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Introduction and Objectives: Liver fibrosis remains a complication derived from a chronic Hepatitis C Virus (HCV) infection even when it is resolved, and no liver antifibrotic drug has been approved. Molecular mechanisms on hepatocytes and activation of hepatic stellate cells (HSCs) play a central role in liver fibrogenesis. To elucidate molecular mechanisms, it is important to analyze pathway regulation during HSC activation and HCV infection. Materials and Methods: We evaluate the fibrosis-associated molecular mechanisms during a co-culture of human HSCs (LX2), with human hepatocytes (Huh7) that express HCV NS5A or Core protein. We evaluated LX2 activation induced by HCV NS5A or Core expression in Huh7 cells during co-culture. We determined a fibrosis-associated gene expression profile in Huh7 that expresses NS5A or Core proteins during the co-culture with LX2. Results: We observed that NS5A induced 8.3-, 6.7- and 4-fold changes and that Core induced 6.5-, 1.8-, and 6.2-fold changes in the collagen1, TGFb1, and timp1 gene expression, respectively, in LX2 co-cultured with transfected Huh7. In addition, NS5A induced the expression of 30 genes while Core induced 41 genes and reduced the expression of 30 genes related to fibrosis in Huh7 cells during the co-culture with LX2, compared to control. The molecular pathways enriched from the gene expression profile were involved in TGFB signaling and the organization of extracellular matrix. Conclusions: We demonstrated that HCV NS5A and Core protein expression regulate LX2 activation. NS5A and Core-induced LX2 activation, in turn, regulates diverse fibrosis-related gene expression at different levels in Huh7, which can be further analyzed as potential antifibrotic targets during HCV infection. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion In kidney transplantation, concerns have been raised regarding increased incidence of viral opportunistic infections in hepatitis C virus (HCV) nucleic acid test (NAT)‐negative (‐) recipients who received HCV NAT‐positive (+) donor kidneys, specifically BK polyomavirus (BKPyV), cytomegalovirus (CMV), and Epstein‐Barr virus (EBV). The purpose of this study was to determine the incidence of these three viral opportunistic infections in HCV NAT‐ recipients who have undergone kidney transplantation with HCV NAT+ donor kidneys at our institution.This was an Institutional Review Board‐approved, single‐center, retrospective case‐control study of HCV NAT‐ kidney transplant recipients with HCV NAT+ donors from 2018 to 2021. The primary outcome was the cumulative incidence of viral infections of BKPyV, CMV, and/or EBV within 1 year following kidney transplantation.A total of 231 patients were included, 77 in the exposed (donor HCV NAT+) group and 154 in the control (donor HCV NAT‐) group. The adjusted cumulative incidence of viremia within 1 year did not statistically differ between groups (77% exposed group versus 66% for the control group, hazard ratio 1.34, 95% confidence interval 0.95–1.89). In addition, no statistically significant differences were observed for secondary outcomes with the exception of CMV viremia (62% exposed versus 49% control, p = 0.021). However, there were more patients in the exposed group at high risk for CMV viremia based on serostatus (CMV Donor+/Recipient‐, D+/R‐).Among patients who received HCV NAT+ donor kidneys, no clear association was observed between exposure to HCV NAT+ donor kidneys and viral infections of BKPyV, CMV, or EBV. [ABSTRACT FROM AUTHOR]

ABSTRACT HCV RNA test determines current active infection and is a requirement prior to initiating HCV treatment. We investigated trends and factors associated with post‐diagnosis HCV RNA testing rates prior to HCV treatment, and risk factors for first positive HCV RNA among people living with HIV (PLHIV) with HCV in the Asia‐Pacific region. PLHIV with positive HCV antibody and in follow‐up after 2010 were included. Patients were considered HCV‐antibody positive if they ever tested positive for HCV antibody (HCVAb). Repeated measures Poisson regression model was used to analyse factors associated with post‐diagnosis HCV RNA testing rates from positive HCVAb test. Factors associated with time to first positive HCV RNA from positive HCVAb test were analysed using Cox regression model. There were 767 HCVAb positive participants included (87% from LMICs) of whom 11% had HCV RNA tests. With 163 HCV RNA tests post positive HCVAb test, the overall testing rate was 5.05 per 100 person‐years. Factors associated with increased testing rates included later calendar years of follow‐up, HIV viral load ≥1000 copies/mL and higher income countries. Later calendar years of follow‐up, ALT >5 times its upper limit of normal, and higher income countries were associated with shorter time to first positive HCV RNA test. Testing patterns indicated that uptake was predominantly in high income countries possibly due to different strategies used to determine testing in LMICs. Expanding access to HCV RNA, such as through lower‐cost point of care assays, will be required to achieve elimination of HCV as a public health issue. [ABSTRACT FROM AUTHOR]

Background: Substance use disorders are a widely recognized problem among hepatitis C-infected patients; moreover, substance abuse by intravenous injection is a common mode of transmission of the hepatitis C virus worldwide. The frequency of substance use disorders and their relation to hepatitis C infection are still unknown in Iraq. This cross-sectional study, conducted among a sample of hepatitis C- infected patients attending the Gastrointestinal Tract Center in Baghdad Medical City, aimed to examine the prevalence of substance use disorders, the sociodemographic characteristics of the abusers, and the relation between intravenous drug abuse and hepatitis C virus infection. All participants were subjected to an Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) questionnaire and a data form to determine sociodemographic characteristics and hepatitis C virus-related risk factors. Results: In a total of 300 hepatitis C virus-infected patients, the prevalence of substance use disorders was 53.6%. Among these patients, 43.6% abused nicotine, 6% abused licit drugs, and 4% abused alcohol. No one reported illicit drug abuse. Intravenous drug abuse was rare, and there was no relationship found between intravenous drug abuse and hepatitis C infection. Cupping (23%) and blood transfusion (20.3%) were both significantly associated with hepatitis C transmission in this study (p > 0.001). Conclusion: This study revealed a high prevalence (53.6%) of substance abuse in this sample of hepatitis C-infected patients, with nicotine being the most commonly abused substance. However, there was no relationship between hepatitis C infection and intravenous drug abuse. Common risk factors that might contribute to hepatitis C transmission among this population include cupping and blood transfusion. [ABSTRACT FROM AUTHOR]

The emergence of drug-resistance-inducing mutations in Hepatitis C virus (HCV) coupled with genotypic heterogeneity has made targeting NS3/4A serine protease difficult. In this work, we investigated the mutagenic variations in the binding pocket of Genotype 3 (G3) HCV NS3/4A and evaluated ligands for efficacious inhibition. We report mutations at 14 positions within the ligand-binding residues of HCV NS3/4A, including H57R and S139P within the catalytic triad. We then modelled each mutational variant for pharmacophore-based virtual screening (PBVS) followed by covalent docking towards identifying a potential covalent inhibitor, i.e., cpd-217. The binding stability of cpd-217 was then supported by molecular dynamic simulation followed by MM/GBSA binding free energy calculation. The free energy decomposition analysis indicated that the resistant mutants alter the HCV NS3/4A–ligand interaction, resulting in unbalanced energy distribution within the binding site, leading to drug resistance. Cpd-217 was identified as interacting with all NS3/4A G3 variants with significant covalent docking scores. In conclusion, cpd-217 emerges as a potential inhibitor of HCV NS3/4A G3 variants that warrants further in vitro and in vivo studies. This study provides a theoretical foundation for drug design and development targeting HCV G3 NS3/4A. [ABSTRACT FROM AUTHOR]

Pakistan harbours a large burden of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. We utilised repeat sero‐surveys to assess progress achieved towards hepatitis elimination in Pakistan. Multilevel logistic regression evaluated the change in HBV infection (HBV surface antigen (HBsAg)‐positive) prevalence and HCV exposure (HCV antibody (HCV‐Ab)‐positive) prevalence between two sero‐surveys from 2007 and 2019 for Sindh province and associated risk factors. Adjusted odds ratios (aORs) were estimated and population‐attributable fractions (PAF) for modifiable risk factors for HCV exposure. The 2007 and 2019 surveys included 8855 and 6672 individuals. HBsAg prevalence decreased from 2.6% (95% confidence intervals (95% CI): 2.2–2.9) in 2007 to 1.1% (95% CI: 0.8–1.3) in 2019, while HCV‐Ab prevalence increased from 5.1% (95% CI: 4.6%–5.5%) to 6.2% (95% CI: 5.6%–6.8%). The age and gender‐adjusted HBsAg prevalence decreased by 80% (aOR = 0.2, 95% CI: 0.1–0.4) among children and 60% (aOR = 0.4, 95% CI: 0.3–0.6) among adults over 2007–2019, while HCV‐Ab prevalence decreased by 60% (aOR = 0.4, 95%CI:0.2–0.7) in children and increased by 40% (aOR = 1.4, 95% CI: 1.2–1.7) in adults. HCV‐Ab prevalence was lower in adults with secondary (aOR = 0.6, 95% CI: 0.5–0.8) and higher (aOR = 0.5, 95%CI:0.3–0.8) education compared to illiterates and higher among adults reporting blood transfusion (aOR = 1.7, 95% CI: 1.2–2.4), family history of hepatitis (aOR = 2.5, 95% CI: 1.9–3.3), past year medical injection (aOR = 2.1, 95% CI: 1.6–2.7), being tattooed (aOR = 1.4, 95% CI: 1.0–1.9) and shaved by traditional barber (aOR = 1.2, 95% CI: 1.0–1.5). Modifiable risk factors accounted for 45% of HCV exposure, with medical injection(s) accounting for 38% (95%CI,25.7–48.4%). Overall HCV has increased over 2007–2019 in Sindh province, while HBV prevalence has decreased. Medical injections should be an important focus of prevention activities. [ABSTRACT FROM AUTHOR]

