HEV Infection Research Articles

The burden of HEV-related acute liver failure in Bangladesh, China and India: a systematic review and meta-analysis

BackgroundHepatitis E can potentially progress to HEV-related acute liver failure (HEV-ALF). East and South Asia bear a substantial burden of HEV infection, with Bangladesh, China, and India facing the most severe threat in this region. Therefore, we conducted a systematic review and meta-analysis to evaluate the burden of HEV-ALF in these three high-risk countries.MethodsA systematic literature search was performed utilizing PubMed, the Cochrane Library, Medline, Embase, and Web of Science databases. Studies in English or Chinese that reported data on the burden of HEV-ALF in Bangladesh, China and India were included. Outcomes were pooled with meta-analysis utilizing R software. Estimates were calculated with random-effects models, and subgroup analysis and sensitivity analysis were conducted to address heterogeneity. Egger’s test and Begg’s test were performed to assess publication bias.ResultsA total of 20 eligible studies were included in this study. The pooled HEV-attributable proportion of viral-related acute liver failure was estimated to be 40.0% (95% CI: 0.28–0.52), 30.0% (95% CI: 0.18–0.44), and 61.0% (95% CI: 0.49–0.72) among non-pregnant individuals in India, China and Bangladesh, while in Indian pregnant females, it was 71.0% (95% CI: 0.62–0.79). The combined prevalence among non-pregnant HEV-infected participants was 28.0% (95% CI: 0.20–0.37) and 10.0% (95% CI: 0.01–0.28) in India and China, and it was 34.0% (95% CI: 0.27–0.42) in Indian pregnant females with HEV infection. The overall mortality of HEV-ALF was estimated to be 32.0% (95% CI: 0.23–0.42) and 64.0% (95% CI: 0.50–0.77) among the non-pregnant and the pregnant participants in India, and it was 23.0% (95% CI: 0.14–0.34) in Chinese non-pregnant participants.ConclusionsThe burden of HEV-ALF in Bangladesh, China, and India is non-negligible despite geographic and population heterogeneity. The prevention of HEV infection and early recognition of HEV-ALF are of great significance, especially in high-risk countries and populations.RegistrationPROSPERO registration ID is CRD42022382101.

Retracted: Automatic Detection and Classification of Epileptic Seizures in Patients with Liver Cirrhosis and Overlapping Hev Infection Based on Deep Multimodal Fusion Technology

Retracted: Automatic Detection and Classification of Epileptic Seizures in Patients with Liver Cirrhosis and Overlapping Hev Infection Based on Deep Multimodal Fusion Technology

Aggregated Hendra virus C-protein activates the NLRP3 inflammasome to induce inflammation

BackgroundHendra virus is an emerging virus with a geographically broad host reservoir. In humans, Hendra virus causes excessive inflammatory disease of the lung and nervous system. Our current understanding as to how Hendra virus or what factors induce inflammation is limited and as such, there are currently no therapeutic options available for patients who contract Hendra virus. Recent studies have identified viral aggregating proteins as drivers of inflammation in influenza A virus and SARS-CoV-2 virus. In this study, we sought to identify potential aggregating Hendra virus proteins as proof-of-concept that inflammasome activation may induce inflammation and contribute to disease pathology.ResultsHere, we have identified that a peptide analogue of Hendra virus C protein (termed HeVc) forms aggregates and activates the NLRP3 inflammasome through phagocytic uptake into cells in vitro. Treatment of cells with the specific NLRP3 inhibitor MCC950 ameliorated IL-1β secretion responses in vitro. Critically, in vivo intranasal inoculation of mice with aggregated HeVc peptide induced pulmonary inflammation, suggesting HeVc may drive immunopathology during infection. Importantly, mice treated with MCC950 demonstrated reduced IL-1β secretion into the bronchoalveolar space, highlighting the role of NLRP3 in host HeV infections and a potential therapeutic strategy to reduce disease pathology.ConclusionTaken together, these results identify Hendra virus C protein as a possible contributor to immunopathology during Hendra virus infections. Importantly, these studies highlight a potential role for NLRP3 in driving disease-associated inflammation, critically identifying a possible therapeutic strategy to alleviate disease-associated inflammation of infected patients through targeting of the NLRP3 inflammasome.

