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HIV and hepatitis C virus (HCV) infection rates among persons, who use drugs, have risen during the US overdose crisis. We elicited patient perspectives about these interconnected infections to identify the areas of misinformation that might prevent appropriate management. We used in-depth interviews and thematic analysis of coded data collected from patients (N = 24) at detox and from key informants (N = 10). Seventy-one per cent reported injecting drugs. We found that patient narratives included misinformation about HIV and HCV transmission, natural history and treatment. Some participants thought that activities such as sharing drinkware or food with persons with HIV could lead to infection, while others believed that mainly men who have sex with men were at risk. Despite significant improvements in treatment, some participants still believed that HIV was a fatal condition, while others noted that treatment was only necessary at later stages. Some participants thought that HCV was a common, mild infection that might not need immediate attention, and others stated that individuals who were actively using drugs were ineligible for treatment. The current study exposes a considerable level of misinformation about HIV prevention and about the importance and benefits of HCV therapy. Educational interventions are necessary to counter misinformation identified. [ABSTRACT FROM AUTHOR]

The prevalence of mixed hepatitis C virus (HCV) genotype infection in a representative Canadian HCV cohort is reported and virological response with direct acting antiviral (DAA) treatment was evaluated. 3272 HCV‐positive participants were enrolled, of which 2945 (90.0%) initiated DAA therapy. 0.8% were identified with mixed genotype infection. Overall sustained virological response (SVR) was 99.1% and did not differ based on mixed genotype status. Any historical disadvantage to achieving cure with HCV treatment in mixed genotype infection has been overcome by current DAA regimens. [ABSTRACT FROM AUTHOR]

Objectives: HIV/hepatitis C virus (HCV) co‐infection among people who inject drugs (PWID) remains a global health problem. The goal of our study was to evaluate, in a real‐world setting, success rates of sustained virological response (SVR) using direct‐acting antivirals (DAAs) to treat a population of PWID living with HCV/HIV. Methods: This was a prospective single‐center observational study. We collected demographic, socioeconomic, and clinical data pertaining to HIV and HCV infection in PWID with several barriers to care. We identified risk factors for SVR failure. Results: Among 130 individuals retained to HIV care, we planned HCV treatment in 119/130 (91.5%); 106/119 (89.1%) started treatment with DAAs and 100/106 (94.3%) completed treatment. People not starting treatment were more often in active opioid drug use (odds ratio [OR] 0.25; 95% confidence interval [CI] 0.07–0.97, p = 0.045) and benzodiazepine abuse (OR 0.25; 95% CI 0.07–0.95, p = 0.042). Only 86/100 (86%) were tested for SVR at 12 weeks (SVR12) and 72/86 (83.7%) achieved SVR. PWID in opioid substitution programmes tended to return for SVR12 testing more often (54.7% vs. 30%, p = 0.081). Individuals in active opioid drug use (OR 0.226; 95% CI 0.064–0.793, p = 0.02) or with poor adherence (OR 0.187; 95% CI 0.043–0.814, p = 0.025) were less likely to achieve SVR. At the end of our study period, 113/119 (95%) treatment‐eligible patients remained alive. HCV infection was cured in 68/113 (61.1%) people. Conclusions: Our findings underscore the importance of prioritizing combatting substance use to achieve HCV elimination goals. A systematic approach with effort to overcome barriers to receiving and completing treatment and encourage to enrol in opioid substitution programmes if not possible to completely abstain from use, can help increase chances of HCV cure. [ABSTRACT FROM AUTHOR]

