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Cyclophilin (Cyp) inhibitors are of clinical interest in respect to their antiviral activities in the context of many viral infections including chronic hepatitis B and C. Cyps are a group of enzymes with peptidyl-prolyl isomerase activity (PPIase), known to be required for replication of diverse viruses including hepatitis B and C viruses (HBV and HCV). Amongst the Cyp family, the molecular mechanisms underlying the antiviral effects of CypA have been investigated in detail, but potential roles of other Cyps are less well studied in the context of viral hepatitis. Furthermore, most studies investigating the role of Cyps in viral hepatitis did not investigate the potential therapeutic effects of their inhibition in already-established infections but have rather been performed in the context of neo-infections. Here, we investigated the effects of genetically silencing Cyps on persistent HCV and HBV infections. We confirm antiviral effects of CypA and CypD knock down and demonstrate novel roles for CypG and CypH in HCV replication. We show, furthermore, that CypA silencing has a modest but reproducible impact on persistent HBV infections in cultured human hepatocytes. [ABSTRACT FROM AUTHOR]

Infection of hepatitis B (HBV) patients with hepatitis D (HDV) can cause the most severe form of viral hepatitis, leading to liver fibrosis, liver failure, and hepatocellular carcinoma. HDV relies on simultaneous infection with HBV for the generation of infectious viral particles. The innate immune response, which is weakly induced in HBV infection, becomes strongly activated upon HDV co-infection. In HBV/HDV co-infection, the immune system comprises a cell-intrinsic strong IFN response, which leads to the induction of interferon-stimulated genes (ISGs), the local activation of liver-resident innate immune cells, and additional immune cell recruitment from the blood. Efficient innate immune responses are indispensable for successful viral control and spontaneous viral clearance. Despite this fact, innate immune cell activation can also contribute to adaptive immune cell inhibition and accelerate liver damage in HBV/HDV infection. While the intrinsic IFN response in HDV-infected cells is well characterized, far less is known about the cellular innate immune cell compartment. In this review, we summarize HBV/HDV replication characteristics and decipher the role of innate immune cell subsets in the anti-viral response in HBV/HDV infections. We further review the impact of epigenetic and metabolic changes in infected heptatocytes on the innate anti-viral response. Moreover, we discuss the potential of exploiting the innate immune response for improving vaccination strategies and treatment options, which is also discussed in this review. [ABSTRACT FROM AUTHOR]

Infection of hepatitis B (HBV) patients with hepatitis D (HDV) can cause the most severe form of viral hepatitis, leading to liver fibrosis, liver failure, and hepatocellular carcinoma. HDV relies on simultaneous infection with HBV for the generation of infectious viral particles. The innate immune response, which is weakly induced in HBV infection, becomes strongly activated upon HDV co-infection. In HBV/HDV co-infection, the immune system comprises a cell-intrinsic strong IFN response, which leads to the induction of interferon-stimulated genes (ISGs), the local activation of liver-resident innate immune cells, and additional immune cell recruitment from the blood. Efficient innate immune responses are indispensable for successful viral control and spontaneous viral clearance. Despite this fact, innate immune cell activation can also contribute to adaptive immune cell inhibition and accelerate liver damage in HBV/HDV infection. While the intrinsic IFN response in HDV-infected cells is well characterized, far less is known about the cellular innate immune cell compartment. In this review, we summarize HBV/HDV replication characteristics and decipher the role of innate immune cell subsets in the anti-viral response in HBV/HDV infections. We further review the impact of epigenetic and metabolic changes in infected heptatocytes on the innate anti-viral response. Moreover, we discuss the potential of exploiting the innate immune response for improving vaccination strategies and treatment options, which is also discussed in this review.

Abstract Background Hepatitis B virus (HBV) infection is a silent epidemic among people who inject drugs (PWID). HBV testing and vaccination are important for PWID to reduce the risk of infection, prevent chronic complications and contribute to public health efforts in addressing HBV transmission. Our objective was to assess the self-reported lifetime uptake of HBV testing and vaccination among PWID in Iran and their associated factors. Method This cross-sectional study was conducted among 2,684 PWID in 11 large cities from July 2019 to March 2020 using a respondent-driven sampling method. Participants were interviewed face-to-face and asked about their lifetime experience of HBV testing and vaccination uptake as the outcome. Logistic regression models were built to identify related factors for reporting HBV testing and vaccination uptake. Results The prevalence of HBV testing and vaccination uptake among PWID was 14.2% (95% confidence intervals [CI]: 12.8–15.6) and 16.4% (95% CI: 14.9–18.1), respectively. Shared needles, syringes, or equipment in the past 12 months decreased the odds of reporting lifetime HBV testing uptake (Adjusted odds ratio [AOR]:0.46, 95% CI: 0.29–0.72). However, having an academic education (AOR: 1.89, 95% CI: 1.09–3.30) and lifetime experience of homelessness (AOR: 1.58, 95% CI: 1.21–2.06) increased the odds of reporting lifetime HBV vaccination uptake. Conclusion Our study highlighted the low prevalence of HBV testing and vaccination uptake among PWID in Iran. It is essential to understand and address the obstacles preventing PWID from getting tested and vaccinated for HBV. Addressing these barriers could significantly reduce the burden of HBV among this socio-economically marginalized population.

Background: Viral hepatitis reactivation occurs during various chemotherapy treatments. Patients with high serum titer levels of Hepatitis B virus (HBV) DNA before chemotherapy and those receiving intensive chemotherapy for hematological malignancies are particularly at risk. Aims and Objectives: This study aimed to determine the incidence, predictors, and clinical significance of HBV and hepatitis C virus reactivations during chemotherapy. Materials and Methods: This prospective observational study was conducted at a tertiary care center. Hepatitis B and C virus status was identified before the initiation of cancer treatment. Liver function was monitored in all patients before each cycle of chemotherapy. Patients with deranged liver function were subjected to repeated viral antigen tests and DNA/RNA titer levels. Results: A total of 110 patients were identified as having hepatitis virus reactivation out of 1190 patients. The sites of malignancy were breast, 39.1% (43 patients); colorectal, 11.8% (13 patients); upper gastrointestinal, 10% (11 patients); ovary, 9.1% (10 patients); hematological malignancies, 8.2% (9 patients); lung, 5.6% (6 patients); genitourinary, 4.5% (5 patients); head-and-neck, 4.5% (5 patients); biliary tract, 3.6% (4 patients); brain tumor, 1.8% (2 patients); and others, 1.8% (2 patients). Most of the patients with reactivation received 5-FU/Capecitabine-based chemotherapy 37.3%, (41 patients), taxane plus platinum (10.9%, 12 patients), taxane only (10%, 11 patients), trastuzumab (8.2%, 9 patients), platinum-based (6.4%, 7 patients), tyrosine kinase inhibitors (6.4%, 7 patients), monoclonal antibodies (MABs) (3.6%, 4 patients), anthracyclines (2.7%, 3 patients), immunomodulators (2.7%, 3 patients), and other agents (11.8%, 13 patients). Conclusion: We recommend that Hepatitis B and C virus Screening must me performed before chemotherapy and that non-reactive patients should be vaccinated.