Hepatitis E; An Emerging Killer

Hepatitis E, caused by the Hepatitis E virus, is a highly contagious disease that poses a global health risk. It is often underestimated and misdiagnosed, despite affecting billions worldwide. HEV has emerged as a global pathogen, with cases reported in both developing and advanced countries. Outbreaks arise when individuals consume water that is contaminated in regions lacking adequate sanitation measures.Factors like population density and limited access to clean water contribute to these outbreaks. Hepatitis E prevalence varies by region, with Africa having the highest rates. Underdeveloped countries have emerging cases of HEV-1 and HEV-2, while developed countries face HEV-3 and HEV-4. In Pakistan, people with weak immune defense systemshave a maximum chance of being affected by HEV. However, the chances of HEV infection in immune people are minimal. The acceptance of contagious food, close contact with infected animals, and blood transfusions are also reasons for HEV transmission. Identification of infected individuals can be challenging due to asymptomatic cases. Treatment mainly involves supportive measures, although severe cases may require ribavirin. A natural recovery without treatment is also possible.

Correlation of hepatitis E and rat hepatitis E viruses urban wastewater monitoring and clinical cases

BackgroundWastewater pathogen monitoring is useful for surveillance of enteric pathogens. Information about the presence of Paslahepevirus balayani (HEV) and emergent Rocahepevirus ratti (RHEV) in untreated water and their correlation with clinical cases is scarce.AimTo longitudinally monitor HEV and RHEV in wastewater and to evaluate their possible correlation with human cases. MethodsThis study was carried out in the city of Cordoba (southern Spain) from March 2021 to March 2023. HEV and RHEV occurrence were evaluated by PCR in three sample types: i) sera from patients with acute hepatitis attended at the reference hospital, ii) liver and faeces from urban rodents, and iii) grab sewage samples collected weekly from the municipal wastewater treatment plant. ResultsWe analysed 106 untreated wastewater samples, 304 individuals with acute hepatitis, and 20 rodents. HEV and RHEV were detected in only one (0.9 %) and almost all samples (94.3 %) of wastewater samples, respectively. A total of 22 cases of acute HEV infection (7.2 %) and two cases of RHEV (0.7 %) were detected from all acute hepatitis cases observed. Only RHEV was found in rodents, with a positive frequency of 55 %. The presence of HEV in wastewater coincided with the detection of one case in which the same HEV genotype was isolated. A concentration of HEV clinical cases between June and July of 2022 was observed but not detected in water. Both RHEV clinical cases were detected in summer 2022, but no correlation was found with wastewater detection. ConclusionsOur study shows that there is no correlation between clinical cases and wastewater detection of HEV or RHEV.

Surveillance for rat hepatitis E in wastewater networks, Italy.

Rat hepevirus is an emerging zoonotic pathogen associated with human hepatitis and distantly related to the hepatitis E virus. By using broadly reactive primers for hepevirus, we detected viral RNA in 68/155 (43.9%) of sewage specimens collected from 14 wastewater treatment plants serving about half of the population of Abruzzo, Italy. On sequence analysis, the 68 strains showed 79.0%-91.6% identities to reference sequences of rodent and human origin, segregating in different genetic groups with a clear geographic/wastewater treatment plant (WWTP)-related pattern.IMPORTANCEHepatitis E virus (HEV) infection constitutes a significant health problem worldwide. In recent years, in addition to the zoonotic HEV3 and HEV4, emerging highly divergent hepevirus of rat origin (rat HEV [RHEV]) has been associated with human acute and chronic hepatitis. As environmental surveillance can be a complementary tool to explore emerging viruses of human and rodent origin, we investigated the epidemiology and the genetic variability of RHEV targeting 14 wastewater treatment plants in an Italian geographic area considered a hot spot for HEV infection in humans. Our results revealed that RHEV is a significant component of the wastewater microbiota with viral RNA detected in 43.9% of the specimens tested, adding further evidence to the need to investigate more in depth the real burden of RHEV infections in humans.