Background: Despite achieving a sustained virological response (SVR) with direct-acting antivirals (DAAs), an unexpected increase in the occurrence rate of hepatocellular carcinoma (HCC) has been observed among HCV-treated patients. This study aims to assess the long-term follow-up of HCV patients treated with DAAs who achieved an SVR to investigate the potential for late-onset HCC. Methods: In this prospective multicenter study, we enrolled consecutive HCV patients treated with DAAs following Italian ministerial guidelines between 2015 and 2018. Exclusion criteria included active HCC on imaging, prior HCC treatment, HBV or HIV co-infection, or liver transplant recipients. Monthly follow-ups occurred during treatment, with subsequent assessments every 3 months for at least 48 months. Abdominal ultrasound (US) was performed within two weeks before starting antiviral therapy, supplemented by contrast-enhanced ultrasonography (CEUS), dynamic computed tomography (CT), or magnetic resonance imaging (MRI) to evaluate incidental liver lesions. Results: Of the 306 patients completing the 48-months follow-up post-treatment (median age 67 years, 55% male), all achieved an SVR. A sofosbuvir-based regimen was administered to 72.5% of patients, while 20% received ribavirin. During follow-up, late-onset HCC developed in 20 patients (cumulative incidence rate of 6.55%). The pattern of HCC occurrence varied (median diameter 24 mm). Multivariate and univariate analyses identified liver stiffness, diabetes, body mass index, and platelet levels before antiviral therapy as associated factors for late HCC occurrence. Conclusions: Our findings suggest that late HCC occurrence may persist despite achieving SVR. Therefore, comprehensive long-term follow-up, including clinical, laboratory, and expert ultrasonography evaluations, is crucial for all HCV patients treated with DAAs. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the real-life efficacy of pangenotypic antivirals in HIV-HCV-positive patients. Research design and methods: The analysis included 5650 subjects who were treated with pangenotypic anti-HCV drugs: 5142 were HCV-positive and 508 were HIV-HCV-positive. Results: Patients with HCV-monoinfection were older (p < 0.0001), however patients with HCV-monoinfection had a higher proportion of advanced fibrosis F4 (p < 0.0001). There were no differences between the study groups in the rate of SVR12 in ITT-analysis (87,6% versus 93,9% in coinfection and monoinfection group, respectively; p > 0.05). However, there was a difference between study groups in PP-analysis, HIV/HCV and HCV, respectively 95.9% vs 97.9%, p = 0.0323. Additionally, there were a higher rate of patients who did not apply for follow-up (SVR12) in coinfected patients (7,9% vs 3,6% respectively p = 0.0001). In multivariante analysis, factors associated with worse response to the pangenotypic anti-HCV therapy included male sex, HCV genotype 3, stage of fibrosis and decompensation of liver function and HIV coinfection. Conclusions: The real-life results of pangenotypic anti-HCV treatment are veryeffective in the group of HIV-HCV-coinfected patients. However, the finaleffectiveness is slightly lower than that obtained in HCV monoinfectedpatients. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C virus (HCV) affects approximately 2-2.5% of the global population. In Egypt, the prevalence was reported at 7% in 2015. Over recent years, new direct-acting antiviral (DAA) therapies have been developed. One of the most widely used regimens in Egypt for treating HCV infection is a combination of sofosbuvir and daclatasvir. However, there is still a limited understanding of the potential dermatological side effects associated with these medications. Objective: This study aimed to evaluate the frequency and clinical manifestations of cutaneous adverse reactions in patients undergoing treatment with direct-acting antiviral drugs. Patients and methods: This research involved 140 HCV-positive patients who were monitored for 12 weeks during their treatment. Of these, 105 patients were treated with a combination of sofosbuvir and daclatasvir (protocol 1), while 35 patients received the same regimen along with ribavirin (protocol 2). Dermatological evaluations were conducted at the start of treatment and weekly during follow-up visits to identify any skin-related side effects. Results: Dermatological adverse reactions were observed in 48 patients (34%), with 38 patients (36%) in protocol 1 and 10 patients (28%) in protocol 2. The skin-related issues noted during treatment included itching, mild generalized drug eruptions, hyperpigmentation, dry mouth, acne flare-ups, telogen effluvium, and ecchymosis. Conclusion: Directly acting antiviral therapy might yield some dermatological adverse effects. Most of them are reversible and don't require stopping of the treatment. [ABSTRACT FROM AUTHOR]

Aim: To assess real-world efficacy and safety of chronic Hepatitis C (HCV) treatment with direct acting antivirals (DAAs) in patients with cirrhosis. Methods: A retrospective chart review of 451 patients with HCV cirrhosis treated between January 2015 and December 2019. Results: In the intention to treat (ITT) analysis of all 451 patients, 88.3% achieved sustained virologic response (SVR), 5.6% experienced treatment failure, 0.9% discontinued treatment and 4.9% were lost to follow-up. In the per protocol (PP) analysis, 93.6% achieved SVR and 6.4% experienced treatment failure. The most common reported adverse effects were headache and fatigue. Conclusion: This study provides more real-world evidence that DAA treatment is both safe and effective for patients with cirrhosis, both compensated and mildly decompensated. Plain Language Summary Hepatitis C virus (HCV) is a virus that can cause serious liver disease, such as cirrhosis (scarring of the liver) and liver cancer. Treatment of hepatitis C is very safe and lowers the risk of complications. Some patients have poorer access to treatment than others, including those in hospitals that are required to provide healthcare regardless of someone's insurance status, known as safety net hospitals and those with cirrhosis. We describe over 400 patients who were treated for HCV at a safety net hospital between 2015 and 2019. These patients had different levels of liver scarring, ranging from moderate to very severe. Our study shows that these medications were safe and effective at treating hepatitis C in these individuals. We found that the treatment cured 88% of patients, overall. This adds to the evidence that patients who have hepatitis C and cirrhosis, even if severe, can and should be treated more often. Article highlights In a real-world, public safety net hospital setting, among a large, racially diverse cohort of patients with cirrhosis, including patients with decompensated cirrhosis, treated for hepatitis C with direct-acting antiviral agents, we observed 88.3% and 93.6% SVR in our intention-to-treat and per-protocol analyses. Treatment outcomes were similar for patients with compensated and decompensated cirrhosis. The most commonly reported adverse effects were headache and fatigue. [ABSTRACT FROM AUTHOR]

