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Hepatitis C virus (HCV) is a hepatotropic virus that can be transmitted through unsafe medical procedures, such as injections, transfusions, and dental treatment. The infection may be self-limiting or manifest as a chronic form that induces liver fibrosis, cirrhosis, or progression into hepatocellular carcinoma (HCC). Epigenetic mechanisms are major regulators of gene expression. These mechanisms involve DNA methylation, histone modifications, and the activity of non-coding RNAs, which can enhance or suppress gene expression. Abnormal activity or the dysregulated expression of epigenetic molecules plays an important role in the pathogenesis of various pathological disorders, including inflammatory diseases and malignancies. In this review, we summarise the current evidence on epigenetic mechanisms involved in HCV infection and progression to HCC. [ABSTRACT FROM AUTHOR]

Universal opt-out antenatal screening for Hepatitis C virus (HCV) is not currently recommened and it is recommended that maternity services offer risk-based testing. We aimed to investigate antenatal HCV testing and adherence to testing guidance. A cross-sectional survey was circulated to maternity service providers between November–December 2020 which included testing policy, training for healthcare staff, and management of women found to be HCV positive. Descriptive data are presented. A total of 75 questionnaires were returned, representing 48 % of English maternity service providers. 87 % of providers reported offering antenatal HCV risk-based testing. Risk factors used to identify pregnant women for testing varied. Less than 15 % of respondents considered women that were ever homeless or with history of incarceraton or from higher HCV prevalence areas as high risk. Current antenatal HCV testing practices are inadequate and HCV infection likely goes undiagnosed in pregnancy, especially among vulnerable population groups. In the absence of universal antenatal screening, re-framing antenatal HCV risk-based testing and management as a quality improvement initiative and developing HCV specific pathway guidance for maternity units is required. [ABSTRACT FROM AUTHOR]

Abstract Background Hepatitis C virus (HCV) infection is a major global concern, with Indigenous Peoples bearing the highest burden. Previous studies exploring HCV prevalence within Indigenous populations have predominantly used a pan-Indigenous approach, consequently resulting in limited availability of Métis-specific HCV data. The Métis are one of the three recognized groups of Indigenous Peoples in Canada with a distinct history and language. The Métis Nation of Ontario (MNO) is the only recognized Métis government in Ontario. This study aims to examine the prevalence of self-reported HCV testing and positive results among citizens of the MNO, as well as to explore the association between sociodemographic variables and HCV testing and positive results. Methods A population-based online survey was implemented by the MNO using their citizenship registry between May 6 and June 13, 2022. The survey included questions about hepatitis C testing and results, socio-demographics, and other health related outcomes. Census sampling was used, and 3,206 MNO citizens responded to the hepatitis C-related questions. Descriptive statistics and bivariate analysis were used to analyze the survey data. Results Among the respondents, 827 (25.8%, CI: 24.3–27.3) reported having undergone HCV testing and 58 indicated testing positive, resulting in a prevalence of 1.8% (CI: 1.3–2.3). Respondents with a strong sense of community belonging, higher education levels, and lower household income were more likely to report having undergone HCV testing. Among those who had undergone testing, older age groups, individuals with lower education levels, and retired individuals were more likely to test positive for HCV. Conclusion This study is the first Métis-led and Métis-specific study to report on HCV prevalence among Métis citizens. This research contributes to the knowledge base for Métis health and will support the MNO’s health promotion program and resources for HCV. Future research will examine the actual HCV incidence and prevalence among MNO citizens.

Objectives. Chronic hepatitis C (CHC) infection still affects a significant portion of the global population. Despite efforts to combat it, the global prevalence remains high. The use of direct antiviral therapy (DAA) has significantly improved cure rates. The study aimed to assess liver parameters and body mass index (BMI dynamics in type 2 diabetes mellitus (T2DM) patients compared to non-diabetics, after obtaining sustained viral response (SVR) under DAA. Material and methods. We conducted a retrospective study on 100 CHC infected patients treated with DAAs between September 2016 and August 2019 at “Prof. Dr. Matei Bals” National Institute for Infectious Diseases, Bucharest (INBI MB). The study group was divided into 2 subgroups according to the presence of diabetes. All patients were evaluated at initiation of treatment and one year after. FibroMax parameters and BMI were monitored. Outcomes. The study found improvements in liver fibrosis, necroinflammatory activity, and steatosis in both groups after treatment. Notably, T2DM patients experienced a more significant decrease in necroinflammatory activity. Moreover, weight gain post-SVR was observed, potentially impacting liver health. Conclusions. Post-SVR, CHC patients showed improvements in liver health markers, emphasizing the importance of early treatment to prevent severe liver complications. Future research should focus on long-term outcomes posttreatment. [ABSTRACT FROM AUTHOR]

Background Hepatitis C virus (HCV) infection is a major global concern, with Indigenous Peoples bearing the highest burden. Previous studies exploring HCV prevalence within Indigenous populations have predominantly used a pan-Indigenous approach, consequently resulting in limited availability of Métis-specific HCV data. The Métis are one of the three recognized groups of Indigenous Peoples in Canada with a distinct history and language. The Métis Nation of Ontario (MNO) is the only recognized Métis government in Ontario. This study aims to examine the prevalence of self-reported HCV testing and positive results among citizens of the MNO, as well as to explore the association between sociodemographic variables and HCV testing and positive results. Methods A population-based online survey was implemented by the MNO using their citizenship registry between May 6 and June 13, 2022. The survey included questions about hepatitis C testing and results, socio-demographics, and other health related outcomes. Census sampling was used, and 3,206 MNO citizens responded to the hepatitis C-related questions. Descriptive statistics and bivariate analysis were used to analyze the survey data. Results Among the respondents, 827 (25.8%, CI: 24.3–27.3) reported having undergone HCV testing and 58 indicated testing positive, resulting in a prevalence of 1.8% (CI: 1.3–2.3). Respondents with a strong sense of community belonging, higher education levels, and lower household income were more likely to report having undergone HCV testing. Among those who had undergone testing, older age groups, individuals with lower education levels, and retired individuals were more likely to test positive for HCV. Conclusion This study is the first Métis-led and Métis-specific study to report on HCV prevalence among Métis citizens. This research contributes to the knowledge base for Métis health and will support the MNO’s health promotion program and resources for HCV. Future research will examine the actual HCV incidence and prevalence among MNO citizens. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to study hepatitis D virus (HDV) prevalence and risk of progression to severe liver-related events (SLRE) in HBsAg positive people living with HIV (PLWH) in Italy; role of HDV-RNA copy levels, HCV coinfection and nadir CD4 counts were also investigated. Methods: People living with HIV (PLWH) from Italian Foundation cohort Naïve antiretrovirals (ICONA) with available HBsAg and HDV Ab were enrolled. HBsAg, HDV Ab, HDV-RNA and HDV genotypes were tested. Primary end-point: time from first HDV screening to Severe Liver Related Events (SLRE: decompensated cirrhosis, liver transplantation, HCC). Fine-grey regression models were used to evaluate the association of HDV Ab, HDV-RNA, HDV/HCV coinfection, CD4 nadir and outcome. Secondary end-points: time to SLRE or death; HDV Ab and HDV-RNA prevalence. Results: A total of 152/809 (18.8%) HBsAg positive PLWH showed HDV Ab reactivity; 63/93 (67.7%) were HDV-RNA positive. Being male, persons who inject drugs (PWID), HCV Ab positive, with FIB-4 > 3.25 were independent factors of HDV Ab positivity. In a median follow-up of 5 years, 37 PLWH (4.1% at 5-year) developed SLRE and 97 (12.0%) reached the SLRE or death end-point. HDV-RNA positive (independently from HDV-RNA copy level) PLWH had a 4.6-fold (95%CI 2.0--10.5) higher risk of SLRE than HDV negatives. PLWH positive for both HCV Ab and HDV Ab showed the highest independent risk of SLRE (ASHR: 11.9, 95%CI: 4.6--30.9 vs. HCV neg/HDV neg). Nadir CD4 < 200/mL was associated with SLRE (ASHR: 3.9, 95% 1.0--14.5). Conclusions: One-fifth of the HBsAg positive PLWH harbour HDV infection, and are at high risk of progression to advanced liver disease. HCV contributes to worse outcomes. This population needs urgently effective treatments. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) is a hepatotropic virus that can be transmitted through unsafe medical procedures, such as injections, transfusions, and dental treatment. The infection may be self-limiting or manifest as a chronic form that induces liver fibrosis, cirrhosis, or progression into hepatocellular carcinoma (HCC). Epigenetic mechanisms are major regulators of gene expression. These mechanisms involve DNA methylation, histone modifications, and the activity of non-coding RNAs, which can enhance or suppress gene expression. Abnormal activity or the dysregulated expression of epigenetic molecules plays an important role in the pathogenesis of various pathological disorders, including inflammatory diseases and malignancies. In this review, we summarise the current evidence on epigenetic mechanisms involved in HCV infection and progression to HCC.

