Characteristics and antiviral treatment eligibility of patients diagnosed with hepatitis B at a teaching hospital in Ghana: Implications for prevention and management.

Hepatitis B virus (HBV) infection poses a considerable public health challenge in limited-resource settings especially in the sub-Saharan African region. Even though HBV infection is incurable, timely treatment is effective in preventing disease progression to liver cirrhosis or hepatocellular carcinoma. However, not all infected patients require treatment. The aim of the study was to determine the clinical, immunological, and virological profiles of treatment naïve patients with HBV infection, seen at the outpatient clinic of the Cape Coast Teaching Hospital. Additionally, the study sought to determine the antiviral treatment eligibility rate based on the 2015 guidelines of the World Health Organization (WHO) compared with the new 2024 guidelines. A hospital-based cross-sectional study involving total sampling of 220 treatment naïve HBV surface antigen positive clients was carried out. A structured questionnaire was used to collect data that were analyzed with STATA version 16. The median age at diagnosis was 34 years (IQR 26.0-41.5) with a male to female ratio of 1:1.5. A total of 138 participants (62.7%) were diagnosed with HBV infection following voluntary testing. There was a median delay of 8.5 months (IQR 3.0-22.5) between initial diagnosis and patients' presentation for medical care. In all, 24 patients (10.9%) had abnormal clinical examination findings, 172 patients (78.2%) had HBV DNA levels ≤ 2000 IU/ml whereas 8 (3.6%) were seropositive for the HBV envelope antigen. A few patients had concomitant human immunodeficiency virus (2.7%) and hepatitis C virus (1.4%) infections. Treatment eligibility rate based on the WHO 2015 guidelines was 6.4% (n = 14), however, with the updated 2024 guidelines, treatment eligibility was 42.3% (n = 93). Increasing the screening rate among the general population, early linkage to clinical care of screen positives and vaccination of screen negatives will help reduce HBV-related clinical conditions in resource-limited settings.

Transfusion-Transmissible Infections Among Blood Donors in a Regional Hospital in Ghana: A 6-Year Trend Analysis (2017-2022).

BACKGROUND: This study determined the trends of transfusion-transmissible infections (TTIs) among blood donors in a regional hospital in Ghana from 2017 to 2022. METHODS: A retrospective analysis was conducted on 6339 blood donor records. Data were analyzed using STATA version 17.0 at the 0.05 significance level. RESULTS: The prevalence of TTIs was 31.4% in 2017, 13.8% in 2018, 20.4% in 2019, 9.5% in 2020, 9.6% in 2021, and 11.7% in 2022. There were significant associations between hepatitis C virus (HCV), Syphilis, and sex (OR = 2.06; 95% CI [1.29-3.30]; P = .003) and (OR = 2.28; 95% CI [1.48-3.54]; P < .001), respectively. Blood donors aged 20-29 were more likely to be infected with hepatitis B virus (OR = 1.96; 95% CI [1.28-2.99]; P = .002). Blood donors aged 40-49 had higher odds of infection with HCV (OR = 3.36; 95% CI [2.02-5.57]; P < .001) and Syphilis (OR = 3.79; 95% CI [2.45-5.87]; P < .001). CONCLUSION: The study highlights the need to implement targeted prevention strategies for donors with a higher TTI prevalence.