This study assesses the prevalence of hepatitis D virus (HDV) in people living with HIV (PLWHIV) in Greece. Given the compounding effects of HDV and hepatitis B (HBV) on liver disease progression, as well as the emergence of new therapeutic options such as bulevirtide, understanding regional disparities and the epidemiological impact of such co-infections is vital. A cross-sectional analysis was conducted utilizing 696 serum samples from PLWHIV attending five major university hospitals. The methodology included HDV antibody detection by ELISA and HDV RNA confirmation. Of the 30 HBsAg-positive samples analyzed, the study population was primarily male (93%), with a median age of 54 years. Participants had been on antiretroviral therapy for a median of 10 years, and the median CD4 count was 738 (539–1006) copies/mL. Additional serological findings revealed a 7% prevalence of hepatitis C virus (HCV) IgG antibodies and a 55% prevalence of hepatitis A virus (HAV) IgG antibodies. Seroreactivity for syphilis (RPR/VDRL/TPHA positive) was identified in 33% of the participants. The results indicated a low HDV prevalence, with only one individual (3%) testing positive for anti-HDV IgG antibodies and none for HDV RNA. This indicates a lower prevalence of HDV among PLWHIV with chronic HBV in Greece compared to global data. [ABSTRACT FROM AUTHOR]

Background: Surveillance for hepatocellular carcinoma (HCC) has been proven to increase the proportion of tumors detected at early stages and the chance of receiving curative therapies, reducing mortality by about 30%. Summary: Current recommendations consist of a semi-annual abdominal ultrasound with or without serum alpha-fetoprotein measurement in patients with cirrhosis and specific subgroups of populations with chronic viral hepatitis. Antiviral therapies, such as nucleot(s)ide analogs that efficiently suppress the replication of hepatitis B virus (HBV) and direct-acting antiviral drugs able to eliminate the hepatitis C virus (HCV) in >90% of patients, have radically changed the outcomes of viral liver disease and decreased, but not eliminated, the risk of HCC in both cirrhotic and non-cirrhotic patients. HCC risk is a key starting point for implementing a cost-effective surveillance and should also guide the decision-making process concerning its modality. As the global number of effectively treated viral patients continues to rise, there is a pressing need to identify those for whom the benefit-to-harm ratio of surveillance is favorable and to determine how to conduct cost-effective screening on such patients. Key Messages: This article addresses this topic and attempts to determine which patients should continue HCC surveillance after HBV suppression or HCV eradication, based on cost-effectiveness principles and the fact that HCC risk declines over time. We also formulate a proposal for a surveillance algorithm that switches the use of surveillance for HCC from the "one-size-fits-all" approach to individualized programs based on oncologic risk (precision surveillance). [ABSTRACT FROM AUTHOR]

Globally, hepatitis B virus (HBV) affects over 250 million people, whereas hepatitis C virus (HCV) affects approximately 70 million people, posing major public health challenges. Despite the availability of vaccines and treatments, a lack of comprehensive diagnostic coverage has left many cases undiagnosed and untreated. To address the need for sensitive, specific, and accessible diagnostics, this study introduced a multiplex loop‐mediated isothermal amplification assay with lateral flow detection for simultaneous HBV and HCV testing. This assay achieved exceptional sensitivity and was capable of detecting HBV and HCV concurrently in a single tube and on a single strip within 25 min, achieving the required clinical sensitivity (10 and 103 genomic copies/reaction for HBV and HCV, respectively). The method was validated in clinical samples of various viral genotypes, achieving an equivalent limit of detection. Additionally, a custom portable heating device was developed for field use. The assay developed here, capable of direct viral detection on the strip, shows promise in supplanting current methods that solely identify antibodies and necessitate additional qPCR for viral activity assessment. This economical and rapid assay aligns with point‐of‐care testing needs, offering significant advancements in enhancing viral hepatitis diagnostics in settings with limited resources. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) remains a significant global health challenge. Approximately 50 million people were living with chronic hepatitis C based on the World Health Organization as of 2024, contributing extensively to global morbidity and mortality. The advent and approval of several direct-acting antiviral (DAA) regimens significantly improved HCV treatment, offering potentially high rates of cure for chronic hepatitis C. However, the promising aim of eventual HCV eradication remains challenging. Key challenges include the variability in DAA access across different regions, slightly variable response rates to DAAs across diverse patient populations and HCV genotypes/subtypes, and the emergence of resistance-associated substitutions (RASs), potentially conferring resistance to DAAs. Therefore, periodic reassessment of current HCV knowledge is needed. An up-to-date review on HCV is also necessitated based on the observed shifts in HCV epidemiological trends, continuous development and approval of therapeutic strategies, and changes in public health policies. Thus, the current comprehensive review aimed to integrate the latest knowledge on the epidemiology, pathophysiology, diagnostic approaches, treatment options and preventive strategies for HCV, with a particular focus on the current challenges associated with RASs and ongoing efforts in vaccine development. This review sought to provide healthcare professionals, researchers, and policymakers with the necessary insights to address the HCV burden more effectively. We aimed to highlight the progress made in managing and preventing HCV infection and to highlight the persistent barriers challenging the prevention of HCV infection. The overarching goal was to align with global health objectives towards reducing the burden of chronic hepatitis, aiming for its eventual elimination as a public health threat by 2030. [ABSTRACT FROM AUTHOR]

Infections of hepatotropic viruses cause a wide array of liver diseases including acute hepatitis, chronic hepatitis and the consequently developed cirrhosis and hepatocellular carcinoma (HCC). Among the five classical hepatotropic viruses, hepatitis B virus (HBV) and hepatitis C virus (HCV) usually infect human persistently and cause chronic hepatitis, leading to major troubles to humanity. Previous studies have revealed that several types of inflammasomes are involved in the infections of HBV and HCV. Here, we summarize the current knowledge about their roles in hepatitis B and C. NLRP3 inflammasome can be activated and regulated by HBV and HCV. It is found to exert antiviral function or mediates inflammatory response in viral infections depending on different experimental models. Besides NLRP3 inflammasome, IFI16 and AIM2 inflammasomes participate in the pathological process of hepatitis B, and NALP3 inflammasome may sense HCV infection in hepatocytes. The inflammasomes affect the pathological process of viral hepatitis through its downstream secretion of inflammatory cytokines interleukin-1β (IL-1β) and IL-18 or induction of pyroptosis resulting from cleaved gasdermin D (GSDMD). However, the roles of inflammasomes in different stages of viral infection remains mainly unclear. More proper experimental models of viral hepatitis should be developed for specific studies in future, so that we can understand more about the complexity of inflammasome regulation and multifunction of inflammasomes and their downstream effectors during HBV and HCV infections. [ABSTRACT FROM AUTHOR]

In 2016, the World Health Organization introduced global targets for the care and management of hepatitis C virus (HCV) infection to eliminate hepatitis C as a public health threat by 2030. Despite significant improvements in testing and treatment, in 2020 only 23% of all persons infected with HCV globally were diagnosed. We explore examples from global hepatitis C programs in Georgia, Rwanda, and Nigeria that have used decentralized and integrated models to increase access to HCV testing. Georgia established the world's first national hepatitis C elimination program in 2015. In 2022, 2.6 million people (80% of the adults) have been screened for antibodies for HCV infection, and 80 000 persons with HCV RNA detected were treated. To achieve these results, Georgia implemented HCV core antigen testing, utilization of point-of-care (POC) HCV RNA testing, and simplification of HCV viremia detection by qualitative HCV RNA testing. Rwanda was the first country in sub-Saharan Africa to commit to HCV elimination in 2018, and as of 2022 it has achieved its screening target of 7 million people and initiated approximately 60 000 patients on hepatitis C treatment by rapid decentralization and integration of HCV services. In Nigeria, the integrated near-POC testing approach in Nasarawa State has been effective in expanding access to HCV viremia testing and enabling the possibility of same-day testing and treatment initiation. Examples of decentralization and integration of HCV testing and linkage to care in Georgia, Rwanda, and Nigeria could help inform effective strategies to reach 2030 hepatitis C elimination goals in other countries. [ABSTRACT FROM AUTHOR]

