Hepatitis E virus ORF3 protein hijacking thioredoxin domain-containing protein 5 (TXNDC5) for its stability to promote viral particle release.

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide, responsible for approximately 20 million infections annually. Among the three open reading frames (ORFs) of the HEV genome, the ORF3 protein is involved in virus release. However, the host proteins involved in HEV release need to be clarified. In this study, a host protein, thioredoxin domain-containing protein 5 (TXNDC5), interacted with the non-palmitoylated ORF3 protein by co-immunoprecipitation analysis. We determined that the overexpression or knockdown of TXNDC5 positively regulated HEV release from the host cells. The 17FCL19 mutation of the ORF3 protein lost the ability to interact with TXNDC5. The releasing amounts of HEV with the ORF3 mutation (FCL17-19SSP) were decreased compared with wild-type HEV. The overexpression of TXNDC5 can stabilize and increase ORF3 protein amounts, but not the TXNDC5 mutant with amino acids 1-88 deletion. Meanwhile, we determined that the function of TXNDC5 on the stabilization of ORF3 protein is independent of the Trx-like domains. Knockdown of TXNDC5 could lead to the degradation of ORF3 protein by the endoplasmic reticulum (ER)-associated protein degradation-proteasome system. However, the ORF3 protein cannot be degraded in the knockout-TXNDC5 stable cells, suggesting that it may hijack other proteins for its stabilization. Subsequently, we found that the other members of protein disulfide isomerase (PDI), including PDIA1, PDIA3, PDIA4, and PDIA6, can increase ORF3 protein amounts, and PDIA3 and PDIA6 interact with ORF3 protein. Collectively, our study suggested that HEV ORF3 protein can utilize TXNDC5 for its stability in ER to facilitate viral release. IMPORTANCE: Hepatitis E virus (HEV) infection is the leading cause of acute viral hepatitis worldwide. After the synthesis and modification in the cells, the mature ORF3 protein is essential for HEV release. However, the host protein involved in this process has yet to be determined. Here, we reported a novel host protein, thioredoxin domain-containing protein 5 (TXNDC5), as a chaperone, contributing to HEV release by facilitating ORF3 protein stability in the endoplasmic reticulum through interacting with non-palmitoylated ORF3 protein. However, we also found that in the knockout-TXNDC5 stable cell lines, the HEV ORF3 protein may hijack other proteins for its stabilization. For the first time, our study demonstrated the involvement of TXNDC5 in viral particle release. These findings provide some new insights into the process of the HEV life cycle, the interaction between HEV and host factors, and a new direction for antiviral design.

Immunological pathways in viral hepatitis-induced hepato-cellular carcinoma. / è‚ç‚Žç— æ¯’æ„ŸæŸ“å¯¼è‡´è‚ç»†èƒžç™Œå‘ç”Ÿçš„å ç–«æœºåˆ¶ç ”ç©¶è¿›å±•.

Hepatocellular carcinoma (HCC) is a serious neoplastic disease with increasing incidence and mortality, accounting for 90% of all liver cancers. Hepatitis viruses are the major causative agents in the development of HCC. Hepatitis A virus (HAV) primarily causes acute infections, which is associated with HCC to a certain extent, as shown by clinicopathological studies. Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections lead to persistent liver inflammation and cirrhosis, disrupt multiple pathways associated with cellular apoptosis and proliferation, and are the most common viral precursors of HCC. Mutations in the HBV X protein (HBx) gene are closely associated with the incidence of HCC, while the expression of HCV core proteins contributes to hepatocellular lipid accumulation, thereby promoting tumorigenesis. In the clinical setting, hepatitis D virus (HDV) frequently co-infects with HBV, increasing the risk of chronic hepatitis. Hepatitis E virus (HEV) usually causes acute infections. However, chronic infections of HEV have been increasing recently, particularly in immuno-compromised patients and organ transplant recipients, which may increase the risk of progression to cirrhosis and the occurrence of HCC. Early detection, effective intervention and vaccination against these viruses may significantly reduce the incidence of liver cancer, while mechanistic insights into the interplay between hepatitis viruses and HCC may facilitate the development of more effective intervention strategies. This article provides a comprehensive overview of hepatitis viruses and reviews recent advances in research on aberrant hepatic immune responses and the pathogenesis of HCC due to viral infection.

