = 0.90) proved to be highly accurate for discriminating HBsAg positive from negative patients, and thus rivals with immunoassay. Therefore, we propose a predictive model based on routine blood tests as a novel diagnostic for early detection of HBV infection. Early prediction of HBV infection via routine pathology markers and pattern recognition algorithms will offer decision-support to clinicians and enhance early diagnosis, which is critical for optimal clinical management and improved patient outcomes. [ABSTRACT FROM AUTHOR]

Viral hepatitis is caused by a heterogenous group of viral agents representing a wide range of phylogenetic groups. Many viruses can involve the liver and cause liver injury but only a subset are delineated as 'hepatitis viruses' based upon their primary site of replication and tropism for hepatocytes which make up the bulk of the liver cell population. Since their discovery, beginning with the agent that caused serum hepatitis in the 1960s, the alphabetic designations have been utilized. To date, we have five hepatitis viruses, A through E, though it is postulated that others may exist. This chapter will focus on those viruses. Note that hepatitis D is included as a subset of hepatitis B, as it cannot exist without concurrent hepatitis B infection. Pregnancy has the potential to affect all aspects of these viral agents due to the unique immunologic and physiologic changes that occur during and after the gestational period. In this review, we will discuss the most common viral hepatitis and their effects during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Hepatitis E Virus is emerging as a public health concern as it causes hepatitis E infection. From 2004, it has gained importance as a transfusion transmissible infectious agent. Objectives: To determine the prevalence of Hepatitis E Virus by detecting IgG antibody levels among blood donors in Kenyatta National Hospital, Nairobi from April 2019 to May, 2020. Study design: Descriptive cross-sectional study Materials and methods: A Total of ninety-five of blood donors from Kenyatta National Hospital Blood Transfusion Unit were recruited into the study. Blood samples were drawn for routine tests and HEV IgG was carried out using HEV immunoglobulin G antibody enzyme linked immunosorbent assay (ELISA) technique. Data management: Data was analyzed using Statistical Package for Social Sciences (SPSS) version 21. Demographic data that was categorical was summarized and presented as frequencies and proportions. Pearson Chi-Square test and Fisher’s Exact tests were used to test association between demographic and laboratory findings. Results: The socio-demographic data revealed that 78 (82%) of the donors were male while 17(18%) were female. The age of the participants ranged between 17-59 years. The HEV IgG was found to be 5.3 %. Conclusions: prevalence of HEV IgG among blood donors at KNH Blood Transfusion Unit is 5.3%. Recommendations: A much broader study at the National level should be conducted to establish the national seroprevalence of Hepatitis E virus in blood donors. This can lay the ground for the inclusion or exclusion of Hep E virus in the Transfusion Transmissible Infections (TTIs) screened in Kenya. [ABSTRACT FROM AUTHOR]

Context: Viral hepatitis caused 1.34 million deaths in 2015, a number comparable to the deaths caused by tuberculosis and higher than that caused by human immunodeficiency virus (HIV). Hepatitis A virus (HAV) and hepatitis E virus (HEV) are important causes of acute viral hepatitis (AVH) and acute liver failure (ALF). Due to the paucity of data, the exact burden of the disease in western India is not established. Objective: Considering this background, the present study aims to determine the prevalence, epidemiology, and biochemical correlation in AVH due to HAV and HEV. Setting and Design: It was a retrospective observational study conducted over 3 years from January 2018 to December 2020 in a tertiary care hospital of Western India. Material and Methods: The study population included 1,807 patients (outdoor and hospitalized) having clinical features of AVH. All serum samples from these patients were tested in duplicate for immunoglobulin M (IgM) anti-HAV and IgM anti-HEV antibodies using commercially available enzyme-linked immunosorbent assay (ELISA) kits. The liver function tests (LFTs) were also monitored. Results: Of the 1,807 specimens processed from the patients with AVH, 120 (6.70%) were positive for IgM anti-HAV antibodies and 154 (8.5%) were positive for IgM HEV antibodies. A total of 11 patients (0.60%) were positive for both anti-HAV IgM and anti-HEV IgM antibodies indicating HAV-HEV coinfection. Our study shows that the HAV infection was more prevalent in the pediatric age group. The HEV infection was seen in all age groups and more prevalent in the age group of 20–30 years. The infection was more prevalent from June to October, that is, during monsoon and post-monsoon seasons. Total serum bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), and alkaline phosphatase (ALP) were elevated at 85.84, 86.79, 91.5, and 83.96%, respectively, in HAV-infected and elevated at 78.12, 93.75, 67.18, and 57.03%, respectively, in HEV-infected patients. The patients with HAV-HEV coinfection had all deranged LFTs indicating more severe disease. Conclusion: The present study emphasizes the importance of screening all hepatitis viral markers (A, B, C, E) for early diagnosis and curtailment of outbreaks and epidemics by the public health sector reducing morbidity and mortality. [ABSTRACT FROM AUTHOR]

