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The multiple regression model statistical technique is employed to analyze the relationship between the dependent variable and several independent variables. The multicollinearity problem is one of the issues affecting the multiple regression model, occurring in regard to the relationship among independent variables. The ordinal least square is the standard method to evaluate parameters in the regression model, but the multicollinearity problem affects the unstable estimator. Liu regression is proposed to approximate the Liu estimators based on the Liu parameter, to overcome multicollinearity. In this paper, we propose a modified Liu parameter to estimate the biasing parameter in scaling options, comparing the ordinal least square estimator with two modified Liu parameters and six standard Liu parameters. The performance of the modified Liu parameter is considered, generating independent variables from the multivariate normal distribution in the Toeplitz correlation pattern as the multicollinearity data, where the dependent variable is obtained from the independent variable multiplied by a coefficient of regression and the error from the normal distribution. The mean absolute percentage error is computed as an evaluation criterion of the estimation. For application, a real Hepatitis C patients dataset was used, in order to investigate the benefit of the modified Liu parameter. Through simulation and real dataset analysis, the results indicate that the modified Liu parameter outperformed the other Liu parameters and the ordinal least square estimator. It can be recommended to the user for estimating parameters via the modified Liu parameter when the independent variable exhibits the multicollinearity problem. [ABSTRACT FROM AUTHOR]

Elimination of hepatitis C virus (HCV) without the need for medical intervention, known as spontaneous clearance (SC), occurs at a significantly lower rate than in the case of hepatitis B virus infection and only in selected individuals, such as reportedly in Keith Richards, a guitarist of The Rolling Stones. The present paper provides an updated narrative review of the research devoted to the phenomenon in order to identify and discuss the demographic, lifestyle-related, clinical, viral genotype-related, and host genetic factors underpinning the SC occurrence. The body of evidence indicates that the likelihood of SC is decreased in older individuals, men, Black people, HIV-coinfected subjects, and intravenous drug and alcohol users. In turn, HBV coinfection and specific polymorphism of the genes encoding interferon lambda 3 (particularly at rs8099917) and interferon lambda 4 (particularly at rs12979860) and HLA genes increase the odds of SC. Numerous other host-specific genetic factors could be implicated in SC, but the evidence is limited only to certain ethnic groups and often does not account for confounding variables. SC of HCV infection is a complex process arising from a combination of various factors, though a genetic component may play a leading role in some cases. Understanding factors influencing the likelihood of this phenomenon justifies better surveillance of high-risk groups, decreasing health inequities in particular ethnic groups, and may guide the development of a prophylactic vaccine, which at present is not available, or novel therapeutic strategies. Further research is needed to elucidate the exact mechanisms underlying SC and to explore potential interventions that could enhance this natural antiviral response. [ABSTRACT FROM AUTHOR]

The paper focuses on the hepatitis C virus (HCV) infection in Egypt, which has one of the highest rates of HCV in the world. The high prevalence is linked to several factors, including the use of injection drugs, poor sterilization practices in medical facilities, and low public awareness. This paper introduces a hyOPTGB model, which employs an optimized gradient boosting (GB) classifier to predict HCV disease in Egypt. The model's accuracy is enhanced by optimizing hyperparameters with the OPTUNA framework. Min-Max normalization is used as a preprocessing step for scaling the dataset values and using the forward selection (FS) wrapped method to identify essential features. The dataset used in the study contains 1385 instances and 29 features and is available at the UCI machine learning repository. The authors compare the performance of five machine learning models, including decision tree (DT), support vector machine (SVM), dummy classifier (DC), ridge classifier (RC), and bagging classifier (BC), with the hyOPTGB model. The system's efficacy is assessed using various metrics, including accuracy, recall, precision, and F1-score. The hyOPTGB model outperformed the other machine learning models, achieving a 95.3% accuracy rate. The authors also compared the hyOPTGB model against other models proposed by authors who used the same dataset. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C virus (HCV) infection presents a significant public health challenge globally, particularly in high-burden countries like Nigeria, where an estimated 2.4 million individuals are living with HCV. HCV self-testing (HCVST) can potentially bridge the significant diagnosis gap and help individuals to determine their HCV status in the privacy of their homes. It offers a solution to overcome barriers related to stigma and limited access to healthcare. In Nigeria, Self-testing for hepatitis C has only been implemented in a pilot research context. This study aimed to assess stakeholder and community awareness and perceptions of HCVST in Nigeria. The findings will provide insights that could inform effective policies and future scale-up programs for HCV control. Methods: A cross-sectional descriptive study was conducted using an online social media survey administered through SurveyMonkey. The survey was disseminated across social media platforms and groups between October–November 2023. Participants included Nigerians (both health professionals and non-health professionals) aged 18 years or older residing in any of the 36 states and the Federal Capital Territory (FCT). Data collected include sociodemographic characteristics, awareness and perceptions of HCVST, and perceived benefits and barriers. Results: Of 321 respondents, 94% perceived HCVST as highly important. While 77% of respondents knew about HIVST, only 58% had prior knowledge of HCVST. The analysis also showed that healthcare workers had greater awareness of HIV self-testing (82.3%) compared to non-healthcare workers (50.0%). Most respondents (88%) were highly likely to recommend HCVST and perceived it as a cost-effective alternative to traditional testing. Key perceived benefits included increased disease detection and control (67%), improved access to testing (21%), and reduced stigma (11%). In the unadjusted model, geographical zone (Southern Nigeria: cOR = 0.49, 95% CI: 0.30–0.77, p = 0.002), work experience (more than 20 years: cOR = 2.79, 95% CI: 1.11–8.07, p = 0.039), and prior awareness of HIV self-testing (cOR = 5.24, 95% CI: 3.00–9.43, p < 0.001) were significant predictors of HCVST awareness. However, in the adjusted model, only prior awareness of HIV self-testing remained significant (aOR = 4.77, 95% CI: 2.62–8.94, p < 0.001). Conclusions: The strong support for HCVST among stakeholders in Nigeria highlights its potential to enhance HCV control, especially within the broader context of infectious diseases like STIs. The greater awareness of HIV self-testing among healthcare workers compared to non-healthcare workers indicates the need for targeted awareness campaigns for non-healthcare populations. Addressing these awareness gaps, leveraging lessons from HIVST, and using existing infrastructure will be crucial. Prioritizing public education, outreach, and effective linkage to care will drive the impact of HCVST in achieving HCV elimination goals and position it as a model for expanding similar STI interventions in Nigeria. [ABSTRACT FROM AUTHOR]

The prevalence of transfusion-transmissible infections (TTIs) among blood donors is critical for ensuring blood safety. Aim: To provide an updated assessment of TTIs at a tertiary care hospital in Mexico over a ten-year period. We conducted a retrospective cross-sectional study. Blood samples were analyzed from potential donors at tertiary care hospital between 2012 and 2022. Donors completed a questionnaire and were screened for HIV, syphilis, hepatitis B, and hepatitis C using nucleic acid testing and serological tests. Prevalence and trends were estimated. Among the 117,756 donors analyzed, 0.48% were positive for syphilis, with a significant annual decrease of −5.9% (p < 0.001), although notable fluctuations occurred, including a peak in 2021. HIV showed a significant annual increase of 9.8% (p = 0.029), with a peak in approximately 2019–2020. Hepatitis C maintained a stable trend, with a slight annual decrease of −5.6% (p = 0.170). Hepatitis B consistently decreased, with an annual decrease of −11.3% (p = 0.06). This study highlights the importance of continuous monitoring and screening of blood donors to ensure blood safety. These findings underscore the need for localized public health interventions, particularly to address the increasing incidence of HIV. Further research should focus on enhancing donor screening practices and public health strategies to reduce the prevalence of TTIs. [ABSTRACT FROM AUTHOR]

The hepatitis C virus (HCV) infection, a global health concern, can lead to chronic liver disease. The HCV core antigen (HCVcAg), a viral protein essential for replication, offers a cost-effective alternative to HCV RNA testing, particularly in resource-limited settings. This review explores the significance of HCVcAg, a key protein in the hepatitis C virus, examining its structure, function, and role in the viral life cycle. It also evaluates its clinical use in diagnosis and treatment monitoring, comparing its performance to the standard HCV RNA assay using data from PubMed and Google Scholar. HCVcAg assays show high pooled sensitivity (93.5%) and pooled specificity (99.2%) compared to HCV RNA assays, correlating closely (r = 0.87) with HCV RNA levels. Hence, HCVcAg testing offers a cost-effective way to diagnose active HCV infections and monitor treatment, especially in resource-limited settings, but its sensitivity can vary and standardization is needed. HCVcAg also predicts liver disease progression and assesses liver damage risk, aiding patient management. It helps to identify patients at risk for fibrosis or carcinoma, making it vital in hepatitis C care. HCVcAg testing can expand access to HCV care, simplify management, and contribute to global elimination strategies, especially in low- and middle-income countries. [ABSTRACT FROM AUTHOR]