Background: The introduction of direct-acting antivirals (DAA) has revolutionized hepatitis C virus (HCV) treatment but has not translated into an appreciable decline in HCV prevalence, which is estimated to be 2.4 million in the United States. Efforts are thought to be limited by the lack of experience among nonspecialist providers in managing HCV. However, there have been no comprehensive surveys assessing HCV knowledge among medical trainees to determine if trends have shifted since the discovery of DAAs. Methods: We performed a retrospective observational study of internal medicine (IM) residents in the United States (n = 1763) who completed the Physician Education and Assessment Center HCV learning module between 2021 and 2022. Participant pre- and post-test performance was compared with further stratified analysis by training year, geography, training program type, and local HCV prevalence using ANOVA and Chi-squared tests of proportions, respectively. Results: IM residents universally lacked baseline HCV knowledge (average score ± standard deviation, 43% ± 19%); less than 50% of participants answered correctly in the majority of tested domains. There were no consistent trends in performance regardless of resident characteristic used to stratify the participants. Knowledge gaps improved after completing an online educational training module (P < .001). Conclusions: HCV knowledge remains limited among IM residents despite expansion of treatment options. Addressing these gaps during clinical training may substantially increase the availability of HCV treatment in the community, and online modules may be one means by which to integrate these efforts into medical training.

Abstract Background Hepatocellular carcinoma (HCC) is the first cause of cancer in Egypt. Recently, HCC developed post direct-acting antivirals (DAAs) differ in some characteristics from those developed without DAAs exposure regarding the biological features and behavior of HCC. We aimed to assess the epidemiological, clinical, laboratory, and radiological findings besides the biological behavior of HCC patients post DAAs in comparison to HCC not exposed to DAAs. An analytic cross-sectional research was performed at the National Liver Institute which is a tertiary multidisciplinary HCC center. Subjects included hepatitis C virus patients and were allocated into two groups: group I included 2036 HCC cases post-DAA treatment and group II included 6338 HCC cases who did not receive DAAs. Subjects were examined to evaluate clinical, laboratory, and radiological findings. Tumor staging was done using the BCLC staging system. Results Group II showed a more advanced Child–Pugh score, FIB-4 index, and MELD score than Group I (P = 0.001). The multiplicity of hepatic focal lesions was elevated in group I than in group II (P = 0.033). AFP level was significantly elevated in group I than in group II (p = 0.012). Portal vein invasion was significantly elevated in group I than in group II patients (P = 0.001). Extrahepatic spread of HCC was significantly elevated in group I than in group II (P = 0.001). Infiltrative lesions were significantly elevated in group I than in group II (P = 0.002). Conclusion Our study detected that the behavior in HCC post DAAs treatment is more aggressive in respect of the number of lesions, PV invasion; local and distant metastasis, and serum AFP level than in patients unexposed to DAAs. Strict surveillance in cirrhotic patients treated with DAA should be followed according to the international guidelines for early diagnosis and treatment of HCC.

Background: Hepatocellular carcinoma (HCC) is the first cause of cancer in Egypt. Recently, HCC developed post direct-acting antivirals (DAAs) differ in some characteristics from those developed without DAAs exposure regarding the biological features and behavior of HCC. We aimed to assess the epidemiological, clinical, laboratory, and radiological findings besides the biological behavior of HCC patients post DAAs in comparison to HCC not exposed to DAAs. An analytic cross-sectional research was performed at the National Liver Institute which is a tertiary multidisciplinary HCC center. Subjects included hepatitis C virus patients and were allocated into two groups: group I included 2036 HCC cases post-DAA treatment and group II included 6338 HCC cases who did not receive DAAs. Subjects were examined to evaluate clinical, laboratory, and radiological findings. Tumor staging was done using the BCLC staging system. Results: Group II showed a more advanced Child–Pugh score, FIB-4 index, and MELD score than Group I (P = 0.001). The multiplicity of hepatic focal lesions was elevated in group I than in group II (P = 0.033). AFP level was significantly elevated in group I than in group II (p = 0.012). Portal vein invasion was significantly elevated in group I than in group II patients (P = 0.001). Extrahepatic spread of HCC was significantly elevated in group I than in group II (P = 0.001). Infiltrative lesions were significantly elevated in group I than in group II (P = 0.002). Conclusion: Our study detected that the behavior in HCC post DAAs treatment is more aggressive in respect of the number of lesions, PV invasion; local and distant metastasis, and serum AFP level than in patients unexposed to DAAs. Strict surveillance in cirrhotic patients treated with DAA should be followed according to the international guidelines for early diagnosis and treatment of HCC. [ABSTRACT FROM AUTHOR]