Frequency, Clinical Presentation, and Outcome of Acute-on-Chronic Liver Failure among Decompensated Cirrhosis of Liver Patients in a Tertiary Care Hospital

Background: Acute-on-chronic liver failure (ACLF) is characterised by the presence of organ failure in patients with decompensated cirrhosis and is associated with high short-term mortality. Different international entities have taken initiatives to define the condition in different times but recommendations and definitions from The European Association for the Study of the Liver- Chronic Liver Failure (EASL-CLIF) Consortium Acute-on-Chronic Liver Failure in Cirrhosis (CANONIC) study are most comprehensive and widely accepted till date. Only limited data are available on the prevalence, clinical characteristics, and short-term outcomes of ACLF in Bangladesh. It would be very useful for clinicians to identify patients with ACLF early and initiate focused therapy including referral to transplant centers if these data are available. Objective: To evaluate frequency, clinical presentation, and outcome of acute-on-chronic liver failure among decompensated cirrhosis of liver patients. Materials and Methods: This prospective observational study was carried out at the Department of Gastrointestinal, Hepatobiliary and Pancreatic Disorders (GHPD), BIRDEM General Hospital, Shahbagh, Dhaka, Bangladesh from July, 2019 to September, 2021. Total 175 patients with decompensated cirrhosis of liver were screened, out of which 22 patients were dropped out due to various reasons. Purposive type of non-probability sampling technique was used. Formal ethical clearance was taken from the Institutional Review Board and ethical measures were ensured in concordance with the Declaration of Helsinki. An informed written consent was taken from all participants. Diagnosis of decompensated cirrhosis was based on clinical, biochemical, radiological and endoscopic findings. Laboratory data sent within 24 hours were collected. Oxygen saturation was measured using fingertip pulse oximeter. Investigations for ACLF triggers were done as necessary which included but not limited to urine routine and microscopic examination, urine culture, blood culture, and Anti HEV IgM. Patients’ prognosis and survivability were observed by follow up phone call at 30 days. All data were recorded in a separate case record form and finally, it was analyzed by SPSS 23. Results: Out of 153 patients, 49 patients (32%) had ACLF: grade 1 ACLF in 26 (17%), grade 2 in 18 (11.8%), and grade 3 in 5 (3.3%) patients. Patients had an average age of 59.54±11.55 years with no significant difference between ACLF and no ACLF groups. Most patients in both groups had others (NAFLD, autoimmune hepatitis, secondary biliary cirrhosis, idiopathic) as the main underlying cause of cirrhosis. Bacterial infection, GI bleeding, HEV infection, reactivation of HBV were the precipitating events in 81.6% of patients with ACLF, with bacterial infection being the most common trigger (63.3%). Overall, 44.9% ACLF patients died within 30 days of admission. Older age, male sex, hepatic encephalopathy, GI bleeding, presence of any trigger and higher Child-Turcotte-Pugh (CTP) score were associated with increased risk of death in ACLF. Conclusion: Follow up of 153 patients with decompensated cirrhosis of liver revealed that 1 in 3 patients had ACLF and 44% of them would die in 30 days. Bacterial infection and GI bleeding were the most common triggers of ACLF. Early identification and intervention with multidisciplinary approach and referral to transplant centers are likely to improve survival outcomes in this population. Bangladesh Crit Care J September 2023; 11 (2): 113-120

Clinical performance of a new multiplex assay for the detection of HIV-1, HIV-2, HCV, HBV, and HEV in blood donations in Catalonia (Spain).

Commercial multiplex nucleic acid tests (NATs) for HIV-1/HIV-2/HCV/HBV are widely used in developed countries to screen blood donations. HEV NAT screening has been implemented in some blood banks but is tested with a different assay. This study describes the clinical sensitivity and specificity of the Procleix® UltrioPlex E (UPxE) assay on the automated Procleix Panther® system for the simultaneous detection of HIV-1/HIV-2/HCV/HBV/HEV. To evaluate routine performance, 10,138 donations were tested in parallel with UPxE (in ID-NAT) and current assays (Procleix Ultrio Elite [UE] assay in ID-NAT and Procleix HEV assay in pool of 16). To assess clinical sensitivity, archived donations positive for HCV, HIV-1, HBV, HEV, or occult HBV infection (OBI) were tested (n = 104-186). Five donations were initially reactive (IR) with UPxE; none of them were reactive with current assays. Two of the three samples IR for HIV-1/HIV-2/HCV/HBV were confirmed positive for HBV (HBV NAT and/or anti-HBV core positive) and classified as OBI. The two samples IR for HEV were confirmed positive (Procleix HEV assay in ID-NAT and in-house RT-PCR HEV assay). One sample IR for HIV-1/HIV-2/HCV/HBV with UPxE and another with UE were not confirmed. UPxE showed a specificity of 99.99% for HIV-1/HIV-2/HCV/HBV and 100% for HEV. Comparable sensitivities were observed for HIV-1, HCV, HBV, OBI, and HEV samples tested in the UPxE, UE, and Procleix HEV assays. UPxE may provide an efficient solution for the simultaneous detection of HIV-1, HIV-2, HCV, HBV, and HEV in blood donations in a single test.