Аim: diagnosis and treatment algorithms in the clinical recommendations intended for general practitioners, gastroenterologists, infectious disease specialists, hepatologists on the of chronic hepatitis C are presented.Summary. Chronic viral hepatitis C is a socially significant infection, the incidence of which in the Russian Federation remains significantly high. Over the past 10 years, great progress has been made in the treatment of hepatitis C — direct acting antiviral drugs have appeared. The spectrum of their effectiveness allows to achieve a sustained virological response in more than 90 % of cases, even in groups that were not previously considered even as candidates for therapy or were difficult to treat — patients receiving renal replacement therapy, after liver transplantation (or other organs), at the stage of decompensated liver cirrhosis, HIV co-infected, etc. Interferons are excluded from the recommendations due to their low effectiveness and a wide range of adverse events. The indications for the treatment have been expanded, namely, the fact of confirmation of viral replication. The terms of dispensary observation of patients without cirrhosis of the liver have been reduced (up to 12 weeks after the end of therapy). Also, these recommendations present approaches to active screening of hepatitis in risk groups, preventive and rehabilitation measures after the end of treatment.Conclusion. Great success has been achieved in the treatment of chronic hepatitis C. In most cases, eradication of viral HCV infection is a real task even in patients at the stage of cirrhosis of the liver, with impaired renal function, HIV co-infection, after solid organs transplantation.

Summary: Background: HCV infection is associated with mortality due to extrahepatic manifestations (EHM). Sustained virologic response (SVR) following direct-acting antiviral (DAA) therapy has been linked to decreased all-cause and liver-related mortality. However, evidence regarding the impact of DAA on EHM-related deaths is lacking. This study aimed to assess the impact of DAA and SVR on EHM-related mortality. Methods: The British Columbia Hepatitis Testers Cohort comprises ∼1.7 million people tested for HCV between 1990 and 2015 and is linked with administrative health data. Among individuals diagnosed with HCV by 12/31/2020, those who received at least one DAA treatment were matched to those who never received treatment by the year of their first HCV RNA positive date. We compared three groups: treated & SVR, treated & no-SVR, and untreated; and generated EHM mortality rates and incidence curves. To account for differences in baseline characteristics, we used inverse probability of treatment weights (IPTW). IPTW-weighted multivariable cause-specific Cox regression models were adjusted for competing risk and confounders. Findings: Study population included 12,815 treated (12,287 SVR, 528 no-SVR) and 12,815 untreated individuals (median follow-up 3.4 years, IQR 2.9). The untreated group had the highest EHM mortality rate (30.9 per 1000 person-years [PY], 95% CI 29.2–32.8), followed by the treated & no-SVR group (21.2 per 1000 PY, 95% CI 14.9–30.1), while the treated & SVR group had the lowest EHM mortality rate (7.9 per 1000 PY, 95% CI 7.1–8.7). In the multivariable model, EHM mortality in the treated & SVR group was significantly decreased (adjusted cause-specific hazard ratio [acsHR] 0.20, 95% CI 0.18–0.23). The treated & SVR group had significant reductions in mortality related to each of the EHMs (78–84%). Interpretation: Treatment of HCV with DAA was associated with significant reductions in EHM-related mortality. These findings emphasize the critical importance of timely diagnosis and treatment of HCV to prevent deaths associated with EHM, and have important implications for clinical practice and public health. Funding: This work was supported by the BC Centre for Disease Control and the Canadian Institutes of Health Research (CIHR) [Grant # NHC-348216, PJT-156066, and PHE-337680]. DJ has received Doctoral Research Award (#201910DF1-435705-64343) from the Canadian Institutes of Health Research (CIHR) and Doctoral fellowship from the Canadian Network on Hepatitis C (CanHepC). CanHepC is funded by a joint initiative of the Canadian Institutes of Health Research (CIHR) (NHC-142832) and the Public Health Agency of Canada (PHAC).

Introduction:To accomplish elimination of hepatitis C virus (HCV) by 2030, as proposed by the World Health Organization, the Brazilian Ministry of Health outlined the Hepatitis C Elimination Plan, which provides coverage of all critical steps in the continuum of care (CoC) of hepatitis C. As expected, the advent of COVID-19 pandemic has disrupted the CoC of hepatitis C worldwide. The Brazilian Liver Institute launched a remote patient monitoring (RPM) program to assist the general population at risk in HCV testing and to provide linkage and retention to care for HCV-positive subjects. The RPM program was also designed to relink HCV-positive patients lost to follow-up during the COVID-19 pandemic due to their limited access to the health care system. Methods:The HCV telemonitoring number was highly advertised in Brazilian media. The RPM program was conducted by dedicated health care personnel trained to follow a predefined script designed to provide awareness, ensure consistent information for educational purposes, and recruit eligible participants to be tested for HCV. Results:From August 2020 to December 2021, 3,738 subjects entered in contact with RPM. There were 26,884 interactions (mean 7.2 interactions per participant), mostly by WhatsApp (78%). Twenty out of those 221 subjects (9%) who tested were HCV positive. Those subjects altogether with 128 other patients with HCV, tested elsewhere, were followed in the HCV CoC. Up to now, 94% of them were linked to care, 24% are undergoing treatment and 8% achieved sustained virological response (SVR). Conclusions:Our preliminary results showed that HCV CoC telemonitoring was a feasible and useful strategy to follow HCV at-risk subjects through all cascade of care until SVR during the COVID-19 health care disruption. It could be used beyond the defervescence of SARS-CoV-2 pandemic to ensure linkage to care of those HCV-positive patients. [ABSTRACT FROM AUTHOR]

