Barriers and facilitators to viral hepatitis testing in Uzbekistan: scoping qualitative study among key stakeholders, healthcare workers, and the general population.

INTRODUCTION: In the World Health Organization European Region, an estimated 14 million people live with a chronic hepatitis B virus infection (HBV), and 12 million are affected by a hepatitis C virus infection (HCV). Uzbekistan bears a major burden of HBV and has one of the highest HCV prevalence in the region. Following a presidential decree in May 2022, significant funds were allocated to the viral hepatitis (VH) elimination program in Uzbekistan. The program expands VH testing to reach 500,000 people annually during 2022-2025 as part of the VH elimination strategy that includes the provision of free testing and affordable treatment. Exploring the existing barriers and facilitators to VH testing is pivotal for informing these interventions. METHODS: This study uses a cross-sectional qualitative design to identify and explore the barriers and facilitators to VH testing among the general population in Uzbekistan. We collected data during October-November 2022 through semi-structured interviews with 12 key informants (KIs) and 7 focus group discussions with two target populations: the general population and healthcare workers (HCW) in Tashkent, Uzbekistan. RESULTS: Following the capability-opportunity-motivation-behavior model (COM-B model) as a framework for the analysis, we identified major capability barriers to VH testing primarily linked to low health literacy and limited knowledge about VH types, symptoms, transmission, testing and treatment. Physical opportunity barriers included the time and financial costs associated with testing, diagnostics, and treatment. Sociocultural opportunity barriers involved anticipated negative reactions and stigmatization, particularly affecting women. Motivational barriers included a reluctance to be tested when asymptomatic and a general fear of receiving positive test results. The involvement of healthcare workers in promoting VH awareness and motivating the general population emerged as a facilitator. CONCLUSIONS: A multi-pronged approach is recommended to achieve VH testing goals among the general population, focusing on raising awareness and health literacy and creating an enabling environment that ensures easy accessibility and minimizing VH testing-associated costs.

Seroprevalence and molecular characterization of viral hepatitis and HIV co-infection in the Central African Republic.

BACKGROUND: The Central African Republic (CAR) is one of the countries with the highest prevalence of viral hepatitis infection in the world. Coinfection with HIV increases the morbidity and mortality beyond that of mono-infection with either hepatitis or HIV. The present study describes the geographic distribution of viral hepatitis infections and molecular characterization of these viruses in the CAR. METHODOLOGY: Out of 12,599 persons enrolled during the fourth Multiple Indicator Cluster Survey of 2010 in the CAR, 10,621 Dried Blood Spot (DBS) samples were obtained and stored at -20°C. Of these DBS, 4,317 samples were randomly selected to represent all regions of the CAR. Serological tests for hepatitis B, D, and C viruses were performed using the ELISA technique. Molecular characterization was performed to identify strains. RESULTS: Of the 4,317 samples included, 53.2% were from men and 46.8% from women. The HBsAg prevalence among participants was 12.9% and that HBc-Ab was 19.7%. The overall prevalence of HCV was 0.6%. Co-infection of HIV/HBV was 1.1% and that of HBV/HDV was 16.6%. A total of 77 HBV, 6 HIV, and 6 HDV strains were successfully sequenced, with 72 HBV (93.5%) strains belonging to genotype E and 5 (6.5%) strains belonging to genotype D. The 6 HDV strains all belonged to clade 1, while 4 recombinants subtype were identified among the 6 strains of HIV. CONCLUSION: Our study found a high prevalence of HBV, HBV/HDV and HBV/HIV co-infection, but a low prevalence of HCV. CAR remains an area of high HBV endemicity. This study's data and analyses would be useful for establishing an integrated viral hepatitis and HIV surveillance program in the CAR.

Current perspectives of viral hepatitis.

Viral hepatitis represents a major danger to public health, and is a globally leading cause of death. The five liver-specific viruses: Hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus, and hepatitis E virus, each have their own unique epidemiology, structural biology, transmission, endemic patterns, risk of liver complications, and response to antiviral therapies. There remain few options for treatment, in spite of the increasing prevalence of viral-hepatitis-caused liver disease. Furthermore, chronic viral hepatitis is a leading worldwide cause of both liver-related morbidity and mortality, even though effective treatments are available that could reduce or prevent most patients' complications. In 2016, the World Health Organization released its plan to eliminate viral hepatitis as a public health threat by the year 2030, along with a discussion of current gaps and prospects for both regional and global eradication of viral hepatitis. Today, treatment is sufficiently able to prevent the disease from reaching advanced phases. However, future therapies must be extremely safe, and should ideally limit the period of treatment necessary. A better understanding of pathogenesis will prove beneficial in the development of potential treatment strategies targeting infections by viral hepatitis. This review aims to summarize the current state of knowledge on each type of viral hepatitis, together with major innovations.

A Longitudinal Analysis of Mortality Related to Chronic Viral Hepatitis and Hepatocellular Carcinoma in the United States.