The treatment of hepatitis C virus (HCV) with direct-acting antivirals (DAA) leads to high sustained virological response (SVR) rates, but hepatocellular carcinoma (HCC) risk persists in people with advanced liver disease even after SVR. We weighted the HCC risk in people with cirrhosis achieving HCV eradication through DAA treatment and compared it with untreated participants in the multicenter prospective Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. Propensity matching with inverse probability weighting was used to compare DAA-treated and untreated HCV-infected participants with liver cirrhosis. Kaplan–Meier analysis and competing risk regression analysis were performed. Within the first 36 months, 30 de novo HCC cases occurred in the untreated group (n = 307), with a weighted incidence rate of 0.34% (95%CI: 0.23–0.52%), compared to 63 cases among SVR patients (n = 1111), with an incidence rate of 0.20% (95%CI: 0.16–0.26%). The 12-, 24-, and 36-month HCC weighted cumulative incidence rates were 6.7%, 8.4%, and 10.0% in untreated cases and 2.3%, 4.5%, and 7.0% in the SVR group. Considering death or liver transplantation as competing events, the untreated group showed a 64% higher risk of HCC incidence compared to SVR patients (SubHR 1.64, 95%CI: 1.02–2.62). Other variables independently associated with the HCC occurrence were male sex, increasing age, current alcohol use, HCV genotype 3, platelet count ≤ 120,000/µL, and albumin ≤ 3.5 g/dL. In real-life practice, the high efficacy of DAA in achieving SVR is translated into high effectiveness in reducing the HCC incidence risk. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization (WHO) has set targets to eliminate viral hepatitis, including hepatitis C virus (HCV) infection, by 2030. We present the results of the in‐hospital Reflex tEsting ALarm‐C (REAL‐C) model, which incorporates reflex HCV RNA testing and sending alerts to physicians. Methods: We conducted a retrospective study analysing the data of 1730 patients who newly tested positive for anti‐HCV between March 2020 and June 2023. Three distinct periods were defined: pre‐REAL‐C (n = 696), incomplete REAL‐C (n = 515) and complete REAL‐C model periods (n = 519). The primary outcome measure was the HCV RNA testing rate throughout the study period. Additionally, we assessed the referral rate to the gastroenterology department, linkage time for diagnosis and treatment and the treatment rate. Results: The rate of HCV RNA testing increased significantly from 51.0% (pre‐REAL‐C) to 95.6% (complete REAL‐C). This improvement was consistent across clinical departments, regardless of patients' comorbidities. Among patients with confirmed HCV infection, the gastroenterology referral rate increased from 57.1% to 81.1% after the REAL‐C model. The treatment rate among treatment‐eligible patients was 92.4% during the study period. The mean interval from anti‐HCV positivity to HCV RNA testing decreased from 45.1 to 1.9 days. The mean interval from the detection of anti‐HCV positivity to direct‐acting antiviral treatment also decreased from 89.5 to 49.5 days with the REAL‐C model. Conclusion: The REAL‐C model, featuring reflex testing and physician alerts, effectively increased HCV RNA testing rates and streamlined care cascades. Our model facilitated progress towards achieving WHO's elimination goals for HCV infection. [ABSTRACT FROM AUTHOR]

Background Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and the leading cause of cancer mortality. Various studies have linked dysregulated microRNA expression to liver cancers, but those related to viral hepatitis–related HCC are limited. Methods We investigated the diagnostic and prognostic roles of circulating miR-331-3p, miR-23b-3p, and miR-3194-5p in EDTA-treated blood samples of 50 hepatitis C virus (HCV) HCC patients, 50 HCV cirrhotic patients, and 50 healthy controls using quantitative real-time polymerase chain reaction. Results We found that miR-23b-3p and miR-3194-5p were significantly downregulated, whereas miR-331-3p was upregulated in HCC patients compared with controls. Also, these miRNAs were significantly dysregulated in HCC compared with cirrhotic patients. For the diagnosis of HCC, miR-331-3p and the combined miRNAs panel had the highest area under the curve (AUC), followed by miR-3194-5p. The highest AUC for differentiating metastatic from nonmetastatic patients was shown by miR-331-3p and the combined miRNAs panel, followed by miR-23b-3p. Dysregulation of miRNAs was associated with poor clinicopathological manifestations. Finally, miR-331-3P was found to be an independent risk factor for metastatic lesions in HCC. Conclusion Overall, the assessed miR-331-3p, miR-23b-3p, and miR-3194-5p were significantly associated with poor clinicopathological features of HCC and could be used to discriminate HCV-related HCC patients from cirrhosis and differentiating metastatic from nonmetastatic patients, primarily miR-331-3p along with combined miRNAs. Moreover, miR-331-3p was found to be an independent factor for metastatic lesions. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is the leading cause of acute viral hepatitis worldwide. HEV RNA detection is the gold standard for HEV infection diagnosis and PCR methods are commonly used but are usually time-consuming and expensive, resulting in low detection efficiency and coverage, especially in low-income areas. Here, we developed a simpler and more accessible HEV RNA detection method based on CRISPR-Cas13a system. A total of 265 samples of different types and sources, including 89 positive samples and 176 negative samples, were enrolled for evaluations. The sensitivity and specificity of the Cas13a-crRNA detection system were evaluated. The World Health Organization reference panel for HEV genotypes was used to evaluate the capability for detecting different HEV genotypes. The validity of the assay was compared with RT-qPCR. The 95 % limits of detection (LOD) of Cas13a-crRNA-based fluorescence assay and strip assay were 12.5 and 200 IU/mL, respectively. They did not show cross-reactivity with samples positive for hepatitis A virus, hepatitis B virus, hepatitis C virus, coxsackievirus A16, rotavirus, enterovirus 71, norovirus or enteropathic Escherichia coli. Different HEV genotypes (HEV1–4) can be detected by the assay. Compared to RT-qPCR, the positive predictive agreements of Cas13a-crRNA-based fluorescence and strip assay were 98.9 % (95 % CI: 93.9–99.8 %) and 91.0 % (95 % CI: 83.3–95.4 %), respectively. The negative predictive agreements were both 100 % (95 % CI: 97.8–100 %). In conclusion, we established a rapid and convenient HEV RNA detection method with good sensitivity and specificity based on CRISPR-Cas13a system, providing a new option for HEV infection diagnosis. [ABSTRACT FROM AUTHOR]

Objective: Multiple observational studies have demonstrated an association between type 2 diabetes mellitus (T2DM) and chronic liver diseases (CLDs). However, the causality of T2DM on CLDs remained unknown in various ethnic groups. Methods: We obtained instrumental variables for T2DM and conducted a twosample mendelian randomization (MR) study to examine the causal effect on nonalcoholic fatty liver disease (NAFLD), hepatocellular carcinoma (HCC), viral hepatitis, hepatitis B virus (HBV) infection, and hepatitis C virus (HCV) infection risk in Europeans and East Asians. The primary analysis utilized the inverse variance weighting (IVW) technique to evaluate the causal relationship between T2DM and CLDs. In addition, we conducted a series of rigorous analyses to bolster the reliability of our MR results. Results: In Europeans, we found that genetic liability to T2DM has been linked with increased risk of NAFLD (IVW : OR =1.3654, 95% confidence interval [CI], 1.2250-1.5219, p=1.85e-8), viral hepatitis (IVW : OR =1.1173, 95%CI, 1.0271- 1.2154, p=0.0098), and a suggestive positive association between T2DM and HCC (IVW : OR=1.2671, 95%CI, 1.0471-1.5333, p=0.0150), HBV (IVW : OR=1.1908, 95% CI, 1.0368-1.3677, p=0.0134). No causal association between T2DM and HCV was discovered. Among East Asians, however, there was a significant inverse association between T2DM and the proxies of NAFLD (ALT: IVW OR=0.9752, 95% CI 0.9597-0.9909, p=0.0021; AST: IVW OR=0.9673, 95%CI, 0.9528-0.9821, p=1.67e-5), and HCV (IVW: OR=0.9289, 95%CI, 0.8852-0.9747, Notably, no causal association was found between T2DM and HCC, viral hepatitis, or HBV. Conclusion: Our MR analysis revealed varying causal associations between T2DM and CLDs in East Asians and Europeans. Further research is required to investigate the potential mechanisms in various ethnic groups, which could yield new insights into early screening and prevention strategies for CLDs in T2DM patients.p=0.0027). [ABSTRACT FROM AUTHOR]