Spatial analysis of food and water-borne diseases in Ahmedabad, India: Implications for urban public health planning.

Spatial analysis of infectious diseases can play an important role in mapping the spread of diseases and can support policy making at local level. Moreover, identification of disease clusters based on local geography and landscape forms the basis for disease control and prevention. Therefore, this study aimed to examine the spatial-temporal variations, hotspot areas, and potential risk factors of infectious diseases (including Viral Hepatitis, Typhoid and Diarrhea) in Ahmedabad city of India. We used Moran's I and Local Indicators of Spatial Association (LISA) mapping to detect spatial clustering of diseases. Spatial and temporal regression analysis was used to identify the association between disease incidence and spatial risk factors. The Moran's I statistics identified presence of positive spatial autocorrelation within the considered diseases, with Moran's I from 0.09 for typhoid to 0.21 for diarrhea (p < 0.001). This indicates a clustering of affected wards for each disease, suggesting that cases were not randomly distributed across the city. LISA mapping demonstrated the clustering of hotspots in central regions of the city, especially towards the east of the river Sabarmati, highlighting key geographical areas with elevated disease risk. The spatial clusters of infectious diseases were consistently associated with slum population density and illiteracy. Furthermore, temporal analysis suggested illiteracy rates could increase risk of viral hepatitis by 13 % (95 % Confidence Interval (CI): 1.01-1.26) and of diarrhea by 18 % (95 % CI: 1.07-1.31). Significant inverse association was also seen between viral hepatitis incidence and the distance of wards from rivers. Conclusively, the study highlight the impact of socio-economic gradients, such as slum population density (indicative of poverty) and illiteracy, on the localized transmission of water and foodborne infections. The evident social stratification between impoverished and affluent households emerges as a notable contributing factor and a potential source of differences in the dynamics of infectious diseases in Ahmedabad.

[Epstein-Barr virus-associated gastritis with perigastric lymphadenopathy accompanied by infectious mononucleosis:a case report].

A 28-year-old female patient with no particular medical history had a sore throat seven days before admission. Subsequently, she developed malaise, right abdominal pain, and a fever of 38°C and visited our hospital. A blood test revealed a mild inflammatory response and elevated liver enzymes, and she was admitted to the hospital for detailed examination and acute liver injury treatment. Various viral tests and autoantibody measurements revealed elevated Epstein-Barr virus (EBV) immunoglobulin M and negative EB nuclear antigen antibodies. Therefore, she was diagnosed with primary infectious mononucleosis-associated EB viral hepatitis. Abdominal computed tomography upon admission revealed swollen lymph nodes around the stomach;thus, esophagogastroduodenoscopy (EGD) was performed. A histopathological examination revealed severe lymphocytic infiltration, and EB encoding region in situ hybridization demonstrated that 10-20% of the lymphocytes were EBV-infected. Drip and rest treatment improved the patient's liver enzymes, and her symptoms resolved. Repeat EGD after two months revealed improved gastric erosions. Here, we report a case of EBV-associated gastritis that was discovered due to perigastric lymphadenopathy accompanied by infectious mononucleosis. This report includes a review of the literature because a few studies reported EBV-associated gastritis.

Responding to STI epidemics among young people: a characterization of the language employed in educational materials. / Enfrentamento de epidemias de ISTs em população jovem: caracterização da linguagem dos materiais educativos.

This article aims to characterize the language employed in educational and communications materials about STIs, HIV/AIDS and viral hepatitis produced by the Ministry of Health between 2010 and 2019, identifying elements related to health promotion and disease prevention. We conducted an exploratory descriptive study. The materials were selected by performing a systematic search of the Ministry of Health website focusing on the period 2010-2019. The materials were analyzed to determine the educational approaches adopted. The preventive, educational and personal development approaches were identified in 100% (201), 24.87% (50) and 7.96% (16) of the materials, respectively. The radical and popular education for health approaches were not observed. The almost exclusive focus on the preventive approach reveals that promoting changes in individual habits and behavior alone is not sufficient to combat and solve the problem of STIs, HIV/AIDS and viral hepatitis in Brazil.