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 can now be cured with well-tolerated direct-acting antiviral (DAA) therapy. However, a potential barrier to HCV elimination is the emergence of resistance-associated substitutions (RASs) that reduce the efficacy of antiviral drugs, but real-world studies assessing the clinical impact of RASs are limited. Here, an analysis of the impact of RASs on retreatment outcomes for different salvage regimens in patients nationally who failed first-line DAA therapy is reported. Methods We collected data from 363 Australian patients who failed first-line DAA therapy, including: age, sex, fibrosis stage, HCV genotype, NS3/NS5A/NS5B RASs, details of failed first-line regimen, subsequent salvage regimens, and treatment outcome. Results Of 240 patients who were initially retreated as per protocol, 210 (87.5%) achieved sustained virologic response (SVR) and 30 (12.5%) relapsed or did not respond. The SVR rate for salvage regimens that included sofosbuvir/velpatasvir/voxilaprevir was 94.3% (n = 140), sofosbuvir/velpatasvir 75.0% (n = 52), elbasvir/grazoprevir 81.6% (n = 38), and glecaprevir/pibrentasvir 84.6% (n = 13). NS5A RASs were present in 71.0% (n = 210) of patients who achieved SVR and in 66.7% (n = 30) of patients who subsequently relapsed. NS3 RASs were detected in 20 patients (20%) in the SVR group and 1 patient in the relapse group. NS5B RASs were observed in only 3 patients. Cirrhosis was a predictor of relapse after retreatment, as was previous treatment with sofosbuvir/velpatasvir. Conclusions In our cohort, the SVR rate for sofosbuvir/velpatasvir/voxilaprevir was higher than with other salvage regimens. The presence of NS5A, NS5B, or NS3 RASs did not appear to negatively influence retreatment outcomes. [ABSTRACT FROM AUTHOR]

Background. Hepatitis C virus (HCV) infection is a leading cause of liver cancer globally. Treating chronic HCV with direct-acting antivirals (DAAs) in cirrhotic patients has raised concerns about their effect on HCC development and progression. Objective: To compare the characteristics of de novo HCC in chronic HCV cirrhotic patients who achieved sustained virological response (SVR) with DAAs therapy, with that of HCC which developed in chronic HCV cirrhotic patients who did not receive DAAs or PEG interferon-based treatments. Methods The study included 200 chronic HCV cirrhotic patients divided into two groups: group 1 with 100 patients who developed de novo HCC post-SVR following DAAs, and group 2 with 100 HCV-related HCC patients who developed HCC without prior antiviral therapy. Non-invasive HCC diagnosis was based on EASL guidelines. Baseline demographic, clinical, and laboratory data were collected. The Child-Turcotte-Pugh (CTP) score, class, and Barcelona Clinic Liver Cancer (BCLC) staging system were determined (stages 0/A as early stages, while BCLC stages B/C/D as late stages of HCC). The types of DAAs used for chronic HCV treatment were also recorded. Results. Post-DAAs HCC was diagnosed approximately 4.3 years post-SVR, characterized by multi-focal or diffuse infiltration compared to HCV-related HCC. The tumor diameter in post-DAAs HCC was larger versus in HCV-related HCC (p= 0.002). Linear regression analysis indicated that DAAs therapy was a significant predictor of a larger tumor diameter. Malignant portal vein thrombosis (PVT) was more prevalent in post-DAAs HCC compared to HCV-related HCC (p= 0.001). CTP score was significantly lower in post-DAAs HCC compared to HCV-related HCC (p< .001). Post-DAAs HCC was diagnosed at later BCLC stages than HCV-related HCC. The serum AFP level was insignificantly higher in post-DAAs HCC than in HCV-related HCC. Platelets were significantly higher in post-DAAs HCC than in HCV-related HCC (p= 0.001). ALT levels were significantly lower in post-DAAs HCC compared to HCV-related HCC (p=0.02). Conclusion Post-DAAs HCC had larger size, a more diffuse pattern, and a higher rate of malignant PVT compared to HCV-related HCC. It was diagnosed at later BCLC stages but had lower CTP scores, lower ALT levels, and higher platelet counts. [ABSTRACT FROM AUTHOR]