The complex epidemiology of hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV) patients in West Mexico remains poorly understood. Thus, this study aimed to investigate the HCV prevalence, HCV-associated risk factors, and HCV genotypes/subtypes and assess their impacts on liver fibrosis in 294 HIV patients (median age: 38 years; 88.1% male). HCV RNA was extracted and amplified by PCR. Hepatic fibrosis was assessed using three noninvasive methods: transient elastography (TE), the aspartate aminotransferase (AST)-to-platelets ratio index score (APRI), and the fibrosis-4 score (FIB4). Patients with liver stiffness of ≥9.3 Kpa were considered to have advanced liver fibrosis. HCV genotypes/subtypes were determined by line probe assay (LiPA) or Sanger sequencing. The prevalence of HIV/HCV infection was 36.4% and was associated with injection drug use (odds ratio (OR) = 13.2; 95% confidence interval (CI) = 5.9–33.6; p < 0.001), imprisonment (OR = 3.0; 95% CI = 1.7–5.4; p < 0.001), the onset of sexual life (OR = 2.6; 95% CI = 1.5–4.5; p < 0.001), blood transfusion (OR = 2.5; 95% CI = 1.5–4.2; p = 0.001), tattooing (OR = 2.4; 95% CI = 1.4–3.9; p = 0.001), being a sex worker (OR = 2.3; 95% CI = 1.0–5.4; p = 0.046), and surgery (OR = 1.7; 95% CI = 1.0–2.7; p = 0.042). The HCV subtype distribution was 68.2% for 1a, 15.2% for 3a, 10.6% for 1b, 3.0% for 2b, 1.5% for 2a, and 1.5% for 4a. The advanced liver fibrosis prevalence was highest in patients with HIV/HCV co-infection (47.7%), especially in those with HCV subtype 1a. CD4+ counts, albumin, direct bilirubin, and indirect bilirubin were associated with liver fibrosis. In conclusion, HCV infection had a significant impact on the liver health of Mexican HIV patients, highlighting the need for targeted preventive strategies in this population. [ABSTRACT FROM AUTHOR]

Hepatitis C, a particularly dangerous form of viral hepatitis caused by hepatitis C virus (HCV) infection, is a major socio-economic and public health problem. Due to the rapid development of deep learning, it has become a common practice to apply deep learning to the healthcare industry to improve the effectiveness and accuracy of disease identification. In order to improve the effectiveness and accuracy of hepatitis C detection, this study proposes an improved denoising autoencoder (IDAE) and applies it to hepatitis C disease detection. Conventional denoising autoencoder introduces random noise at the input layer of the encoder. However, due to the presence of these features, encoders that directly add random noise may mask certain intrinsic properties of the data, making it challenging to learn deeper features. In this study, the problem of data information loss in traditional denoising autoencoding is addressed by incorporating the concept of residual neural networks into an enhanced denoising autoencoder. In our experimental study, we applied this enhanced denoising autoencoder to the open-source Hepatitis C dataset and the results showed significant results in feature extraction. While existing baseline machine learning methods have less than 90% accuracy and integrated algorithms and traditional autoencoders have only 95% correctness, the improved IDAE achieves 99% accuracy in the downstream hepatitis C classification task, which is a 9% improvement over a single algorithm, and a nearly 4% improvement over integrated algorithms and other autoencoders. The above results demonstrate that IDAE can effectively capture key disease features and improve the accuracy of disease prediction in hepatitis C data. This indicates that IDAE has the potential to be widely used in the detection and management of hepatitis C and similar diseases, especially in the development of early warning systems, progression prediction and personalised treatment strategies. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization (WHO) has outlined a set of targets to achieve eliminating hepatitis C by 2030. In May 2022, Lithuanian health authorities initiated a hepatitis C virus (HCV) screening program to start working towards elimination. In the program, bonus was given to general practitioners (GPs) to promote and conduct anti-HCV tests for two situations: (1) one time testing for individuals born in 1945–1994 and (2) annual HCV testing for persons who inject drugs or are living with human immunodeficiency virus (HIV) regardless of age. This study aimed to model the current viral hepatitis C epidemiological status in Lithuania and to outline the requirements for WHO elimination targets using the first-year HCV screening results. Methods: Individuals were invited to participate in the anti-HCV screening by GPs during routine visits. Patients who tested positive were then referred to a gastroenterologist or infectious disease doctor for further confirmatory testing. If a patient received a positive RNA test and a fibrosis staging result of ≥ F2, the doctor prescribed direct-acting antivirals. Information on the patients screened, diagnosed, and treated was obtained from the National Health Insurance Fund. The Markov disease progression model, developed by the CDA Foundation, was used to evaluate the screening program results and HCV elimination progress in Lithuania. Results: Between May 2022 and April 2023, 790,070 individuals underwent anti-HCV testing, with 11,943 individuals (1.5%) receiving positive results. Anti-HCV seroprevalence was found to be higher among males than females, 1.9% and 1.2%, respectively. Within the risk population tested, 2087 (31.1%) seropositive individuals were identified. When comparing the screening program results to WHO elimination targets through modelling, 2180 patients still need to be treated annually until 2030, along with expanding fibrosis restrictions. If an elimination approach was implemented, 1000 new infections would be prevented, while saving 150 lives and averting 90 decompensated cirrhosis cases and 110 hepatocellular carcinoma cases. Conclusions: During the first year of the Lithuanian screening program, GPs were able to screen 44% of the target population. However, the country will not meet elimination targets as it currently stands without increasing treatment levels and lifting fibrosis restrictions. [ABSTRACT FROM AUTHOR]

Obesity is a global health problem and has been increasing in Egypt over the last several decades. A national population screening program for hepatitis C included screening for obesity. Here we report the outcome of body mass index (BMI) calculation for the screened population and for patients with hepatitis C. Methods Adults 18 years and older (a target population of 62.5 million) were invited to participate in a screening program between October 2018 and April 2019. Persons had their BMI calculated. All data were entered in real-time to a central database via cellular networks. BMI data for patients with hepatitis C virus (HCV) infection before starting direct antiviral therapy were obtained from the National Committee for the Control of Viral Hepatitis (NCCVH) Findings 49.6 million persons (25.6 million females and 24.0 million males) voluntarily participated and had valid height and weight data. 12.7 million females (49.51%) and 7.09 million males (29.53%) were affected by obesity (BMI ≥ 30kg/m2). Obesity increased with age, was more prevalent in females, was more prevalent in the Nile Delta states and in urban areas. Detailed district-level prevalence for the whole country is identified. Prevalence of obesity among 335,504 patients with HCV was higher in females, increased with age, and was significantly lower overall and in males and females than in the screened general population. Conclusion This is the largest population screening program for obesity. We show that obesity prevalence in the general population is currently among the highest in the world, starting in young adults, and highlight the high prevalence areas. Prevalence is lower in patients with HCV. [ABSTRACT FROM AUTHOR]

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

The hepatitis C virus (HCV) infection affects 58 million people worldwide. In the United States, the incidence rate of acute hepatitis C has doubled since 2014; during 2021, this increased to 5% from 2020. Acute hepatitis C is defined by any symptom of acute viral hepatitis plus either jaundice or elevated serum alanine aminotransferase (ALT) activity with the detection of HCV RNA, the anti-HCV antibody, or hepatitis C virus antigen(s). However, most patients with acute infection are asymptomatic. In addition, ALT activity and HCV RNA levels can fluctuate, and a delayed detection of the anti-HCV antibody can occur among some immunocompromised persons with HCV infection. The detection of specific biomarkers can be of great value in the early detection of HCV infection at an asymptomatic stage. The high rate of HCV replication (which is approximately 1010 to 1012 virions per day) and the lack of proofreading by the viral RNA polymerase leads to enormous genetic diversity, creating a major challenge for the host immune response. This broad genetic diversity contributes to the likelihood of developing chronic infection, thus leading to the development of cirrhosis and liver cancer. Direct-acting antiviral (DAA) therapies for HCV infection are highly effective with a cure rate of up to 99%. At the same time, many patients with HCV infection are unaware of their infection status because of the mostly asymptomatic nature of hepatitis C, so they remain undiagnosed until the liver damage has advanced. Molecular mechanisms induced by HCV have been intensely investigated to find biomarkers for diagnosing the acute and chronic phases of the infection. However, there are no clinically verified biomarkers for patients with hepatitis C. In this review, we discuss the biomarkers that can differentiate acute from chronic hepatitis C, and we summarize the current state of the literature on the useful biomarkers that are detectable during acute and chronic HCV infection, liver fibrosis/cirrhosis, and hepatocellular carcinoma (HCC). [ABSTRACT FROM AUTHOR]