The aim of the study was to analyze the effectiveness and safety of anti-HCV treatment based on a pangenotypic direct-acting antiviral (DAA) regimen with glecaprevir/pibrentasvir (GLE/PIB) in children. The multi-center study was conducted in HCV-infected children who were treated in the period from November 2022 to January 2023. The analysis included 23 pediatric patients with a mean (SD) age of 9.61 (3.68) years. The cohort included 13 girls and 10 boys. The most common HCV genotypes were GT1b (n = 9, 39.1%), GT1a (n = 6, 26.1%) and GT3 (n = 5, 21.7%). The SVR was assessed at 12 weeks after the end of treatment and was 100% for both girls and boys. The conducted study showed a very good tolerance of the treatment in the entire analyzed group and confirmed a very high efficacy and safety for 8-week treatment with GLE/PIB in children over three years of age. It seems that our study is the first on the real-world use of an 8-week GLE/PIB pangenotypic therapy in a group of children aged 3–12 years and the first in Europe for adolescents aged 12–17. [ABSTRACT FROM AUTHOR]

There is an urgent need for the identification of new drugs that inhibit HCV-induced hepatocellular carcinoma (HCC). Our work demonstrates that cyclophilin inhibitors (CypIs) represent such new drugs. We demonstrate that the nonimmunosuppressive cyclosporine A (CsA) analog (CsAa) rencofilstat possesses dual therapeutic activities for the treatment of HCV infection and HCV-induced HCC. Specifically, we show that the HCV infection of humanized mice results in the progressive development of HCC. This is true for the four genotypes tested (1 to 4). Remarkably, we demonstrate that rencofilstat inhibits the development of HCV-induced HCC in mice even when added 16 weeks after infection when HCC is well established. Importantly, we show that rencofilstat drastically reduces HCC progression independently of its anti-HCV activity. Indeed, the CypI rencofilstat inhibits HCC, while other anti-HCV agents such as NS5A (NS5Ai) and NS5B (NS5Bi) fail to reduce HCC. In conclusion, this study shows for the first time that the CypI rencofilstat represents a potent therapeutic agent for the treatment of HCV-induced HCC. [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]

ABSTRACT Aim: Viral hepatitis agents include Hepatitis B and Hepatitis C virus, which cause an important public health problem due to serious complications. Patients examined at the outpatient clinics of internal medicine are among main risk groups, as they have concomitant diseases and undergo various procedures. We aimed to investigate retrospectively the seroprevalence of viral hepatitis in outpatients in internal medicine in our region. Material and Methods: HBsAg and Anti-HCV parameters, and demographic data such as age and gender of patients admitted at the outpatient clinics of internal medicine at our hospital between January 2017 and July 2022 were retrospectively evaluated, with HBV-DNA and HCV-RNA levels of those who showed reactivity. Results: HBsAg test results of 2618 patients and Anti-HCV test results of 2943 patients were obtained in this study. The mean age of patients with HBsAg tests was 34.2±15.7, and mean age of patients with Anti-HCV test was 34.3±15.7 years. HBsAg reactivity rate was 0.9%; and the mean age of patients showing reactivity was 47.7±14.4 years. Anti-HCV reactivity rate was %0.1, with a mean age of 52.6±21.3 years. Both HBsAg and Anti-HCV reactivity was not present at the same patient in our study. Conclusion: Early diagnosis of Hepatitis B and Hepatitis C viruses decrease the risk of developing complications, easing treatment processes and decreasing the risk of contagion. Thus, increasing use of screening tests as part of preventive medicine is very important.

Objective: To determine the usefulness of Sofosbuvir-Daclatasvir combination in the treatment of hepatitis c virus infection in paediatric cancer. Method: The retrospective study was conducted at the Oncology Department of the National Institute of Child Health, Karachi, and comprised medical charts of patients who received sofosbuvir and daclatasvir from January 2018 to January 2022. Efficacy was documented by clearance of hepatitis C virus ribonucleic acid as rapid viral response, early viral response and sustained viral response at weeks 4, 12 and 24, respectively. Drug efficacy was determined by monitoring and recording adverse effects. Chemotherapy protocol for the treatment of patients concomitantly receiving direct acting antivirals was modified while looking at drug-drug interactions. The total duration of direct acting antiviral therapy was 12 weeks. Data was analysed using SPSS 24. Results: Of the 804 patients with different malignancies, 132(16.4%) were found positive for hepatitis C virus. Of them, 28(21.21%) patients were started on direct acting antivirals; 17(60.71%) boys and 11(39.28%) girls. The overall mean age was 9.93±6.12 years. The diagnosis was pre-B acute lymphoblastic leukaemia in 18(64.28%) cases, 16(57.14%) were on maintenance chemotherapy, and 18(64.28%) had genotype 1. Pre- and post-treatment mean alanine transaminase levels were 328.00±324.00IU and 36.00±29.00IU, respectively (p=0.003). Pre- and post-treatment mean serum bilirubin levels were 3.13±3.95mg/dl and 0.61±0.21mg/dl (p=0.022). Rapid viral response was achieved in 26(92.85%) children, while early viral response and sustained viral response were achieved in all 28(100%) patients. Minor side effects were noted in 4(14.28%) patients and chemotherapy was continued in all 28(100%) cases as per the designed protocol. Conclusion: The sofosbuvir-daclatasvir combination was found to be effective in hepatitis C virus treatment in paediatric cancer patients. Key Words: Childhood cancer, HCV infection, Direct acting antiviral agents.

Background: The initial stage in the cascade of care for Hepatitis C Virus (HCV) infection involves the identification of infected individuals, which enables the initiation of the care sequence. This study aimed to assess the prevalence of HCV infection and estimate its burden. Study design: This retrospective study was conducted in a hospital setting. Materials and Methods: All consecutive samples received by the Microbiology department between February 2019 and December 2022 were subjected to HCV infection testing using ELISA to detect Ag/Ab, and were included in the study. Results: Out of the 82,614 samples tested for HCV infection, 1,580 were found positive, resulting in a seroprevalence rate of 1.9%. More than half of the seropositive individuals fell within the 19-40-year age group. Conclusion: The implementation of widespread HCV infection screening programs in the community, coupled with awareness initiatives on HCV transmission and prevention, is crucial. [ABSTRACT FROM AUTHOR]