Trends in transfusion-transmissible infections among blood donors in a Regional Hospital in Ghana: 2017 to 2022BackgroundDespite efforts to enhance the safety of the blood supply, transfusion-transmissible infections (TTIs) continue to pose a significant problem. This study determined the trends of TTIs among blood donors in a Regional Hospital in Ghana from 2017 to 2022.MethodsA retrospective analysis was conducted on the records of 6,339 blood donors to determine the presence of anti- human immunodeficiency virus 1/2 IgG/IgM, hepatitis B virus (HBV), anti-hepatitis C virus (HCV) IgG/IgM, and anti-Treponema pallidum IgG/IgM/IgA. Data were analyzed using STATA version 17.0. Both descriptive and inferential statistics were employed at a significance level of 0.05.ResultsOf the 6339 blood donors, 16.1% showed serological evidence of at least one TTI. The trend analysis showed that the prevalence rates of TTIs were 31.4% in 2017, 13.8% in 2018, 20.4% in 2019, decreased to 9.5% in 2020, 9.6% in 2021 and increased to 11.7% in 2022. TTIs were dominant among male blood donors compared to female blood donors. There was a significant association between HCV, Syphilis, and sex (aOR = 2.06; 95% CI [0.59-1.73]; P = .003) and (aOR = 2.28; 95% CI [0.15-0.69]; P < .001) respectively. Donors aged 20 to 29 were more likely to be infected with HBV (aOR = 1.96; 95%CI [1.28-2.99]; P = .002). Also, donors aged 40 to 49 years were more likely to be infected with HCV and Syphilis (aOR = 3.36; 95% CI [2.02-5.57]; P < .001) and (aOR = 3.79; 95% CI [2.45-5.87]; P < .001) respectively.ConclusionThe study identified a high overall prevalence of TTIs, highlighting the need to encourage female donor participation, raise awareness among young adults about safe practices, and implement targeted prevention strategies for males with a higher TTI prevalence.

Hepatitis B virus infection, infertility, and assisted reproduction. / ä¹™è‚ã€ä¸å­•ä¸è‚²ä¸Žè¾ åŠ©ç”Ÿæ®–.

BACKGROUND: Hepatitis B virus (HBV) is one of the most widespread viruses worldwide and a major cause of hepatitis, cirrhosis, and hepatocellular carcinoma. Previous studies have revealed the impacts of HBV infection on fertility. An increasing number of infertile couples with chronic hepatitis B (CHB) virus infection choose assisted reproductive technology (ART) to meet their fertility needs. Despite the high prevalence of HBV, the effects of HBV infection on assisted reproduction treatment remain limited and contradictory. OBJECTIVE: The aim of this study was to provide a comprehensive overview of the effect of HBV infection on fertility and discuss its effects on pregnancy outcomes, vertical transmission, pregnancy complications, and viral activity during ART treatment. METHODS: We conducted a literature search in PubMed for studies on HBV infection and ART published from 1996 to 2022. RESULTS: HBV infection negatively affected fertility in both males and females. Existing research shows that HBV infection may increase the risk of pregnancy complications in couples undergoing assisted reproduction treatment. The impact of HBV infection on the pregnancy outcomes of ART is still controversial. Current evidence does not support that ART increases the risk of vertical transmission of HBV, while relevant studies are limited. With the development of ART, the risk of HBV reactivation (HBVr) is increasing, especially due to the wide application of immunosuppressive therapy. CONCLUSIONS: Regular HBV infection screening and HBVr risk stratification and management are essential to prevent HBVr during ART. The determination of optimal strategy and timing of prophylactic anti-HBV therapy during ART still needs further investigation.

Patient perspective on the elimination mother-to-child transmission of HIV, syphilis, and hepatitis B in Bali, Indonesia: a qualitative study.

BACKGROUND: This study aimed to explore the facilitators and barriers to the elimination of human immunodeficiency virus (HIV), syphilis, and hepatitis B transmission based on the perspectives of mothers living with HIV, syphilis, and hepatitis B. METHODS: This study employed a descriptive, qualitative design. Semi-structured interviews were conducted with mothers living with HIV, syphilis, and/or hepatitis B virus. A total of 25 participants were included in the study. This study used a triangulation method conducted by members to enhance the validity and dependability of the findings. The study was conducted at referral hospitals and community health centers between September 2022 and February 2023. Data analysis utilized deductive content analysis and categorized themes based on a socio-ecological framework. RESULTS: The findings revealed facilitators and barriers across five levels of the socio-ecological framework and 21 subcategories. The findings included the following: (1) At the policy level, facilitators were mandatory testing programs, and barriers were separating testing services from antenatal care facilities. (2) At the community level, facilitators included the involvement of non-governmental organizations (NGOs) and cross-sector support. Barriers included challenges faced by non-residents and fear of stigma and discrimination. (3) At the healthcare system level, facilitators included tracking and follow-up by midwives, positive relationships with healthcare providers, and satisfaction with healthcare services. Barriers included prolonged waiting times, insufficient information from healthcare providers, and administrative limitations. (4) At the interpersonal level, facilitators included partner and family support, open communication, and absence of stigma. Barriers included the reluctance of sexual partners to undergo screening. (5) At the individual level, facilitators included the desire for a healthy baby, adequate knowledge, self-acceptance, and commitment to a healthy lifestyle; barriers included the lack of administrative discipline. CONCLUSION: Mothers living with HIV, syphilis, or hepatitis B require tailored healthcare approaches. Healthcare professionals must understand and meet the needs of mothers within a comprehensive care continuum. The findings of this study advocate for the development and implementation of integrated care models that are responsive to the specific challenges and preferences of affected mothers, aiming to improve health outcomes for both mothers and their children.