Despite the advent of direct‐acting antiviral agents (DAAs) as a definitive therapy for chronic hepatitis C virus (HCV) infection, the burden of the disease remains globally elevated. The emerging big data on different HCV paradigms fostered the introduction of artificial intelligence/machine learning (AI/ML) applications to help decrease that burden by providing more optimised strategies for early diagnosis and treatment prioritisation. The current review provides descriptive and analytical insight into the recently published AI/ML applications in five medical aspects of HCV infection. In addition, it highlights the opportunities these powerful tools offer in designing national health policies that prioritise HCV patients for the costly DAAs and developing broadly neutralising HCV antibodies. Finally, this paper highlights the challenges encountered in developing and applying these AI/ML models to clinical practice and suggests schemes to overcome some of them. The presented models were primarily evaluated using the Matthews correlation coefficient and the F1‐score to make a more reliable inference about their predictive power under imbalanced datasets. Many published AI/ML applications offered great utilities for predicting novel HCV treatments and prioritising patients for DAAs receipt, especially in settings of limited resources and high HCV burden. Some outperformed the classical diagnostic tools, such as third‐generation serological tests, alpha‐fetoprotein, and ultrasound, in detecting HCV infections and early HCV‐associated hepatocellular carcinoma, respectively. However, further statistical and clinical validation of AI/ML models is highly advocated before incorporating these applications into clinical practice. [ABSTRACT FROM AUTHOR]

Le virus de l'hépatite C (VHC) est un virus à ARN hépatotrope, capable d'établir des infections aiguës et chroniques chez l'humain. Le VHC induit dans la majorité des cas une infection persistante à l'origine d'une hépatite chronique associée à des degrés divers à une activité nécrotico-inflammatoire et à une fibrose hépatique. Les principales complications sont la cirrhose et le carcinome hépatocellulaire (CHC) à l'origine de près de 270 000 décès dans le monde chaque année. Le développement de thérapies antivirales puissantes et bien tolérées et la mise à disposition de nouveaux outils virologiques ont révolutionné la prise en charge. Au regard des objectifs de l'Organisation mondiale de la santé (OMS), il est urgent de simplifier et d'élargir le dépistage et le diagnostic de l'infection par le VHC, de simplifier le parcours de soins et d'augmenter l'accès au traitement. Hepatitis C virus (HCV) is a hepatotropic RNA virus capable of establishing acute and chronic infections in humans. In the majority of cases, HCV induces persistent infections leading to chronic hepatitis, associated to various degrees with necrotic-inflammatory activity and hepatic fibrosis. The main complications are cirrhosis and hepatocellular carcinoma (HCC), responsible for almost 270,000 deaths a year world-wide.The development of potent, well-tolerated antiviral therapies and the availability of new virological tools have revolutionized management of hepatitis C infection. In line with the objectives of the World Health Organization (WHO), there is an urgent need to simplify and expand screening and diagnosis of HCV infection, simplify the cascade of care and increase access to antiviral treatment. [ABSTRACT FROM AUTHOR]

The human immunodeficiency virus (HIV) persists in HIV viral reservoirs despite antiretroviral therapy (ART). Hepatitis C virus (HCV) coinfection is associated with increased HIV reservoir size and residual HIV transcription during ART. Herein, we investigated the impact of direct acting antivirals (DAA)-mediated HCV cure on the size/transcriptional activity of the HIV reservoirs and investigated predictors of HIV reservoirs decline in HCV+/HIV+ coinfected individuals. HCV+/HIV+ (n = 20) and HCV+/HIV- (n = 14) participants were examined prior to DAA treatment (baseline), at the end of treatment (EOT), and at 12-24 weeks after EOT (follow-up). In HCV+/HIV+ individuals, DAA-mediated HCV cure significantly reduced integrated HIV DNA levels, mainly in participants infected with HCV prior to HIV. Integrated HIV DNA, unspliced (US), and multiply spliced (MS) HIV RNA levels were quantified in sorted CD4+ T-cells. Despite the transient elevation of US HIV RNA at EOT, changes in US and MS HIV RNA were not statistically significant. Plasma inflammation markers were measured and DAA also reduced plasma sCD163 and sCD14. Changes in immunological/virological parameters were analyzed using multivariate random forest analysis where pre-ART peak HIV viremia and HCV viral load predicted integrated HIV DNA and US RNA changes. In conclusion, we demonstrate the beneficial impact of DAA on HIV reservoirs and immune activation, with a fraction of HIV reservoirs being DAA-sensitive in people infected with HCV before HIV. Furthermore, we identify HIV/HCV viremia as the top predictors of DAA-mediated changes in the HIV reservoirs. These findings support the need for early ART and DAA treatment in HIV/HCV coinfections. [ABSTRACT FROM AUTHOR]