The zoonotic transmission of Hepatitis E virus (HEV) is a well-established fact and pigs are known reservoirs of the virus. The human and swine HEV from countries such as the USA, Japan and Taiwan, show a remarkable sequence identity. Swine liver samples from markets in Japan and US were shown to be HEV RNA positive. In contrast, in India, viruses belonging to different genotypes, that is, genotypes 1 and 4 circulate in humans and pigs respectively, at least for the last 20 years. To assess possible exposure of the Indian population to swine HEV, 240 pig liver samples were collected from retail markets of Pune, western India. Two (0.83%) samples were found positive for HEV RNA by nested RT-PCR. Nucleotide sequence-based phylogenetic analysis showed the presence of genotype 4 HEV with 90-91% similarity and clustering with Indian swine HEV sequences generated earlier. The data suggest the possibility of HEV infection in persons consuming infected pig liver. So far, it has not been possible to detect any type 4 HEV infection in humans. The absence of type 4 infections in humans may be attributed to cooking leading to the inactivation of the virus. J. Med. Virol. 80:1387-1390, 2008. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Background: Considering the diverse socio-economic and demographic factors in a vast country like India, it is important to study the long-term trends of hepatitis A (HAV) and hepatitis E (HEV) viruses. This study describes their seroprevalence and long-term trends in a tertiary care center of North India. Methods: The present retrospective observational study was conducted over a period of 8 years (January 2011–December 2018). Serological testing was done for detecting IgM antibodies against HAV and HEV using enzyme-linked immunosorbent assay. Results: A total of 5319 samples were received during the study period, of which 903 (16.9%) were reactive for anti-HAV IgM antibodies and 795 (14.9%) were reactive for anti-HEV IgM antibodies. Majority of the cases occurred from June to October while HEV cases had a constant presence during the later years. Among HAV group, 534 (59.1%) were children, 336 (37.2%) were adults, and 33 (3.7%) were pregnant females. In HEV group, 632 (79.5%) were adults, 114 (14.3%) were pregnant females, whereas only 49 (6.2%) were children. Among those who were co-infected (n = 87), 48 (55.2%) were adults, 22 (25.3%) were pregnant females, and the rest 17 (19.5%) were children. Conclusions: The shift in seroprevalence toward adults, along with an increasing trend of the number of cases reporting to the hospital, warrants active surveillance of HAV. Similarly, screening protocols for HEV should be set up as part of the antenatal management for early detection of the cases among pregnant females. [ABSTRACT FROM AUTHOR]

Summary: The human pegivirus type 1 (HPgV‐1)—as known as hepatitis G virus and GB virus C—is a common single‐stranded RNA flavivirus. Because few studies have demonstrated an association between HPgV‐1 infection and disease, screening for HPgV‐1 is not performed routinely. Nonetheless, a beneficial impact of HPgV‐1 infection on HIV disease progression has been reported in multiple studies. Given the burden of HIV in Asia and the complex interactions between viral co‐infections and the host, we provide a comprehensive overview of the existing data from Asia on HPgV‐1 infection, including the prevalence and circulating genotypes in all Asian countries with data reported. This review highlights the research conducted thus far and emphasizes the need for additional studies on HPgV‐1 across the Asian continent. [ABSTRACT FROM AUTHOR]