Hepatitis A, B and C prevalence among transgender women and travestis in five Brazilian capitals between 2019-2021.

OBJECTIVE: To estimate the prevalence and factors associated with hepatitis A, B, and C in transgender women and travestis's networks, in 5 regions of Brazil. METHODS: This cross-sectional study includedtransgender women and travestis in five Brazilian capitals (Campo Grande, Manaus, Porto Alegre, Salvador, and São Paulo), between December/2019 and July/2021. All samples were subjected to detection of serological markers of hepatitis virus A (HAV), B (HBV), and C (HCV) infections through rapid tests and chemiluminescent microparticle immunoassays. Positive samples in the screening tests were submitted to detect HBV DNA and HCV-RNA by real-time PCR and genotyped by Sanger sequencing. RESULTS: Analysis of 1,317 samples showed network prevalence rates of 69.1%, 25.1%, and 1.5% for HAV, HBV, and HCV exposure, respectively. A high susceptibility rate to HBV infection (35.7%) and low prevalence of vaccine response markers (40%) were also observed. Age greater than 26 years, self-declared black/brown skin color, having only primary education, history of incarceration, and use of a condom in the last sexual intercourse with a casual partner were associated with total anti-HAV. Exposure to HBV was associated with age greater than 26 years, self-declared black/brown, history of being a sex worker, and incarceration. Age > 37 years, history of sexual abuse, and frequent alcohol consumption were associated with hepatitis C infection. CONCLUSION: The highest prevalence of HAV in this population was found in the North and Northeast regions, and the prevalence found was higher than that in the general population, suggesting greater vulnerability. The prevalence of HCV infection in our study was similar to that observed in the general population.

Factors associated with prior testing for HIV, Syphilis, and Hepatitis B and C among transgender women and travestis in Brazil.

OBJECTIVE: To investigate the prior testing for HIV, syphilis, hepatitis B (HBV), and hepatitis C (HCV) among transgender women and travestis (TGW) in five Brazilian cities and identify factors associated with each of these previous tests. METHODS: This is a cross-sectional study with the recruitment of TGW through respondent-driven sampling (TransOdara Study). The investigated outcome variable was prior testing for HIV, syphilis, HBV, and HCV in the last 12 months. The association between sociodemographic and behavioral factors with the outcome was analyzed using a binomial logistic regression with mixed effects. Adjusted odds ratios (aOR) and 95% confidence intervals (CI95%) were estimated. RESULTS: The proportions of individuals with prior testing in the past year were as follows: 56.3% for HIV, 58.0% for syphilis, 42.1% for HBV, and 44.7% for HCV. Negative associations with prior testing were observed for individuals aged 35 years or older, whereas positive associations were found for those with high school education, those who experienced verbal or psychological violence in the last 12 months, and those who had commercial or casual partners in the last 6 months. CONCLUSION: There was low frequency of testing in the 12 months preceding the study for HIV, syphilis, HBV, and HCV compared to the guidelines established by the Ministry of Health. Expanding access to and engagement with healthcare and prevention services for TGW is an essential strategy in reducing the transmission chain of HIV and other sexually transmitted infections (STIs).

Prevalence and factors associated with transfusion-transmissible infections (HIV, HBV, HCV and Syphilis) among blood donors in Gabon: Systematic review and meta-analysis.