Introduction: In Poland, active HCV infection affects between 0.4 and 0.5% of the population, i.e., about 150,000 people, while the number of patients with epilepsy is estimated to be 350,000–400,000. Currently available antiviral therapies show little interaction with neurological drugs. The aim of our study was to evaluate the effectiveness and safety of the treatment of chronic HCV infection in patients with coexisting epilepsy. Methods: A total of 184 epilepsy patients were selected from the group of 10,152 HCV-infected patients treated for HCV infection within the Epiter-2 database from 2015 to 2018. Comparing the effectiveness and safety of anti-HCV regimens between the patients with comorbid epilepsy and 3573 patients without comorbidities was our study's objective. Results: The effectiveness of anti-HCV treatment was high in both the sample and the control group. No statistically significant SVR difference was observed between the sample group, with ITT = 93.5% and mITT = 95.5%, and the control group, with ITT = 95.2% and mITT = 97.5%, regardless of the genotype and the stage of liver disease at the start of therapy. The treatment was safe in patients with epilepsy. Conclusions: The effectiveness and safety of HCV treatment in patients with epilepsy are comparable to those of patients with no significant comorbidities. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection is a major public health concern, and almost two million people are infected per year globally. This is occurred by the diverse spectrum of viral genotypes, which are directly associated with chronic liver disease (fibrosis, and cirrhosis). Indeed, the viral genome encodes three principal proteins as sequentially core, E1, and E2. Both E1 and E2 proteins play a crucial role in the attachment of the host system, but E2 plays a more fundamental role in attachment. The researchers have found the "E2-CD81 complex" at the entry site, and therefore, CD81 is the key receptor for HCV entrance in both humans, and chimpanzees. So, the researchers are trying to block the host CD81 receptor and halt the virus entry within the cellular system via plant-derived compounds. Perhaps that is why the current research protocol is designed to perform an in silico analysis of the flavonoid compounds for targeting the tetraspanin CD81 receptor of hepatocytes. To find out the best flavonoid compounds from our library, web-based tools (Swiss ADME, pKCSM), as well as computerized tools like the PyRx, PyMOL, BIOVIA Discovery Studio Visualizer, Ligplot+ V2.2, and YASARA were employed. For molecular docking studies, the flavonoid compounds docked with the targeted CD81 protein, and herein, the best-outperformed compounds are Taxifolin, Myricetin, Puerarin, Quercetin, and (-)-Epicatechin, and outstanding binding affinities are sequentially − 7.5, − 7.9, − 8.2, − 8.4, and − 8.5 kcal/mol, respectively. These compounds have possessed more interactions with the targeted protein. To validate the post docking data, we analyzed both 100 ns molecular dynamic simulation, and MM-PBSA via the YASARA simulator, and finally finds the more significant outcomes. It is concluded that in the future, these compounds may become one of the most important alternative antiviral agents in the fight against HCV infection. It is suggested that further in vivo, and in vitro research studies should be done to support the conclusions of this in silico research workflow. [ABSTRACT FROM AUTHOR]

We evaluated the acceptability of a patient activation toolkit for hepatitis C virus (HCV) testing amidst universal adult guidelines. We developed a patient-facing toolkit that included a letter to the patient from their healthcare provider, HCV factsheet, and question prompt list, which contained questions for their provider about HCV infection and testing. We conducted qualitative interviews with patients ages 18–78 (n = 17), using a semi-structured interview guide based on learner verification. We assessed attraction, comprehension, cultural-linguistic acceptability, self-efficacy, and persuasiveness of toolkit materials using direct content analysis. Participants reported materials were attractive, offering suggestions to improve readability. They reported some understanding of materials but requested use of less medical jargon, particularly for the factsheet. Participants discussed cultural acceptability and suggested ways to improve language inclusiveness and comfort with content, given stigma surrounding HCV risk factors. Participants reported that including a letter, factsheet, and QPL improved the persuasiveness of materials, and they conveyed their motivation to be tested for HCV. Results indicate preliminary acceptability for use of the patient activation toolkit, which will be refined based on participants' recommendations. Overall, this patient activation toolkit holds promise for increasing HCV testing rates. [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.

Background. Children and adolescents with infection caused by the hepatitis C virus (HCV) have not been given sufficient attention due to mild forms of HCV and delays in approval of antiviral treatment regimens. Omissions in the studies of pediatric cohorts and shortcomings of management policies aimed at children should be eliminated by improving screening coverage and access to treatment. The aim of the study was to present the results of the cascade sequence of diagnostic testing, care and treatment of children with HCV in the Moscow Region (MR). Materials and methods. The study included all HCV seropositive children of MR (n = 175), who underwent screening tests, and it did not include patients living with HIV/HCV coinfection. Children were observed from 2017 to 2022. The HCV RNA was detected in 164 children and HCV genotypes were identified in 99 children. The stage of liver fibrosis was assessed in 73 children by transient elastography and by FIB-4 index calculation. Results. In MR, 93.7% of seropositive children were tested for HCV RNA; 71.2% of adolescents over 12 years of age received treatment. The prevalence of HCV seropositivity was estimated at 0.113/1,000 children population; the prevalence of chronic HCV infection was at least 0.059/1,000. The dominant HCV subtypes were GT 1b (43.4% [the 95% confidence interval, 33.553.8%]), GT 3a (23.2% [15.332.8%]) and GT 3a/3b (20.2% [12.829.5%]). The incidence of viremic HCV infection per 100,000 children was 3.3 among children under 3 years of age; 7.0 among children aged 36 years; 7.7 among children aged 711 years, 4.4 among adolescents older than 12 years. Natural HCV clearance was reported at the frequency of 19.5% [13.826.4%]. Extrahepatic manifestations were of rare occasion 2.9% [0.96.5%]. Vertical transmission was the primary route of HCV transmission (78.3% [71.484.2%]); infection is assumed to occur during medical invasive procedures 7.4% [4.012.4%], drug using 0.6% [0.013.10%], in the family household 0.6% [0.013.10%]. New cases of HCV infection were more frequently detected during routine examination of children prior to hospitalization or children born to mothers with HCV. Viremic HCV was confirmed in 90.2% [84.694.3%], including HCV infection in 53.4% [45.061.6%], chronic liver disease in 35.8% [28.144.1%] having low activity and occasional consequences (the fibrosis METAVIR score of F1 and F1-2 17.8% [9.828.5%]). No significant clinical and epidemiological differences between the natural course of chronic HCV infection and the liver disease caused by HCV have been found. The burden of pediatric HCV in MR is aggravated by a significant proportion of socially vulnerable patients and patients with comorbid conditions. Conclusion. One of the solutions for detection of new pediatric cases of HCV infection in MR can be offered by improvement of collaboration and continuity of care among healthcare organizations and early treatment of women of childbearing age. Further research is required to evaluate the effectiveness of routine testing of all socially vulnerable pediatric groups. Early application of pan-genotypic antiviral treatment regimens can contribute significantly to control of the HCV infection incidence in children.

Key messages For individuals with beta-thalassemia major, transient elastography is a noninvasive method for assessing liver fibrosis A further contributing factor to liver fibrosis in these patients is HCV infection acquired during transfusional therapy. Patients' advanced age and a history of numerous transfusions may increase their chance of developing liver fibrosis.

Hepatitis C virus (HCV) is a positive-stranded RNA virus causing chronic liver diseases. The chemical modification of RNA is a research hotspot in related fields in recent years, including the methylation and acetylation of adenine, guanine, cytosine and other bases, among which methylation is the most important modification form. m6A (N6-methyladenosine), as the most abundant RNA modification form, plays an important role in HCV virus infection by modifying viral RNA and cell transcripts. This review aims to summarize the current knowledge on the roles of m6A modification in HCV infection, and discuss the research prospect. • m6A RNA modification plays an important role in HCV virus infection by modifying viral RNA and cell transcripts. • The roles of m6A modification in HCV genome was summarized, helping understanding the mechanism of HCV chronic infection. • m6A modification in cellular RNA during HCV infection was summarized, helping understanding HCV and host cells' interaction. [ABSTRACT FROM AUTHOR]

HCV is a hepatotropic RNA virus recognized for its frequent virulence and fatality worldwide. Despite many vaccine development programs underway, researchers are on a quest for natural bioactive compounds due to their multivalent efficiencies against viral infections, considering which the current research aimed to figure out the target-specificity and therapeutic potentiality of α, β, and δ subunits of amyrin, as novel bioactive components against the HCV influx mechanism. Initially, the novelty of amyrin subunits was conducted from 203 pharmacophores, comparing their in-silico pharmacokinetic and pharmacodynamic profiles. Besides, the best active site of CD81 was determined following the quantum tunneling algorithm. The molecular dynamic simulation was conducted (100 ns) following the molecular docking steps to reveal the parameters- RMSD (Å); Cα; RMSF (Å); MolSA (Å2); Rg (nm); PSA (Å); SASA (Å2), and the MM-GBSA dG binding scores. Besides, molecular strings of CD81, along with the co-expressed genes, were classified, as responsible for encoding CD81-mediated protein clusters during HCV infection, resulting in the potentiality of amyrins as targeted prophylactics in HCV infection. Finally, in vivo profiling of the oxidative stress marker, liver-specific enzymes, and antioxidant markers was conducted in the DMN-induced mice model, where β-amyrin scored the most significant values in all aspects. [ABSTRACT FROM AUTHOR]