Viruses are the most common congenital infections in humans and an important cause of foetal malformations, neonatal morbidity, and mortality. The effects of these infections, which are transmitted in utero (transplacentally), during childbirth or in the puerperium depend on the timing of the infections. These vary from miscarriages (usually with infections in very early pregnancy), congenital malformations (when the infections occur during organogenesis) and morbidity (with infections occurring late in pregnancy, during childbirth or after delivery). The most common of these viruses are cytomegalovirus, hepatitis, herpes simplex type-2, parvovirus B19, rubella, varicella zoster and zika viruses. There are currently very few efficacious antiviral agents licensed for use in pregnancy. For most of these infections, therefore, prevention is mainly by vaccination (where there is a vaccine). The administration of immunoglobulins to those exposed to the virus to offer passive immunity or appropriate measures to avoid being infected would be options to minimise the infections and their consequences. In this review, we discuss some of the congenital and perinatal infections and their consequences on both the mother and fetus and their management focusing mainly on prevention. [ABSTRACT FROM AUTHOR]

Primary hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China. Chronic hepatitis B and chronic hepatitis C are the main risk factors for HCC. Chronic infection promotes the release of immune co-inhibitory molecules such as programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1), which leads to immune tolerance and tumorigenesis. In recent years.comprehensive treatment based on immune checkpoint inhibitors (ICIs) has been widely used in the treatment of advanced tumors. However, there are few reports on the reactivation of hepatitis B virus (HBV) and hepatitis C virus (HCV) caused by ICIs. This article reviews the viral reactivation of PD-1/PD-L1 inhibitors in the treatment of hepatitis-related primary liver cancer. [ABSTRACT FROM AUTHOR]

Background: Viral hepatitis reactivation occurs during various chemotherapy treatments. Patients with high serum titer levels of Hepatitis B virus (HBV) DNA before chemotherapy and those receiving intensive chemotherapy for hematological malignancies are particularly at risk. Aims and Objectives: This study aimed to determine the incidence, predictors, and clinical significance of HBV and hepatitis C virus reactivations during chemotherapy. Materials and Methods: This prospective observational study was conducted at a tertiary care center. Hepatitis B and C virus status was identified before the initiation of cancer treatment. Liver function was monitored in all patients before each cycle of chemotherapy. Patients with deranged liver function were subjected to repeated viral antigen tests and DNA/RNA titer levels. Results: A total of 110 patients were identified as having hepatitis virus reactivation out of 1190 patients. The sites of malignancy were breast, 39.1% (43 patients); colorectal, 11.8% (13 patients); upper gastrointestinal, 10% (11 patients); ovary, 9.1% (10 patients); hematological malignancies, 8.2% (9 patients); lung, 5.6% (6 patients); genitourinary, 4.5% (5 patients); head-and-neck, 4.5% (5 patients); biliary tract, 3.6% (4 patients); brain tumor, 1.8% (2 patients); and others, 1.8% (2 patients). Most of the patients with reactivation received 5-FU/Capecitabine-based chemotherapy 37.3%, (41 patients), taxane plus platinum (10.9%, 12 patients), taxane only (10%, 11 patients), trastuzumab (8.2%, 9 patients), platinum-based (6.4%, 7 patients), tyrosine kinase inhibitors (6.4%, 7 patients), monoclonal antibodies (MABs) (3.6%, 4 patients), anthracyclines (2.7%, 3 patients), immunomodulators (2.7%, 3 patients), and other agents (11.8%, 13 patients). Conclusion: We recommend that Hepatitis B and C virus Screening must me performed before chemotherapy and that non-reactive patients should be vaccinated. [ABSTRACT FROM AUTHOR]

Izere Salomon,1,2 Sibomana Olivier,1 Ndayambaje Egide1 1Department of General Medicine and Surgery, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda; 2YP-CDN Rwanda (Rwanda Young Professional Chronic Disease Network), Kigali RwandaCorrespondence: Izere Salomon, Email izesajw73@gmail.comAbstract: The hepatitis C virus (HCV) poses a significant risk to global public health and is linked to life-threatening clinical outcomes. According to the WHO, there are an estimated 58 million people worldwide who have a chronic hepatitis C virus (HCV) infection; there are 1.5 million new cases and more than 350,000 fatalities from HCV-related illnesses each year. Even though there are numerous diagnostic techniques, the lack of funding, inadequate healthcare infrastructure, and low public awareness of the Hepatitis C virus can make diagnosis and treatment difficult to obtain throughout the continent. The frequency of hepatitis C virus infection is highest in African nations (1– 26%), raising serious concerns about the virus’s impact on public health. The world’s highest rate of Hepatitis C virus infection was found in Egypt, an African nation. Its nationwide hepatitis C elimination program stands out as a prime example of achievement, having screened, and treated over 60 million people, significantly reducing the disease’s incidence and prevalence. Other African nations facing similar difficulties might benefit greatly from Egypt’s methods, which provide valuable insights and flexible frameworks. This review aims to shed light on Egypt’s successes and challenges while offering strategic recommendations to African nations to quicken their progress in eliminating hepatitis C.Keywords: hepatitis C, elimination, Africa, Egypt, direct-acting antivirals, policy insights, hepatitis virus

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AbstractDomestic cat hepadnavirus (DCH), a relative hepatitis B virus (HBV) in human, has been recently identified in cats; however, association of DCH infection with lymphoma in cats is not investigated. To determine the association between DCH infection and feline lymphoma, seven hundred and seventeen cats included 131 cats with lymphoma (68 blood and 63 tumor samples) and 586 (526 blood and 60 lymph node samples) cats without lymphoma. DCH DNA was investigated in blood and formalin-fixed paraffin-embedded (FFPE) tissues by quantitative polymerase chain reaction (qPCR). The FFPE lymphoma tissues were immunohistochemically subtyped, and the localization of DCH in lymphoma sections was investigated using in situ hybridization (ISH). Feline retroviral infection was investigated in the DCH-positive cases. DCH DNA was detected in 16.18% (11/68) (p = 0.002; odds ratio [OR], 5.15; 95% confidence interval [CI], 2.33–11.36) of blood and 9.52% (6/63) (p = 0.028; OR, 13.68; 95% CI, 0.75–248.36) of neoplastic samples obtained from lymphoma cats, whereas only 3.61% (19/526) of blood obtained from non-lymphoma cats was positive for DCH detection. Within the DCH-positive lymphoma, in 3/6 cats, feline leukemia virus was co-detected, and in 6/6 were B-cell lymphoma (p > 0.9; OR, 1.93; 95% CI, 0.09–37.89) and were multicentric form (p = 0.008; OR, 1.327; 95% CI, 0.06–31.18). DCH was found in the CD79-positive pleomorphic cells. Cats with lymphoma were more likely to be positive for DCH than cats without lymphoma, and infection associated with lymphoma development needs further investigations.