Cost-effectiveness analysis of hepatitis E vaccination strategies among patients with chronic hepatitis B in China.

This study aimed to evaluate the cost-effectiveness of hepatitis E vaccination strategies in the chronic hepatitis B (CHB) patients. Based on the societal perspective, cost-effectiveness of three hepatitis E vaccination strategies: vaccination without screening, screening-based vaccination, and no vaccination among CHB patients was evaluated using a decision tree-Markov model, and incremental cost-effectiveness ratios (ICERs) were calculated. Values for treatment costs and health utilities were estimated from a prior investigation on disease burden, and values for transition probabilities and vaccination-related costs were obtained from previous studies and government agencies. Sensitivity analyses were performed for assessing model uncertainties. It was estimated that CHB patients superinfected with HEV incurred significantly longer disease course, higher economic burden, and more health loss compared to those with HEV infection alone (all P < 0.05). The ICERs of vaccination without screening and screening-based vaccination compared to no vaccination were 41,843.01 yuan/QALY and 29,147.32 yuan/QALY, respectively, both lower than China's per-capita GDP in 2018. The screening-based vaccination reduced the cost and gained more QALYs than vaccination without screening. One-way sensitivity analyses revealed that vaccine price, vaccine protection rate, and decay rate of vaccine protection had the greatest impact on the cost-effectiveness analysis. Probabilistic sensitivity analyses confirmed the base-case results, and if the willingness-to-pay value reached per-capita GDP, the probability that screening-based vaccination would be cost-effective was approaching 100%. The disease burden in CHB patients superinfected with HEV is relatively heavy in China, and the screening-based hepatitis E vaccination strategy for CHB patients is the most cost-effective option. This article is protected by copyright. All rights reserved.

Butchering activity is the main risk factor for hepatitis E virus (Paslahepevirus balayani) infection in southwestern Nigeria: a prospective cohort study.

Paslahepevirus balayani (Hepatitis E virus; HEV) is an emerging virus that poses as a public health threat. The virus is now reported to be the leading cause of acute viral hepatitis, with a unique impact on African settings. Our aim was to evaluate the prevalence and risk factors for HEV infection in three cohorts (animal handlers, villagers, and students). A prospective cross-sectional study was carried out on a total of 752 subjects from southwestern Nigeria. In all individuals, anti-HEV IgG and anti-HEV IgM antibodies were evaluated by using ELISA (confirming positive results via immunoblotting), and serum viral RNA was evaluated by using two RT-PCR assays. The overall seroprevalence of HEV IgG and HEV IgM was 14.9% (95% CI: 12.5-17.6%) and 1.3% (95% CI: 0.7-2.5%), respectively. We observed the highest seroprevalence among animal contact individuals, with butchers being the population with the highest HEV IgG seroprevalence (31.1%). Similarly, HEV IgM was higher in the animal contact group (2.2%) than in the non-animal contact cohort (0%). Viral RNA was not detected in any of the samples. Butchering was significantly associated with higher HEV prevalence. Although all efforts to prevent HEV in Africa have focused on the chlorination of water, our study suggests that most new infections could currently be linked to animal manipulation. Therefore, education and guidelines must be provided in southwest Nigeria to ensure that animal handling and processing methods are safe.