In this review, recent advances in the combination of CRISPR–Cas systems with graphene-based electrolyte-gated transistors are discussed in detail. In the first part, the functioning of CRISPR–Cas systems is briefly explained, as well as the most common ways to convert their molecular activity into measurable signals. Other than optical means, conventional electrochemical transducers are also developed. However, it seems that the incorporation of CRISPR/Cas systems into transistor devices could be extremely powerful, as the former provides molecular amplification, while the latter provides electrical amplification; combined, the two could help to advance in terms of sensitivity and compete with conventional PCR assays. Today, organic transistors suffer from poor stability in biological media, whereas graphene materials perform better by being extremely sensitive to their chemical environment and being stable. The need for fast and inexpensive sensors to detect viral RNA arose on the occasion of the COVID-19 crisis, but many other RNA viruses are of interest, such as dengue, hepatitis C, hepatitis E, West Nile fever, Ebola, and polio, for which detection means are needed. [ABSTRACT FROM AUTHOR]

Hepatitis C is a disease for which in approximately 30 years we have gone from the discovery of the causative agent in 1989, to the introduction of direct-acting antiviral (DAAs) therapies starting from 2011, and to a proposal for its elimination in 2016, with some countries being on track for this goal. Elimination efforts, in the absence of a vaccine, rely on prevention measures and antiviral therapies. However, treatment rates have declined in recent years and are not considered adequate to achieve this goal at a global level. This poses a great epidemiological challenge, as HCV in many countries still causes a significant burden and most infected people are not yet diagnosed. Consequently, efforts are needed at different levels with common purposes: to facilitate access to screening and diagnosis and to improve linkage to care pathways. In this review, we discuss the latest epidemiological findings on HCV infection, the obstacles to its elimination, and strategies that are believed to be useful to overcome these obstacles but are applied unevenly across the world. [ABSTRACT FROM AUTHOR]

NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) is an intracellular complex that upon external stimuli or contact with specific ligands, recruits other components, forming the NLRP3 inflammasome. The NLRP3 inflammasome mainly mediates pyroptosis, a highly inflammatory mode of regulated cell death, as well as IL-18 and IL-1β production. Acute and chronic liver diseases are characterized by a massive influx of pro-inflammatory stimuli enriched in reactive oxygen species (ROS) and damage-associated molecular patterns (DAMPs) that promote the assemblage and activation of the NLRP3 inflammasome. As the major cause of inflammatory cytokine storm, the NLRP3 inflammasome exacerbates liver diseases, even though it might exert protective effects in regards to hepatitis C and B virus infection (HCV and HBV). Here, we summarize the current knowledge concerning NLRP3 inflammasome function in both acute and chronic liver disease and in the post liver transplant setting, focusing on the molecular mechanisms involved in NLRP3 activity. [ABSTRACT FROM AUTHOR]

Background: Direct oral anticoagulants (DOACs) are recommended for the management of thrombosis prophylaxis, especially in patients with atrial fibrillation. As substrates of cytochrome P450 (CYP) 3A4 and/or P-glycoprotein, they are implicated in potential drug–drug interactions. NS5A/NS5B inhibitors are direct-acting agents (DAAs) against the Hepatitis C Virus (HCV) infection that exert a mild inhibition of P-glycoprotein without effects on CYP3A4. A DOAC and NS5A/NS5B inhibitor co-administration may lead to an increased risk of bleeding. Real-world data on the concomitant use of DOACs and DAAs are scarce. On this purpose, we perform a retrospective analysis on the risk of vascular adverse events (bleeding and thrombosis) among HCV patients under DOAC/DAA therapy, even in advanced liver disease. Methods: Between May 2015 and April 2023, patients treated with sofosbuvir-based DAA regimens and DOACs were consecutively included in this study from 12 Italian medical centers. Baseline characteristics, especially concerning bleeding risk and liver function, were collected. The occurrence of bleeding events, classified as major and minor, was the primary endpoint. Secondary endpoints were the rate of any thrombotic events and/or the need for discontinuation of one or both treatments. Moreover, a cohort of patients, matched by demographic characteristics (age and sex), that switched to vitamin K antagonists (VKAs) during the antiviral treatment was compared with the DOAC/DAA group. Results: A total of 104 patients were included. Thirty-eight of them (36.5%) were cirrhotic. Atrial fibrillation was an indication for anticoagulation in almost all cases (76%). Rivaroxaban (35.6%) was the most used DOAC, followed by apixaban (26.9%), dabigatran (19.2%) and edoxaban (18.3%). Sofosbuvir/velpatasvir (78.8%) was the most prescribed DAA, and all patients were already on anticoagulant therapy before the start of DAAs. During concomitant DOAC/DAA treatment, no major bleeding events were recorded, while four minor bleeding events occurred, but none resulted in DAA or DOAC discontinuation. At univariate analysis, the only additional risk factor statistically related to bleeding events was the anticoagulant therapy (hazard ratio [HR]: 13.2, 95% confidence interval 1,6-109). Performing an evaluation by a LOGIT binomial analysis with demographic characteristics, the antiplatelet therapy remained statistically associated to bleeding events. No significant differences were found in the rate of clinically relevant bleeding when the main population was compared with the VKA-switched cohort. A single major bleeding event leading to anticoagulation and DAA discontinuation was reported in VKA-switched matched cohort. Conclusions: In our study, the concomitant use of NS5A/NS5B inhibitors with DOAC showed good safety, and the only risk factor associated with bleeding events was the concomitant antiplatelet therapy. These findings support the use of DOACs during sofosbuvir-based HCV treatment, even in advanced liver disease. Replacing DOACs with VKAs does not appear to be of clinical benefit. [ABSTRACT FROM AUTHOR]

Viral hepatitis (A–E) presents a major global health challenge. In 2015, the World Health Organization (WHO) launched an initiative to eliminate viral hepatitis, with the aim of reducing new infections by 90% and deaths by 65% by 2030. Mexico is one of 38 focus countries identified by the WHO, collectively accounting for 80% of global infections and deaths. While hepatitis B and C are commonly diagnosed in Mexico, routine diagnosis for hepatitis D and E is lacking, with no specific epidemiological data available. In 2020, Mexico implemented the National Hepatitis C Elimination Program, focusing on preventing new infections, reducing complications like cirrhosis and hepatocellular carcinoma, ensuring access to treatment, and improving patient care. However, this program has not been extended to hepatitis B and E. Addressing the challenges of viral hepatitis control in Mexico requires increased resource allocation, expanded diagnosis, vaccination for hepatitis A and B, and treatment coverage for hepatitis B and C, along with multisectoral engagement. This work provides an overview of Mexico's response to the global initiative, highlighting its progress, challenges, and areas of opportunity. [ABSTRACT FROM AUTHOR]

The Hepatitis C Virus (HCV) is a significant public health challenge in European countries. Historically, healthcare-related procedures were the primary source of HCV infection in Europe. However, with the implementation of blood safety programs, injection drug use has become the main transmission route. The infection's distribution and genotype prevalence vary widely across the continent. Even with the availability of highly effective direct-acting antiviral (DAA) therapies, HCV infection is far from being controlled. A significant proportion of patients remain undiagnosed, contributing to the ongoing transmission of the virus. Additionally, several barriers hinder the widespread use of DAAs, including high treatment costs, stigma, poor linkage to care, and considerable geographical variations in prevalence and transmission routes. The World Health Organization has set ambitious targets to reduce liver-related deaths, decrease new viral hepatitis infections, and ensure that 90% of infected individuals are diagnosed by 2030. However, most European countries face challenges, highlighting the need for screening programs, funding mechanisms, and public health strategies to effectively control HCV infection in Europe. [ABSTRACT FROM AUTHOR]