Abstract According to a paper released and submitted to WHO by IARC scientists, there would be 905,700 new cases of liver cancer diagnosed globally in 2020, with 830,200 deaths expected as a direct result. Hepatitis B virus (HBV) hepatitis C virus (HCV), and hepatitis D virus (HDV) all play critical roles in the pathogenesis of hepatocellular carcinoma (HCC), despite the rising prevalence of HCC due to non-infectious causes. Liver cirrhosis and HCC are devastating consequences of HBV and HCV infections, which are widespread worldwide. Associated with a high mortality rate, these infections cause about 1.3 million deaths annually and are the primary cause of HCC globally. In addition to causing insertional mutations due to viral gene integration, epigenetic alterations and inducing chronic immunological dysfunction are all methods by which these viruses turn hepatocytes into cancerous ones. While expanding our knowledge of the illness, identifying these pathways also give possibilities for novel diagnostic and treatment methods. Nuclear factor erythroid 2-related factor 2 (NRF2) activation is gaining popularity as a treatment option for oxidative stress (OS), inflammation, and metabolic abnormalities. Numerous studies have shown that elevated Nrf2 expression is linked to HCC, providing more evidence that Nrf2 is a critical factor in HCC. This aberrant Nrf2 signaling drives cell proliferation, initiates angiogenesis and invasion, and imparts drug resistance. As a result, this master regulator may be a promising treatment target for HCC. In addition, the activation of Nrf2 is a common viral effect that contributes to the pathogenesis, development, and chronicity of virus infection. However, certain viruses suppress Nrf2 activity, which is helpful to the virus in maintaining cellular homeostasis. In this paper, we discussed the influence of Nrf2 deregulation on the viral life cycle and the pathogenesis associated with HBV and HCV. We summed up the mechanisms for the modulation of Nrf2 that are deregulated by these viruses. Moreover, we describe the molecular mechanism by which Nrf2 is modulated in liver cancer, liver cancer stem cells (LCSCs), and liver cancer caused by HBV and HCV. Video Abstract

Tol-like receptor (TLR) agonists, as potent adjuvants, have gained attention in vaccine research for their ability to enhance immune responses. This study focuses on their application in improving vaccine efficacy against key viral infections, including hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), SARS-CoV-2, influenza virus, and flaviviruses, including West Nile virus, dengue virus, and chikungunya virus. Vaccines are crucial in preventing microbial infections, including viruses, and adjuvants play a vital role in modulating immune responses. However, there are still many diseases for which effective vaccines are lacking or have limited immune response, posing significant threats to human health. The use of TLR agonists as adjuvants in viral vaccine formulations holds promise in improving vaccine effectiveness. By tailoring adjuvants to specific pathogens, such as HBV, HCV, HIV, SARS-CoV-2, influenza virus, and flavivirus, protective immunity against chronic and emerging infectious disease can be elicited. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is the most common cause of AVH in developing countries. HEV causes a self-limiting infection that is transmitted mainly through the consumption of contaminated food and water. Our study aimed to find out the seroprevalence of HEV infection. Detected both IgG & IgM antibodies from 100 asymptomatic antenatal women. ELISA (DIA PRO, Italy) was used to detect antibodies. Seropositivity was found in 9% of pregnant women, all might have been exposed to HEV infection previously. It could be unnoticed due to its self-limiting nature. IgG was 5% and IgM was 6%. Both IgM & IgG were detected in two pregnant women. Untreated water was used by the majority of women irrespective of their educational status. Though it is a self-limiting disease, it is necessary to screen for its antibody. Awareness about the modes of transmission & complications needs to be addressed in the community. It is necessary to do further studies for screening for HEV infection as there is a very limited number of studies published from South India.

Abstract Background Sanitation or sanitary workers are exposed to hepatitis virus infections because of filthy and dangerous working conditions. The current global systematic review and meta-analysis aimed to estimate the pooled sero-prevalence of occupationally associated hepatitis virus infection among them. Methods Preferred Reporting Items for Systematic Reviews (PRISMA), and Population, Intervention, Comparison, Outcome and study design (PICOS) were used for flow diagram, and review questions, respectively. Four databases other methods were used published articles from 2000 to 2022. Boolean logic (AND, OR), MeSH, and keywords were used: (Occupation *OR Job *OR Work) AND (Hepatitis A *OR Hepatitis B virus *OR Hepatitis C virus *OR Hepatitis E virus) AND (Solid waste collectors [SWCs] *OR Street sweepers [SS] *OR Sewage workers [STWs] *OR health care facilities cleaners [HCFCs)) AND (Countries). Stata MP/17 software was used for pooled prevalence analysis, meta-regression analysis (Hedges) at a 95% confidence interval (CI:95%). Results A total of 182 studies were identified studies, a total of 28 studies were included from twelve countries. Of these, from developed (n = 7) and developing countries (n = 5). From total a of 9049 sanitary workers, 5951(66%), 2280 (25%) and 818 (9%) were STWs, SWCs and SS, respectively. Globally, the pooled sero-prevalence of occupational-related hepatitis viral infections among sanitary workers was 38.06% (95% CI: 30–0.46.12). Of this, it was 42.96% (95% CI: 32.63–53.29) and 29.81% (95% CI: 17.59–42.02) for high-income and low-income countries, respectively. Meanwhile, by sub-analysis, the highest pooled sero-prevalence of hepatitis viral infections by categories, type and year were 47.66% (95%CI: 37.42–57.90), 48.45% (95% CI: 37.95–58.96), and 48.30% (95% CI: 36.13–60.47) for SWTs, HAV, and 2000 to 2010 year, respectively. Conclusion The consistency of the evidence suggests that sanitation workers, particularly sewage workers, are susceptible to occupationally acquired hepatitis regardless of their working conditions, necessitating significant changes to occupational health and safety regulations from governmental policies and other initiatives to reduce risks among sanitary workers.

Tol-like receptor (TLR) agonists, as potent adjuvants, have gained attention in vaccine research for their ability to enhance immune responses. This study focuses on their application in improving vaccine efficacy against key viral infections, including hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), SARS-CoV-2, influenza virus, and flaviviruses, including West Nile virus, dengue virus, and chikungunya virus. Vaccines are crucial in preventing microbial infections, including viruses, and adjuvants play a vital role in modulating immune responses. However, there are still many diseases for which effective vaccines are lacking or have limited immune response, posing significant threats to human health. The use of TLR agonists as adjuvants in viral vaccine formulations holds promise in improving vaccine effectiveness. By tailoring adjuvants to specific pathogens, such as HBV, HCV, HIV, SARS-CoV-2, influenza virus, and flavivirus, protective immunity against chronic and emerging infectious disease can be elicited.