O objetivo do artigo é caracterizar a linguagem utilizada nos materiais educativos e comunicacionais vinculados à temática das IST, do HIV/Aids e hepatites virais produzidos e veiculados pelo Ministério da Saúde no período de 2010 a 2019, identificando elementos de promoção à saúde e de prevenção de doenças. Metodologia descritiva exploratória para a caracterização da linguagem utilizada nos materiais educativos e comunicacionais sobre as IST, do HIV/Aids e hepatites virais. Para a seleção dos materiais educativos, adotou-se a estratégia de busca sistemática realizada no site do Ministério da Saúde do Brasil por um período de dez anos: de 2010 a 2019. Os materiais foram observados por meio dos enfoques educativos. O enfoque preventivo foi identificado em 100% dos materiais analisados (201). O enfoque educativo foi encontrado em 24,87% (50) dos materiais, e o enfoque de desenvolvimento pessoal foi encontrado em 7,96% (16). Os enfoques radical e da educação popular em saúde não foram observados. A atenção quase exclusiva ao enfoque preventivo revela que cuidados individuais isoladamente não são suficientes para combater e sanar o problema das IST, do HIV/Aids e das hepatites virais no Brasil.

Seroprevalence of hepatitis B, C, and D and associated factors in the semi-isolated Yanomami Amazonian indigenous community.

BACKGROUND: Viral hepatitis is a significant health concern among indigenous population in the Americas. In Brazil, reports find high endemicity of HBV and HDV infections has been reported in several indigenous groups. However, few studies have documented the prevalence of HBV, HCV and HDV in the Yanomami. In this study, the prevalence of hepatitis B, C, and D serological markers and potential risk factors were investigated to provide guidance for the development of strategies aimed at reducing viral transmission in the Yanomami indigenous villages. METHODS: This cross-sectional study was carried out in March 2015 and included 430 individuals from four Yanomami villages: Alapusi (n = 78), Castanha/Ahima (n = 126), Gasolina (n = 105), and Taibrapa (n = 121). A rapid test was used for detection of HBsAg and anti-HCV and chemiluminescent immunoassay for anti-HBs, anti-HBc, and anti-HDV antibodies. RESULTS: HBsAg, anti-HBc, and anti-HBs were detected in 8.8, 45.5, and 49.4% of the participants, respectively. The estimated HBV status: current infection 9.6% (38/395); resolved infection 43.3% (171/395); vaccine immunity 20.5% (81/395), and susceptible to HBV 26.6% (105/395). Gasolina presented the lowest prevalence of HBV infection (6.5%) and the highest prevalence of vaccine immunity (26.9%). Children < 15 years old were highly susceptible to infection, as 53.1% did not have antibodies to HBV, while more than 80% of individuals over 45 years of age had been exposed to HBV. The markers for HDV were founded among 12.5% (4/32) of the HBsAg carriers. Anti-HCV was identified in all villages, with the highest prevalence in Alapusi (5.1%). Possible risk factors such as the use of piercings, tattoos, and contact with prospectors showed no statistical difference between the groups. CONCLUSIONS: Viral hepatitis B and serological markers for HCV and HDV were found to be widely distributed among the Yanomami indigenous community, while the prevalence of vaccine immunity to HBV was low. This finding reinforces the importance of promoting systematized diagnostic and vaccination strategies in indigenous communities. Our data confirm that isolated and difficult-to-reach indigenous communities lack appropriate access to diagnosis, treatment, and vaccination.

Evidence for the elimination of viral hepatitis B and C in Egypt: Results of a nationwide survey in 2022.