Background: This study aims to assess the efficacy of combining automated machine learning (AutoML) and explainable artificial intelligence (XAI) in identifying metabolomic biomarkers that can differentiate between hepatocellular carcinoma (HCC) and liver cirrhosis in patients with hepatitis C virus (HCV) infection. Methods: We investigated publicly accessible data encompassing HCC patients and cirrhotic controls. The TPOT tool, which is an AutoML tool, was used to optimize the preparation of features and data, as well as to select the most suitable machine learning model. The TreeSHAP approach, which is a type of XAI, was used to interpret the model by assessing each metabolite's individual contribution to the categorization process. Results: TPOT had superior performance in distinguishing between HCC and cirrhosis compared to other AutoML approaches AutoSKlearn and H2O AutoML, in addition to traditional machine learning models such as random forest, support vector machine, and k-nearest neighbor. The TPOT technique attained an AUC value of 0.81, showcasing superior accuracy, sensitivity, and specificity in comparison to the other models. Key metabolites, including L-valine, glycine, and DL-isoleucine, were identified as essential by TPOT and subsequently verified by TreeSHAP analysis. TreeSHAP provided a comprehensive explanation of the contribution of these metabolites to the model's predictions, thereby increasing the interpretability and dependability of the results. This thorough assessment highlights the strength and reliability of the AutoML framework in the development of clinical biomarkers. Conclusions: This study shows that AutoML and XAI can be used together to create metabolomic biomarkers that are specific to HCC. The exceptional performance of TPOT in comparison to traditional models highlights its capacity to identify biomarkers. Furthermore, TreeSHAP boosted model transparency by highlighting the relevance of certain metabolites. This comprehensive method has the potential to enhance the identification of biomarkers and generate precise, easily understandable, AI-driven solutions for diagnosing HCC. [ABSTRACT FROM AUTHOR]

Background: Analyzing hospitalizations of patients with hepatitis C virus (HCV) infection is essential for an effective action plan to eliminate hepatitis C as a public health threat. This study aimed to explore trends in hospitalizations of patients with HCV infection and factors related to these hospitalizations. Methods: This 11-year retrospective study (2012–2022) explored trends in hospitalizations of patients with HCV infection in Poland based on data from the Nationwide General Hospital Morbidity Study. Results: The mean age of individuals was 55 years, with hospitalization rates among men and women of 15.5 and 13.7 per 100,000 population, respectively. Hospitalizations were 1.8-fold higher among urban residents. The most frequent comorbidities were digestive (24%) and cardiovascular (18%) diseases. During the studied period, the hospitalization rates significantly decreased from 31.9 per 100,000 in 2012 to 5.0 per 100,000 in 2022, with stays requiring 0–3, 4–7, and ≥8 days becoming 8-fold, 6-fold, and 4-fold less frequent, respectively. The flattening of hospitalizations was apparent across all age groups, including children. Conclusions: While significant progress has been made in managing HCV in Poland, continued efforts are required to eliminate disparities in care and to sustain the momentum toward HCV elimination, particularly through enhanced political commitment and the implementation of comprehensive national screening programs. [ABSTRACT FROM AUTHOR]

To clarify the risk factors for the aggravation of esophagogastric varices (EGVs) after hepatitis C virus (HCV) eradication with direct-acting antiviral (DAA) therapy, we enrolled 167 consecutive patients with HCV-related compensated cirrhosis who achieved a sustained virological response (SVR) after DAA therapy. During a median of 69 months, EGVs were aggravated in 42 (25%) patients despite SVR. The cumulative 1-, 3-, 5-, and 10-year aggravated EGV rates were 7%, 23%, 25%, and 27%, respectively. Multivariate analysis identified a platelet count < 11.0 × 104/μL, LSM ≥ 18.0 kPa, total bile acid ≥ 33.0 μmol/L, and a diameter of left gastric vein (LGV) ≥ 5.0 mm at HCV eradication as independent risk factors for EGV aggravation post-SVR. In groups that met all of these risks, the cumulative EGV aggravation rates at 1, 3, and 5 years were 27%, 87%, and 91%, respectively. However, none of the patients who had only one or none of the risk factors experienced EGV aggravation. Platelet count, LSM, total bile acid, and diameter of LGV at HCV eradication were associated with aggravated EGV post-SVR. EGVs tend to worsen as two or more of these risk factors increase. [ABSTRACT FROM AUTHOR]

Background and Objectives: Sustained virologic responses (SVRs) lead to a decrease in portal hypertension, the regression of fibrosis, and the improvement in the hepatic synthesis of procoagulant and anticoagulant factors. We aimed to assess the influence of SVR on coagulation parameters in cirrhotic patients with HCV treated with DAAs. Methods: We performed a prospective study in the Institute of Gastroenterology and Hepatology Iasi, Romania, between January 2022 and February 2024. We included patients diagnosed with compensated and decompensated HCV-related liver cirrhosis, treated with direct antivirals (PrOD ± RBV or SOF/LED ± RBV) for 12/24 weeks. Blood samples for biochemical, immunological, and coagulation tests were collected at the baseline, end of treatment (EOT), and once sustained virological response had been achieved over a period of 12/24 weeks (SVR12/24). Results: We analyzed a group of 52 patients with HCV-related liver cirrhosis, predominantly female (68.0%), and the degree of severity of cirrhosis placed the patients mainly in Child–Pugh classes B (40%) and C (36%). All patients achieved SVRs. The MELD score decreased at EOT (13.48 ± 4.273; p = 0.001) and SVR (9.88 ± 2.774; p = 0.000), compared to the baseline (14.92 ± 4.707). The FibroScan values decreased at SVR (17.596 ± 3.7276; p = 0.000) compared to the baseline (26.068 ± 7.0954). For all common coagulation parameters (platelets, INR, PT, fibrinogen, aPTT), there was a trend towards improvement during treatment, including changes which were statistically significant for the majority of patients. Factor II was low at the baseline (75.40 ± 7.506) but increased at EOT (87.40 ± 9.587) and, later, at SVR (99.12 ± 11.695; p = 0.000). The FVIII values increased at the baseline (175.52 ± 16.414) and decreased at EOT (151.48 ± 13.703) and SVR (143.40 ± 13.937). The FvW values decreased during treatment (146.84 ± 9.428, at baseline; 141.32 ± 9.690, p = 0.000, at EOT; and 126.68 ± 17.960, at SVR). In regard to the anticoagulant factors (PC, PS, ATIII), a significant improvement was brought on by SVR. Advanced stages of liver disease showed the most diminished FII activity, while at the baseline and in Child–Pugh C patients we recorded the highest values of FVIII and FvW. Conclusions: Our study proved that the "reset" of coagulopathy might be due to the improvement in liver function due to viral eradication secondary to AAD therapy. [ABSTRACT FROM AUTHOR]

Hepatitis C (HCV) treatment for people who use drugs (PWUD) decreases injection drug use and injection equipment sharing. We examined changes in injection drug use and injection equipment sharing following HCV treatment in a randomized trial comparing peer-assisted telemedicine for HCV treatment (TeleHCV) versus peer-assisted usual care in rural PWUD. We hypothesize that TeleHCV reduces risky behaviors and peers facilitate this change. We used mixed-effects logistic regression to describe participant-level (n = 203) associations between both injection drug use and injection equipment sharing and randomized groups, frequency of peer contact, HCV treatment initiation, HCV cure, and time. Risky behaviors were surveyed at baseline and 12 and 36 weeks after HCV treatment completion. Injection drug use declined more over time in TeleHCV participants vs. control at 12 weeks (adjusted odds ratio [aOR] = 0.42, 95% CI 0.20–0.87, p = 0.02) and 36 weeks (aOR = 0.48, 95% CI 0.21–1.08, p = 0.076). Injection drug use decreased more with a greater number of peer interactions, with reductions among participants in the 3rd quartile exceeding those in the 1st quartile of peer interactions at 12 weeks (aOR = 0.75, 95% CI 0.57–0.99, p = 0.04). Similarly, injection equipment sharing decreased over time, with reductions among participants in the 3rd quartile exceeding those in the 1st quartile of peer interactions at 36 weeks (aOR = 0.08, 95% CI 0.01–0.97, p = 0.047). Peer-assisted telemedicine for HCV treatment decreases injection drug use and injection equipment sharing; peers contribute to this effect. [ABSTRACT FROM AUTHOR]