According to a paper released and submitted to WHO by IARC scientists, there would be 905,700 new cases of liver cancer diagnosed globally in 2020, with 830,200 deaths expected as a direct result. Hepatitis B virus (HBV) hepatitis C virus (HCV), and hepatitis D virus (HDV) all play critical roles in the pathogenesis of hepatocellular carcinoma (HCC), despite the rising prevalence of HCC due to non-infectious causes. Liver cirrhosis and HCC are devastating consequences of HBV and HCV infections, which are widespread worldwide. Associated with a high mortality rate, these infections cause about 1.3 million deaths annually and are the primary cause of HCC globally. In addition to causing insertional mutations due to viral gene integration, epigenetic alterations and inducing chronic immunological dysfunction are all methods by which these viruses turn hepatocytes into cancerous ones. While expanding our knowledge of the illness, identifying these pathways also give possibilities for novel diagnostic and treatment methods. Nuclear factor erythroid 2-related factor 2 (NRF2) activation is gaining popularity as a treatment option for oxidative stress (OS), inflammation, and metabolic abnormalities. Numerous studies have shown that elevated Nrf2 expression is linked to HCC, providing more evidence that Nrf2 is a critical factor in HCC. This aberrant Nrf2 signaling drives cell proliferation, initiates angiogenesis and invasion, and imparts drug resistance. As a result, this master regulator may be a promising treatment target for HCC. In addition, the activation of Nrf2 is a common viral effect that contributes to the pathogenesis, development, and chronicity of virus infection. However, certain viruses suppress Nrf2 activity, which is helpful to the virus in maintaining cellular homeostasis. In this paper, we discussed the influence of Nrf2 deregulation on the viral life cycle and the pathogenesis associated with HBV and HCV. We summed up the mechanisms for the modulation of Nrf2 that are deregulated by these viruses. Moreover, we describe the molecular mechanism by which Nrf2 is modulated in liver cancer, liver cancer stem cells (LCSCs), and liver cancer caused by HBV and HCV. EW1h6cVcK6kCY2-xSiZ8DW Video Abstract [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) accounts for 80% of liver cancers, while 70%–80% of HCC developed from chronic liver disease with hepatitis B virus (HBV) and hepatitis C virus (HCV) infection as the major etiology. Immunotherapy is assuming a role as a pillar of HCC treatment, but the remarkable immune‐mediated responses are restricted in a minority of patients. Nucleic acid sensing (NAS) pathways are the central pathway of the innate immune system and antiviral immune response to viral infection, but their role in hepatitis virus‐related HCC remains undetermined. In our study, we performed a comprehensive bioinformatics analysis based on transcriptomic data of hepatitis virus related‐HCC tissues collected from multiple public data sets. Two subgroups were validated based on NAS‐related genes in virus‐related HCC patients, which were defined as NAS‐activated subgroups and NAS‐suppressed subgroups based on the expression of NAS‐related genes. On this basis, a NAS‐related risk score (NASRS) predictive model was established for risk stratification and prognosis prediction in the hepatitis virus‐related HCC (TCGA‐LIHC and ICGC cohorts). The predictive values of the NASRS in prognosis and immunotherapy were also verified in multiple data sets. A nomogram was also established to facilitate the clinical use of NASRS and demonstrate its effectiveness through different approaches. Additionally, six potential drugs binding to the core target of the NAS signature were predicted via molecular docking strategy. We subsequently evaluated the cytotoxic capabilities of potential drug in vitro and in vivo. Based on these results, we conclude that the NASRS model could serve as a power prognostic biomarker and predict responses to immunotherapy, which is meaningful in clinical decision‐making of hepatitis virus‐related HCC patients. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide that seriously threatens human health. Chronic infection of hepatitis virus B, C and D is closely related to the occurrence of HCC, about 80% HCC cases are caused by chronic viral hepatitis. Effective antiviral therapy can control liver inflammation, reduce the occurrence of HCC and reduce the recurrence of HCC after surgery treatment. In addition, during chemotherapy such as transarterial chemoembolization (TACE) or hepatic artery infusion chemotherapy (HAIC), targeted therapy and immunotherapy for HCC, antiviral therapy is also needed to prevent hepatitis virus reactivation. Therefore, antiviral therapy plays an important role in the prevention and treatment of HCC.

Objective: To analyze the main etiology and clinical features of cirrhosis in Shangri-La area of Yunnan and provide clinical data for prevention and control in such area. Methods: A total of 104 patients with cirrhosis admitted to the People’s Hospital of Diqing Tibetan Autonomous Prefecture from January 2019 to June 2021 were enrolled, and the etiological composition and main clinical characteristics of patients with cirrhosis in Shangri-La were analyzed retrospectively. Results: Patients with cirrhosis ranged from 33 to 86 years old, with an average age of (59.5±11.3) years old. The male to female ratio was 9 to 4. It revealed that 62.5% patients were Tibetans, 17.31% were Han Nationality, 15.38% were Yi Nationality. For Child-Pugh grading, 38 cases (37%) were with Child-PughA, 56 cases(54%) were with Child-pugh grade B, and 10 cases (9%) cases were with Child-pugh grade C. The main reason for the visit was abdominal distension. For etiological composition, alcoholic cirrhosis accounted for 38%. Hepatitis B cirrhosis accounted for 48%. Hepatitis C cirrhosis accounted for 1%. Mixed sclerosis accounted for 13%. The age of onset of cirrhosis caused by all causes is younger than those in other parts of the country, especially the age of onset of alcoholic cirrhosis is younger and the prognosis remission rate after standard treatment was only 1%. Conclusions: Viral hepatitis is still the main cause of cirrhosis in this region, followed by alcoholic liver disease and mixed cirrhosis. Attention should be paid to the harm of alcohol to human body education in this region, and strengthen the prevention and treatment of viral hepatitis.

Viral hepatitis remains one of the largest public health concerns worldwide. Especially in Central Africa, information on hepatitis virus infections has been limited, although the prevalence in this region has been reported to be higher than the global average. To reveal the current status of hepatitis B and C virus (HBV and HCV) infections and the genetic diversity of the viruses, we conducted longitudinal surveillance in Gabon. We detected 22 HBV and 9 HCV infections in 2047 patients with febrile illness. Genetic analyses of HBV identified subgenotype A1 for the first time in Gabon and an insertion generating a frameshift to create an X-preC/C fusion protein. We also revealed that most of the detected HCVs belonged to the "Gabon-specific" HCV subtype 4e (HCV-4e), and the entire nucleotide sequence of the HCV-4e polyprotein was determined to establish the first reference sequence. The HCV-4e strains possessed resistance-associated substitutions similar to those of other HCV-4 strains, indicating that the use of direct-acting antiviral therapy may be complex. These results provide a better understanding of the current situation of hepatitis B and C virus infections in Central Africa and will help public health organizations develop effective countermeasures to eliminate chronic viral hepatitis in this region. [ABSTRACT FROM AUTHOR]

Surveillance of viral pathogens in both point-of-care and clinical settings is imperative to preventing the widespread propagation of disease—undetected viral outbreaks can pose dire health risks on a large scale. Thus, portable, accessible, and reliable biosensors are necessary for proactive measures. Polymeric microparticles have recently gained popularity for their size, surface area, and versatility, which make them ideal biosensing tools. This review cataloged recent investigations on polymeric microparticle-based detection platforms across eight virus families. These microparticles were used as labels for detection (often with fluorescent microparticles) and for capturing viruses for isolation or purification (often with magnetic microparticles). We also categorized all methods by the characteristics, materials, conjugated receptors, and size of microparticles. Current approaches were compared, addressing strengths and weaknesses in the context of virus detection. In-depth analyses were conducted for each virus family, categorizing whether the polymeric microparticles were used as labels, for capturing, or both. We also summarized the types of receptors conjugated to polymeric microparticles for each virus family. [ABSTRACT FROM AUTHOR]