During January 2017–March 2020, approximately 2.2 million noninstitutionalized civilian US adults had hepatitis C; one-third were unaware of their infection. Prevalence was substantially higher among persons who were uninsured or experiencing poverty. Unrestricted access to testing and curative treatment is needed to reduce disparities and achieve 2030 elimination goals. [ABSTRACT FROM AUTHOR]

Introduction: Hepatitis C virus (HCV) infection was the primary reason causing critical hepatic Q7 diseases. Although direct-acting antiviral agents (DAA) were widely used in clinics, anti-drug mutation, the outcome of patients with different viral subtypes, and recurrence suggested that HCV pathogenic mechanism should be studied further. HCV infection, replication, and outcome were influenced by the IFNL4 and itsdownstream genes (MxA and MxB). However, whether genetic polymorphisms of these genes played necessary roles required verification in the Yunnan population. Methods and Results: After analyzing the genotypes and allele frequencies of seven single nucleotide polymorphisms (SNP), we found the association between the genotype and allele frequencies of rs11322783 in the IFNL4 gene and HCV infection in Yunnan population. Furthermore, the genetic polymorphisms of the MxA and MxB genescould influence liver function of HCV patients. The indirect bilirubin (IBIL) and albumin (ALB) levels showed significant differences among HCV patients, who carried various genotypes. The IBIL levels were associated with genotypes of rs17000900 (P= 0.025) and rs2071430 (P= 0.037) in the MxA gene, and ALB levels were associated with genotypes of rs2838029 (P= 0.010) in the MxB gene. Similarly, the genotypes of SNPs also showed significant difference in patients infected with subtype 3a (P=0.035) and 2a (P=0.034). However, no association was identified between expression level and SNPs of the MxA and MxB genes. Furthermore, HCV subtype 3b was found to be the predominantly epidemic strain in Yunnan Province. Conclusion: In conclusion, the association between biochemical indices/HCV subtypes and SNPs in the MxA and MxB genes was identified in Yunnan HCV population. [ABSTRACT FROM AUTHOR]

Direct-acting antiviral (DAA) therapies are efficacious for the achievement of sustained virologic response (SVR) in almost all treated hepatitis C virus (HCV)-infected patients. However, the impacts of HCV eradication on immune function and chronic immune activation in the long-term remain controversial and limited, especially in patients co-infected with human immunodeficiency virus (HIV). Indeed, although restoration of many immune responses clearly can be observed, several features of immune perturbations persist over time after HCV clearance. Understanding the degree and reasons of the partial recovery of the immune system in chronic HCV/HIV co-infection after HCV elimination is pivotal to avoid disease progression and possible long-term clinical outcomes in cured patients, as well as contributing to the development of immunotherapy drug design. [ABSTRACT FROM AUTHOR]

Orally administered direct-acting antivirals (DAAs) have dramatically changed the possibility of curing HCV (hepatitis C virus) infection, with the two principal HCV regimens based on the combination of glecaprevir + pibrentasvir (GLE-PIB) and sofosbuvir + velpatasvir (SOF-VEL). A combination of drugs containing NS3/4A protease inhibitors, as well as the fact that almost all HCV patients can be treated at present, may expose patients to a higher rate of drug–drug interactions (DDIs). The hepatitis C treatment recommendations from the EASL (European Association for the Study of the Liver) state that, prior to starting treatment with a DAA, a detailed drug history should be taken; yet, the decision on managing the potential DDIs is not always clear. For this reason, a group of Italian cardiologists and hepatologists promoted a survey among colleagues to assess the controversial issues when treating patients with chronic hepatitis C taking concomitant cardiovascular drugs, aiming to reach a consensus on the best practice to apply when treating a patient with chronic hepatitis C who is taking concomitant drugs for cardiovascular diseases. Two consecutive questionnaires were proposed between June and July 2022 to a qualitative Expert Panel (EP) of 14 gastroenterologists, infectologists, hepatologists, and internists, with statistical analyses performed on 100% of the responses for both questionnaires. Agreement among experts was assessed following the Delphi method as developed by the RAND Corporation. The interviewed experts consider DDIs a critical clinical problem to be evaluated in HCV patients. Therefore, dose changes, drug substitution, and discontinuation of concomitant cardiovascular drugs should be discouraged, even if planned for a relatively short period. Since oral DAAs have different DDIs profiles, hepatologists should prefer the antiviral DAA combination presenting the lowest instance of potential interactions. [ABSTRACT FROM AUTHOR]

Background: In the present study we evaluated the efficacy of an innovative model of HCV micro-elimination in a hospital setting in an area of high HCV prevalence. Patients and metods: Between January and December 2019, a prospective, interventional study for a program of HCV case-finding and linkage-to-care was performed in S. Anna and S. Sebastiano hospital of Caserta, in Campania, a region in southern Italy. All adult patients who were admitted to the Caserta hospital in the study period and resulted positive for anti-HCV were included in the study. The outcomes evaluated were the number of subjects resulting HCV-RNA-positive, those linked-to-care and treated with a DAA and the subjects whose anti-HCV-status was unknown. Results: In the study period, 14,396 subjects, admitted to the hospital for different reasons, were tested for anti-HCV: 529 (3.7%) subjects resulted positive for anti-HCV. Of the 529 anti-HCV-positive subjects, 10 died during hospitalization and 243 were already treated with a DAA. The remaining 276 subjects were contacted and agreed to be evaluated. Of these 276 subjects, 68 patients resulted HCV- RNA-negative and 194 HCV-RNA-positive and 180 of these were treated with a DAA according to the international guidelines. Discussion: A simple, rapid, inexpensive model of HCV micro-elimination in the hospital setting allowed us to find anti-HCV-positive subjects with unknown anti-HCV status or not linked to a clinical center.

Background: Epidermal growth factor (EGF) is a mitogen for hepatocytes, and plays a critical role in liver tissue regeneration. Many signaling pathways especially pathways that regulate the physiological processes such as tumor cells growth, differentiation, migration, apoptosis, and angiogenesis had been studied in the era of HCC development such as the EGF signal pathway.During the past few years, there have been enormous efforts to understand the structure and life cycle of hepatitis C virus (HCV) as well as to develop specific medications targeting different viral proteins such as NS3/4A protease, NS5B polymerase, and NS5A replication complex. The discovery of direct acting antiviral agents (DAAs) represented a revolution in the management of chronic hepatitis C virus infection Objectives: to investigate polymorphism of the gene encoding EGF in HCV-induced liver cirrhosis whether receiving antiviral treatment or not.Methods: Sixty Egyptian patients were enrolled in the study. Twenty patients pre-diagnosed as HCV-induced liver cirrhosis and received antiviral treatment in the form of Daklatasvir, Sofosbuvir and Ribavirin for 3 months and sustained virological response (SVR) was obtained, 20 patients diagnosed as HCV-induced liver cirrhosis and not receiving treatment yet, and 20 healthy person of matched age and sex as control group). Genotyping for EGF gene was performed by real time PCR.Results: With regards to polymorphism of EGF gene there are three genotypes; A/A, A/G and G/G that were detected in the three studied groups. The frequency of EGF gene polymorphism in HCV patients who received treatment was (AA 5%, AG 60%, GG 35%), while was (AA10%, AG 45%, GG 45%) in HCV patients who did not receive treatment. In control group, the frequency was (AA 65 %, AG 15%, GG 20%). Upon examining the allelic discrimination, A allele was present in 35% of HCV patient who received treatment versus 32.5% of HCV patient who did not receive treatment and 72.5% of control group. On the other hand, G allele was present in 65% of HCV patients who received treatment versus 67.5% of HCV patients who did not receive treatment and 17.5% of control group. Conclusion: No significant effect of antiviral treatment on EGF gene.