Simple Summary: The mortality of hepatocellular carcinoma (HCC) is rising globally, against the trend of other cancers. People with liver cirrhosis, even after hepatitis C treatment still face a high risk of HCC, requiring ongoing enrolment in HCC surveillance, and new technologies to improve diagnostic sensitivity are being explored. However, their impact on HCC survival remains uncertain relative to improving adherence to existing surveillance methods. This study uses mathematical modeling to assess how different strategies can reduce deaths from liver cancer in people with cirrhosis after being cured of hepatitis C. We compared the impact of improved adherence to ultrasound screening with increased HCC imaging sensitivity on HCC survival. Notably, we found that even modest enhancements in surveillance adherence (5–10 percentage point increases) exhibited significant survival benefits for people with hepatitis C-related cirrhosis, outperforming improvements in diagnostic sensitivity. Background & Aims: Hepatocellular carcinoma (HCC) presents a significant global health challenge, particularly among individuals with liver cirrhosis, with hepatitis C (HCV) a major cause. In people with HCV-related cirrhosis, an increased risk of HCC remains after cure. HCC surveillance with six monthly ultrasounds has been shown to improve survival. However, adherence to biannual screening is currently suboptimal. This study aimed to evaluate the effect of increased HCC surveillance uptake and improved ultrasound sensitivity on mortality among people with HCV-related cirrhosis post HCV cure. Methods: This study utilized mathematical modelling to assess HCC progression, surveillance, diagnosis, and treatment among individuals with cirrhosis who had successfully been treated for HCV. The deterministic compartmental model incorporated Barcelona Clinic Liver Cancer (BCLC) stages to simulate disease progression and diagnosis probabilities in 100 people with cirrhosis who had successfully been treated for hepatitis C over 10 years. Four interventions were modelled to assess their potential for improving life expectancy: realistic improvements to surveillance adherence, optimistic improvements to surveillance adherence, diagnosis sensitivity enhancements, and improved treatment efficacy Results: Realistic adherence improvements resulted in 9.8 (95% CI 7.9, 11.6) life years gained per cohort of 100 over a 10-year intervention period; 17.2 (13.9, 20.3) life years were achieved in optimistic adherence improvements. Diagnosis sensitivity improvements led to a 7.0 (3.6, 13.8) year gain in life years, and treatment improvements improved life years by 9.0 (7.5, 10.3) years. Conclusions: Regular HCC ultrasound surveillance remains crucial to reduce mortality among people with cured hepatitis C and cirrhosis. Our study highlights that even minor enhancements to adherence to ultrasound surveillance can significantly boost life expectancy across populations more effectively than strategies that increase surveillance sensitivity or treatment efficacy. [ABSTRACT FROM AUTHOR]

This study is a secondary analysis of a randomized clinical trial (October 2013–April 2017) involving 150 People Who Inject Drugs (PWIDs) with hepatitis C virus (HCV) seen in opioid agonist treatment programs in the Bronx, New York, and investigates the impact of distrust in the healthcare system on adherence to Direct-Acting Antivirals (DAAs) HCV treatment therapy among PWIDs. The distrust was scaled on a 9-item instrument and the adherence to DAA medications was measured using electronic blister packs. This study demonstrated a significant inverse relationship between levels of distrust and medication adherence: 71.8 ± 2.2% (se) vs. 77.9 ± 1.8%, p = 0.024 between participants with higher and lower distrust levels. Despite the absence of significant association of distrust with sociodemographic or substance use characteristics, these findings suggest that building trust within the healthcare system is paramount for improving adherence to DAAs among PWIDs. The results call for a healthcare approach that emphasizes trust-building through patient-centered care, sensitivity training, peer support, and health system reform to effectively address the treatment needs of this marginalized population. [ABSTRACT FROM AUTHOR]

Flavonoids are a group of natural compounds that have been described in the literature as having anti-inflammatory, antioxidant, and neuroprotective compounds. Although they are considered versatile molecules, little has been discussed about their antiviral activities for neurotropic viruses. Hence, the present study aimed to investigate the pharmacological potential of flavonoids in the face of viruses that can affect the central nervous system (CNS). We carried out research from 2011 to 2021 using the Pubmed platform. The following were excluded: articles not in the English language, letters to editors, review articles and papers that did not include any experimental or clinical tests, and papers that showed antiviral activities against viruses that do not infect human beings. The inclusion criteria were in silico predictions and preclinical pharmacological studies, in vitro, in vivo and ex vivo, and clinical studies with flavonoids, flavonoid fractions and extracts that were active against neurotropic viruses. The search resulted in 205 articles that were sorted per virus type and discussed, considering the most cited antiviral activities. Our investigation shows the latest relevant data about flavonoids that have presented a wide range of actions against viruses that affect the CNS, mainly influenza, hepatitis C and others, such as the coronavirus, enterovirus, and arbovirus. Considering that these molecules present well-known anti-inflammatory and neuroprotective activities, using flavonoids that have demonstrated both neuroprotective and antiviral effects could be viewed as an alternative for therapy in the course of CNS infections. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection is a global health concern with significant systemic implications, including a range of oral manifestations. This review aims to provide a comprehensive overview of the oral and dental pathologies related to HCV, the etiopathogenetic mechanisms linking such conditions to HCV and the impact of direct-acting antiviral (DAA) therapy. Common oral manifestations of HCV include oral lichen planus (OLP), periodontal disease, and xerostomia. The pathogenesis of these conditions involves both direct viral effects on oral tissues and indirect effects related to the immune response to HCV. Our literature analysis, using PubMed, Scopus, Web of Science, and Google Scholar, suggests that both the HCV infection and the immune response to HCV contribute to the increased prevalence of these oral diseases. The introduction of DAA therapy represents a significant advancement in HCV treatment, but its effects on oral manifestations, particularly OLP, are still under evaluation. Although a possible mechanism linking HCV to OSCC is yet to be determined, existing evidence encourages further investigation in this sense. Our findings highlight the need for established protocols for managing the oral health of patients with HCV, aiming to improve outcomes and quality of life. [ABSTRACT FROM AUTHOR]

The optimal strategy for the microelimination of HCV within community settings remains ambiguous. We evaluated the percentage of participants who achieved linkage to care (LTC) following the conclusion of a screening campaign and examined the diverse factors influencing LTC among these individuals. The effectiveness of recall intervention for the non-LTC population and its barriers were analyzed. We initiated an HCV patient recall program to identify HCV participants who might not be treated after the HCV screening campaign. The program staff recalled HCV participants who were lost to follow-up via telephone from March 2019 to June 2019. They were informed of HCV treatment's importance, efficacy, availability, and safety. Among 185 participants infected with HCV, 109 (58.9%) obtained LTC. Compared with those who had LTC, those without LTC were older, had lower education levels, were less aware of their HCV infection, less frequently lived in urban areas, and had less health insurance. At the end of the recall program, 125 (67.6%) persons had linkage to care. The proportion of LTC increased by 8.7%. In total, 119 persons had an HCV RNA test, and 82 (68.9%) had viremia. Of the 82 patients with viremia, 78 (95.1%) received antiviral therapy, and 76 (97.4%) achieved a sustained virological response. After a community screening campaign, 59% of participants with anti-HCV-positive tests had LTC. The recall program increased this by 9%. However, 32% of HCV participants still could not be linked to care. Outreach care for non-LTC patients is a method worth trying in order to achieve the microelimination of HCV in rural communities. [ABSTRACT FROM AUTHOR]

In Mexico, hepatitis B and C infections are a significant burden on the health system. The aim of this narrative review was to analyze the state of the art on hepatitis B and C in Mexico by searching and studying available data in academic articles and government reports and statements on epidemiology, prevention, treatment, and elimination strategies undertaken by the Mexican government. Even where the government has implemented a hepatitis B vaccination strategy to reduce its incidence, a very low proportion of people complete the vaccination schedule. Regarding hepatitis C, there is a National Elimination Program that emphasizes the importance of screening, diagnosis, and treatment focused on the population at risk. With the implementation of this program, more than a million fast tests have been carried out and the positive cases have been verified by viral load. Infected patients are tested to determine liver function, fibrosis stage, and coinfection with HBV and/or HIV. Patients without cirrhosis and/or coinfections are treated in first-level care centers, while those with cirrhosis and/or comorbidities are referred to specialists. The possibility of hepatitis C eradication in Mexico seems more likely than eradication of hepatitis B; however, major challenges remain to be overcome to reach both infections' elimination. [ABSTRACT FROM AUTHOR]

This study aims to evaluate the impact of liver fibrosis stages of chronic infection with hepatitis C virus (HCV) on the in vivo activity of organic cation transporters (hepatic OCT1 and renal OCT2) using metformin (MET) as a probe drug. Participants allocated in Group 1 (n = 15, mild to moderate liver fibrosis) or 2 (n = 13, advanced liver fibrosis and cirrhosis) received a single MET 50 mg oral dose before direct-acting antiviral (DAA) drug treatment (Phase 1) and 30 days after achieving sustained virologic response (Phase 2). OCT1/2 activity (MET AUC0–24) was found to be reduced by 25% when comparing the two groups in Phase 2 (ratio 0.75 (0.61–0.93), p < 0.05) but not in Phase 1 (ratio 0.81 (0.66–0.98), p > 0.05). When Phases 1 and 2 were compared, no changes were detected in both Groups 1 (ratio 1.10 (0.97–1.24), p > 0.05) and 2 (ratio 1.03 (0.94–1.12), p > 0.05). So, this study shows a reduction of approximately 25% in the in vivo activity of OCT1/2 in participants with advanced liver fibrosis and cirrhosis after achieving sustained virologic response and highlights that OCT1/2 in vivo activity depends on the liver fibrosis stage of chronic HCV infection. [ABSTRACT FROM AUTHOR]