Various foodborne viruses have been associated with human health during the last decade, causing gastroenteritis and a huge economic burden worldwide. Furthermore, the emergence of new variants of infectious viruses is growing continuously. Inactivation of foodborne viruses in the food industry is a formidable task because although viruses cannot grow in foods, they can survive in the food matrix during food processing and storage environments. Conventional inactivation methods pose various drawbacks, necessitating more effective and environmentally friendly techniques for controlling foodborne viruses during food production and processing. Various inactivation approaches for controlling foodborne viruses have been attempted in the food industry. However, some traditionally used techniques, such as disinfectant‐based or heat treatment, are not always efficient. Nonthermal techniques are considered a new platform for effective and safe treatment to inactivate foodborne viruses. This review focuses on foodborne viruses commonly associated with human gastroenteritis, including newly emerged viruses, such as sapovirus and Aichi virus. It also investigates the use of chemical and nonthermal physical treatments as effective technologies to inactivate foodborne viruses. [ABSTRACT FROM AUTHOR]

Background: Sanitation or sanitary workers are exposed to hepatitis virus infections because of filthy and dangerous working conditions. The current global systematic review and meta-analysis aimed to estimate the pooled sero-prevalence of occupationally associated hepatitis virus infection among them. Methods: Preferred Reporting Items for Systematic Reviews (PRISMA), and Population, Intervention, Comparison, Outcome and study design (PICOS) were used for flow diagram, and review questions, respectively. Four databases other methods were used published articles from 2000 to 2022. Boolean logic (AND, OR), MeSH, and keywords were used: (Occupation *OR Job *OR Work) AND (Hepatitis A *OR Hepatitis B virus *OR Hepatitis C virus *OR Hepatitis E virus) AND (Solid waste collectors [SWCs] *OR Street sweepers [SS] *OR Sewage workers [STWs] *OR health care facilities cleaners [HCFCs)) AND (Countries). Stata MP/17 software was used for pooled prevalence analysis, meta-regression analysis (Hedges) at a 95% confidence interval (CI:95%). Results: A total of 182 studies were identified studies, a total of 28 studies were included from twelve countries. Of these, from developed (n = 7) and developing countries (n = 5). From total a of 9049 sanitary workers, 5951(66%), 2280 (25%) and 818 (9%) were STWs, SWCs and SS, respectively. Globally, the pooled sero-prevalence of occupational-related hepatitis viral infections among sanitary workers was 38.06% (95% CI: 30–0.46.12). Of this, it was 42.96% (95% CI: 32.63–53.29) and 29.81% (95% CI: 17.59–42.02) for high-income and low-income countries, respectively. Meanwhile, by sub-analysis, the highest pooled sero-prevalence of hepatitis viral infections by categories, type and year were 47.66% (95%CI: 37.42–57.90), 48.45% (95% CI: 37.95–58.96), and 48.30% (95% CI: 36.13–60.47) for SWTs, HAV, and 2000 to 2010 year, respectively. Conclusion: The consistency of the evidence suggests that sanitation workers, particularly sewage workers, are susceptible to occupationally acquired hepatitis regardless of their working conditions, necessitating significant changes to occupational health and safety regulations from governmental policies and other initiatives to reduce risks among sanitary workers. [ABSTRACT FROM AUTHOR]

Purpose: To assess etiological differences in extracellular volume fraction (ECV) and evaluate its influence on staging performance. Methods: A total of 166 patients with normal liver (n = 14) and chronic liver disease related to viral hepatitis (n = 71), alcohol (n = 44), and nonalcoholic steatohepatitis (NASH) (n = 37) underwent dual-energy CT (DECT) of the liver (5-min equilibrium-phase images) between January 2020 and July 2022. The iodine densities of the parenchyma and aorta were measured and ECV was calculated. Comparisons of ECV between each etiology and METAVIR fibrosis stage were statistically analyzed (p < 0.05). Results: ECV in each etiology and all patients significantly increased with higher fibrosis stage (p < 0.001) and showed a strong or moderate correlation with fibrosis stage (Spearman's ρ; all patients, 0.701; viral hepatitis, 0.638; alcoholic, 0.885; NASH, 0.791). In stages F2–F4, ECV in alcoholic liver disease was significantly larger than those for viral hepatitis and NASH (p < 0.05); however, no significant difference in stage F1 was found among the three etiologies. The cutoff values and areas under the receiver operating characteristic curve (AUC-ROCs) for discriminating fibrosis stage (≥ F1– ≥ F4) were higher for alcohol (cutoff values and AUC-ROC; 20.1% and 0.708 for ≥ F1, 23.8% and 0.990 for ≥ F2, 24.3% and 0.968 for ≥ F3, and 26.6% and 0.961 for ≥ F4, respectively) compared with those for the others. Conclusion: ECV in alcoholic liver disease is higher than that in other etiologies in the advanced stages of fibrosis, and etiological differences in ECV affect the staging performance of fibrosis. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is the most common cause of AVH in developing countries. HEV causes a self-limiting infection that is transmitted mainly through the consumption of contaminated food and water. Our study aimed to find out the seroprevalence of HEV infection. Detected both IgG & IgM antibodies from 100 asymptomatic antenatal women. ELISA (DIA PRO, Italy) was used to detect antibodies. Seropositivity was found in 9% of pregnant women, all might have been exposed to HEV infection previously. It could be unnoticed due to its self-limiting nature. IgG was 5% and IgM was 6%. Both IgM & IgG were detected in two pregnant women. Untreated water was used by the majority of women irrespective of their educational status. Though it is a self-limiting disease, it is necessary to screen for its antibody. Awareness about the modes of transmission & complications needs to be addressed in the community. It is necessary to do further studies for screening for HEV infection as there is a very limited number of studies published from South India. [ABSTRACT FROM AUTHOR]

A number of studies are underway to gain a better understanding of the role of immunity in the pathogenesis of hepatocellular carcinoma and to identify subgroups of individuals who may benefit the most from systemic therapy according to the etiology of their tumor. Human leukocyte antigens play a key role in antigen presentation to T cells. This is fundamental to the host's defense against pathogens and tumor cells. In addition, HLA-specific interactions with innate lymphoid cell receptors, such those present on natural killer cells and innate lymphoid cell type 2, have been shown to be important activators of immune function in the context of several liver diseases. More recent studies have highlighted the key role of members of the non-classical HLA-Ib and the transcript adjacent to the HLA-F locus, FAT10, in hepatocarcinoma. The present review analyzes the major contribution of these molecules to hepatic viral infection and hepatocellular prognosis. Particular attention has been paid to the association of natural killer and Vδ2 T-cell activation, mediated by specific HLA class Ib molecules, with risk assessment and novel treatment strategies to improve immunotherapy in HCC. [ABSTRACT FROM AUTHOR]