Background: Globally, viral hepatitis is a leading cause of death and is highly prevalent in Ethiopia. Military personnel are more vulnerable to hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, and there are no data on such populations in the study area. Therefore, this study aimed to determine the seroprevalence of HBV and HCV infections and their associated factors among military personnel in military camps in Central Gondar, Ethiopia. Materials and Methods: This institutional-based cross-sectional study was conducted with 277 military personnel from April to August 2022 at military camps in Central Gondar, Ethiopia. A systematic random sampling technique was used to select the study participants. Sociodemographic and other relevant data were collected using a structured questionnaire. Five milliliters of venous blood were collected using a vacutainer tube and tested for hepatitis B surface antigens and anti-hepatitis C virus antibodies using an enzyme-linked immunosorbent assay. Data were analyzed using STATA version 14 software and logistic regression models were used to determine the association between HBV/HCV infection and risk factors. Results: Out of 277 participants, the overall seroprevalence of HBV and HCV infections was 19 (6.9%) and 9 (3.3%), respectively. The rate of HBV and HCV co-infection was 2 (0.7%). Having multiple sexual partners (p = 0.048), frequent alcohol use (p = 0.034), hospitalization (p = 0.014), and history of receiving injections from traditional practitioners (p = 0.040) were significant predictors of HBV infection. In contrast, a history of blood transfusion (p = 0.048) and sexually transmitted infections (p = 0.039) were significant risk factors for HCV infection. Conclusion and Recommendations: An intermediate prevalence of HBV and HCV infections was observed among the military personnel. Continuous screening, adherence to healthcare service guidelines, and strengthening of vaccination are crucial for preventing HBV and HCV infections. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) and hepatitis C virus (HCV) are major health concerns worldwide. Recent data indicate a decline in prevalence in the Saudi population; however, there are no data on the prevalence in prisoners. This study is the first to investigate the prevalence of viral hepatitis in female inmates in Jeddah, Saudi Arabia. This study aimed to explore the prevalence of HBV and HCV infections and to assess the knowledge and attitudes related to these infections among inmates. Methods: Inmates were interviewed using a pre-designed questionnaire, and their blood samples were tested for HBV and HCV infections using serology, PCR, and phylogenetic analysis. Results: The overall prevalence of HBV infection in the study population was 4.4%. The age group > 25 years was predominantly affected; 11.1% of the infected cases were Saudi nationals, and 88.9% were non-Saudis. The prevalence of HCV infection was 2.4%. Among the studied variables, age and previous employment were significantly associated with positive HBV PCR, while conviction, knowledge about protection from sexually transmitted infections (STIs), knowledge about condom use for protection against STIs, and condom use for protection against STIs were significantly associated with HCV infection. Conclusions: This study shows higher HBV and HCV prevalence in the female prisoners in Briman prison compared to the general population. Uneducated prisoners, over 25 years old, and convicted of prostitution are more associated with both HBV and HCV infection. Future preventive plans should include screening new prisoners with these risk factors for HBV and HCV at the time of entry. [ABSTRACT FROM AUTHOR]

The indigenous populations of the Arctic regions of Russia experience the lowest coverage of health-related services. We assessed the prevalence of hepatitis A, B, C, D and E viruses (HAV, HBV, HCV, HDV and HEV) among 367 healthy adult Native people of the Arctic zone of Yakutia. The HAV seroprevalence was above and increased with age. The anti-HEV IgM and IgG antibody detection rates were 4.1% and 2.5%, respectively. The average HBsAg detection rate was 4.6%, with no positive cases identified in participants aged under 30 years, confirming the effectiveness of the newborn vaccination program that began in 1998. Anti-HDV antibodies were detected in 29.4% of HBsAg-positive cases. The anti-HCV and HCV RNA detection rates peaked in the age cohort of 50–59 years (10.8% and 3.9%). No statistically significant gender differences in the prevalence of different viral hepatitis were observed. The time-scaled phylogenetic analysis demonstrated that all HBV genotype A and D strains isolated in this study were autochthonous and had an estimated most common recent ancestor (MCRA) age of around the 11th to 14th century. Unlike HBV, the HCV strains of subtypes 1b, 2a and 2k/1b were introduced from other regions of Russia in the 1980s and 1990s. The HCV 1b sequence analysis revealed a series of transmission events. In conclusion, these data emphasize the urgent need for expanded viral hepatitis screening and care programs in the indigenous populations of the Arctic zone of Yakutia. [ABSTRACT FROM AUTHOR]

Chronic viral infections present serious public health challenges; however, direct-acting antivirals (DAAs) are now able to cure nearly all patients infected with hepatitis C virus (HCV), representing the only cure of a human chronic viral infection to date. DAAs provide a valuable opportunity to study immune pathways in the reversal of chronic immune failures in an in vivo human system. To leverage this opportunity, we used plate-based single-cell RNA-seq to deeply profile myeloid cells from liver fine needle aspirates in patients with HCV before and after DAA treatment. We comprehensively characterised liver neutrophils, eosinophils, mast cells, conventional dendritic cells, plasmacytoid dendritic cells, classical monocytes, non-classical monocytes, and macrophages, and defined fine-grained subpopulations of several cell types. We discovered cell type-specific changes post-cure, including an increase in MCM7+STMN1+ proliferating CD1C+ conventional dendritic cells, which may support restoration from chronic exhaustion. We observed an expected downregulation of interferon-stimulated genes (ISGs) post-cure as well as an unexpected inverse relationship between pre-treatment viral load and post-cure ISG expression in each cell type, revealing a link between viral loads and sustained modifications of the host's immune system. We found an upregulation of PD-L1/L2 gene expression in ISG-high neutrophils and IDO1 expression in eosinophils, pinpointing cell subpopulations crucial for immune regulation. We identified three recurring gene programmes shared by multiple cell types, distilling core functions of the myeloid compartment. This comprehensive single-cell RNA-seq atlas of human liver myeloid cells in response to cure of chronic viral infections reveals principles of liver immunity and provides immunotherapeutic insights. This study is registered at ClinicalTrials.gov (NCT02476617). Chronic viral liver infections continue to be a major public health problem. Single-cell characterisation of liver immune cells during hepatitis C and post-cure provides unique insights into the architecture of liver immunity contributing to the resolution of the first curable chronic viral infection of humans. Multiple layers of innate immune regulation during chronic infections and persistent immune modifications after cure are revealed. Researchers and clinicians may leverage these findings to develop methods to optimise the post-cure environment for HCV and develop novel therapeutic approaches for other chronic viral infections. [Display omitted] • A comprehensive definition of human liver myeloid cell subsets in chronic viral hepatitis and post-cure. • MCM7+STMN1+ proliferating conventional dendritic cells were increased post-cure. • PD-L1+ ISG-high neutrophils and IDO1-high eosinophils may be immunoregulatory during chronic infections. • S100, MHC-II, and ISG were recurring gene programmes in the myeloid compartment. • Pre-treatment viral load was inversely related to post-cure ISG expression in each cell type in the host. [ABSTRACT FROM AUTHOR]

Background and Aims: Viral hepatitis is one of the top five reasons people die from infections all around the world. The present study aimed to assess the epidemiological features of hepatitis B and hepatitis C infections in Kohgiluyeh and Boyer‐Ahmad province. Methods: The data were obtained via the census method from the registered hepatitis B and hepatitis C data in the reportable disease care system of Yasuj University of Medical Sciences. The collected data are the result of serological tests. The χ2 test was used to evaluate the important risk factors for hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. The joinpoint regression was performed to investigate the trend of HBV and HCV in recent years. Results: Here, 1270 cases of hepatitis B and C were identified and reported in Kohgiluyeh and Boyer‐Ahmad province from 2008 to 2021. The median age of patients was 38 (interquartile range: 31–51), varying significantly according to the type of hepatitis. The most common hepatitis in males was hepatitis C and in females, hepatitis B. Regarding the place of residence, HBV and HCV were both more prevalent in urban areas. The age group of 25–34 years has the highest prevalence of HBV and HCV. According to the joinpoint regression analysis, there is a decrease in the 14‐year trend of incidence rate due to total hepatitis B and C: the annual percent change was −5.2% (95% confidence interval [CI]: −8.4 to −1.9, p = 0.005) for hepatitis B and −0.2% (95% CI: −10.7 to 11.6, p = 0.976) for hepatitis C. Conclusion: This study shows the incidence rate of hepatitis B has been decreasing during the years of study but this trend has been stable for hepatitis C. Also, the highest number of cases of hepatitis B and C were reported in the age groups of 25–34 years. Hence, preventive interventions are vital in reducing the burden of these diseases. [ABSTRACT FROM AUTHOR]