Hepatitis C is regarded as a global health issue caused by hepatitis C virus (HCV) infection. HCV is targeted for elimination by 2030 as a global public health goal. However, the COVID-19 pandemic has changed human circulation and prevented access to diagnostics and treatment to many other diseases, including hepatitis C. COVID-19 impacted HCV global elimination efforts with implications not fully comprehended yet. The high genetic variability in HCV makes the development of vaccines and pan-genotypic drug therapies a difficult task. Changes in the dynamics of HCV impose new challenges for public health and opportunities for future research. Meta-analysis, the follow up of new cases and sampling of HCV patients compared with previously available data are options for investigating the possible changes. The determination of HCV genotypes and subtypes is important for understanding viral dynamics and treatment; therefore, the changes in genotype and subtype prevalences can directly affect such processes. Recent results in the literature already suggest changes in HCV dynamics during the COVID-19 pandemic, both considering viral circulation and differential genotypic frequencies in distinct geographic areas. In this context, we propose a further examination of these trends using different approaches to provide support for the hypothesis that the COVID-19 pandemic affected HCV circulation, since these findings would have important implications for hepatitis C prevention, treatment and research. [ABSTRACT FROM AUTHOR]

Prior to the Food and Drug Administration approval of ledipaspavir/sofosbuvir (Harvoni®) in 2014, the treatment of hepatitis C was interferon plus or minus ribavirin. This treatment had low cure rates for hepatitis C virus and was teratogenic and therefore avoided in pregnant patients. Vertical transmission is the most common transmission of hepatitis C in pediatric patients, whereas medical equipment that was not properly cleaned and sterilized, blood products which were not checked (historically), sharing and reusing syringes and needles, and dialysis are the most common forms of hepatitis C transmission in adults. The treatment of pregnant women with direct-acting antivirals is important because the treatment of pediatric patients cannot begin until three years of age and does not always occur prior to the symptom development of hepatitis C. This review article will include glecaprevir/pibrentasvir (Mayvret®), sofosbuvir/velpatasvir (Epclusa®), and sofosbuvir/velpatasvir plus voxilaprevir (Vosevi®). We aim to review the teratogenic risk of direct-acting antivirals as well as currently published clinical trials and ongoing research on direct-acting antiviral hepatitis C treatment in pregnancy in this publication. [ABSTRACT FROM AUTHOR]

Simple Summary: Immunotherapy has evolved as a leading therapeutic modality for several malignancies, and increasing evidence has shown its utility in the treatment of hepatocellular carcinoma. Specifically, immune checkpoint inhibitors have shown promise as an alternative treatment for this neoplasm. However, given their ability to reactivate the immune system, these treatments pose significant risks, specifically hepatitis viral reactivation, autoimmune hepatitis, and hepatotoxicity. Here, we aim to review the potential hepatic side effects associated with immune checkpoint inhibitors in the treatment of hepatocellular carcinoma. In doing so, we hope to provide an effective summary detailing our current understanding of the true risk of developing these side effects for providers considering immune checkpoint inhibitor therapy for their patients with hepatocellular carcinoma. Primary liver cancer is one of the leading causes of cancer mortality worldwide, with hepatocellular carcinoma (HCC) being the most prevalent type of liver cancer. The prognosis of patients with advanced, unresectable HCC has historically been poor. However, with the emergence of immunotherapy, specifically immune checkpoint inhibitors (ICIs), there is reason for optimism. Nevertheless, ICIs do not come without risk, especially when administered in patients with HCC, given their potential underlying poor hepatic reserve. Given their novelty in the management of HCC, there are few studies to date specifically investigating ICI-related side effects on the liver in patients with underlying HCC. This review will serve as a guide for clinicians on ICIs' role in the management of HCC and their potential side effect profile. There will be a discussion on ICI-related hepatotoxicity, the potential for hepatitis B and C reactivation with ICI use, the potential for the development of autoimmune hepatitis with ICI use, and the risk of gastrointestinal bleeding with ICI use. As ICIs become more commonplace as a treatment option in patients with advanced HCC, it is imperative that clinicians not only understand the mechanism of action of such agents but also understand and are able to identify hepatic-related side effects. [ABSTRACT FROM AUTHOR]

Endoplasmic reticulum (ER) stress, a type of cellular stress, always occurs when unfolded or misfolded proteins accumulating in the ER exceed the protein folding capacity. Because of the demand for rapid viral protein synthesis after viral infection, viral infections become a risk factor for ER stress. The hepatocyte is a cell with large and well-developed ER, and hepatitis virus infection is widespread in the population, indicating the interaction between hepatitis viruses and ER stress may have significance for managing liver diseases. In this paper, we review the process that is initiated by the hepatocyte through ER stress against HBV and HCV infection and explain how this information can be helpful in the treatment of HBV/HCV-related diseases. [ABSTRACT FROM AUTHOR]

Injection drug use represents an important contributor to hepatitis C virus (HCV) transmission, hence therapeutic communities (TCs) are promising points of care for the identification and treatment of HCV-infected persons who inject drugs (PWIDs). We evaluated the effectiveness and efficacy of an HCV micro-elimination program targeting PWIDs in the context of a drug-free TC; we applied the cascade of care (CoC) evaluation by calculating frequencies of infection diagnosis, confirmation, treatment and achievement of a sustained virological response (SVR). We also evaluated the risk of reinfection of PWIDs achieving HCV eradication by collecting follow-up virologic information of previously recovered individuals and eventual relapse in drug use, assuming the latter as a potential source of reinfection. We considered 811 PWIDs (aged 18+ years) residing in San Patrignano TC at the beginning of the observation period (January 2018–March 2022) or admitted thereafter, assessing for HCV and HIV serology and viral load by standard laboratory procedures. Ongoing infections were treated with direct-acting antivirals (DAA), according to the current national guidelines. Out of the 792 individuals tested on admission, 503 (63.5%) were found to be seropositive for antibodies against HCV. A total of 481 of these 503 individuals (95.6%) underwent HCV RNA testing. Out of the 331 participants positive for HCV RNA, 225 were ultimately prescribed a DAA treatment with a sustained viral response (SVR), which was achieved by 222 PWIDs (98.7%). Of the 222 PWIDs, 186 (83.8%) with SVR remained HCV-free on follow-up (with a median follow-up of 2.73 years after SVR ascertainment). The CoC model in our TC proved efficient in implementing HCV micro-elimination, as well as in preventing reinfection and promoting retention in the care of individuals, which aligns with the therapeutic goals of addiction treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Lichen planus (LP) is a chronic inflammatory mucocutaneous disease of autoimmune nature and unknown etiology, which can affect the oral mucosa, skin, nails, scalp, genitalia, and other mucous membranes. The anatomical location most frequently affected by LP is the oral cavity—called oral lichen planus (OLP)—where white reticular lesions may also be accompanied by erosive, atrophic, bullous, papular, or plaque lesions. The most important feature of OLP is its capacity to develop into oral cancer throughout the course of the disease, which is why OLP is currently recognized as an oral potentially malignant disorder (OPMD). New primary-level studies (n = 20; 11,512 patients suffering from OLP or related lesions) have been published in the last 5 years on this topic. In the present meta-analysis, we provide an updated OLP malignant transformation ratio, which is higher than what was previously reported; resolve some remaining controversies; and provide new recommendations for clinical practice in the management of OLP patients. A systematic review and a meta-analysis is presented on published articles on the malignant transformation of oral lichen planus (OLP) and related conditions, which, based on current evidence, updates an earlier systematic review published by our research group that included publications until November 2018. In this updated study (Nov-2023) we searched MEDLINE, Embase, Web of Science, and Scopus. We evaluated the methodological quality of studies (QUIPS tool) and carried out meta-analyses. The inclusion criteria were met by 101 studies (38,083 patients), of which, 20 new primary-level studies (11,512 patients) were published in the last 5 years and were added to our updated study. The pooled malignant transformation ratio was 1.43% (95% CI = 1.09–1.80) for OLP; 1.38% (95% CI = 0.16–3.38) for oral lichenoid lesions; 1.20% (95% CI = 0.00–4.25) for lichenoid reactions; and 5.13% (95% CI = 1.90–9.43) for OLP with dysplasia. No significant differences were found between the OLL or LR groups and the OLP subgroup (p = 0.853 and p = 0.328, respectively), and the malignant transformation was significantly higher for the OLP with dysplasia group in comparison with the OLP group (p = 0.001). The factors that had a significant impact with a higher risk of malignant transformation were the presence of epithelial dysplasia, a higher methodological quality, the consumption of tobacco and alcohol, the location of lesions on the tongue, the presence of atrophic and erosive lesions, and infection by the hepatitis C virus. In conclusion, OLP behaves as an oral potentially malignant disorder (OPMD), whose malignancy ratio is probably underestimated as a consequence essentially of the use of inadequate diagnostic criteria and the low methodological quality of the studies on the subject. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Liver cirrhosis, hepatitis B, hepatitis C, and non-alcoholic fatty liver disease represent major risk factors of HCC. Multiple different treatment options are available, depending on the Barcelona Clinic Liver Cancer (BCLC) algorithm. Systemic treatment is reserved for certain patients in stages B and C, who will not benefit from regional treatment methods. In the last fifteen years, the arsenal of available therapeutics has largely expanded, which improved treatment outcomes. Nevertheless, not all patients respond to these agents and novel combinations and drugs are needed. In this review, we aim to summarize the pathway of trials investigating the safety and efficacy of targeted therapeutics and immunotherapies since the introduction of sorafenib. Furthermore, we discuss the current evidence regarding resistance mechanisms and potential novel targets in the treatment of advanced HCC. [ABSTRACT FROM AUTHOR]