Azetidine substituent group has a wide range of application in organic chemistry and medical field. In this study, a novel azetidine derivative and its reaction mechanism has been reported. Using quantum chemical method spectroscopic analysis and other parameters such as electronic and thermodynamic properties were studied to understand the physical as well as chemical behavior of the reported compound. Additionally, to study the antiviral activity, molecular docking studies were carried out against Hepatitis virus C (HCV) NS5B genotype and Norovirus as target protein. In order to validate the docking results molecular dynamic (MD) simulation and Molecular Mechanics‐Poisson‐Boltzmann Surface Area (MM‐PBSA) were calculated at 90 ns. The RMSD was obtained within the range 0.75 Å to 1.5 Å and binding energies (ΔGbind) for the two complexes was found to be −18.34 kJ/mol and −16.10 kJ/mol for each respective targets.It was found that reported compound can act as potential inhibitor for HCVand Norovirus. [ABSTRACT FROM AUTHOR]

The sodium taurocholate cotransporting polypeptide (NTCP; gene name SLC10A1) is the primary hepatic basolateral uptake transporter for conjugated bile acids and the entry receptor for the hepatitis B and D virus (HBV/HDV). Regulation of human NTCP remains a knowledge gap due to significant species differences in substrate and inhibitor selectivity and plasma membrane expression. In the present study, various kinase inhibitors were screened for inhibition of NTCP function and taurocholate (TCA) uptake using NTCP-transfected HuH-7 cells. This study identified everolimus, an mTOR inhibitor and macrocyclic immunosuppressive drug, as an NTCP inhibitor with modest potency (IC50 = 6.7--8.0 µM). Further investigation in differentiated HuH-7 cells expressing NTCP and NTCP-overexpressing Flp-In T-REx 293 cells revealed that the mechanism of action of everolimus on NTCP is direct inhibition and mTOR-independent. Structural analogs of everolimus inhibited NTCP-mediated TCA uptake, however, functional analogs did not affect NTCP-mediated TCA transport, providing further evidence for direct inhibition. This work contributes to the growing body of literature suggesting that NTCP-mediated bile acid uptake may be inhibited by macrocyclic peptides, which may be further exploited to develop novel medications against HBV/HDV. [ABSTRACT FROM AUTHOR]

The sodium taurocholate cotransporting polypeptide (NTCP; gene name SLC10A1) is the primary hepatic basolateral uptake transporter for conjugated bile acids and the entry receptor for the hepatitis B and D virus (HBV/HDV). Regulation of human NTCP remains a knowledge gap due to significant species differences in substrate and inhibitor selectivity and plasma membrane expression. In the present study, various kinase inhibitors were screened for inhibition of NTCP function and taurocholate (TCA) uptake using NTCP-transfected HuH-7 cells. This study identified everolimus, an mTOR inhibitor and macrocyclic immunosuppressive drug, as an NTCP inhibitor with modest potency (IC50 = 6.7–8.0 µM). Further investigation in differentiated HuH-7 cells expressing NTCP and NTCP-overexpressing Flp-In T-REx 293 cells revealed that the mechanism of action of everolimus on NTCP is direct inhibition and mTOR-independent. Structural analogs of everolimus inhibited NTCP-mediated TCA uptake, however, functional analogs did not affect NTCP-mediated TCA transport, providing further evidence for direct inhibition. This work contributes to the growing body of literature suggesting that NTCP-mediated bile acid uptake may be inhibited by macrocyclic peptides, which may be further exploited to develop novel medications against HBV/HDV.

Simple Summary: Hepatocellular carcinoma (HCC) is a global health challenge. Hepatitis virus infection (including HBV, HCV and HDV) is one of the major risk factors for HCC development. These viruses induce hepatocyte cancer by causing chronic hepatitis and by a variety of complex mechanisms. Here we discuss the mechanisms by which several hepatitis viruses induce HCC, as well as new diagnostic and therapeutic approaches to HCC based on the findings of these mechanisms. Finally, we also discuss the potential relationship between HEV and HCC. Hepatocellular carcinoma (HCC) remains a global health challenge, causing 600,000 deaths each year. Infectious factors, including hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus (HDV), have long been considered the major risk factors for the development and progression of HCC. These pathogens induce hepatocyte transformation through a variety of mechanisms, including insertional mutations caused by viral gene integration, epigenetic changes, and the induction of long-term immune dysfunction. The discovery of these mechanisms, while advancing our understanding of the disease, also provides targets for new diagnostic and therapeutic approaches. In addition, the discovery and research of chronic HEV infection over the past decade indicate that this common hepatitis virus also seems to have the potential to induce HCC. In this review, we provide an overview of recent studies on the link between hepatitis virus and HCC, as well as new diagnostic and therapeutic approaches to HCC based on these findings. Finally, we also discuss the potential relationship between HEV and HCC. In conclusion, these associations will further optimize the diagnosis and treatment of infection-associated HCC and call for better management policies. [ABSTRACT FROM AUTHOR]

Background: Unsafe blood transfusion proves very costly from both human as well as economic point of view. With every unit of blood transfused, there is 1% chance of transfusion transmitted infections (TTIs). In India, blood is screened for all those infections mandated by the World Health Organization, i.e., human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), syphilis, and also malaria. The aim of the present study is to determine the seroprevalence of TTIs and associated factors among healthy blood donors in North Indian population. Materials and Methods: A retrospective observational study was conducted by reviewing the records of all blood donors for a period of 4 years from January 2016 to December 2019 at Blood Bank of our institution. Results: Out of total 10,797 healthy voluntary donors, 2338 (21.65%) were the motivated donors and 8459 (78.35%) were voluntary unpaid family donors. Majority of the donors were males, i.e., 10,332 (95.69%); female donors were 465 (4.31% only. Overall prevalence of TTI was 1.07% (116/10,797). The seroprevalence of the HIV, HBV, HCV, malaria, and syphilis was found to be 0.03%, 0.49%, 0.50%, 0.009% and 0.05%, respectively, which was found to be statistically significant (P < 0.001). Coinfection was not seen in any of the donors. Conclusion: The present study shows a seroprevalence of 1.07% for TTI with positivity of 0.50% for HCV and 0.49% for HBV. Individuals donating in blood camps made only 21.65%. Female donor participation was lean 4.31%. Efforts to motivate and ensure active participation of voluntary blood donors including females are needed.

Infections caused by viruses are one of the foremost causes of morbidity and mortality in the world. Although a number of antiviral drugs are currently used for treatment of various kinds of viral infection diseases, there is still no available therapeutic agent for most of the viruses in clinical practice. Coumarin is a chemical compound which is found naturally in a variety of plants, it can also be synthetically produced possessing diverse biological effects. More recently, reports have highlighted the potential role of coumarin derivatives as antiviral agents. This review outlines the advances in coumarin-based compounds against various viruses including human immunodeficiency virus, hepatitis virus, herpes simplex virus, Chikungunya virus and Enterovirus 71, as well as the structure activity relationship and the possible mechanism of action of the most potent coumarin derivatives.