BACKGROUND: Transfusion-transmissible infections (TTIs) remain a major public health problem in countries with limited resources, particularly in Gabon. Complete information on the prevalence in Gabon of the main TTIs among blood donors is still lacking in the national context. The purpose of this systematic review and meta-analysis was to determine the prevalence and factors associated with TTIs among blood donors in Gabon. METHODS: This systematic review and meta-analysis was reported in accordance with the PRISMA 2020 guidelines. It was the result of data from several comprehensive studies published between 2014 and 2022, the purpose of which focused on the prevalence and factors associated with TTIs among blood donors in Gabon. The quality of the articles was assessed using the Joanna Briggs Institute critical appraisal checklist for studies reporting prevalence data. The overall prevalence of TTIs among blood donors was determined using the random effects model. Heterogeneity between studies was assessed using I2 statistics. Publication bias was assessed by visual inspection of the funnel plot and Egger's statistics. RESULTS: A total of 175,140 blood donors from the nine eligible studies were admitted to this study. The combined prevalence of HIV, HBV, HCV and syphilis obtained in the random effects model was 3.0%, 6.0%, 4.0% and 3.0%, respectively. Moreover, being a male blood donor and aged between 25 and 44 years was significantly associated with HBV infection and being a female blood donor and aged 35 years and over was significantly associated with HIV infection. Family or replacement blood donors had a high infection burden for all four TTIs of study. CONCLUSION: The overall prevalence of transfusion-transmissible infections remains high in the country's blood banks. Improving current prevention (selection criteria) and screening strategies may be necessary in a global approach.

Genetic variants of m6A modification genes are associated with survival of HBV-related hepatocellular carcinoma.

N6-methyladenosine (m6A) is a dynamic and reversible modification process involving in a series of important biological and pathophysiological processes, including the progression of cancers. Herein, we aimed to assess the relationships of genetic variants in m6A modification genes with the survival of hepatitis B virus -related hepatocellular carcinoma (HBV-HCC). We performed a two-stage survival analysis to investigate the associations of 4425 single nucleotide polymorphisms (SNPs) in 36 m6A modification genes with the overall survival (OS) of HBV-HCC patients. Then, the identified SNPs were further used to functionally annotate. We identified that METTL3 rs1263790 (A > G) and ADARB1 rs57884102 (C > T) were significantly associated with the HBV-HCC OS (hazard ratios [HR] = 0.68, 95% confidence interval [CI] = 0.52-0.89, p = 0.004; and HR = 1.70, 95% CI = 1.33-2.18, p < 0.001, respectively). Combined analysis revealed that patients carrying more risk genotypes of two variants had a progressively poorer OS. Moreover, the expression quantitative trait loci (eQTL) analysis indicated that rs1263790 G allele decreased mRNA expression levels of METTL3 in 483 cell-cultured fibroblasts samples. And we found the mRNA expression levels of METTL3 and ADARB1 in HCC tissues were higher than in normal tissues, and the higher METTL3 and the lower ADARB1 were associated with poorer HCC OS. Our results demonstrated that two novel genetic variants (METTL3 rs1263790 and ADARB1 rs57884102) may be potential prognostic markers for HBV-HCC, but these results need larger different ethnic cohorts and functional experiments to validate in the future.

Progress Toward the Elimination of Hepatitis B and Hepatitis C in the Country of Georgia, April 2015-April 2024.

Hepatitis B and hepatitis C are leading causes of cirrhosis and liver cancer and caused 1.3 million deaths worldwide in 2022. Hepatitis B is preventable with vaccination, and hepatitis C is curable with direct-acting antivirals. In 2015, in collaboration with CDC and other partners, Georgia, a country at the intersection of Europe and Asia, launched a hepatitis C elimination program to reduce the prevalence of chronic hepatitis C; at that time, the prevalence was 5.4%, more than five times the global average of 1.0%. In 2016, the World Health Assembly endorsed a goal for the elimination of viral hepatitis as a public health problem by 2030. In 2024, 89% of the Georgian adult population have received screening for hepatitis C, 83% of persons with current chronic HCV infection have received a diagnosis, and 86% of those with diagnosed hepatitis C have started treatment. During 2015-2023, vaccination coverage with the hepatitis B birth dose and with 3 doses of hepatitis B vaccine among infants exceeded 90% for most years. In 2021, the prevalence of hepatitis B surface antigen was 0.03% among children and adolescents aged 5-17 years and 2.7% among adults. Georgia has demonstrated substantial progress toward hepatitis B and hepatitis C elimination. Using lessons from the hepatitis C elimination program, scale-up of screening and treatment for hepatitis B among adults would prevent further viral hepatitis-associated morbidity and mortality in Georgia and would accelerate progress toward hepatitis B and hepatitis C elimination by 2030.