Seroepidemiology of Hepatitis E virus among the voluntary blood donors in the coastal region of Karnataka, India

Background: Hepatitis E is a fecal orally transmitted disease and an emerging transfusion transmissible infection with potential transfusion safety implications. Hepatitis E Virus screening among blood donors is not routinely done despite the fact that it is endemic in India. As there are very few reports and evidence, the justification for mandating HEV screening among blood donors is still only marginally convincing. Therefore, the present study was carried out to determine the incidence and prevalence of HEV infection among blood donors in Coastal Karnataka, India. Methods: This cross-sectional study was conducted in a tertiary care hospital in Udupi district of Karnataka, India. A total of 1939 blood donors were randomly selected between June 2020 to June 2022 to participate in the study, where anti-HEV IgM antibody screening was performed using HEV IgM ELISA test kit (DiaPro, Italy). Further, a randomly selected 588 and 1620 pooled donor samples were screened for anti-HEV IgG antibodies and HEV RNA, respectively. Results: The overall prevalence of HEV IgM antibodies among study population is found to be 1.39%, with a statistically significant difference between males and females (n=20, 1.18% vs. n=7, 3.07 %; p=0.027). The prevalence of HEV IgG antibodies was 11.39%. Exposure to agriculture, animal husbandry, and poor hand hygiene were significant risk factors for HEV IgG reactivity. Conclusions: Given the high prevalence of HEV viral markers in the study population, routine screening of blood donors for risk factors and implementation of serologic testing in endemic areas may be considered.

Genotype 4 HEV infection triggers the initiation and development of acute pancreatitis

The role of HEV infection in AP remains unclear. 1000 patients with AP and 1000 HCs were enrolled, and pancreatitis was evaluated in HEV-infected rhesus macaques. The positive rates of anti-HEV IgG, IgM, and HEV RNA in the AP patients were significantly higher than HCs. With the increase in the severity of AP, the percentage of HEV infection increased. AP patients were divided into AP- and AP + AHE groups. The percentage of severe AP in the AP + AHE group was significantly higher than in the AP- group. HEV infection was one of the main independent risk factors and had high predictive power for AP outcomes. A high level of HEV titer would prolong the recovery time and increase the risk of recurrent AP. Moreover, AP + AHE patients receiving conservative treatment showed a better prognosis. Furthermore, HEV can replicate in the pancreas of rhesus macaques. The pancreatic islet structure was damaged, the tissue was loose after 272 dpi, and a large amount of hyperemia appeared after 770 dpi. HEV infection also caused a large number of inflammatory cells in the pancreas. The pancreas and liver had a comparable viral load. HEV infection affects AP's occurrence, development, and prognosis.

Paslahepevirus balayani (Hepatitis E Virus) in Italian Nonungulate Wildlife: Molecular Detection and Characterization of an Isolate from a Crested Porcupine (Hystrix cristata).

Paslahepevirus balayani (hepatitis E virus [HEV]) is the causative agent of hepatitis E, a worldwide zoonosis involving a wide range of hosts among domestic and wild animals. This species is characterized by a great genomic heterogeneity and includes eight genotypes, HEV-1 to HEV-8. The HEV-3 genotype is one of the most common types circulating in Italy in humans and Suidae. Although domestic and wild Sus scrofa and deer (Cervidae) are recognized as the main reservoirs of HEV, several other wild species are potential carriers. A total of 228 liver samples were collected from nonungulate wild animals, found dead, in the framework of the regional passive surveillance program in Umbria and Marche regions (central Italy) during 2018-20. These were tested using real-time reverse-transcriptase PCR (RT-PCR) for detection of RNA of HEV-1 to HEV-4 and confirmed by nested RT-PCR assay. One of the 11 samples collected from crested porcupines (Hystrix cristata) tested positive for the presence of HEV RNA; all other samples were negative. Sequence analysis based on the full-length genome revealed that this isolate, 49434/UM/2018 (accession no. OL658617), belongs to the HEV-3e subtype. These findings suggest a potential role of crested porcupines as a carrier of HEV infection.