Hepatitis viral infections are the most common cause of hepatitis liver disease, which eventually leads to cancer and fibrosis if not detected early. Therefore, early detection would allow for preventive and therapeutic actions. Here, a surface-enhanced Raman spectroscopy (SERS)-based biosensor was developed using plasmonic molybdenum trioxide quantum dots (MoO3-QDs) as the SERS substrates. The nanostructured substrate of MoO3-QDs was functionalized with a proteoglycan (syndecan-1) as a novel bioreceptor for the target hepatitis E virus (HEV). The innovative biodetection system achieved a detection limit of 1.05 fg/mL for the tested HEV target (ORF2), indicating superb clinically relevant sensitivity and performance. The designed biosensing system incorporating a glycan motif as a bioreceptor instead of the conventional antibodies or aptamers presents new insights for the ultrasensitive detection of HEV and other infectious viruses.

Hepatitis B, C and D viruses (HBV, HCV, HDV, respectively) specifically infect human hepatocytes and often establish chronic viral infections of the liver, thus escaping antiviral immunity for years. Like other viruses, hepatitis viruses rely on the cellular machinery to meet their energy and metabolite requirements for replication. Although this was initially considered passive parasitism, studies have shown that hepatitis viruses actively rewire cellular metabolism through molecular interactions with specific enzymes such as glucokinase, the first rate-limiting enzyme of glycolysis. As part of research efforts in the field of immunometabolism, it has also been shown that metabolic changes induced by viruses could have a direct impact on the innate antiviral response. Conversely, detection of viral components by innate immunity receptors not only triggers the activation of the antiviral defense but also induces in-depth metabolic reprogramming that is essential to support immunological functions. Altogether, these complex triangular interactions between viral components, innate immunity and hepatocyte metabolism may explain why chronic hepatitis infections progressively lead to liver inflammation and progression to cirrhosis, fibrosis and hepatocellular carcinoma (HCC). In this manuscript, we first present a global overview of known connections between the innate antiviral response and cellular metabolism. We then report known molecular mechanisms by which hepatitis viruses interfere with cellular metabolism in hepatocytes and discuss potential consequences on the innate immune response. Finally, we present evidence that drugs targeting hepatocyte metabolism could be used as an innovative strategy not only to deprive viruses of key metabolites, but also to restore the innate antiviral response that is necessary to clear infection. [ABSTRACT FROM AUTHOR]

The number of new cases of hepatocellular carcinoma (HCC) worldwide reached 910,000, ranking the sixth, 80% HCC is associated with viruses, so exploring the molecular mechanism of viral carcinogenicity is imperative. The study showed that both HBVand HCV associated HCC and non-viral HCC have the same molecular phenotype (low gene expression and inhibition of immune pathways), but in the tumor immune micro-environment, there is excessive M2-type macrophage polarization in virus-associated hepatocellular carcinoma. To address this phenomenon, the data sets were analyzed and identified five hub genes (POLR2A, POLR2B, RPL5, RPS6, RPL23A) involved in viral gene expression and associated with PI3K-Akt-mTOR pathway activation by six algorithms. In addition, numerous studies have reported that M2-type macrophages participate in the hepatic fibro-pathological process of the development of HCC and are regulated by the PI3K-Akt-mTOR pathway. On this basis, the study showed that hepatitis virus causes abnormal expression of hub genes, leading to the activation of the pathway, which in turn promote the differentiation of M2-type macrophages and eventually promote the formation of liver fibrosis, leading to the occurrence of HCC. In addition, these hub genes are regulated by transcription factors and m6A enzyme, and have good prognosis and diagnostic value. With regard to drug reuse, the results suggest that patients with virus-related HCC for whom Cytidine triphosphate disodium salt and Guanosine-5'-Triphosphate are used as supplementary therapy, and may have a better prognosis. In conclusion, the study has identified novel molecules that are carcinogenic to hepatitis viruses and are expected to serve as molecular markers and targets for diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Since the dawn of time, several viral epidemics have swept the globe, among them the current COVID-19 outbreak. The ongoing emergence and propagation of novel viral illnesses have compelled researchers to seek new therapeutic approaches that can get beyond the drawbacks of antivirals that are available right now. Medicinal plants have historically offered treatments for a range of illnesses. These bioactive compounds serve as the foundation for many "modern" pharmaceuticals. One of the essential polyphenols in various medicinal plants is Chlorogenic acid (CA), an ester of caffeic and quinic acid. Extensive research has revealed that CA possesses anti-inflammatory, anticarcinogenic, and antioxidant properties. This review aims to briefly summarise CA and its derivative's antiviral properties on various human viral diseases and their ability to fight the current COVID-19 disease. This review summarises CA antiviral action on the following viruses: influenza A virus (H1N1/H3N2/H7N9), hepatitis C virus (HCV) and hepatitis B virus (HBV), human immunodeficiency virus (HIV), infectious bronchitis virus (IBV), porcine reproductive and respiratory syndrome virus (PRRSV), herpes simplex virus (HSV)-1, enterovirus 71 (Ent 71), adenoviruses (AdenV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This review will open the way for developing and designing potentially effective and broad-spectrum CA-based antiviral medicines. [ABSTRACT FROM AUTHOR]

Chronic liver diseases still represent a worrying public health issue in Sub-Saharan Africa. In this region, emphasis is generally made on hepatocellular carcinoma (HCC) albeit liver cirrhosis (LC) is also responsible for an important death toll. Very few studies have compared the presentation and etiologies of cancer and cirrhosis of the liver in Middle Africa. We conducted a comparative retrospective analysis of 74 and 134 cases of patients with HCC and LC treated in Libreville, Gabon. Viral or lifestyle risk factors, clinical symptoms, and biological features were compared. We observed that ages of diagnosis were 53.2 ± 15.7 years and 48.6 ± 18.6 years for HCC and LC with remarkably low M:F sex ratios (1.3-1.8). Ethanol consumption was highly prevalent in both disease types (65.0%-70.0%). Chronic viral infections with hepatitis B (HBV) or C (HCV) virus were alsowidespread with slight domination of the former in both diseases (43.4% vs. 34.3%, and 35.9% vs. 28.5%). Patients with HCC were presenting very late with a mean diameter of the main nodule of 84 ± 50mmand a multifocal pattern in 72.7% of cases. HCC developed on a cirrhotic liver in 91.7% of cases. Serum AFP was frankly elevated (>400 ng/ml) in only 35.8% of HCC cases. The most striking feature of the HCC series was the contrasted contribution of distinct pathogenic etiologies involving sex, viral, metabolic, and toxic factors. A frequently dysmetabolic condition synergizing with hepatitis C (anti-HCV, 73.8% vs 22.7%, p < 0.0001) in females and a male cancer promoted by recreational toxicants and chronic hepatitis B (HBsAg, 83.5% vs 35.9%, p < 0.0001) were observed. Men with HCC were considerably younger than women (46.8 ± 14.5 years vs. 62.2 ± 12.2 years, p < 0.0001). Further studies are now warranted to identify routes of HCV transmission and if they are still fueling reservoirs of future patients. Public policies to prevent alcohol-related harm have also to be urgently implemented in Gabon. [ABSTRACT FROM AUTHOR]