INTRODUCTION: Viral hepatitis C (HCV) and B (HBV) were at the top of Egypt's most significant public health challenges, with an estimated 14.7% of its population having antibodies to HCV in 2008. Egypt issued an ambitious action plan in 2014 to eliminate viral hepatitis through strengthening infection control and improving patient care. In 2018, an extensive HCV mass screening campaign was conducted for the entire country's population with treating more than 4 million patients with antivirals. This study aimed to evaluate the current prevalence of viral hepatitis in Egypt after all these efforts. METHODS: A cross-sectional household cluster survey was conducted in all 27 Egyptian governorates to obtain a representative sample of Egypt's population. Subjects aged 1-70 years were interviewed using a standardised questionnaire that included demographics, viral hepatitis knowledge, previous infection and risk factors data. Laboratory testing was performed for all subjects for anti-HCV and HBsAg using chemiluminescence. Subjects positive for anti-HCV were further tested for HCV-RNA by RT-PCR. Prevalence rates were calculated by demographic groups and compared to the demographic health survey 2015 results. RESULTS: Of 20 881 subjects interviewed, 48.8% were males, 20.2% were children <15 years of age, and 53.7% were residents of rural areas. Of all subjects, 92 (0.4%) were HCV-infected, 1577 (7.6%) were anti-HCV positive and 177 (0.8%) were HBV-chronically infected, including one patient who had mixed HBV and HCV current infection. The prevalence of HCV-current and HBV chronic infections decreased by 93% and 20%, respectively, compared to 2015. CONCLUSIONS: Egypt achieved the elimination of the viral hepatitis goal. To maintain low rates of viral hepatitis, community health education, in addition to maintaining infection control and blood safety programs, is essential.

Prevention of Viral Hepatitis and HIV Infection among People Who Inject Drugs: A Systematic Review and Meta-Analysis.

This study aimed to explore the current evidence on preventing blood-borne virus infections among people who inject drugs (PWID). We conducted a comprehensive search across three databases (PubMed, Embase, Cochrane Library) for relevant articles published in English between 2014 and 2023. We followed the Preferred Reporting Items for Systematic Reviews and Meta Analysis (PRISMA) guidelines, assessed the quality of the paper using the revised Cochrane Risk of Bias Tool (ROB 2), and conducted a meta-analysis using RevMan 5.3. Completing the harm reduction program (HRP) participation and receiving all three vaccine doses resulted in a 28% reduction in the risk of HBV infection (OR: 0.72, 95% CI: 0.37-1.42). Various interventions increased the willingness of PWIDs to undergo HCV treatment (OR: 5.91, 95% CI: 2.46-14.24) and promoted treatment adherence (OR: 15.04, 95% CI: 2.80-80.61). Taking PrEP, participating in HRP, and modifying risky behaviors were associated with a 33% reduction in the risk of HIV infection (OR: 0.67, 95% CI: 0.61-0.74). Conducting referrals, providing counseling, and implementing antiretroviral therapy resulted in a 44% reduction in the risk of viral transmission (OR: 0.56, 95% CI: 0.47-0.66). Co-infection may potentially compromise effectiveness, so it is important to consider drug resistance.

Sleep patterns, genetic predisposition, and risk of chronic liver disease: A prospective study of 408,560 UK Biobank participants.

BACKGROUND: Little is known about the role that combined sleep behaviors play in the association with chronic liver disease (CLD) risk. METHODS: We included 408,560 participants initially free of CLD from the UK Biobank. A healthy sleep pattern was defined by early chronotype, sleep duration of 7-8 h/day, no insomnia, no snoring, and no excessive daytime sleepiness. Cox regression models were used to examine the association of healthy sleep pattern with incident CLD and their interaction with PNPLA3 genetic risk. RESULTS: During a median 12.5 years of follow-up, we documented 10,915 incident all-cause CLD cases, including 388 viral hepatitis, 4782 non-alcoholic fatty liver disease (NAFLD), 1356 cirrhosis, 973 alcoholic liver disease, and 725 liver cancer cases. Compared to participants with a healthy sleep score of 0-1, the hazard ratio (HR) (95 % confidence interval [CI]) for those with a sleep score of 5 was 0.54 (0.49, 0.60) for CLD, 0.52 (0.30, 0.90) for viral hepatitis, 0.47 (0.41, 0.55) for NAFLD, 0.57 (0.43, 0.75) for cirrhosis, 0.32 (0.23, 0.44) for alcoholic liver disease, and 0.53 (0.37, 0.77) for liver cancer. Healthy sleep pattern and PNPLA3 genetic risk exerted significant additive effects on CLD risk (relative excess risk due to the interaction: 0.05; attributable proportion due to the interaction: 13 %). LIMITATIONS: Measurement error was unavoidable for self-reported data on sleep behaviors. CONCLUSIONS: Our analyses provide evidence that healthy sleep pattern was inversely associated with the development of CLD, and participants with higher genetic risk were more likely to develop CLD when exposed to the unhealthy sleep pattern.