The spatial-temporal distribution of hepatitis B virus infection in China,2006-2018.

OBJECTIVES: Hepatitis B is a liver disease caused by Hepatitis B virus (HBV) infection and is highly prevalent in China. To better understand the epidemiological characteristics of hepatitis B in China and develop effective disease control strategies, we employed temporal and spatial statistical methods. METHODS: We obtained HBV incidence data from the Public Health Science Data Center of the Chinese Center for Disease Control and Prevention for the years 2006 to 2018. Using Geographic Information System (GIS) and SaTScan scanning technology, we conducted spatial autocorrelation analysis and spatiotemporal scan analysis to create a map and visualize the distribution of hepatitis B incidence. RESULTS: While hepatitis B incidence rebounded in 2011 and 2017, the overall incidence in China decreased.In the trend analysis by item, the incidence varies from high to low. The global spatial autocorrelation analysis revealed a clustered distribution, and the Moran index analysis of spatial autocorrelation within local regions identified five provinces as H-H clusters (hot spots), while one province was an L-L cluster (cold spot). Spatial scan analysis identified 11 significant spatial clusters. CONCLUSIONS: We found significant clustering in the spatial distribution of hepatitis B incidence and positive spatial correlation of hepatitis B incidence in China. We also identified high-risk times and regional clusters of hepatitis B incidence.

Evolution and diversity of the hepatitis B virus genome: Clinical implications.

Hepatitis B virus (HBV) infection remains a significant global health burden. The genetic variation of HBV is complex. HBV can be divided into nine genotypes, which show significant differences in geographical distribution, clinical manifestations, transmission routes and treatment response. In recent years, substantial progress has been made through various research methods in understanding the development, pathogenesis, and antiviral treatment response of clinical disease associated with HBV genetic variants. This progress provides important theoretical support for a deeper understanding of the natural history of HBV infection, virus detection, drug treatment, vaccine development, mother-to-child transmission, and surveillance management. This review summarizes the mechanisms of HBV diversity, discusses methods used to detect viral diversity in current studies, and the impact of viral genome variation during infection on the development of clinical disease.

Disparities in hepatitis B virus healthcare service access among marginalised poor populations: a mixed-method systematic review.

BACKGROUND: Marginalised poor populations, characterised by poverty and social exclusion, suffer disproportionately from hepatitis B virus (HBV) infections and encounter substantial disparities in access to healthcare. This has further exacerbated the global HBV burden and precluded progress towards HBV elimination. This mixed-method systematic review aimed to synthesise their utilisation and influencing factors in HBV healthcare services, including screening, vaccination, treatment, and linkage-to-care. METHODS: Eleven databases were searched from their inception to May 4, 2023. Quantitative and qualitative studies examining the factors influencing HBV healthcare access among marginalised poor populations were included. A meta-analysis was conducted to synthesise the pooled rates of HBV healthcare utilisation. The factors influencing utilisation were integrated and visualised using a health disparity research framework. RESULTS: Twenty-one studies were included involving 13,171 marginalised poor individuals: sex workers, rural migrant workers, irregular immigrants, homeless adults, and underprivileged individuals. Their utilisation of HBV healthcare ranged from 1.5% to 27.5%. Meta-analysis showed that the pooled rate of at least one dose of the HBV vaccine barely reached 37% (95% confidence interval: 0.26‒0.49). Fifty-one influencing factors were identified, with sociocultural factors (n = 19) being the most frequently reported, followed by behavioural (n = 14) and healthcare system factors (n = 11). Socio-cultural barriers included immigration status, prison history, illegal work, and HBV discrimination. Behavioural domain factors, including previous testing for sexually transmitted diseases, residential drug treatment, and problem-solving coping, facilitated HBV healthcare access, whereas hostility coping exerted negative influences. Healthcare system facilitators comprised HBV health literacy, beliefs, and physician recommendations, whereas barriers included service inaccessibility and insurance inadequacies. The biological and physical/built environments were the least studied domains, highlighting that geographical mobility, shelter capacity, and access to humanitarian health centres affect HBV healthcare for marginalised poor populations. CONCLUSIONS: Marginalised poor populations encounter substantial disparities in accessing HBV healthcare, highlighting the need for a synergistic management approach, including deploying health education initiatives to debunk HBV misperceptions, developing integrated HBV management systems for continuous tracking, conducting tailored community outreach programmes, and establishing a human rights-based policy framework to guarantee the unfettered access of marginalised poor populations to essential HBV services.