Seroepidemiology of Hepatitis E virus among the voluntary blood donors in the coastal region of Karnataka, India

Background: Hepatitis E is a fecal orally transmitted disease and an emerging transfusion transmissible infection with potential transfusion safety implications. Hepatitis E Virus screening among blood donors is not routinely done despite the fact that it is endemic in India. As there are very few reports and evidence, the justification for mandating HEV screening among blood donors is still only marginally convincing. Therefore, the present study was carried out to determine the incidence and prevalence of HEV infection among blood donors in Coastal Karnataka, India. Methods: This cross-sectional study was conducted in a tertiary care hospital in Udupi district of Karnataka, India. A total of 1939 blood donors were randomly selected between June 2020 to June 2022 to participate in the study, where anti-HEV IgM antibody screening was performed using HEV IgM ELISA test kit (DiaPro, Italy). Further, a randomly selected 588 and 1620 pooled donor samples were screened for anti-HEV IgG antibodies and HEV RNA, respectively. Results: The overall prevalence of HEV IgM antibodies among study population is found to be 1.39%, with a statistically significant difference between males and females (n=20, 1.18% vs. n=7, 3.07 %; p=0.027). The prevalence of HEV IgG antibodies was 11.39%. Exposure to agriculture, animal husbandry, and poor hand hygiene were significant risk factors for HEV IgG reactivity. Conclusions: Given the high prevalence of HEV viral markers in the study population, routine screening of blood donors for risk factors and implementation of serologic testing in endemic areas may be considered.

Seroprevalence of hepatitis E viral infection among apparently healthy personnels and patients with certain neurological disorders in Alexandria University Hospitals

IntroductionHepatitis E virus (HEV) is one of the leading causes of acute viral hepatitis. There are thought to be 20 million infections per year in poorer nations with inadequate sanitation. In Egypt, awareness about the possible hazards linked to HEV infection is limited due to low socioeconomic and educational levels. Only a small number of sequences have been characterized, making HEV study in Egypt constrained. Numerous factors may have contributed to this neglect. Various extra-hepatic symptoms of HEV infection include neurological problems are recognized. Many European nations have implemented regular HEV monitoring, or targeted screening of blood provided by patients at greater risk to stop the spread of HEV by transfusion.AimAssess the prevalence of HEV infection in asymptomatic blood donors. Increasing awareness about HEV testing in patients with some unexplained neurological disorders.MethodsCross-sectional study involving 550 patients: 500 apparently healthy blood donors and 50 patients with some neurological disorders. All subjects were tested for serological markers (IgG and IgM) for HEV using ELISA technique in addition to HEV RNA PCR testing for seropositive patients.ResultsFive hundred asymptomatic blood donors (370 males and 130 females), ages ranging from 20 to 50 years (median 33), 22.6% of them tested positive for HEV (IgG and IgM) of which 2 subjects only had positive HEV RNA PCR testing. In the second group 50 patients (26 males and 24 females) with various unexplained neurological disorders. Liver functions were within normal or showed only a mild increase. Forty-four percent of the patients had positive serology for HEV, with 6 patients testing positive for HEV RNA on PCR.ConclusionNo need for mass screening for HEV serology among blood donors. HEV infection needs to be considered in patients with unexplained neurological disorders even if the liver functions are not markedly elevated.

Evidence of a Link between Hepatitis E Virus Exposure and Glomerulonephritis Development.

GN patients (n = 43) and matched healthy subjects (n = 36) enrolled in Assiut University hospitals were included in this study. Blood samples were screened for hepatotropic pathogens. Tests for HEV markers such as HEV RNA and anti-HEV antibodies (IgM and IgG) were performed. Laboratory parameters were compared in HEV-seropositive and HEV-seronegative GN patients. Anti-HEV IgG was detected in 26 (60.5%) out of 43 GN patients. HEV seroprevalence was significantly higher in GN than in healthy controls, suggesting that HEV exposure is a risk factor for GN development. None of the GN patients nor the healthy subjects were positive for anti-HEV IgM or HEV RNA. There was no significant difference between seropositive and seronegative GN patients in terms of age, gender, albumin, kidney function profiles, or liver transaminases. However, anti-HEV IgG positive GN patients had higher bilirubin levels than anti-HEV IgG negative GN patients. HEV-seropositive GN patients had a significantly elevated AST level compared to HEV-seropositive healthy subjects. exposure to HEV infection could be complicated by the development of GN.

Quantification of host proteomic responses to genotype 4 hepatitis E virus replication facilitated by pregnancy serum

BackgroundHepatitis 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.MethodsIn 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.ResultsA 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.ConclusionsThe 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.