Only a minority of the patients with acute febrile jaundice evaluated through the Yellow Fever surveillance program were found positive for antibodies against Yellow Fever Virus (YFV). In order to characterize patients with acute febrile jaundice negative for YFV, we collected 255 sera between January to December 2019. We screened for HBV antigens, and antibodies against HCV and HEV. The seroprevalences observed were 10.6% (27/255) for HBV, 2% (5/255) for HCV, 17.3% (44/255) for HEV IgG, 4.3% (11/255) for HEV IgM, and 12.5% (32/255) for both IgG and IgM HEV. Prevalence of HEV was significantly higher in females than males (p < 0.01). HEV IgG prevalence was highest in those 20–29 years old, but the highest incidence rate (IgM positive) was in children 0–9 years old. Exposure to HEV was higher in the Sahelian zone (55.8%, 95% CI: 40.97–70.66) than in the Sudanese zone (30.2%, 95% CI: 24.01–36.37, p = 0.003). The high prevalence rates and hepatitis virus diversity underline the challenge of routine clinical diagnosis in Chad’s Yellow Fever surveillance program.

Hepatitis B, C and D viruses (HBV, HCV, HDV, respectively) specifically infect human hepatocytes and often establish chronic viral infections of the liver, thus escaping antiviral immunity for years. Like other viruses, hepatitis viruses rely on the cellular machinery to meet their energy and metabolite requirements for replication. Although this was initially considered passive parasitism, studies have shown that hepatitis viruses actively rewire cellular metabolism through molecular interactions with specific enzymes such as glucokinase, the first rate-limiting enzyme of glycolysis. As part of research efforts in the field of immunometabolism, it has also been shown that metabolic changes induced by viruses could have a direct impact on the innate antiviral response. Conversely, detection of viral components by innate immunity receptors not only triggers the activation of the antiviral defense but also induces in-depth metabolic reprogramming that is essential to support immunological functions. Altogether, these complex triangular interactions between viral components, innate immunity and hepatocyte metabolism may explain why chronic hepatitis infections progressively lead to liver inflammation and progression to cirrhosis, fibrosis and hepatocellular carcinoma (HCC). In this manuscript, we first present a global overview of known connections between the innate antiviral response and cellular metabolism. We then report known molecular mechanisms by which hepatitis viruses interfere with cellular metabolism in hepatocytes and discuss potential consequences on the innate immune response. Finally, we present evidence that drugs targeting hepatocyte metabolism could be used as an innovative strategy not only to deprive viruses of key metabolites, but also to restore the innate antiviral response that is necessary to clear infection.

Chronic liver diseases still represent a worrying public health issue in Sub-Saharan Africa. In this region, emphasis is generally made on hepatocellular carcinoma (HCC) albeit liver cirrhosis (LC) is also responsible for an important death toll. Very few studies have compared the presentation and etiologies of cancer and cirrhosis of the liver in Middle Africa. We conducted a comparative retrospective analysis of 74 and 134 cases of patients with HCC and LC treated in Libreville, Gabon. Viral or lifestyle risk factors, clinical symptoms, and biological features were compared. We observed that ages of diagnosis were 53.2 ± 15.7 years and 48.6 ± 18.6 years for HCC and LC with remarkably low M:F sex ratios (1.3–1.8). Ethanol consumption was highly prevalent in both disease types (65.0%–70.0%). Chronic viral infections with hepatitis B (HBV) or C (HCV) virus were also widespread with slight domination of the former in both diseases (43.4% vs. 34.3%, and 35.9% vs. 28.5%). Patients with HCC were presenting very late with a mean diameter of the main nodule of 84 ± 50 mm and a multifocal pattern in 72.7% of cases. HCC developed on a cirrhotic liver in 91.7% of cases. Serum AFP was frankly elevated (>400 ng/ml) in only 35.8% of HCC cases. The most striking feature of the HCC series was the contrasted contribution of distinct pathogenic etiologies involving sex, viral, metabolic, and toxic factors. A frequently dysmetabolic condition synergizing with hepatitis C (anti-HCV, 73.8% vs 22.7%, p < 0.0001) in females and a male cancer promoted by recreational toxicants and chronic hepatitis B (HBsAg, 83.5% vs 35.9%, p < 0.0001) were observed. Men with HCC were considerably younger than women (46.8 ± 14.5 years vs. 62.2 ± 12.2 years, p < 0.0001). Further studies are now warranted to identify routes of HCV transmission and if they are still fueling reservoirs of future patients. Public policies to prevent alcohol-related harm have also to be urgently implemented in Gabon.

Hepatitis B virus (HBV) and Hepatitis C virus (HCV) chronic infections cause liver immunopathological diseases such as hepatitis, fibrosis, cirrhosis, and hepatocellular carcinomas, which are difficult to treat and continue to be major health problems globally. Due to the species-specific hepato-tropism of HBV and HCV, conventional rodent models are limited in their utility for studying the infection and associated liver immunopathogenesis. Humanized mice reconstituted with both functional human immune system and hepatocytes (HIS-HuHEP mice) have been extremely instrumental for in vivo studies of HBV or HCV infection and human-specific aspects of the progression of liver immunopathogenesis. However, none of the current HIS-HuHEP mice can model the progression of viral hepatitis to hepatocarcinogenesis which may be a notorious result of HBV or HCV chronic infection in patients, suggesting that they were functionally compromised and that there is still significant space to improve and establish next-generation of HIS-HuHEP mice with more sophisticated functions. In this review, we first summarize the principal requirements to establish HIS-HuHEP mice. We then discuss the respective protocols for current HIS-HuHEP mice and their applications, as well as their advantages and disadvantages. We also raise perspectives for further improving and establishing next-generation HIS-HuHEP mice.

Viral hepatitis remains one of the largest public health concerns worldwide. Especially in Central Africa, information on hepatitis virus infections has been limited, although the prevalence in this region has been reported to be higher than the global average. To reveal the current status of hepatitis B and C virus (HBV and HCV) infections and the genetic diversity of the viruses, we conducted longitudinal surveillance in Gabon. We detected 22 HBV and 9 HCV infections in 2047 patients with febrile illness. Genetic analyses of HBV identified subgenotype A1 for the first time in Gabon and an insertion generating a frameshift to create an X-preC/C fusion protein. We also revealed that most of the detected HCVs belonged to the “Gabon-specific” HCV subtype 4e (HCV-4e), and the entire nucleotide sequence of the HCV-4e polyprotein was determined to establish the first reference sequence. The HCV-4e strains possessed resistance-associated substitutions similar to those of other HCV-4 strains, indicating that the use of direct-acting antiviral therapy may be complex. These results provide a better understanding of the current situation of hepatitis B and C virus infections in Central Africa and will help public health organizations develop effective countermeasures to eliminate chronic viral hepatitis in this region.