Developing a safe and effective vaccine against the hepatitis C virus (HCV) remains a top priority for global health. Despite recent advances in antiviral therapies, the high cost and limited accessibility of these treatments impede their widespread application, particularly in resource-limited settings. Therefore, the development of the HCV vaccine remains a necessity. This review article analyzes the current technologies, future prospects, strategies, HCV genomic targets, and the governmental role in HCV vaccine development. We discuss the current epidemiological landscape of HCV infection and the potential of HCV structural and non-structural protein antigens as vaccine targets. In addition, the involvement of government agencies and policymakers in supporting and facilitating the development of HCV vaccines is emphasized. We explore how vaccine development regulatory channels and frameworks affect research goals, funding, and public health policy. The significance of international and public-private partnerships in accelerating the development of an HCV vaccine is examined. Finally, the future directions for developing an HCV vaccine are discussed. In conclusion, the review highlights the urgent need for a preventive vaccine to fight the global HCV disease and the significance of collaborative efforts between scientists, politicians, and public health organizations to reach this important public health goal. [ABSTRACT FROM AUTHOR]

The hepatitis C virus (HCV) is a major causative agent of hepatitis that may also lead to liver cancer and lymphomas. Chronic hepatitis C affects an estimated 2.4 million people in the USA alone. As the sole member of the genus Hepacivirus within the Flaviviridae family, HCV encodes a single-stranded positive-sense RNA genome that is translated into a single large polypeptide, which is then proteolytically processed to yield the individual viral proteins, all of which are necessary for optimal viral infection. However, cellular innate immunity, such as type-I interferon (IFN), promptly thwarts the replication of viruses and other pathogens, which forms the basis of the use of conjugated IFN-alpha in chronic hepatitis C management. As a countermeasure, HCV suppresses this form of immunity by enlisting diverse gene products, such as HCV protease(s), whose primary role is to process the large viral polyprotein into individual proteins of specific function. The exact number of HCV immune suppressors and the specificity and molecular mechanism of their action have remained unclear. Nonetheless, the evasion of host immunity promotes HCV pathogenesis, chronic infection, and carcinogenesis. Here, the known and putative HCV-encoded suppressors of innate immunity have been reviewed and analyzed, with a predominant emphasis on the molecular mechanisms. Clinically, the knowledge should aid in rational interventions and the management of HCV infection, particularly in chronic hepatitis. [ABSTRACT FROM AUTHOR]

(1) Background. Hepatitis C infection often leads to extrahepatic manifestations, including cryoglobulinemic vasculitis. This systematic review aimed to assess the efficacy and safety of rituximab in treating hepatitis C-associated cryoglobulinemic vasculitis. (2) Methods. Following PRISMA guidelines, databases were searched for relevant studies. Eligibility criteria included studies on hepatitis C-associated cryoglobulinemic vasculitis treated with rituximab. (3) Results. Nine studies met the eligibility criteria and were included in this analysis. Rituximab was commonly administered at 375 mg/m2 weekly for one month. The results consistently demonstrated the efficacy of rituximab, whether as a standalone treatment or as part of a therapeutic regimen. The combination of rituximab with Peg-IFN-α and ribavirin significantly increased the complete response rate compared to Peg-IFN-α and ribavirin alone (54.5% vs. 33.3%, p < 0.05). The 3-year sustained response rate was notably higher in the rituximab combination group (83.3% vs. 40%). In another trial, rituximab achieved remission in 83.3% of patients at 6 months, compared to only 8.3% in the control group. The efficacy of rituximab was supported by long-term experience, with clinical benefits in patients with severe cryoglobulinemic vasculitis, including those resistant to standard therapies. Mild adverse events were generally reported, with rare severe reactions in some studies. (4) Conclusions: In conclusion, rituximab appeared to be effective and safe in managing hepatitis C-associated cryoglobulinemic vasculitis, either alone or with antiviral therapy. [ABSTRACT FROM AUTHOR]

Introduction: Eradication of HCV in the global population remains one of the greatest challenges faced by the WHO. An insufficient level of knowledge and the lack of a national screening test strategy are obstacles to HCV eradication. Aim: This work aimed to summarize surveys assessing risk factors and awareness of the respondents regarding the prevention and course of HCV infection. The summary also includes the most important European and global attempts at eliminating HCV. Materials and Methods: A cross-sectional, population-based study was conducted in the Mazowieckie district in Poland using anonymous surveys and conducted on people who willingly reported for a test. Results: In the study cohort of n = 7397 adults, there were 5412 women (73.16%). The analysis of the quota sample (n = 1303) reflected the actual proportions in the population of the Mazowieckie Voivodeship. Conclusions: Insufficient knowledge about HCV decreases the probability of higher detection of infections, fast diagnostics, and treatment. According to the WHO model, assuming a 90% detection rate and treatment of 80% of infected by 2030, and taking into account 120–150 thousand infected persons in Poland, the number of detections of HCV should be increased 4–5 times and all diagnosed persons should be offered antiviral treatment. [ABSTRACT FROM AUTHOR]

The hepatitis C virus (HCV), a single-stranded RNA virus belonging to the Flaviviridae family, is a major cause of hepatocellular carcinoma (HCC) worldwide. Tumors caused by HCC have an increased mortality rate globally, which is more accentuated in Western countries. The carcinogenic potential of this virus is mediated through a wide range of mechanisms, spanning from the induction of chronic inflammation to oxidative stress and deregulation of cellular pathways by viral proteins. As the number of new infections continues unabated, HCC-related mortality should be prioritized through early detection, continued prevention of HCV transmission, and treatment of HCV with safe and efficacious direct antiviral agents (DAAs). People who inject drugs (PWID) are a significant reservoir of new HCV infections globally, and in order to eliminate hepatitis C as a global health threat, as set out by the World Health Organization, an integrated approach based on the optimization of care delivery and increased access to harm reduction and treatment for PWID is needed. Thanks to the development of safe and effective antiviral agents, eradication of the infection is now possible in almost all treated patients, leading to a significant reduction but not the elimination of the risk for HCC in cured patients. This is particularly relevant among aged populations who have cofactors of morbidity known to accelerate HCC progression, such as diabetes, obesity, and excessive alcohol consumption. Given the restless accumulation of individuals with cured HCV infection, the implementation of risk-stratified surveillance programs becomes impellent from a cost-effectiveness perspective, whereas the availability of a performant biomarker to predict HCC in cured patients remains an unmet clinical need. [ABSTRACT FROM AUTHOR]

Pediatric acute liver failure (PALF) has recently become a subject of great interest when multiple clusters of non-A to non-E severe acute hepatitis in otherwise healthy young children with a median age of 2 years were reported around the world. Future studies should aim to better characterize the mechanisms of PALF that could provide therapeutic opportunities, validate prognostic modeling scoring systems [[21]], and help to develop new mechanistic and clinical models to examine treatment strategies and transplant decisions which will further improve outcomes. AIH, autoimmune hepatitis; GALD, gestational alloimmune liver disease; HEV, hepatitis E virus; HLH, hemophagocytic lymphohistiocytosis; NANBNC, non-A-non-B-non-C hepatitis virus; PALF, pediatric acute liver failure. Both NASPGHAN and ESPGHAN societies highlight the importance of an etiology-based therapies for some conditions with specific treatments when available (Table 3). [Extracted from the article]