Abstract Background Hepatitis C virus (HCV) infection is a blood borne infection that remains potentially transmissible through blood transfusions. Sickle cell disease (SCD) is a common inheritable haemoglobinopathy in Ghana that requires multiple blood transfusions as part of its management. The SCD patient is therefore at a high risk of HCV infection; however, data on the occurrence of HCV in SCD patients has not been documented in Ghana. This study sought to determine the prevalence and genotypes of HCV infection in SCD patients. Materials and methods This was a cross-sectional study which enrolled 141 sickle-cell disease patients from the Ghana Institute for Clinical Genetics, Korle-Bu Teaching Hospital (KBTH). Patient information was obtained through a structured questionnaire. Aliquots of the plasma obtained was used for both serology with Advanced Quality Rapid Anti-HCV Test Strip and molecular testing by RT-PCR with primers targeting the HCV core gene. The amplified DNA were purified and subjected to phylogenetic analysis to characterize HCV genotypes. Results Twelve (9%) out of the 141 patients were sero-positive for HCV total antibodies. HCV RNA was amplified from 8 (6%) out of the total number of patients’ samples. One of the 12 sero-positives was HCV RNA positive. Five (63%) out of the 8 HCV RNA positive samples were successfully sequenced. The phylogenetic tree constructed with the study and GenBank reference sequences, clustered all five study sequences into HCV genotype 1. Conclusion The HCV seroprevalence of 9% among sickle cell disease patients is higher than reported for the general Ghanaian population which is 3%. Genotype 1 is the common HCV genotype infecting SCD patients. Sickle cell disease is likely to be a high-risk group for HCV inapparent infections in Ghana as seroprevalence does not correlate with viremia. However, even with higher seroprevalence, the group must be given priority in resource allocation for preventive, diagnostic and therapeutic strategies.

There is an urgent need for the identification of new drugs that inhibit HCV-induced hepatocellular carcinoma (HCC). Our work demonstrates that cyclophilin inhibitors (CypIs) represent such new drugs. We demonstrate that the nonimmunosuppressive cyclosporine A (CsA) analog (CsAa) rencofilstat possesses dual therapeutic activities for the treatment of HCV infection and HCV-induced HCC. Specifically, we show that the HCV infection of humanized mice results in the progressive development of HCC. This is true for the four genotypes tested (1 to 4). Remarkably, we demonstrate that rencofilstat inhibits the development of HCV-induced HCC in mice even when added 16 weeks after infection when HCC is well established. Importantly, we show that rencofilstat drastically reduces HCC progression independently of its anti-HCV activity. Indeed, the CypI rencofilstat inhibits HCC, while other anti-HCV agents such as NS5A (NS5Ai) and NS5B (NS5Bi) fail to reduce HCC. In conclusion, this study shows for the first time that the CypI rencofilstat represents a potent therapeutic agent for the treatment of HCV-induced HCC.

Abstract Background Understanding the extent of viral hepatitis burden in specific subgroups, such as pregnant women and people living with HIV/AIDS (PLWHA), and their geographic distribution is essential for evidence-informed policy and mobilizing resources for targeted treatment and prevention efforts. However, in Cambodia, the epidemiology of hepatitis C remains uncertain. We estimated the hepatitis C virus (HCV) burden and transmission risk factors among PLWHA and pregnant women attending antenatal care (ANC) in Cambodia. Methods Between March and April 2016, we conducted a cross-sectional survey in four diverse geographical areas: the capital city of Phnom Penh and three provinces. We collected information on demographic characteristics and risk behaviors and performed HCV antibody (Anti-HCV) testing among pregnant women attending public ANC clinics and among those receiving HIV care at the hospitals. We computed the prevalence of HCV among the two population subsets and performed logistic regression analyses to identify risk factors associated with HCV antibody positivity. Results Of 935 participants enrolled, 510 (54.6%) were pregnant women and 425 (45.4%) were PLWHA. Anti-HCV prevalence was significantly higher in PLWHA than in pregnant women (29/425, 6.8% vs 5/510, 0.9%, P

BackgroundSeveral epidemiological studies have established the association between hepatitis C virus (HCV) infection and type 2 diabetes mellitus (T2DM). However, the determinants and reasons for the high prevalence of HCV infection in people with T2DM are not well understood especially in sub-Saharan African populations. In this study, we aimed to assess determinants of the association between HCV infection and T2DM.MethodsWe performed a cross-sectional study amongst 442 T2DM patients recruited from an out-patient adult diabetes clinic in a tertiary hospital and 442 non-diabetic controls recruited from the general population. Serological testing for HCV antibody was performed using standard ELISA technique. Anti-HCV antibody prevalence was reported by age group in participants with diabetes and the non-diabetic controls. Logistic regression was used to examine for factors associated with the HCV infection in patients with diabetes.ResultsWe reported an overall HCV prevalence of 11.5% [95% CI: 9.4-13.6] irrespective of diabetes status in this study. The seroprevalence of HCV infection in diabetics patients was 17.6% [95% CI: 14.0-21.2] compared to 5.5% [95% CI: 3.4-7.6] in non-diabetics (p< 0.001). We did not find a significant HCV seropositivity difference in diabetic patients with common risk factors of HCV infection. When investigating the HCV seroprevalence by age group in diabetic and non-diabetic patients, no case of HCV infection was found in patients less than 30 years old while the highest HCV seropositivity was reported in patients older than 60 years (36.7% T2DM and 11.1% for non-diabetics) followed by the patients belonging to 50-59 years age group (16% in T2DM and 5.8% in non-diabetics) and those in 40-49 years age group (4.4% in diabetic, 0.8% in non-diabetic). To support this finding, in a multivariate logistic regression, only diabetic patients belonging to age group > 65 years had a significant risk (OR: 16.7 [95% CI: 1.7-160.0]) to acquire HCV infection.ConclusionThe seroprevalence of HCV infection is higher among T2DM adult patients than in non-diabetic patients, and is associated with increased age. This age-dependent association may suggest a generational exposure that may no longer exist overtime.

Introduction. Lichen planus (LP) is a mucocutaneous T-cell mediated disorder of unknown etiology. There is growing evidence that oxidative stress is an important player in the pathogenesis of LP. Therefore, we have investigated oxidative stress markers in LP and the influence of hepatitis C virus (HCV) infection, a frequently associated condition, on oxidative stress in LP patients.