Background: Hepatitis E virus (HEV) is the leading cause of acute hepatitis throughout the world. Increasing blood component transfusion-associated HEV infections highlight the need for reliable virus inactivation procedures for plasma derivatives from pooled plasma donations.Study Design and Methods: An animal infection study was conducted to evaluate the efficiency of HEV inactivation by pasteurization during the manufacturing process of the von Willebrand Factor/Factor VIII (VWF/FVIII) concentrate Haemate P/Humate-P (CSL Behring, Marburg, Germany). For this purpose, groups of pigs were inoculated with stabilized VWF/FVIII intermediate spiked with HEV-positive liver homogenate and exposed to increasing incubation times of 0, 3, 6, and 10 h at 60°C. Animals were evaluated for virus replication over 27 days and in a subsequent trial over 92 days.Results: Virus replication was detected in animals up to the 6-h pasteurization group. In contrast, pasteurization for 10 h did not reveal virus detection when the observation period was 27 days. In an additional experiment using the 10-h pasteurized material, two individuals started virus excretion and seroconverted when the observation period was extended to 92 days. Based on the total infection rate (2 of 12) of the animals inoculated with the sample pasteurized for 10 h, a virus reduction factor of at least 4.7 log10 is calculated.Conclusion: This study demonstrates that pasteurization at 60°C for 10 h of an HEV-positive plasma derivative leads to the effective reduction of infectivity, resulting in a VWF/FVIII product with an appropriate margin of safety for HEV. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is a causative agent of acute viral hepatitis globally. Evolutionary phylogeny classifies the HEV into eight genotypes that correlate with the viral transmission. Only four genotypes have been proven to be responsible for transmission in humans. However, there has been no report on the genomics and genotyping of HEV in Thailand during the past ten years. Here, we identified the genotype distributions of the Thai isolates of HEV and we sequenced two HEV genomes. We screened for 18 Thai isolates of HEV from Siriraj Hospital in Bangkok, from 2014–2016. The HEV genomes were sequenced from the serum and feces of a patient. The results showed that all Thai isolates of HEV were identified as genotype 3 (HEV-3). The ORF2 and genome phylogenies suggested two subgenotypes, called 3.1 and 3.2. The Thai isolates of HEV were frequently found in the subgenotype 3.1. The genome sequences of the two Thai isolates of HEV from the serum and fecal samples of the same patient showed 91% nucleotide similarity with the HEV genotype 3. Comparisons between the HEV genome and the ORF2 phylogenies illustrated that the ORF2 tree can be used to identify HEV genotypes, but it has less phylogenetic power for the HEV evolution. The two new genome sequences of HEV-3 from Thailand could contribute valuable information to the HEV genome study. (226 words) [ABSTRACT FROM AUTHOR]

Background: Hepatitis E virus (HEV) is usually transmitted by faecal–oral route. Recent reports have documented HEV viraemia in donated blood units and HEV transmission through blood transfusion. This systematic review summarizes the available data on prevalence of HEV viraemia in blood donors. Methods: Electronic databases were searched on 17 December 2018 to identify full‐text English papers reporting original data on prevalence of HEV RNA in donated blood units. Two authors independently extracted the relevant data, which were pooled using simple aggregation as well as a random‐effects meta‐analysis; heterogeneity was assessed using the I2 method. Results: In all, 59 data sets from 28 countries were identified. The available data showed marked heterogeneity. Of a total of 2 127 832 units studied, 561 (263·6 [95% confidence intervals = 242·7–286·4] per million units) tested positive for HEV RNA. On random‐effects meta‐analysis, the pooled prevalence was 60·9 [6·7–155·4] per million units. In the viraemic units, HEV RNA titre varied by nearly one million‐fold, and most had genotype 3 HEV. The prevalence was higher in blood units with anti‐HEV antibodies or elevated alanine aminotransferase. Only nearly one‐fourth of viraemic units had anti‐HEV antibodies. Conclusions: The prevalence of HEV viraemia among healthy blood donors is low, though the available data had limited geographical representation and marked heterogeneity. There is a need for further data on HEV viraemia in blood donors from areas with non‐3 HEV genotype preponderance. [ABSTRACT FROM AUTHOR]

Background and objectives: The local prevalence of HPgV‐1 has been reported from different countries worldwide, but the global prevalence of HPgV‐1 remains unknown. The aim of this systematic review and meta‐analysis was to gather data from the literature to estimate the prevalence of HPgV‐1 in healthy volunteer blood donors in the world. Materials and methods: We searched PubMed, EMBASE, Scopus and Google Scholar databases for records up to January 2019 and included studies reporting HPgV‐1 virus prevalence amongst healthy volunteer blood donors based on the detection of HPgV‐1 RNA. Results: In all, we included 79 studies for the systematic review and 63 for the meta‐analysis. Based on the random effect meta‐analysis of 35 468 volunteer blood donors, we found the global prevalence of HPgV‐1 to be 3·1% (95% CI, 2·4–4·1). The pooled prevalences of HPgV‐1 were 1·7% (95% CI, 1·1–2·6) in North America, 9·1% (95% CI, 6·4–12·7) in South America, 2·3% (95% CI, 2%, 2·8) in Europe and 2·4% (95% CI, 1·4–4) in Asia. Subgroup analyses based on age, gender or risk factors were not possible. Conclusion: Approximately 3 in 100 blood donations worldwide are positive for HPgV‐1 increasing the risk of infection from transfusion of their components to subsequent recipients. Further research on virus pathogenicity is required before recommending routine screening of HPgV‐1 for healthy volunteer blood donors. [ABSTRACT FROM AUTHOR]