Abstract Background Hepatitis C is curable with direct-acting antivirals (DAAs). However, treatment uptake remains low among marginalized populations such as people who inject drugs. We sought to understand challenges to treatment uptake with DAAs among people living with hepatitis C and compare treatment experiences between people who do and do not inject prescription and/or unregulated drugs. Methods We conducted a qualitative study using focus groups with 23 adults aged 18 years and over who completed DAA treatment or were about to begin such treatment at the time of the study. Participants were recruited from hepatitis C treatment clinics across Toronto, Ontario. We drew upon stigma theory to interpret participants’ accounts. Results Following analysis and interpretation, we generated five theoretically-informed themes characterizing the experiences of individuals accessing DAAs: “being ‘worthy’ of the cure”, “spatially enacted stigma”, “countering social and structural vulnerability: the importance of peers”, “identity disruption and contagion: attaining a ‘social cure’” and “challenging stigma with population-based screening”. Overall, our findings suggest that structural stigma generated and reproduced through healthcare encounters limits access to DAAs among people who inject drugs. Peer-based programs and population-based screening were proposed by participants as mechanisms for countering stigma within health care settings and ‘normalizing’ hepatitis C among the general population. Conclusions Despite the availability of curative therapies, access to such treatment for people who inject drugs is limited by stigma enacted in and structured within healthcare encounters. Developing novel, low-threshold delivery programs that remove power differentials and attend to the social and structural determinants of health and reinfection are needed to facilitate further scale up of DAAs and support the goal of eradicating hepatitis C as a public health threat.

Abstract Background Hepatitis C virus (HCV) transmission is primarily driven by injection drug use, and acute HCV infection rates are increased in rural communities with substantial barriers to care. Treatment of HCV in persons who use drugs (PWUD) is cost effective, decreases high risk behaviors and HCV transmission, and achieves high rates of treatment completion and sustained viral response. Adapting HCV care delivery to utilize peer support specialists, telemedicine technology, and streamlined testing and treatment strategies can better reach rural populations living with HCV. Methods This is an open label, two-arm, non-blinded, randomized controlled trial designed to test the superiority of peer-facilitated and streamlined telemedicine HCV care (peer tele-HCV) compared to enhanced usual care (EUC) among PWUD in rural Oregon. In the intervention arm, peers conduct HCV screening in the community, facilitate pretreatment evaluation and linkage to telemedicine hepatitis C treatment providers, and support participants in HCV medication adherence. For participants assigned to EUC, peers facilitate pretreatment evaluation and referral to community-based treatment providers. The primary outcome is sustained virologic response at 12 weeks post treatment (SVR12). Secondary outcomes include: (1) HCV treatment initiation, (2) HCV treatment completion, (3) engagement with harm reduction resources, (4) rates of substance use, and (5) engagement in addiction treatment resources. The primary and secondary outcomes are analyzed using intention-to-treat (ITT) comparisons between telemedicine and EUC. A qualitative analysis will assess patient, peer, and clinician experiences of peer-facilitated telemedicine hepatitis C treatment. Discussion This study uses a novel peer-based telemedicine delivery model with streamlined testing protocols to improve access to HCV treatment in rural communities with high rates of injection drug use and ongoing disease transmission. We hypothesize that the peer tele-HCV model will increase treatment initiation, treatment completion, SVR12 rates, and engagement with harm reduction services compared to EUC. Trial registration This trial has been registered with ClinicalTrials.gov (clinicaltrials.gov NCT04798521)

Abstract Background Hepatitis C virus is the underlying cause of chronic hepatitis which frequently progresses to cirrhosis and hepatocellular carcinoma. In addition, HCV is thought to cause steatosis, dyslipidemia, insulin resistance, diabetes, obesity, and cardiovascular events. The aim of this study is to evaluate the role of serum RBP-4 in the prediction of fibrosis regression and the response of treatment among chronic HCV patients receiving direct-acting antiviral agents. Methods This study included 40 chronic HCV Egyptian patients, divided into two groups: Naive cases, 20 chronic HCV patients before starting first line of treatment; Relapser cases, 20 chronic HCV patients who were non-responders before starting second line treatment; and 10 healthy subjects as control. Laboratory investigations including complete blood count, full hepatic profile, fibroscan assessment, and retinol-binding protein-4 level at baseline and re-assessed 12 weeks after the end of treatment [sustained virological response SVR12]. Student T test, analysis of variance, chi-square, Tukey’s test, and Pearson correlation coefficient tests were used for statistical analysis. Results Baseline retinol-binding protein-4 level was significantly higher in the naïve case group than in the relapser and control groups with a P value of P value of