Background: Pakistan has second highest prevalence of HCV in the world. The epidemiology and burden of HCV infection varies in people of different ages. Objective: Present study was designed to measure the prevalence of HCV among children in selected public and private hospitals of Lahore Methods: Children in the study were screened for anti-HCV test through ELISA (third generation ELISA Kit and Qaigen kit) for detecting the viral load from June 2018 to May 2019. Results: Children in the study were screened for anti-HCV test through ELISA (third generation ELISA Kit and Qaigen kit) for detecting the viral load. The average age of non-reactive and reactive children was 7.28±3.36 and 5.50±3.8 years respectively. Socio-economic status was found associated with anti-HCV. An association was found significant for birthplace, delivery assisted by, and type of milk given to the child. Conclusion: This study shows that the prevalence of HCV is 3.85% in childern in lahore city of Pakistan, which is alarming situation for healthcare providers, researchers and policy makers. [ABSTRACT FROM AUTHOR]

The objective: to conduct a retrospective clinical and statistical analysis of the pregnancy course, childbirth and the condition of newborns in women with HCV infection. Materials and methods. A retrospective clinical and statistical analysis of the pregnancy course, childbirth and the condition of newborns was carried out according to the data of 351 birth histories of women with HCV infection based on the materials of the archive of the communal non-commercial enterprise “Kyiv Municipal Center of Reproductive and Perinatal Medicine” for the period from 2016 to 2021. The control group (CG) included 50 healthy pregnant women. Statistical processing of research results was carried out using standard programs “Microsoft Excel 5.0” and “Statistica 8.0”. Results. In women with HCV infection compared to the group of healthy pregnant women a significantly high frequency (p<0.001) of such pregnancy complications was found: threat of pregnancy interruption - 64 (18.2 %) patients versus 2 (4.0 %) persons, edema of pregnant women - 72 (20.5 %) and 4 (8.0 %), respectively; preeclampsia - 45 (12.8 %) versus 2 (4.0 %), gestational anemia - 131 (37.3 %) versus 6 (12.0 %), as well as placental insufficiency with fetal growth retardation syndrome (FGR) - 69 (19.6 %) versus 3 (6.0 %; p<0.05) and intrahepatic cholestasis of pregnant women - 42 (11.9 %) versus 1 (2.0 %; p<0.05). In 73 (20.8 %) pregnant women with HCV infection the childbirth was complicated by premature rupture of the membranes, of which almost half of the cases (42 (11.9 %) of the patients) finished with premature birth, while in CG only some women had such complications. Fetal distress during childbirth was reliably detected more often in pregnant women with HCV infection than in CG women (χ2 =4.76; p=0.024). Caesarean section was performed in 86 (24.5 %) patients with HCV infection versus 2 (4.0 %) persons in CG (p<0.001). The newborns from mothers with HCV infection had lower indicators of physical development and decreased Apgar score assessment, increased frequency of conjugation jaundice. Conclusions. Pregnant women with HCV infection are characterized by a significant increase in the number of pregnancy complications, such as the threat of pregnancy interruption, the threat of premature birth, gestational anemia, placental dysfunction, fetal growth retardation syndrome, and preeclampsia; during childbirth - premature and antepartum rupture of amniotic membranes, premature birth, weakness of uterine activity in labor, increased blood loss. The condition of newborns from women with HCV infection is characterized by a significant increase in the frequency of asphyxia during childbirth, CNS hypoxic-ischemic damage, prematurity and conjugation jaundice. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infected patients have been found to be more susceptible to metabolic syndrome (MetS), but the results remain unclear and lack of a meta-analysis. Databases including PubMed, Web of Science, EMBASE and the Cochrane Library were searched to identify all studies concerning HCV and MetS. Funnel plots combined with Begg's tests and Egger's tests were used to analysis the possible publication bias. The odds ratios (ORs) with 95% confidence intervals (CIs) were used to access the effect of HCV infection on the risk of MetS. Eight articles, involving a total of 57387 HCV patients were included. HCV infection was significantly associated with an increased incidence of MetS (OR = 1.73; 95% CI, 1.19–2.52). After adjustment according to the sensitivity analysis, one included article was removed to decrease the publication bias and high heterogeneity, of which the results showed that HCV infection was still associated with an increased incidence of MetS (OR = 1.93; 95% CI, 1.39–2.68). HCV patients tend to have a significant increased risk for MetS, but more large-scale studies are needed to confirm this and explore the exact mechanism. [ABSTRACT FROM AUTHOR]

Herein, we propose a fractional-order delay differential model for the dynamics of Hepatitis-C Virus (HCV), with interferon-α(IFN-α) treatment. A fractional-order derivative is considered to represent the long-run immune memory required for intermediate cellular interactions. A discrete time-delay τ is also incorporated to represent the intracellular delay between initial infection of a cell by HCV and the release of new virions. By using time-delay τ as a bifurcation parameter, the stability of infection-free and infected steady states is investigated. The coefficients of the corresponding characteristic equation depend on τ, and geometric stability switch criteria is used to study the stability switching properties. The fractional-order delay differential model has been verified with real observations. Incorporating fractional-order and immune memory, in the model, greatly enriches the dynamics of the system and improves the consistency of the model with the observations.

Abstract Background Increasing evidence suggests that hepatitis C virus (HCV) infection is associated with non-Hodgkin’s lymphoma (NHL). However, no clear consensus has been reached about the clinical features and effective treatment of HCV-associated NHL patients. We therefore performed a systematic review and meta-analysis to explore the clinical characteristics and effectiveness of antiviral treatment or rituximab administration among NHL patients with HCV infection. Methods Eight electronic databases, including PubMed, OVID, EMBASE, Cochrane Library, ClinicalTrials, WANFANG, CNKI, and VIP, were searched for eligible studies up to July 31, 2021. The hazard ratio (HR) or odds ratio (OR) corresponding to the 95% confidence interval (CI) was calculated to estimate the outcomes. Publication bias was assessed by Egger’s and Begg’s tests. Statistical analysis was performed with RevMan 5.4 software and Stata version 15. Results There were 27 shortlisted articles out of a total of 13,368 NHL patients included in the current meta-analysis. Our results demonstrated that NHL patients with HCV infection had a significantly shorter overall survival (OS: HR 1.89; 95% CI 1.42–2.51, P

Hepatitis C virus (HCV) infection is a potential risk factor for Sjögren's syndrome (SS). However, it is unclear whether anti-HCV intervention therapy could decrease SS risk. A retrospective cohort analysis from 1997–2012 comprising 17,166 eligible HCV-infected adults was conducted. By 1:2 propensity score matching, a total of 2123 treated patients and 4246 untreated patients were subjected to analysis. The incidence rates and risks of SS and death were evaluated through to the end of 2012. In a total follow-up of 36,906 person-years, 177 (2.8%) patients developed SS, and 522 (8.2%) died during the study period. The incidence rates of SS for the treated and untreated cohorts were 5.3 vs. 4.7/1000 person-years, and those of death for the treated and untreated cohorts were 10.0 vs. 14.8/1000 person-years. A lower risk of death (adjusted hazard ratio, 0.68; 95% CI, 0.53–0.87) was present in HCV-infected patients receiving anti-HCV therapy in multivariable Cox regression, and this remained consistent in multivariable stratified analysis. However, there were no relationships between anti-HCV therapy and its therapeutic duration, and SS risk in multivariable Cox regression. In conclusion, anti-HCV intervention therapy was not associated with lower SS risk in HCV-infected patients, but associated with lower death risk. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic significantly compromised screening, laboratory controls, clinical surveillance and treatment of chronic hepatitis patients and worsened their outcome, as evidenced by its significant correlation with advanced cirrhosis, liver decompensation and mortality. Results: This pandemic significantly impaired also the sector of liver transplantation, whose wards, operating rooms, outpatients' facilities, and healthcare personnel have been dedicated to patients with COVID-19. In addition, screening and treatment for HBV infection have been delayed or suspended in in most countries, with an increased risk of viral reactivation. Similar delay or suspension have also occurred for universal hepatitis B vaccination programs in many countries. Likewise, COVID-19 pandemic has made unreachable the goal of elimination of HCV infection as a worldwide public-health issue predicted for 2030 by the WHO. Conclusion: This review article demonstrates how COVID-19 pandemic is causing serious damage to the sector of liver disease, which has quickly lost the beneficial effects of years of study, research, and clinical and technological application, as well as considerable financial investments. [ABSTRACT FROM AUTHOR]