(1) Background: Hepatocellular carcinoma (HCC) contributes to the significant burden of cancer mortality in the United States (US). Despite highly efficacious antivirals, chronic viral hepatitis (CVH) remains an important cause of HCC. With advancements in therapeutic modalities, along with the aging of the population, we aimed to assess the contribution of CVH in HCC-related mortality in the US between 1999-2020. (2) Methods: We queried all deaths related to CVH and HCC in the multiple-causes-of-death files from the CDC Wide-ranging Online Data for Epidemiologic Research (WONDER) database between 1999-2020. Using the direct method of standardization, we adjusted all mortality information for age and compared the age-adjusted mortality rates (AAMRs) across demographic populations and by percentile rankings of social vulnerability. Temporal shifts in mortality were quantified using log-linear regression models. (3) Results: A total of 35,030 deaths were identified between 1999-2020. The overall crude mortality increased from 0.27 in 1999 to 8.32 in 2016, followed by a slight reduction to 7.04 in 2020. The cumulative AAMR during the study period was 4.43 (95% CI, 4.39-4.48). Males (AAMR 7.70) had higher mortality rates compared to females (AAMR 1.44). Mortality was higher among Hispanic populations (AAMR 6.72) compared to non-Hispanic populations (AAMR 4.18). Higher mortality was observed in US counties categorized as the most socially vulnerable (AAMR 5.20) compared to counties that are the least socially vulnerable (AAMR 2.53), with social vulnerability accounting for 2.67 excess deaths per 1,000,000 person-years. (4) Conclusions: Our epidemiological analysis revealed an overall increase in CVH-related HCC mortality between 1999-2008, followed by a stagnation period until 2020. CVH-related HCC mortality disproportionately affected males, Hispanic populations, and Black/African American populations, Western US regions, and socially vulnerable counties. These insights can help aid in the development of strategies to target vulnerable patients, focus on preventive efforts, and allocate resources to decrease HCC-related mortality.

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.

Comparative analysis of perioperative and long-term outcomes of patients with hepatocellular carcinoma: Nonalcoholic fatty liver disease versus viral hepatitis.

BACKGROUND: Despite the accumulating evidence regarding the oncological differences between nonalcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC) and viral infection-related HCC, the short- and long-term outcomes of surgical resection of NAFLD-related HCC remain unclear. While some reports indicate improved postoperative survival in NAFLD-related HCC, other studies suggest higher postoperative complications in these patients. METHODS: Patients with NAFLD and those with hepatitis viral infection who underwent hepatectomy for HCC at our department were retrospectively analyzed. The clinical, surgical, pathological, and survival outcomes were compared between the two groups. RESULTS: Among the 1047 consecutive patients who underwent hepatectomy for HCC, 57 had NAFLD-related HCC (NAFLD group), and 727 had virus-related HCC (VH group). The body mass index and serum glycated hemoglobin levels were significantly higher in the NAFLD group than in the VH group. There were no significant differences in operative time and bleeding amount. Moreover, the morbidity and the length of postoperative hospital stays were similar across both groups. The pathological results showed that the tumor size was significantly larger in the NAFLD group than in the VH group. No significant differences between the groups in overall or recurrence-free survival were found. In a subgroup analysis with matched tumor diameters, patients in the NAFLD group had a better prognosis after hepatectomy than those in the VH group. CONCLUSION: Surgical outcomes after hepatectomy were comparable between the groups. Subgroup analysis reveals early detection and surgical intervention in NAFLD-HCC may improve prognosis.

Viral hepatitis-induced acute liver failure.

Viral hepatitis-induced acute liver failure (ALF) is a preventable cause for liver-related mortality worldwide. Viruses are the most common cause for ALF in developing nations in contrast to the west, where acetaminophen is largely responsible. Viruses may be hepatotropic or affect the liver secondary to a systemic infection. In tropical countries, infections such as leptospirosis, scrub typhus and malaria can mimic the symptoms of ALF. Differentiating these ALF mimics is crucial because they require etiology-specific therapy. Treatment of viral hepatitis-induced ALF is two-pronged and directed towards providing supportive care to prevent organ failures and antiviral drugs for some viruses. Liver transplantation (LT) is an effective modality for patients deteriorating despite adequate supportive care. Early referral and correct identification of patients who require a transplant are important. Liver support devices and plasma exchange have evolved into "bridging modalities" for LT. Preventive strategies such as hand hygiene, use of clean and potable water and inclusion of vaccines against viral hepatitis in the national program are simple yet very effective methods focusing on the preventive aspect of this disease.

A comparative study of uncomplicated acute non-A-E hepatitis with acute viral hepatitis and acute onset autoimmune hepatitis.