Causes of pre and post-donation deferrals among blood donors, at Kwale Satellite Blood Transfusion Center, Kwale County, Kenya, 2018-2022.

BACKGROUND: Both pre-donation and post-donation deferrals pose challenges to blood safety and availability. This study delved into the deferral rates before donations and their underlying reasons, as, transfusion transmissible infections (TTIs) leading to post-donation deferrals among potential blood donors at the Kwale Satellite Blood Transfusion Centre (KSBTC) in Kenya. METHODS: We performed a retrospective electronic record review of pre- and post-donation deferrals among blood donors at KSBTC, 2018-2022. The pre-donations deferral rate and reasons for deferral were analyzed. Accepted donations were analyzed to determine the prevalence of HIV, hepatitis B (HBV), hepatitis C (HCV), and syphilis. Descriptive statistics were calculated and both crude odds ratio (COR) and adjusted odds ratio (AOR), and their 95% confidence intervals (CI) were calculated. Variables with p < 0.05 were considered statistically significant. RESULTS: A review was conducted on 12,633 blood donation records. Among these, individuals 2,729/12,633 (21.60%) were deferred from donating with the primary reason being low hemoglobin levels, constituting 51.86% of deferrals. Around 773/9,904 (7.80%) of blood units, were discarded due to at least one TTI. Among these, HBV accounted for 4.73%, HIV for 2.01%, HCV for 1.21%, and Syphilis for 0.59% of cases. The adjusted odds ratio for male donors were, (aOR = 1.3, 95% CI 1.01-1.57), donors with none or primary education level (aOR = 1.4 95% CI 1.11-1.68), first-timer donors (aOR = 1.2, 95% CI 1.01-1.44), and static strategy for blood collection (aOR = 1.4, 95%CI 1.12-1.63) were independently potentially associated with testing positive for at least one TTI. CONCLUSION: The study indicates that TTIs continue to pose a risk to the safety of Kenya's bloodstock, with a notable prevalence of HBV infections. Male donors, individuals with limited education, first-time donors, and utilizing a fixed strategy for blood collection were identified as potential risk factors independently associated with TTIs.

HIV and hepatitis B virus co-infection in Mozambique: Policy review and health professionals' knowledge and practices.

BACKGROUND: Human Immunodeficiency Virus (HIV) and Hepatitis B Virus (HBV) co-infection is a public health problem affecting 2.7 million worldwide. In Mozambique, the prevalence of this co-infection is 9.1%, calling for specific policies on prevention, diagnosis and adequate management in health facilities caring for HIV patients. This study aimed to review the existing policies and to assess the knowledge and practices of health professionals about HIV/HBV co-infection. METHODS: A document and literature review to describe the existing policies and guidelines on HIV/HBV co-infection in Mozambique was performed. Key informants were contacted to clarify or add information. Health Professionals who care for HIV-positive patients in four health centers in Maputo City, the capital of Mozambique, responded to a questionnaire on knowledge and practices about this co-infection. Qualitative analysis was done to identify main themes using content analysis. Descriptive statistics of socio-demographic, knowledge and practice variables was presented using the SPSS Program version 20 and bivariate analysis was applied to describe the association between variables. RESULTS: Twenty-one policy documents were found, and five key informants were interviewed. Fifty-two participants answered the questionnaire. Only one policy document explicitly referred to HIV/HBV co-infection treatment. Most Health Professionals (96%) were aware of HIV/HBV co-infection. Although the only existing policy is on the treatment, few (33%) referenced antiretroviral formulations containing Tenofovir and Lamivudine. Only 29% of Health Professionals reported screening HIV patients for HBV and 21% practiced HIV/HBV co-infection counselling. No statistically significant differences were found when relating the socio-demographic variables with knowledge and practices. CONCLUSION: Policy documents relating to prevention, diagnosis and clinical management of HIV/HBV co-infection were rare or absent. Health Professionals had little knowledge about HIV/HBV co-infection. Defining adequate policies and training of Health Professionals may help increase awareness, increase counselling of patients for disease prevention, diagnosis and proper management of HIV/HBV co-infected patients.