P2X7R-NLRP3 and AIM2 inflammasomes activate caspase-1 and the release of cytokines involved in viral-related liver disease. Little is known about their role in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steato-hepatitis (NASH). We characterized the role of inflammasomes in NAFLD, NASH, and HCV. Gene expression and subcellular localization of P2X7R/P2X4R-NLRP3 and AIM2 inflammasome components were examined in histopathological preparations of 46 patients with biopsy-proven viral and metabolic liver disease using real-time PCR and immunofluorescence. P2X7R, P2X4R, and Caspase-1 are two- to five-fold more expressed in patients with NAFLD/NASH associated with chronic HCV infection than those with metabolic damage only (p ≤ 0.01 for all comparisons). The AIM2 inflammasome is 4.4 times more expressed in patients with chronic HCV infection, regardless of coexistent metabolic abnormalities (p = 0.0006). IL-2, a cytokine playing a pivotal role during chronic HCV infection, showed a similar expression in HCV and NASH patients (p = 0.77) but was virtually absent in NAFLD. The P2X7R-NLRP3 complex prevailed in infiltrating macrophages, while AIM2 was localized in Kupffer cells. Caspase-1 expression correlated with elastography-based liver fibrosis (r = 0.35, p = 0.02), whereas P2X7R, P2X4R, NRLP3, Caspase-1, and IL-2 expression correlated with circulating markers of disease severity. P2X7R and P2X4R play a major role in liver inflammation accompanying chronic HCV infection, especially when combined with metabolic damage, while AIM2 is specifically expressed in chronic viral hepatitis. We describe for the first time the hepatic expression of IL-2 in NASH, so far considered a peculiarity of HCV-related liver damage. [ABSTRACT FROM AUTHOR]

Introduction: Hepatitis C is a significant public health problem worldwide due to late-stage detection, when complications arise, because many cases of the disease are oligosymptomatic. Administration of direct antiviral treatment at the early stage of the disease leads to the eradication of the infection but involves many adverse effects that lead to waivers on the part of beneficiaries although the high costs are covered by national programs. Objective: To identify the risk factors involved in HCV transmission and to evaluate adverse reactions to antiviral administration, reason for discontinuing therapy that contributes to complications and increased HCV transmission. Method: Knowing the many adverse effects produced by the administration of direct antivirals, within the Faculty of Medicine in Brasov a prospective quantitative observational-transversal study was conducted between April and June 2021 having as data collection method the questionnaire addressed to patients diagnosed with hepatitis C distributed with the help of the non-governmental Organization Association of patients with liver disease in Romania and which included a number of 125 respondents-patients. Results: The study looked at the identification and frequency of risk factors that cause HCV contamination. Unfortunately, there is no vaccine to prevent hepatitis C infection, and the key to the problem is prevention and testing. The result of taking direct antivirals in addition to the undeniable benefits also brings adverse effects and their frequency is a reason for discontinuation of treatment for a fairly small percentage of patients, as evidenced by the present study, late initiation or its interruption leading to complications. Conclusion: The study found that the main risk factor identified by the respondents is dental treatment, more than half of the study participants had undetectable viremia from direct antiviral therapy, and nearly half of the 125 patients claimed that it had no adverse effect, in which case the benefits outweigh the risks. [ABSTRACT FROM AUTHOR]

Objectives: Therapeutic advances make the cure of chronic hepatitis C virus (HCV) infection achievable for individuals aware of their diagnosis who can access care. Identifying barriers to accessing care is critical to achieve population-level HCV elimination and improve the cascade of care from diagnosis to cure.Methods: To identify barriers to HCV care, we performed a retrospective observational analysis of outcomes for patients with chronic HCV referred to an infectious diseases clinic at an academic medical center in Charleston, South Carolina between January 1, 2015 and January 1, 2020. We categorized outcomes in the cascade of care between "never presenting for evaluation" and "completed treatment with documented cure." Patient demographic factors, referral source, ZIP code of residence, insurance status, clinical characteristics, antiviral regimen, psychiatric and substance use history, and route of infection were assessed for associations with care outcomes.Results: Of 407 referrals, 32% of patients never presented for an initial evaluation, an outcome that was associated with active substance use, mental health disease, and referral from an emergency department or obstetrics-gynecology provider. Of the patients who presented for an initial evaluation, 78% of patients initiated treatment. Active substance use was the only variable associated with lack of therapy initiation after presenting for an initial evaluation (odds ratio 2.5, 95% confidence interval 1.07-5.84). Once treatment had been initiated, no clinical or demographic variables were associated with odds of achieving documented or presumed HCV cure.Conclusions: Active substance use, mental health disease, and referral from an emergency department or obstetrics-gynecology provider were associated with a lower odds of presenting for evaluation and initiation of HCV treatment. Innovative models to improve access to care and increase outreach to vulnerable populations will be essential to eliminate HCV. [ABSTRACT FROM AUTHOR]

Migrants from Africa are vulnerable to viral infections during their journey. Migrants who arrived in western Sicily were offered early screening for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infection. A questionnaire was administered to evaluate risk factors, and antiviral therapy was offered to subjects with active infection. A multiple regression analysis and adjusted odds ratio were obtained to evaluate risk factors. Overall, 2,639 of 2,751 (95.9%) migrants who arrived between 2015 and 2017 accepted screening and 1,911 (72.4%) completed the questionnaire. HBsAg was positive in 257 (9.7%) migrants, 24 (0.9%) were anti-HCV positive and 57 (2.2%) had HIV infection. The prevalence of HBV infection was higher in women (aOR 2.47,95%CI 1.90–3.20), p = 0.003) and in people who endured physical and/or sexual violence (aOR 2.24,95%CI 1.87–3.55, p <0.001), while HIV infection was more frequent in women (aOR 5.40,95%CI 3.09–9.43, p <0.001) who were in Libya for a long period (aOR 5.66,95%CI 2.90–10.70, p = 0.004) and endured physical and/or sexual violence (aOR 14.77,95%CI 8.34–22.11, p <0.001). Being older than 18 was associated with HCV infection (p <0.001). Overall, 77% of 57 subjects with HIV infection were retained in care, 79% of 70 chronic HBV hepatitis cases started nucleot(s)ide analogues and 61% of 18 HCV-RNA positive cases received direct-acting antiviral therapy. These findings evidence the effectiveness and feasibility of infectious disease screening programs for migrants. [ABSTRACT FROM AUTHOR]