BACKGROUND AND AIMS: Non-A-E hepatitis (NAEH) not leading to acute liver failure (ALF) is poorly documented. The objective was to compare clinical and laboratory features of uncomplicated acute NAEH with acute viral (AVH) and autoimmune hepatitis (AIH) and histopathology in NAEH and AIH. METHODS: Cases of hepatocellular jaundice were included. These were grouped into AVH, AIH and NAEH based on clinical, laboratory and, when indicated, liver biopsy findings. NAEH and AIH were followed up at three months. RESULTS: Of 336 patients with hepatocellular jaundice, 15 (5%) were NAEH, 25 (7%) acute AIH and 45 (14%) AVH. Among NAEH patients, seven (46.7%) were males with a mean age of presentation 39 years. Jaundice (100%) was the most common presentation of NAEH. Peak bilirubin was 10.7 mg/dL. Peak aspartate and alanine aminotransferase (AST, ALT) were 512 and 670 U/L. Five (33.3%) patients had positive anti-nuclear antibody and one had anti-smooth muscle antibody. Mean immunoglobulin G (IgG) levels were 1829. On liver biopsy, all had ballooning degeneration, four (26.7%) had mild and three (20%) moderate interface hepatitis, four (26.7%) mild lymphoplasmacytic infiltrate, one (6.7%) rosette formation, bridging necrosis in none and stage 1 fibrosis in one. Comparing NAEH with AIH, AIH showed significantly older age at presentation, female predisposition, past history of jaundice, lower ALT, more autoantibodies, higher IgG, higher grade interface hepatitis, lymphoplasmacytic infiltrate, rosette formation and higher bilirubin, AST at three months. NAEH and viral hepatitis had similar features. CONCLUSION: Etiology of NAEH is unlikely to be autoimmune and is probably viral, unidentified as yet. Uncomplicated NAEH likely has self-limiting course even without specific treatment.

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.

Global burden and trends of acute viral hepatitis among children and adolescents from 1990 to 2019: a systematic analysis of the Global Burden of Disease Study 2019.

BACKGROUND: Children and adolescents are at high risk for acute viral hepatitis (AVH), but epidemiological research focusing on them has been overshadowed by adult chronic B and C. We provide global, regional, and national estimates of the AVH burden and their trends on people under 20 years from 1990 to 2019. METHODS: AVH data from Global Burden of Disease Study (GBD) 2019 was used. Incidence and disability-adjusted life years (DALYs) were calculated, analyzing trends with estimated annual percentage change (EAPC) and Joinpoint regression. RESULTS: In 2019, 156.39 (95% uncertainty interval 145.20-167.16) million new cases of AVH were reported among children and adolescents globally, resulting in 1.98 (1.50-2.55) million DALYs. Incidence rates for young children (< 5 years), older children (5-9 years), and adolescents (10-19 years) were 12,799 (11,068-14,513), 5,108 (4829-5411), and 3020 (2724-3339) per 100,000 population, respectively. The global AVH incidence displayed a linear decline with an EAPC of - 0.66 (- 0.68 to - 0.65). High-incidence regions included sub-Saharan Africa, Oceania, South Asia, and Central Asia, with India, Pakistan, and Nigeria facing the greatest burden. Leading causes were hepatitis A, followed by hepatitis E, B, and C. All hepatitis types showed declining trends, especially hepatitis B. Furthermore, we confirmed the association between the AVH incidence and the socioeconomics, vaccine, and advanced liver diseases. CONCLUSION: Effective vaccines and treatments for hepatitis B and C offer eradication opportunities. Broadening diagnostic and therapeutic coverage is vital to address disparities in service provision for children and adolescents.

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.

A cross-sectional survey of viral hepatitis education within pharmacy curricula in the United States.

BACKGROUND: The Viral Hepatitis National Strategic Plan emphasizes the importance of a collaborative provider workforce trained in hepatitis prevention and treatment to eliminate viral hepatitis in the United States by 2030. Although pharmacists play a key role in hepatitis management, literature lacks documentation of the amount of viral hepatitis education provided to pharmacy students. AIM: Our study goal was to describe viral hepatitis education provided at United States pharmacy schools. METHOD: In this cross-sectional survey study, investigators developed a 19-item Qualtrics questionnaire, sent questionnaire links to curricula content experts at 140 accredited pharmacy colleges/schools in May-June 2022, and allotted 28 days for completion. Questions assessed the viral hepatitis instruction provided to students and hepatitis instructors' training/experience. We used descriptive statistics for analysis. RESULTS: Forty-eight pharmacy institutions across 29 states/territories responded; 44% had 50-99 students/class, and 58% used lecture and discussion to provide required hepatitis education. Students received more lecture (average = 3.4 h, range 0.8-1.6 h/hepatitis topic) than discussion (average = 1.7 h, range 0.6-0.9 h/hepatitis topic), with the most time spent on hepatitis C, followed by hepatitis B virus. Respondents reported 93% of their instructors had post-graduate training/certifications and 67% worked in clinical settings with hepatitis patients. CONCLUSION: Survey results demonstrate variability in hepatitis education across United States pharmacy curricula. Data offer stakeholders in hepatitis elimination efforts knowledge about the viral hepatitis education provided to Doctor of Pharmacy students. Future directions include consideration of implementation of minimum hepatitis education standards to further support work toward national hepatitis elimination.

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.

[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.