Altered gut microbiota has been connected to hepatocellular carcinoma (HCC) occurrence and advancement. This study was conducted to identify a gut microbiota signature in differentiating between viral-related HCC (Viral-HCC) and non-hepatitis B-, non-hepatitis C-related HCC (NBNC-HCC). Fecal specimens were obtained from 16 healthy controls, 33 patients with viral-HCC (17 and 16 cases with hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, respectively), and 18 patients with NBNC-HCC. Compositions of fecal microbiota were assessed by 16S rRNA sequencing. Bioinformatic analysis was performed by the DADA2 pipeline in the R program. Significantly different genera from the top 50 relative abundance were used to classify between subgroups of HCC by the Random Forest algorithm. Our data demonstrated that the HCC group had a significantly decreased alpha-diversity and changed microbial composition in comparison with healthy controls. Within the top 50 relative abundance, there were 11 genera including Faecalibacterium, Agathobacter, and Coprococcus that were significantly enhanced in Viral-HCC, while 5 genera such as Bacteroides, Streptococcus, Ruminococcus gnavus group, Parabacteroides, and Erysipelatoclostridium were enhanced in NBNC-HCC. Compared to Viral-HCC, the NBNC-HCC subgroup significantly reduced various short-chain fatty acid-producing bacteria, as well as declined fecal butyrate but elevated plasma surrogate markers of microbial translocation. Based on the machine learning algorithm, a high diagnostic accuracy to classify HCC subgroups was achieved with an area under the receiver-operating characteristic (ROC) curve (AUC) of 0.94. Collectively, these data revealed that gut dysbiosis was distinct according to etiological factors of HCC, which might play an essential role in hepatocarcinogenesis. These findings underscore the possible use of a gut microbiota signature for the diagnosis and therapeutic approaches regarding different subgroups of HCC. Key points: • Gut dysbiosis is connected to hepatocarcinogenesis and can be used as a novel biomarker. • Gut microbiota composition is significantly altered in different etiological factors of HCC. • Microbiota-based signature can accurately distinguish between Viral-HCC and NBNC-HCC. [ABSTRACT FROM AUTHOR]

Background and Aim: The prevalence of metabolic dysfunction‐associated fatty liver disease (MAFLD) and its interplay with hepatitis B virus (HBV) and hepatitis C virus (HCV) in terms of liver disease severity is elusive. Methods: A mass surveillance program was conducted in a viral hepatitis endemic area. The objective was to identify MAFLD/non‐MAFLD subjects with advanced liver disease. Results: Two thousand two hundred and forty‐two (41.7%) of the 5378 subjects were identified as having MAFLD, and 375 (7.0%) had advanced liver disease. The proportions of anti‐HCV and HBsAg seropositivity were 19.3% and 9.7%, respectively. The proportions of advanced fibrosis in subjects with non‐viral hepatitis (NBNC), HBV and HCV infection were 2.8%, 5.7% and 23.4%, respectively. Subjects with MAFLD had a significantly higher proportion of advanced fibrosis (8.7% vs 5.7%, P < 0.001). Factors associated with advanced fibrosis included age (odds ratio [OR]/95% confidence interval [CI]: 4.8/3.7–6.0, P < 0.001), male sex (OR/CI: 1.3/1.0–1.7, P = 0.019), anti‐HCV seropositivity (OR/CI: 5.9/4.6–7.5, P = 0.019), MAFLD‐lean metabolic dysregulation (MS) (OR/CI: 2.6/1.3–5.2, P = 0.005; compared with the non‐MAFLD group) and MAFLD‐diabetes (OR/CI: 1.5/1.1–2.1, P = 0.008; compared with the non‐MAFLD group). MAFLD did not aggravate liver disease severity in patients with viral hepatitis. However, among NBNC subjects, factors associated with advanced liver disease included MAFLD‐lean MS group (OR/CI: 9.1/2.4–34.6, P = 0.001; compared with non‐MAFLD group) and MAFLD‐DM group (OR/CI: 2.0/1.2–3.2, P = 0.004; compared with non‐MAFLD group). Conclusions: MAFLD patients with diabetes and metabolic dysregulation had a higher risk of advanced liver disease. The effect was more significant in non‐viral hepatitis subjects in a community level. [ABSTRACT FROM AUTHOR]

Background Hepatitis C virus (HCV) infection has been related in the etiology of many lymphomas. Follicular lymphoma (FL) is the most common subtype of indolent non-Hodgkin lymphoma. This comparative retrospective study aimed to identify a relationship between HCV and FL clinicopathologic features and neoplasm outcome. Patients and methods This study was conducted on 103 patients with FL who attended our institution during 2008– 2019. Results The prevalence of patients with HCV FL was 49.5% and showed significant B symptoms (P=0.023), advanced stages (P=0.016) with higher Follicular Lymphoma International Prognostic Index scores (P=0.042). Progression-free survival showed no differences regarding the viral infection or histological grades. Median overall survival showed significant improvement with histological grades 1–2 (P<0.0001), low Follicular Lymphoma International Prognostic Index, and HCV negative patients with FL, especially in the younger subgroup. Conclusion HCV positive patients with FL had a significantly more aggressive clinicopathological presentation and shorter overall survival. Thus, early virology screening and eradication of HCV infection in FL patients may improve the neoplasm course. [ABSTRACT FROM AUTHOR]

Background: Compliance with hemodialysis (HD) precautions is essential in preventing the transmission of viral hepatitis C Virus (HCV) and hepatitis B (HBV) in hemodialysis units. Aim of study: the study aimed to assess knowledge and practice of nurses toward Preventive measures of elderly patients with viral hepatitis B and C in the dialysis unit in Beni-Suef governorate. Research design: A descriptive design was used to achieve the aim of the current study. Setting, Beni-Suef university hospital and Elwasta general hospital Sample: A convenient sample of all hemodialysis nurses (76 nurses) in two hemodialysis units at Beni-suef and Elwasta general hospital, Egypt; include 42 nurses, form Beni-Suef university hospitaland 34 nurses, fromElwasta general hospital. Tools: one tool were designed to collect date pertinent to the study: Self-administered questionnaire to assess the subjects' level of knowledge, and observational checklist, used to assess subjects' level of practice. Results: More than half of nurses have fair level of total knowledge. Less than three quarters of nurses were incompetent regarding general preventive practices related to dialysis unit. Conclusion: Less than half of nurses have satisfactory of total knowledge about preventive measures of elderly patients with viral hepatitis B&C in dialysis unit. More than half of nurses have unsatisfactory regarding practices toward patient care.Recommendations: Conducting standards educational program that emphasize on improving knowledge level regarding prevention of viral hepatitis B&C transmission in dialysis units in order to raise awareness and correct misconceptions. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated fatty liver disease (MAFLD) has now affected nearly one-third of the global population and has become the number one cause of chronic liver disease in the world because of the obesity pandemic. Chronic hepatitis resulting from hepatitis B virus (HBV) and hepatitis C virus (HCV) remain significant challenges to liver health even in the 21st century. The co-existence of MAFLD and chronic viral hepatitis can markedly alter the disease course of individual diseases and can complicate the management of each of these disorders. A thorough understanding of the pathobiological interactions between MAFLD and these two chronic viral infections is crucial for appropriately managing these patients. In this comprehensive clinical review, we discuss the various mechanisms of chronic viral hepatitis-mediated metabolic dysfunction and the impact of MAFLD on the progression of liver disease. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is the most common cancer in Mongolia. The relative importance of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in HCC etiology is known to vary greatly from one part of the world to another. Principally, 95% of HCC patients have chronic viral hepatitis, including 53% hepatitis B virus, 38.9% HCV, and 5.6% have HBV/HCV coinfection. Hepatitis D virus (HDV) infection is widely spread in our country, anti-HDV has been found in more than 25% of carriers who have HBsAg. Materials and methods: We analyzed data of patients who had been diagnosed with acute viral hepatitis in the Department of adult hepatitis, National Center for Communicable Diseases in Mongolia from 1952 to 2018. Results: A total of 318,831 cases of acute viral hepatitis were registered in Mongolia between 1981 and 2019, which is 34.9 cases per 10,000 population. Of these, 265,931 cases of acute viral hepatitis A, or 28.6 per 10,000 populations, 48,855 cases of acute viral hepatitis B, or 5.5 cases per 10,000 populations, and 2,607 cases of acute viral hepatitis C, or 0.4 cases per 10,000 populations were recorded. Conclusion: The prevalence of viral hepatitis in our country was the highest in 1981-1991, but since 2012, the prevalence of infection has steadily decreased. In Mongolia, since 1960, multifaceted programs and activities to combat viral hepatitis have been successfully implemented at the national level. [ABSTRACT FROM AUTHOR]

More than 2 million adults have hepatitis C virus (HCV) infection in the United States, and new infections continue to increase. Without treatment, HCV infection can lead to advanced liver disease and death. Treatment is recommended for nearly everyone with hepatitis C, resulting in a cure in >95% of people treated and raising the possibility of hepatitis C elimination. Testing is the first step to accessing life-saving treatment. The Centers for Disease Control and Prevention recommends hepatitis C screening for all adults, all pregnant persons, and anyone with risk; yet about one-third of people with hepatitis C remain unaware of their infection. Testing begins with a hepatitis C antibody test, followed, when reactive, by a nucleic acid test to detect HCV RNA. This antibody-first, 2-step testing strategy misses early infections and can result in incomplete diagnoses. Advancements in hepatitis C diagnostics and the US regulatory landscape have created an opportunity to include viral-first testing strategies and improve hepatitis C diagnosis. This journal supplement features 8 articles detailing challenges and opportunities for improving hepatitis C diagnostics in support of advancing hepatitis C elimination in the United States. [ABSTRACT FROM AUTHOR]