Background: Hepatitis C Virus (HCV) remains a challenging health problem worldwide, with increasing incidence despite being curable with Direct Acting Antiviral (DAA) agents. Objective: This study aimed to describe the utilization, reimbursement, and price trends of HCV treatments and evaluate the influence of treatment guidelines and policies. Methods: A retrospective, descriptive drug utilization study conducted using the outpatient pharmacy data extracted from the Centers for Medicaid and Medicare Services State Drug Utilization Data between 2001 and 2021. All HCV treatments approved in the US were included, conventional therapy (CT), and DAA agents. The annual secular trends were calculated for each medication's total number of prescriptions, reimbursements, and prices. The average reimbursement per prescription was calculated and utilized as a proxy of prices. The HCV treatment guideline and policies and legislation were evaluated overtime to measure the impact on the trends. Results: Despite CT having a higher total utilization, DAA agents commanded significantly greater reimbursements, with 4.1 billion USD for CT and 19.45 billion USD for DAA agents. CT utilization increased rapidly and dominated the market until 2011, peaking at 379,696 prescriptions in 2003 but declining afterward. DAA agents' utilization increased rapidly in their first year: i.e., sofosbuvir reached 50,377 prescriptions with 1.3 billion USD in 2014, while ledipasvir/sofosbuvir reached 79,387 prescriptions with 2 billion USD in 2015. The average price per prescription was high for the DAA agents, like 24,992 USD for sofosbuvir and 22,787 USD for ledipasvir/sofosbuvir, compared to CT medications ribavirin, around 500 USD, and pegINF, around 3000 USD. The new DAA agents replaced CT, and initiating market competition among DAA agents. Conclusion: The introduction of multiple DAA agents slightly changed their prescription prices but remained high during the study period. The recent increase in HCV incidence cases indicates accessibility issues for costly and effective DAA agents, with treatment guidelines and policies playing a critical role in shaping these trends.

Background and Aims: The aim of this non‐commercial, open‐label, real‐life, non‐randomized clinical trial was to analyse the efficacy and safety of a pangenotypic regimen sofosbuvir/velpatasvir (SOF/VEL) in patients aged 6–18 years with chronic hepatitis C virus (HCV) infection. Methods: Fifty patients qualified for the 12‐week treatment were divided into two weight groups: 15 children weighting between 17 and <30 kg received a fixed dose of 200/50 mg of SOF/VEL (tablet) once daily, and 35 patients weighting ≥30 kg were treated with 400/100 mg SOF/VEL. The primary endpoint of the study was efficacy defined as sustained viral response (undetectable HCV RNA using an real‐time polymerase chain reaction method) at 12 weeks posttreatment (SVR12). Results: Median age of the participants was 10 (IQR 8–12) years, 47 were infected vertically, and 3 patients were previously ineffectively treated with pegylated interferon and ribavirin. Thirty‐seven participants were infected with HCV genotype 1, 10 with HCV genotype 3 and the remaining 3 with genotype 4. There was no case of cirrhosis. SVR12 was 100%. Thirty‐three reported adverse events (AEs) were considered related to the administration of SOF/VEL, all of them were mild or moderate. Children presenting with AEs were older compared to these without AEs: 12 (9.5–13) versus 9 (IQR 8–11) years (p = 0.008). Conclusions: Results of the PANDAA‐PED study indicated a 100% effectiveness of a 12‐week therapy with SOF/VEL in children aged 6–18 years with chronic HCV infection and its good safety profile, in particular in younger patients. [ABSTRACT FROM AUTHOR]

Sofosbuvir (S), daclatasvir (D), ledipasvir, or velpatasvir (V) containing first-line hepatitis C virus (HCV) treatment regimens fail to cure viremia in 5–10%. We report our experience of HCV retreatment using these first-line drugs, in a setting where second-line anti-HCV drugs are not available. Adults, who had relapsed after first complete course of a sofosbuvir-containing first-line, pegylated interferon free, anti-HCV treatment regimen with or without ribavirin (Riba) were included. Retreatment regimen, tailored to the failed anti-HCV regimen, was based on principle of using first-line drugs for 24 weeks with ribavirin and swapping between pangenotypic and genotype-specific regimens. Retreatment outcome was categorized as successful (achieved undetectable HCV RNA at the end of treatment [ETR] and sustained viral response at week 12 [SVR12]), non-responder (failed to achieve ETR), or relapse (achieved ETR but not achieved SVR12). Twelve patients (9 male; 7 cirrhosis; all genotype 3) who had relapsed to prior anti-HCV treatment (4 SD12, 4 SD24, 1 SDRiba12, 1 SDRiba24, 2 SV12) were included. Following retreatment (2 SDRiba24, 10 SVRiba24), all achieved ETR but only 9 (75%) achieved SVR12. Two among three, in whom retreatment failed, achieved SVR12 following another course of sofosbuvir/velpatasvir/ribavirin for 24 weeks. Overall, 11/12 (92%) patients achieved SVR12 following retreatment with the first-line anti-HCV drugs. HCV retreatment could be a treatment option if second-line anti-HCV drugs are not available. Successful retreatment could be achieved, in a large proportion, with the use of first-line drugs for 24 weeks with ribavirin and swapping of pangenotypic/genotype-specific regimens (NCT03483987). [ABSTRACT FROM AUTHOR]