For many years, we have faced the complications of viral hepatitis and alcohol-related liver diseases such as cirrhosis, decompensation, portal hypertension, and hepatocellular carcinoma (HCC). Recently, we have seen a dynamic change in the field of hepatology. With the significant achievements in eradicating the hepatitis C virus by direct-acting antiviral agents and the rising epidemic of obesity, diabetes mellitus, and metabolic syndrome, there is a paradigm shift in the leading cause of liver cirrhosis and cancer to nonalcoholic fatty liver disease (NAFLD). Current data highlight the rapidly rising incidence of NAFLD-related HCC worldwide and expose the unseen part of the iceberg. In this review, we aim to update knowledge about the pathogenesis of NAFLD-induced HCC, surveillance difficulties, and promising disease markers. Molecular biomarkers, for example, may become a promising cornerstone for risk-stratified surveillance, early detection, and treatment selection for NAFLD-related HCC. Physicians can offer personalized and tailor-made clinical decisions for this unique patient subgroup. [ABSTRACT FROM AUTHOR]

Underserved populations have a wide heterogeneity on healthcare provision and use. They also represent the key populations according to WHO 2030 goals for HCV micro-elimination. Our review evaluated the available literature on HCV diagnosis, staging, and treatment among underserved populations, such as incarcerated people, patients with psychiatric disorders, and migrants. A narrative review of literature was performed using key electronic databases (Scopus, Pubmed—MEDLINE) and search engines (Google Scholar). Peer-reviewed publications, grey literature on HCV, and recent models proposed for micro-elimination in underserved populations were included. An insight into the COVID-19 pandemic and its influence on HCV micro-elimination pathways will be also provided. Regarding prison settings, a progressive reduction in HCV epidemiology among incarcerated people in the last years was found (one-third of the level it had been before). People suffering from psychiatric disorders have a high anti-HCV prevalence, but there is a lack of data on active infections. A bidirectional relationship between HCV and psychiatric disorders was found. Migrants showed a very inconsistent assessment of HCV. Furthermore, available studies recorded data from populations with high heterogeneity of anti-HCV prevalence, Therefore, the reported results need caution in their evaluation. [ABSTRACT FROM AUTHOR]

Flaviviridae infections, such as those caused by hepatitis C (HCV) and dengue viruses (DENVs), represent global health risks. Infected people are in danger of developing chronic liver failure or hemorrhagic fever, both of which can be fatal if not treated. The tropical parasites Trypanosoma brucei and Trypanosoma cruzi cause enormous socioeconomic burdens in Sub-Saharan Africa and Latin America. Anti-HCV chemotherapy has severe adverse effects and is expensive, whereas dengue has no clinically authorized treatment. Antiparasitic medicines are often toxic and difficult to administer, and treatment failures are widely reported. There is an urgent need for new chemotherapies. Based on our previous research, we have undertaken structural modification of lead compound V with the goal of producing derivatives with both antiviral and trypanocidal activity. The novel spirocarbocyclic-substituted hydantoin analogs were designed, synthesized, and tested for antiviral activity against three HCV genotypes (1b, 3a, 4a), DENV, yellow fever virus (YFV), and two trypanosome species (T. brucei, T. cruzi). The optimization was successful and led to compounds with significant antiviral and trypanocidal activity and exceptional selectivity. Several modifications were made to further investigate the structure–activity relationships (SARs) and confirm the critical role of lipophilicity and conformational degrees of freedom. [ABSTRACT FROM AUTHOR]

Hepatitis C Virus (HCV) infection is a leading etiology of liver cirrhosis and its associated complications, namely, decompensated cirrhosis. As such, hepatitis C potentially necessitates liver transplantation and may result in death. Recently, HCV treatment has evolved. Current HCV treatment is effective in curing HCV; some of the agents are pan-genotypic. Numerous countries have adopted an initiative to eliminate HCV. Achieving elimination poses many challenges; it requires improved availability and accessibility of pan-genotypic therapy. Barriers exist at the level of the collective healthcare system and at the level of the individual healthcare providers and patients. Therefore, organized national and local efforts are needed. Surmounting these barriers calls for interventions concerning screening, linkage to care, and treatment delivery. Pertinent barriers include inadequate availability of screening, ill-equipped laboratory testing before treatment, and insufficient access to treatment. Interventions should seek to decentralize laboratory testing and treatment provision, increase funding for resources and personnel, and spread awareness. Special consideration should be allocated to at-risk populations, such as intravenous drug users, refugees, and prisoners. Computerized medical filing and telemedicine have the potential to refine HCV management by enhancing detection, availability, accessibility, and cost-effectiveness. [ABSTRACT FROM AUTHOR]

Simple Summary: Liver cancer is often used as a general term for cancers of the liver (hepatocellular carcinoma, HCC), the gallbladder, and the bile ducts. The well-known risk factors are alcohol and viral hepatitis, but these are risk factors of mainly HCC. For gallbladder cancer, gallstones are important risk factors, and for bile ducts, infections in the ducts are important. For all these cancers, autoimmune diseases and diabetes increase risk. This study shows that these risk factors, in combination, explain 50% or more of the causes of these cancers. The novelty of the present study was the use of national Swedish hospital records for potential risk factors (comorbidities) of hepatobiliary cancers and the estimation of subsequent risks of hepatobiliary cancers in these patients. The underlying mechanism for these cancers is a chronic infection which should be considered a marker of disease progression and a possible target for intervention. Background: We aim to estimate population-attributable fractions (PAF) for 13 comorbidities potentially predisposing to hepatobiliary cancer of hepatocellular carcinoma (HCC), gallbladder cancer (GBC), cancers of the intrahepatic and extrahepatic bile ducts (ICC and ECC), and ampullary cancer. Methods: Patients were identified from the Swedish Inpatient Register from 1987 to 2018 and cancers from the Swedish Cancer Registry from 1997 through 2018. PAFs were calculated for each comorbidity-associated cancer using a cohort study design. Results: For male HCC, the major individual comorbidities (PAF > 10) were diabetes, alcohol-related liver disease, and hepatitis C virus infection. For female HCC, diabetes and autoimmune diseases were important contributors. For female GBC, gallstone disease was an overwhelming contributor, with a PAF of 30.57%, which was also important for men. The overall PAF for male ICC was almost two times higher than the female one. For ECC and ampullary cancer, infection of bile ducts was associated with the highest PAF. Conclusions: The 13 comorbidities accounted for 50% or more of the potential etiological pathways of each hepatobiliary cancer except female ICC. The underlying convergent mechanism for these cancers may be chronic inflammation lasting for decades and thus offering possibilities for intervention and disease monitoring. [ABSTRACT FROM AUTHOR]

Numerous reports have explored the roles of different genetic variants in miRNA biogenesis mechanisms and the progression of various types of carcinomas. The goal of this study is to explore the association between XPO5*rs34324334 and RAN*rs14035 gene variants and susceptibility to hepatocellular carcinoma (HCC). In a cohort of 234 participants (107 HCC patients and 127 unrelated cancer-free controls) from the same geographic region, we characterized allelic discrimination using PCR-RFLP and performed subgroup analysis and multivariate regression. We found that the frequency of the XPO5*rs34324334 (A) variant was correlated with elevated risk of HCC under allelic (OR = 10.09, p-value < 0.001), recessive (OR = 24.1, p-value < 0.001), and dominant (OR = 10.1, p-value < 0.001) models. A/A genotype was associated with hepatitis C cirrhosis (p-value = 0.012), ascites (p-value = 0.003), and higher levels of alpha-fetoproteins (p-value = 0.011). Carriers of the RAN*rs14035 (T) variant were more likely to develop HCC under allelic (OR = 1.76, p-value = 0.003) and recessive (OR = 3.27, p-value < 0.001) models. Our results suggest that XPO5*rs34324334 and RAN*rs14035 variants are independent risk factors for developing HCC. [ABSTRACT FROM AUTHOR]

Hepatitis C is a liver infection caused by a virus, which results in mild to severe inflammation of the liver. Over many years, hepatitis C gradually damages the liver, often leading to permanent scarring, known as cirrhosis. Patients sometimes have moderate or no symptoms of liver illness for decades before developing cirrhosis. Cirrhosis typically worsens to the point of liver failure. Patients with cirrhosis may also experience brain and nerve system damage, as well as gastrointestinal hemorrhage. Treatment for cirrhosis focuses on preventing further progression of the disease. Detecting cirrhosis earlier is therefore crucial for avoiding complications. Machine learning (ML) has been shown to be effective at providing precise and accurate information for use in diagnosing several diseases. Despite this, no studies have so far used ML to detect cirrhosis in patients with hepatitis C. This study obtained a dataset consisting of 28 attributes of 2038 Egyptian patients from the ML Repository of the University of California at Irvine. Four ML algorithms were trained on the dataset to diagnose cirrhosis in hepatitis C patients: a Random Forest, a Gradient Boosting Machine, an Extreme Gradient Boosting, and an Extra Trees model. The Extra Trees model outperformed the other models achieving an accuracy of 96.92%, a recall of 94.00%, a precision of 99.81%, and an area under the receiver operating characteristic curve of 96% using only 16 of the 28 features. [ABSTRACT FROM AUTHOR]