Clinical diagnosis of viral hepatitis: Current status and future strategies.

Viral hepatitis (VH) is a significant public health issue with tremendous potential to aggravate into chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Recent decade has witnessed remarkable uprising in the drug development and effective treatment of VH. An upsurge is seen in identification of antiviral therapies with low rates of viral resistance, the improvement of Hepatitis B Virus (HBV) vaccination and the development of direct-acting antivirals for Hepatitis C Virus (HCV). But unfortunately, the "2030 worldwide eradication" objective of World Health Organization (WHO) is still unmet. It can be largely attributed to the deficit faced by the healthcare system concerning screening and diagnosis. A timely, accurate and comprehensive screening; encompassing maximum population coverage is essential to combat this disease. However, advancements in VH diagnostics remain inadequate and with a marginal use in routine practice. This paper deliberates upon the lacunae in traditional and prevailing diagnostic methodology of viral hepatitis, especially their inadequacy in meeting the unique situations prevailing low- and middle-income countries (LMIC).

Prevalence of viral hepatitis (A, B, C, and E) infection and co-infection among hospitalized children in Cairo, Egypt.

Viral hepatitis is considered a public health issue facing the entire world. The World Health Organization encouraged all countries to work together to eliminate this fatal infection and achieve the 2030 agenda. The present study aimed to investigate the silent infection of viral hepatitis (A, B, C, and E) among hospitalized children in Cairo, Egypt, to control and avoid chronic infection early on. This cross-sectional study included 184 randomly selected hospitalized children from three different hospitals in Cairo, Egypt. They were children aged between a few months to 15 years to determine viral hepatitis infection and co-infection. Antibodies to hepatitis A virus (HAV IgM), hepatitis E virus (HEV IgM), hepatitis C virus (HCV Ab), and hepatitis B virus surface antigen (HBs Ag) were performed by ELISA. If the ELISA results were positive, the viral load was quantified by real-time polymerase chain reaction (RT-PCR). Other laboratory investigations included alanine aminotransferase, aspartate aminotransferase, albumin, and complete blood count. Only five children (2.71%) had HCV Ab positive with no other viral (A, B, and E) co-infections as determined by ELISA. Also, the RT-PCR detected HCV RNA in these ELISA positive children. The remaining children (179/184) were all negative for all hepatitis viruses' markers (HAV IgM, HEV IgM, HBs Ag, and HCV Ab). In conclusion, this study documented that, Cairo hospitals serving Egyptian children had a low prevalence of viral hepatitis (A, B, C, and E). More research with larger sample sizes from hospitals across Egypt is needed.

Viral Hepatitis Necessitating Liver Transplantation in Children.

Viral hepatitis accounts for a significant global disease burden and mortality, both in children and adults. There are significant differences in the viral etiology, epidemiology, and complications in children worldwide. Children of all ages may have devastating complications with a significant risk of mortality and long-term morbidity because of viral hepatitis. Liver transplantation is the only curative option for pediatric patients with end-stage liver disease, hepatocellular carcinoma, or acute liver failure because of viral hepatitis. The introduction of universal vaccination for hepatitis B across the world and hepatitis A in some countries had led to significant changes in the incidence of disease and the need for liver transplantation for the complications of viral hepatitis in children. The development of effective treatment with directly acting antiviral agents for hepatitis C has already transformed outcomes in adults and children and reduced the need for liver transplantation. Although newer therapy for hepatitis B is being evaluated in adults, current therapy for children is not curative, indicating the need for lifelong therapy and potential necessity for liver transplantation. The recent epidemic of acute hepatitis in children across the world has highlighted the importance of understanding the etiology of unusual causes for acute liver failure and the urgent need for liver transplantation.