Hepatitis-E-induced cholestasis in a child: a case report.

An 8-year-old male child presented to a Pediatrics emergency with fever and features of acute cholestasis. On abdominal examination, there was non-tender hepatomegaly. The rest of the systemic examinations were normal. Ultrasonography findings were suggestive of acute hepatitis. The liver biopsy report showed hepatic cholestasis and hepatitis. The serological test for hepatitis E IgM was positive. The child was managed symptomatically. Although cholestasis is uncommon in children with HEV infection, it should be considered for non-improving clinical status in children with hepatitis. Also, patients with jaundice and Hepatitis E should be followed up by treating physicians until resolution occurs. To the authors' knowledge, this is the first case report from Nepal describing cholestasis in a child due to HEV infection.

Frequency, Clinical Presentation, and Outcome of Acute-on-chronic Liver Failure among Decompensated Cirrhosis of Liver Patients in a Tertiary Care Hospital

Background: Acute-on-chronic liver failure (ACLF) is characterised by the presence of organ failure in patients with decompensated cirrhosis and is associated with high short-term mortality. Different international entities have taken initiatives to define the condition in different times but recommendations and definitions from The European Association for the Study of the Liver- Chronic Liver Failure (EASL-CLIF) Consortium Acute-on-Chronic Liver Failure in Cirrhosis (CANONIC) study are most comprehensive and widely accepted till date. Only limited data are available on the prevalence, clinical characteristics, and short-term outcomes of ACLF in Bangladesh. It would be very useful for clinicians to identify patients with ACLF early and initiate focused therapy including referral to transplant centers if these data are available. Objective: To evaluate frequency, clinical presentation, and outcome of acute-on-chronic liver failure among decompensated cirrhosis of liver patients. Methods: This prospective observational study was carried out at the Department of Gastrointestinal, Hepatobiliary and Pancreatic Disorders (GHPD), BIRDEM General Hospital, Shahbagh, Dhaka, Bangladesh from July, 2019 to September, 2021. Total 175 patients with decompensated cirrhosis of liver were screened, out of which 22 patients dropped out due to various reasons. Purposive type of non-probability sampling technique was used. Formal ethical clearance was taken from the IRB and ethical measures were ensured in concordance with the Declaration of Helsinki. An informed written consent was taken from all participants. Diagnosis of decompensated cirrhosis was based on clinical, biochemical, radiological and endoscopic findings. Laboratory data sent within 24 hours were collected. Oxygen saturation was measured using fingertip pulse oximeter. Investigations for ACLF triggers were done as necessary which included but not limited to urine routine and microscopic examination, urine culture, blood culture, and Anti HEV IgM. Patients’ prognosis and survivability were observed by follow up phone call at 30 days. All data were recorded in a separate case record form and finally, it was analyzed by SPSS 23. Results: Out of 153 patients, 49 patients (32%) had ACLF: grade 1 ACLF in 26 (17%), grade 2 in 18 (11.8%), and grade 3 in 5 (3.3%) patients. Patients had an average age of 59.54±11.55 years with no significant difference between ACLF and no ACLF groups. Most patients in both groups had others (NAFLD, autoimmune hepatitis, secondary biliary cirrhosis, none) as the main underlying cause of cirrhosis. Bacterial infection, GI bleeding, HEV infection, reactivation of HBV were the precipitating events in 81.6% of patients with ACLF, with bacterial infection being the most common trigger (63.3%). Overall, 44.9% ACLF patients died within 30 days of admission. Older age, male sex, hepatic encephalopathy, GI bleeding, presence of any trigger and higher CTP score were associated with increased risk of death in ACLF. Conclusion: Follow up of 153 patients with decompensated cirrhosis of liver revealed that 1 in 3 patients had ACLF and 44% of them would die in 30 days. Bacterial infection and GI bleeding were the most common triggers of ACLF. Early identification and intervention with multidisciplinary approach and referral to transplant centers are likely to improve survival outcomes in this population. J Medicine 2023; Vol. 34, No. 2(1) Supplement: 221-222

Deciphering the role of soluble ORF2 protein in virus-host interaction in HEV infection.

Deciphering the role of soluble ORF2 protein in virus-host interaction in HEV infection.