Lenvatinib has been approved as one of the first‐line treatments for advanced hepatocellular carcinoma (HCC) due to its high treatment efficacy being non‐inferior to sorafenib. Previous studies have shown well‐controlled viremia contributes to the prognosis of HCC patients receiving first‐line sorafenib; hence, we postulated this association might also exist in HCC patients with lenvatinib treatment. From April 2018 to December 2021, 201 unresectable HCC patients with first‐line lenvatinib treatment in our institute were assessed. High‐effect nucleoside analogues were administered for hepatitis B virus (HBV) control, while direct‐acting antivirals were used for hepatitis C virus (HCV) elimination. Based on our previous study, well‐controlled viremia was defined as patients who had undetectable viremia, or who had been receiving antivirals at least 6 months before lenvatinib. This study enrolled 129 patients, including 85 patients with HBV‐related HCC (HBV‐HCC) and 44 patients with HCV‐related HCC (HCV‐HCC), respectively. Progression‐free survival (PFS) and overall survival (OS) rates between the two groups were not different. Before administration of lenvatinib, 57.1% of the HBV‐HCC patients and 88.4% of the HCV‐HCC patients had well‐controlled viremia, and their PFS (8.8 vs. 3.1 months, p < 0.001) and OS (30.2 vs. 12.8 months, p = 0.041) were better than those who had uncontrolled viremia; moreover, well‐controlled viremia reduced tumor progression in multivariate analysis (Hazard ratio: 0.41, 95% confidence interval: 0.25–0.68, p = 0.001) after adjusting for albumin–bilirubin grade and concurrent treatment. HBV or HCV infection was not associated with tumor progression of HCC patients receiving lenvatinib, but viremia, controlled or not, was. [ABSTRACT FROM AUTHOR]

Patients suffering from hemodialysis, thalassemia, transfusions of blood, or any other form of liver disease have lately been found to have a high prevalence rate of hepatitis C and B viruses. They are containing and regaining control of this epidemic., The hepatitis C virus (HCV) is a small, enveloped, single-stranded, positive-sense RNA virus. It is a member of the genus Hepacivirus in the family Flaviviridae. There are seven major genotypes of HCV, which are known as genotypes one to seven., Several clinical pictures have been associated with this type of infection. It may be found in people with anti-hepatitis-C antibodies but with normal serum levels of liver enzymes; in antibody-negative people with ongoing elevated liver enzymes of unknown cause; in healthy populations without evidence of liver disease; and in groups at risk for HCV infection including those on hemodialysis or family members of people with occult HCV. [ABSTRACT FROM AUTHOR]

Objectives: Metabolic syndrome (MetS) and hepatitis C virus (HCV) are associated with a higher risk of impaired pulmonary function (iPF). This study aimed to investigate the relationships among MetS, iPF, and viral hepatitis. Methods: This community-based study enrolled participants undergoing annual health check-ups in southern Taiwan between March and December 2019. We performed multivariable logistic regression analyses adjusted for demographics and characteristics to identify the factors associated with iPF. Results: A total of 2337 participants completed examinations, of whom 928 (39.7%) had iPF. The participants with iPF were elderly (68.8 ± 12.8 years old) and predominately female (63%). MetS increased the risk of iPF (odds ratio (OR) 1.51, 95% confidence interval (CI) 1.27–1.81, p < 0.001). Beyond age (OR 1.03, 95% CI 1.02–1.04) and smoking (OR 1.309, 95% CI 1.004–1.705), female sex (OR 0.74, 95% CI 0.59–0.93) and high education level (OR 0.96, 95% CI 0.94–0.98, p < 0.001) protected against iPF. HCV was not significantly associated with iPF (OR 1.17, 95% CI 0.90–1.52, p = 0.235) in multivariable analysis. MetS was associated with a higher risk of iPF in the non-HBV/HCV group (OR 1.86, 95% CI 1.54–2.26) and HBV alone group (OR 3.44, 95% CI 1.89–6.28), but not in the HCV alone group (OR 1.02, 95% CI 0.64–1.62). Discussion: MetS was an independent predictor of iPF, especially the restrictive type, and had different effects in the HBV/non-viral hepatitis and HCV groups. Female sex and education were inversely associated with iPF. [ABSTRACT FROM AUTHOR]

Background: The United Kingdom (UK) has committed to the World Health Organization's viral hepatitis elimination targets. New case finding strategies, such as antenatal testing, may be needed to achieve these targets. We conducted a rapid review to understand hepatitis C-specific antibody (anti-HCV) and HCV RNA test positivity in antenatal settings in the United Kingdom to inform guidance. Methods: Articles and conference abstracts published between January 2000 and June 2022 reporting anti-HCV testing in antenatal settings were identified through PubMed and Web of Science searches. Results were synthesised using a narrative approach. Results: The search identified 2,011 publications; 10 studies were included in the final synthesis. Seven studies used anonymous testing methods and three studies used universal opt-out testing. Anti-HCV test positivity ranged from 0.1 to 0.99%, with a median value of 0.38%. Five studies reported HCV RNA positivity, which ranged from 0.1 to 0.57% of the testing population, with a median value of 0.22%. One study reported cost effectiveness of HCV and found it to be cost effective at £9,139 per quality adjusted life years. Conclusion: The relative contribution of universal opt-out antenatal testing for HCV should be reconsidered, as antenatal testing could play an important role in new case-finding and aid achieving elimination targets. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) and hepatitis C virus (HCV) are amongst the most common causative agents of viral hepatitis with its severe complications, including liver cirrhosis, decompensation, and hepatocellular carcinoma (HCC). Elimination of viral hepatitis, a significant challenge, has become an adopted global goal with certainly designed targets set by the World Health Assembly to be met by 2030. While many countries, including Egypt, have started executive plans for viral hepatitis elimination and achieved remarkable progress, the emergence of the COVID-19 pandemic has markedly affected all the machinery of the healthcare systems and specifically laid countries off their track in their viral hepatitis elimination process. The pandemic disrupted most healthcare services, and health staff and hospital resources were recruited mainly for managing the crisis, which significantly negatively impacted the management of other less severe diseases, including viral hepatitis. Social distancing and restrictive measures applied by most countries to contain the pandemic have affected medical services offered to patients with hepatitis. All supply chains of medications and vaccinations concerned with treating and preventing viral hepatitis have been markedly compromised. Many efforts and strategies are required to combat the severe and deleterious implications of the pandemic on the management of viral hepatitis worldwide in an attempt to get the situation under control and resume the pathway towards viral hepatitis elimination. [ABSTRACT FROM AUTHOR]

This article provides an overview of the role of lipid droplets (LDs) in metabolic-associated fatty liver disease (MASLD), alcohol-associated liver disease (ALD), and hepatitis C. LDs are involved in the storage of lipids and other compounds in cells. The article discusses the biogenesis of LDs, their impact on disease progression, and the role of LD proteins. It highlights the deleterious effects of LD accumulation in the liver and its association with the development of other metabolic diseases. The article also explores how alcohol impairs hepatic lipid metabolism and LD biology in ALD, as well as the interaction between the HCV virus and LDs in hepatitis C. The text emphasizes the importance of understanding LD biology for the development of diagnostic and therapeutic approaches for liver diseases. [Extracted from the article]

Hepatitis C virus (HCV) alters gene expression epigenetically to rearrange the cellular microenvironment in a beneficial way for its life cycle. The host epigenetic changes induced by HCV lead to metabolic dysfunction and malignant transformation. Lysine-specific demethylase 1 (LSD1) is an epigenetic controller of critical cellular functions that are essential for HCV propagation. We investigated the putative role of LSD1 in the establishment of HCV infection using genetic engineering and pharmacological inhibition to alter endogenous LSD1 levels. We demonstrated for the first time that HCV replication was inhibited in LSD1-overexpressing cells, while specific HCV proteins differentially fine-tuned endogenous LSD1 expression levels. Electroporation of the full-length HCV genome and subgenomic replicons in LSD1 overexpression enhanced translation and partially restored HCV replication, suggesting that HCV might be inhibited by LSD1 during the early steps of infection. Conversely, the inhibition of LSD1, followed by HCV infection in vitro, increased viral replication. LSD1 was shown to participate in an intriguing antiviral mechanism, where it activates endolysosomal interferon-induced transmembrane protein 3 (IFITM3) via demethylation, leading endocytosed HCV virions to degradation. Our study proposes that HCV-mediated LSD1 oscillations over countless viral life cycles throughout chronic HCV infection may promote epigenetic changes related to HCV-induced hepatocarcinogenesis. [ABSTRACT FROM AUTHOR]