Solamargine acts as an antiviral by interacting to MZF1 and targeting the core promoter of the hepatitis B virus gene.

BACKGROUND: Hepatitis B virus (HBV) infection is still a serious threat to global health and can lead to a variety of liver diseases, including acute and chronic hepatitis, liver cirrhosis, liver failure, hepatocellular carcinoma (HCC), and so on. At present, there are mainly two kinds of drugs for the treatment of hepatitis B at home and abroad: interferon (IFN) and nucleoside/nucleotide analogs (NAs). In recent years, natural compounds have been considered an important source for the development of new anti-HBV drugs due to their complex structure, diverse components, high efficiency, and low toxicity. Many studies have demonstrated that Solamargine has significant anticancer activity, but the antiviral effect is rarely studied. This study aimed to verify the anti-HBV effect of Solamargine and to explore the specific mechanism. METHOD: The relative expression of HBV pregenomic RNA (pgRNA) was detected by reverse transcription real-time fluorescence quantitative PCR (RT-qPCR). Northern blot and western blot were used to detect the relative expression of HBV pgRNA and target protein. PCR was used in the construction of HBV pg-promoter, ENII/BCP, and a series of gene deletion mutant fluorescent reporter vectors. The fluorescence relative expression of each mutant was detected by Renilla luciferase assay. RESULTS: By binding to MZF1 (Myeloid zinc finger protein 1, MZF1), Solamargine inhibits HBV core promoter activity, reduces pregenomic RNA level, and inhibits HBV, achieving antiviral effects.

S100A8/A9-activated IFNγ+ NK cells trigger ß-cell necroptosis in hepatitis B virus-associated liver cirrhosis.

BACKGROUND AND AIMS: Hepatitis B virus (HBV)-associated liver cirrhosis (LC), a common condition with high incidence and mortality rates, is often associated with diabetes mellitus (DM). However, the molecular mechanisms underlying impaired glucose regulation during HBV-associated LC remain unclear. METHODS: Data from 63 patients with LC and 62 patients with LC-associated DM were analysed. Co-culture of NK cells and islet ß cell lines were used to study the glucose regulation mechanism. A mouse model of LC was used to verify the effect of S100A8/A9 on the glucose regulation. RESULTS: Higher levels of interferon (IFN)-γ derived from natural killer (NK) cells and lower levels of insulin emerged in the peripheral blood of patients with both LC and DM compared with those from patients with LC only. IFN-γ derived from NK cells facilitated ß cell necroptosis and impaired insulin production. Furthermore, S100A8/A9 elevation in patients with both LC and DM was found to upregulate IFN-γ production in NK cells. Consistently, in the mouse model for LC, mice treated with carbon tetrachloride (CCL4) and S100A8/A9 exhibited increased blood glucose, impaired insulin production, increased IFN-γ, and increased ß cells necroptosis compared with those treated with CCL4. Mechanistically, S100A8/A9 activated the p38 MAPK pathway to increase IFN-γ production in NK cells. These effects were diminished after blocking RAGE. CONCLUSION: Together, the data indicate that IFN-γ produced by NK cells induces ß cell necroptosis via the S100A8/A9-RAGE-p38 MAPK axis in patients with LC and DM. Reduced levels of S100A8/A9, NK cells, and IFN-γ could be valuable for the treatment of LC with DM. Accumulation of S100A8/A9 in patients with LC may indicate the emergence of DM.