Simple Summary: Oral lichenoid conditions are common potentially malignant disorders affecting oral mucosa. The 2003 modified WHO criteria is the most widely used criteria in diagnosing oral lichen planus; however, the concern on the implementation of epithelial dysplasia as an exclusion criterion may result in the remarkable underestimation of the potential malignancy of this disease continuing. This systemic review and meta-analysis attempted to provide an objective view by comparing the malignant transformation rate of oral lichen planus diagnosed according to the 2003 modified WHO criteria and non-2003 criteria, and to determine risk variables associated with malignant transformation of oral lichenoid conditions. We found that the malignant transformation rate of oral lichen planus differed based on diagnostic criteria, with lower rates for the 2003 modified WHO criteria than non-2003 criteria, albeit not statistically significant. A higher incidence of malignant transformation was found for red-type lesions and patients who are smokers, alcohol consumers, and HCV positive. Objectives: This systematic review and meta-analysis aims to evaluate the evidence on the malignant potential of oral lichenoid conditions (OLCs) including oral lichen planus (OLP), oral lichenoid lesions (OLL), and lichenoid mucositis dysplasia (LMD). In addition, it aims to compare the rate of malignant transformation (MT) in OLP patients diagnosed according to different diagnostic criteria, and to investigate the possible risk factors for OLP MT into OSCC. Materials and methods: A standardized search strategy was applied across four databases (PubMed, Embase, Web of Science, and Scopus). Screening, identification and reporting followed the PRISMA framework. Data on MT were calculated as a pooled proportion (PP), subgroup analyses and possible risk factors for MT were pooled as odds ratios (ORs). Results: Among 54 studies with 24,277 patients, the PP for OLCs MT was 1.07% (95% CI [0.82, 1.32]). The estimated MT rate for OLP, OLL and LMD was 0.94%, 1.95% and 6.31%, respectively. The PP OLP MT rate using the 2003 modified WHO criteria group was lower than that using the non-2003 criteria (0.86%; 95% CI [0.51, 1.22] versus 1.01%; 95% CI [0.67, 1.35]). A higher odds ratio of MT was observed for red OLP lesions (OR = 3.52; 95% CI [2.20, 5.64]), smokers (OR = 1.79; 95% CI [1.02, 3.03]), alcohol consumers (OR = 3.27, 95% CI [1.11, 9.64]) and those infected with HCV (OR = 2.55, 95% CI [1.58, 4.13]), compared to those without these risk factors. Conclusions: OLP and OLL carry a low risk of developing OSCC. MT rates differed based on diagnostic criteria. A higher odds ratio of MT was observed among red OLP lesions, smokers, alcohol consumers, and HCV-positive patients. These findings have implications for practice and policies. [ABSTRACT FROM AUTHOR]

Background: Patients with hereditary bleeding disorders (HBDs) have always been vulnerable to transfusion-transmitted infections (TTIs) such as hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infections due to being regular recipients of blood and blood products. This study aimed to detect the trends in the prevalence of HBV, HCV, and HIV infections by birthyear in Iranian patients with HBDs to show the efficacy of national interventions implemented to administrate control and to prevent these infections, i.e., blood safety, newborn HBV vaccination, and safe replacement treatments. Methods: In this retrospective study, the trends in the prevalence of hepatitis B core antibody (HBcAb), HCV antibody (HCV-Ab), and HIV antibody (HIV-Ab) in Iranian patients with HBDs born before 2012 were assessed using patients' clinical archives. The determinants of HBV, HCV, and HIV infections were investigated in bivariable and multivariable logistic regression analyses. Results: Out of 1475 patients with HBDs, most were male (87.7%) and diagnosed with hemophilia A (52.1%) and severe bleeding disorder (63.7%). The prevalence of HBcAb, HCV-Ab, and confirmed HIV-Ab was 22.9%, 59.8%, and 1.2%, respectively. The trends in HBcAb, HCV-Ab, and HIV-Ab were all decreasing by birthyear and reached a stable level of 0% for patients with birthyears in 1999, 2000, and 1984, respectively. In multivariable analysis, birthyear was significantly associated with HBcAb prevalence. In the multivariable analysis, type of HBD; birthyear; bleeding severity; histories of receiving packed cells, fresh frozen plasma, and cryoprecipitate before 1996; and history of receiving factor concentrate before 1997 were highly associated with the prevalence of HCV-Ab. Moreover, in the bivariable analysis, birthyear and type of HBD were associated with HIV-Ab prevalence. Conclusion: This study demonstrated the decreasing trends in HBV, HCV, and HIV seroprevalence in Iranian patients with HBDs following preventive interventions such as HBV vaccination, blood safety measures, and the provision of safe replacement treatments. [ABSTRACT FROM AUTHOR]

Different cells differ regarding their expression of TLRs, with high levels of TLR4 and TLR2 expressed by macrophages and endothelial cells, but low levels by alveolar lung cells. Primary PDL cells were studied for cell signaling downstream of key molecules involved in the process of sterile inflammation via TLR4. Toll-like receptors (TLRs) belong to a powerful system for the recognition and elimination of pathogen-associated molecular patterns (PAMPs) from bacteria, viruses, and other pathogens. Graph: Figure 2 SARS-CoV-2 infection causes DAMPs and PAMPs that are recognized by a broad variety of toll-like receptors (TLRs), leading to the expression of pro-inflammatory cytokines and interferons. [Extracted from the article]

This study evaluates the feasibility of a local action program for HCV micro-elimination in highly endemic areas. Retrospective analysis: administrative and laboratory data (Local Health Unit, southern Italy) were integrated to quantize the anti-HCV-positive subjects not RNA tested and untreated HCV-infected subjects (2018–2022). Prospective analysis: all subjects admitted to a division of the LHU largest hospital (2021–2022) were tested for HCV, with linkage of active-infected patients to care. Overall, 49287 subjects were HCV-Ab tested: 1071 (2.2%) resulted positive without information for an HCV RNA test and 230 (0.5%) had an active infection not yet cured. Among 856 admitted subjects, 54 (6.3%) were HCV-Ab+ and 27 (3.0%) HCV RNA+. Of HCV-infected patients, 22.2% had advanced liver disease, highlighting the need for earlier diagnosis; 27.7% were unaware of HCV infection; and 20.4% were previously aware but never referred to a clinical center. Of these, 26% died and 74% received treatment. Our study emphasizes the value of an active HCV hospital case-finding program to enhance diagnosis in patients with several comorbidities and to easily link them to care. Our data strongly suggest extending this program to all hospital wards/access as a standard of care, particularly in highly endemic areas, to help HCV disease control and take steps in achieving the elimination goals. [ABSTRACT FROM AUTHOR]

A mass spectrometry-based lipidomic investigation of 30 patients with chronic hepatitis C virus (HCV) infection and 30 age- and sex-matched healthy blood donor controls was undertaken. The clustering and complete separation of these two groups was found by both unsupervised and supervised multivariate data analyses. Three patients who had spontaneously cleared the virus and three who were successfully treated with direct-acting antiviral drugs remained within the HCV-positive metabotype, suggesting that the metabolic effects of HCV may be longer-lived. We identified 21 metabolites that were upregulated in plasma and 34 that were downregulated (p < 1 × 10−16 to 0.0002). Eleven members of the endocannabinoidome were elevated, including anandamide and eight fatty acid amides (FAAs). These likely activated the cannabinoid receptor GPR55, which is a pivotal host factor for HCV replication. FAAH1, which catabolizes FAAs, reduced mRNA expression. Four phosphosphingolipids, d16:1, d18:1, d19:1 sphingosine 1-phosphate, and d18:0 sphinganine 1-phosphate, were increased, together with the mRNA expression for their synthetic enzyme SPHK1. Among the most profoundly downregulated plasma lipids were several lysophosphatidylinositols (LPIs) from 3- to 3000-fold. LPIs are required for the synthesis of phosphatidylinositol 4-phosphate (PI4P) pools that are required for HCV replication, and LPIs can also activate the GPR55 receptor. Our plasma lipidomic findings shed new light on the pathobiology of HCV infection and show that a subset of bioactive lipids that may contribute to liver pathology is altered by HCV infection. [ABSTRACT FROM AUTHOR]