Data on the acceptability and usability of hepatitis C virus self‐testing (HCVST) remain scarce. We estimated the pooled rates of acceptability/feasibility and re‐reading/re‐testing agreement of HCVST using oral fluid tests (PROSPERO‐CRD42022349874). We searched online databases for studies that evaluated acceptability, usability and inter‐reader/operator variability for HCVST using oral fluid tests. Pooled estimates of feasibility, agreement and post‐testing perspectives were analysed. Sensitivity analyses were performed in men who have sex with men (MSM) and people who inject drugs (PWID). Heterogeneity was assessed using the I2 statistics. A total of six studies comprising 870 participants were identified: USA (n = 95 with liver disease), Kenya (n = 150 PWID), Egypt (n = 116 from the general population), Vietnam (n = 104 MSM and n = 105 PWID), China (n = 100 MSM) and Georgia (n = 100 MSM and n = 100 PWID)]. All studies used OraQuick® HCV Rapid Antibody Test. The pooled overall estimates for correct sample collection and for people who performed HCVST without needing assistance in any step (95% confidence interval [CI]) were 87.2% [76.0–95.3] (n = 755; I2 = 93.7%) and 62.6% [37.2–84.8] (n = 755; I2 = 98.0%), respectively. The pooled estimate of agreement for re‐reading was 95.0% [95% CI 91.5–97.6] (n = 831; I2 = 74.0%) and for re‐testing was 94.4% [90.3–97.5] (n = 726; I2 = 77.1%). The pooled estimate of those who would recommend HCVST was 94.4% [84.7–99.6] (n = 625; I2 = 93.7%). Pooled estimates (95% CI) of correct sample collection (72.8% [63.3–81.5] vs. 90.8% [85.9–94.8]) and performance of HCVST without needing assistance (44.1% [14.1–76.7] vs. 78.1% [53.4–95.3]) was lower in PWID compared to MSM. In summary, HCV testing with oral fluid HCVST was feasible and well‐accepted. Oral fluid HCVST should be considered in key populations for uptake HCV testing. [ABSTRACT FROM AUTHOR]

Viral hepatitis is a global health concern mostly caused by hepatitis B virus (HBV) and hepatitis C virus (HCV). The late diagnosis and delayed treatment of HBV and HCV infections can cause irreversible liver damage and the occurrence of cirrhosis and hepatocellular carcinoma. Detecting the presence and activity of HBV and HCV is the cornerstone of the diagnosis and management of related diseases. However, the traditional method shows limitations. The utilization of nanomaterials has been of great significance in the advancement of virus detection technologies due to their unique mechanical, electrical, and optical properties. Here, we categorized and illustrated the novel approaches used for the diagnosis of HBV and HCV. [ABSTRACT FROM AUTHOR]

Viral infections in humans are responsible for fatalities worldwide and contribute to the incidence of various human ailments. Controllable targeted medicine delivery against many illnesses, including viral infection, may be significantly aided by using bacteria and bacteria-derived products. They may accumulate in diseased tissues despite physical obstacles, where they can launch antiviral immunity. The ability to genetically and chemically modify them means that vaccinations against viral infections may be manufactured and delivered to affected tissues more safely and effectively. The objective of this study is to provide an overview of the latest advancements in the field of utilizing bacteria and bacterial derivatives as carriers for administering medication to treat viral diseases such as SARS-CoV-2, hepatitis B virus, hepatitis C virus, human immunodeficiency virus, human papillomavirus, influenza, and Ebola virus. [ABSTRACT FROM AUTHOR]

Although hepatitis B virus (HBV) and hepatitis C virus (HCV) are hepatotrophic viruses, they may affect pulmonary diseases. The purpose of this study was to assess whether chronic viral hepatitis (CVH) infection was associated with a rapid decline in lung function. Repeated measurements of lung function were obtained from a well-curated health check-up database. A case was defined as an individual positive for HBsAg or anti-HCV antibody. A control was randomly selected (from the same dataset) after 1:1 matching in terms of age, sex, height, the body mass index, and smoking status. Separate analyses of non-smokers and smokers were performed. A total of 701 cases were enrolled (586 with HBV and 115 with HCV). In cross-sectional analysis, both forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) decreased significantly only in smokers (smoking cases vs. smoking controls) (adjusted p = 6.6 × 10−5 and adjusted p = 2.2 × 10−3, respectively). In longitudinal analysis, smoking cases showed significantly greater FEV1 and FVC decline rates than did smoking controls (adjusted p = 8.5 × 10−3 and adjusted p = 1.2 × 10−5, respectively). Such associations were particularly high in smoking cases at intermediate-to-high risk of hepatic fibrosis, as evaluated by the non-invasive Fibrosis-4 index. In summary, CVH was associated with both decreased lung function and accelerated lung function decline in smokers. A non-invasive measurement of hepatic fibrosis may be useful in predicting rapid lung function decline in smokers with CVH. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) represents one of the most common cancers worldwide, and it is a very important reason for cancer-related death. Infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) is considered the major leading cause of HCC. The pathophysiology of HB and HC viral-related HCC includes chronic inflammation, deorganization of cell signaling pathways, and oxidative stress. Contrary to HCV, HBV is oncogenic by itself, due to its integration into the DNA of cell. Six months of ultrasound monitoring is recommended for high-risk patients. Using antiviral drugs to manage viral hepatitis decreases the risk of evolution and reoccurrence of HCC. Also, effective preventive measures are very important in decreasing the risk of HCC. The prevention involves primary prevention which is based on HBV vaccination, treatment of acute infection, and eliminating the route of transmission, while secondary prevention is based on using antiviral drugs against HBV and HCV infection to prevent the progress of disease into carcinoma. However, tertiary prevention involves treating the carcinoma to prevent the reoccurrence of the cancer. [ABSTRACT FROM AUTHOR]

Nonprofit and nongovernmental organizations have driven and continue to drive hepatitis C elimination by putting people with viral hepatitis and their affected communities at the center of hepatitis elimination efforts. They have been key in driving the decentralization of services and community-based delivery in the hepatitis care pathway to improve the health and well-being of the populations most affected by hepatitis C. This article explores how the formation of the World Hepatitis Alliance (WHA), an international network of community organizations in >100 countries, led to powerful advocacy from community leaders and people with hepatitis, resulting in the establishment of World Hepatitis Day. Since then, the World Health Organization (WHO) has recognized the importance of viral hepatitis by setting the 2030 global elimination targets. WHA and WHO have collaborated on 3 World Hepatitis Summits, which have built momentum across many sectors to help elevate hepatitis through the global health agenda. The article discusses their paradigm-shifting campaigns and also presents civil society organizations' hepatitis elimination efforts in Egypt, Mongolia, Bangladesh, and the United Kingdom and their significant impact through local resource mobilization and engagement of national governments. [ABSTRACT FROM AUTHOR]

Background Pakistan has a high hepatitis burden for both hepatitis C virus (HCV) and hepatitis B virus (HBV). To achieve World Health Organization (WHO) 2030 targets for hepatitis elimination, there is a need to constitute progress in the country, find the barriers and strategies for HCV elimination, and take actions to address the gaps. Methods We collected data from (1) WHO estimates in 2020, (2) midterm review questionnaire of the WHO regional action plan, and (3) WHO estimates on immunization. We analyzed these data to inform (1) the burden defined as prevalence and mortality and (2) response in 3 thematic areas: governance, policy, and finance; strategic information; and service delivery. Results The prevalence of hepatitis B in the general population is 1.6% with 12 000 deaths/year. The prevalence of hepatitis C in the general population is 7.5% with 19 000 deaths and 545 000 new cases (incidence)/year. The selected indicators to monitor progress on viral hepatitis in Pakistan were governance and financing, policies and guidelines, and strategic information. The overall governance indicators are good with a focal point, a national hepatitis strategy, an operational plan, strategy for price reduction, and involvement of civil society but the costed action plan and the advocacy strategy are missing. The indicators on policies and guidelines are also adequately addressed. The hepatitis B and C testing and treatment guidelines are available, there is a policy to screen all blood donations, and there is an injection safety policy, but the policy for timely hepatitis B vaccine birth dose and hepatitis B vaccination for the vulnerable is missing. Both indicators regarding strategic information, that is measures of key hepatitis indicators and regular data review, are missing. The status of 5 key interventions in Pakistan show that the hepatitis B vaccination coverage is 74% and only 3% of newborn children are given the hepatitis B vaccine birth dose. Only 22% of HCV cases have been diagnosed and 2% have received treatment. Treatment response is 96%. Same-day testing and treatment of hepatitis C reduced the overall dropout rate and improved the cascade of care. Decentralization and task shifting are important tools to improve service delivery and reach communities. Finances to implement hepatitis elimination is a major barrier. Conclusions Pakistan has the highest hepatitis disease burden. With the current pace, hepatitis elimination appears impossible. Introduction of the birth dose of hepatitis B vaccine and improving access and affordability of testing can improve the testing and treatment numbers. Finances need to be mobilized from within the country and outside to support disease elimination. [ABSTRACT FROM AUTHOR]