Introduction Methods Results Discussion and Conclusions Evaluating progress towards hepatitis C virus (HCV) elimination among Aboriginal and Torres Strait Islander peoples is critical given the disproportionate burden of infection. We examined factors associated with current HCV infection and self‐reported treatment among Aboriginal and Torres Strait Islander (hereafter referred to as Aboriginal peoples) and non‐Aboriginal peoples who inject drugs (PWID) in Australia.ETHOS Engage is an observational cohort study of PWID attending drug treatment and needle and syringe programs in Australia. Participants underwent point‐of‐care HCV RNA testing (Xpert HCV RNA Viral Load Fingerstick) and completed a questionnaire including self‐reported history of HCV treatment.Between May 2018 and June 2021, 2395 participants were enrolled and 555 (23%) identified as Aboriginal (median age 42 years, 58% were men, 63% injected drugs in last month, 76% ever incarcerated). HCV RNA prevalence was 23% among Aboriginal PWID (24% in 2018–2019 and 21% in 2019–2021; p = 0.44), and 21% among non‐Aboriginal PWID (24% in 2018–2019 and 16% in 2019–2021; p < 0.001). Self‐reported HCV treatment was 65% among Aboriginal PWID (63% in 2018–2019 and 69% in 2019–2021; p = 0.30), and 70% among non‐Aboriginal PWID (67% in 2018–2019 and 75% in 2019–2021; p < 0.001). Among Aboriginal PWID, current HCV infection was associated with recently injecting drugs and receiving opioid agonist treatment, and self‐reported HCV treatment was negatively associated with younger age, homelessness and recently injecting drugs.Equitable access to HCV care and prevention is needed to ensure Australia meets its elimination targets among Aboriginal PWID. [ABSTRACT FROM AUTHOR]

Background Mathematical models explain how antivirals control viral infections. Hepatitis C virus (HCV) treatment results in at least 2 phases of decline in viremia. The first phase reflects clearance of rapidly produced virions. The second phase is hypothesized to derive from loss of infected cells but has been challenging to prove. Methods Using single-cell methods, we quantified the number of hepatitis C virus (HCV)-infected hepatocytes in liver biopsies taken before and within 7 days of initiating direct-acting antivirals (DAAs) in a double-blinded randomized controlled trial testing 2 (sofosbuvir-velpatasvir) versus 3 (sofosbuvir-velpatasvir-voxilaprevir) DAAs. Results We employed thousands of intrahepatic measurements in 10 persons with chronic genotype 1a HCV infection: median proportion of infected hepatocytes declined from 11.3% (range, 1.3%–59%) to 0.6% (range, <0.3%–5.8%), a loss of 75%–95% infected hepatocytes. Plasma viremia correlated with numbers of HCV-infected hepatocytes (r = 0.77; P <.0001). Second-phase plasma dynamics and changes in infected hepatocytes were indistinct (P =.16), demonstrating that second-phase viral dynamics derive from loss of infected cells. DAAs led to a decline in intracellular HCV RNA and interferon-stimulated gene expression (P <.05 for both). Conclusions We proved that second-phase viral dynamics reflect decay of intrahepatic burden of HCV, partly due to clearance of HCV RNA from hepatocytes. Clinical Trials Registration NCT02938013. [ABSTRACT FROM AUTHOR]

Copyright of Viral Hepatitis Journal / Viral Hepatit Dergisi is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background and Aims: Hepatitis B virus (HBV) reactivation has been reported in patients co-infected with hepatitis C virus (HCV) during direct acting antiviral (DAA) therapy, leading the United States Food and Drug Administration (U.S. FDA) to issue a black box warning on all DAA drug labels recommending monitoring for HBV reactivation. We conducted a comprehensive evaluation to assess the rate of HBV reactivation among patients with chronic hepatitis C (CHC) during DAA therapy. Methods: Patients with CHC and recovered HBV infection (hepatitis B surface antigen negative (HBsAg)/anti-hepatitis B core positive), treated with DAAs were included if stored sera were available. Samples were tested for HBV DNA, HBsAg, and ALT. HBV reactivation was considered if (1) HBV DNA was undetectable pre-DAA therapy and became detectable post-therapy, or (2) HBV DNA was detectable pre-treatment, but not quantifiable (< 20 IU/mL) and became quantifiable post-treatment. Result: 79 patients with median age of 62 years were included. 68% were male and Caucasian. Various DAA regimens were administered for 12–24 weeks. Reactivation occurred in 8/79 (10%) of patients and occurred more frequently in men compared to women: 6 during treatment and 2 after treatment. Neither an ALT flare nor HBsAg seroreversion were observed. Detectable HBV DNA was transient in 5/8 and could not be determined in 3/8 but ALT flares were not observed in follow-up of these patients. Conclusion: The risk of HBV reactivation was low in CHC patients with resolved HBV during DAA therapy. Our data support testing for HBV DNA only in selected patients with ALT flares or failure of ALT normalization during DAA treatment. [ABSTRACT FROM AUTHOR]

Abstract Background Hepatitis C virus (HCV) infection is associated with serum lipid abnormalities, which partly normalize following direct-acting antiviral (DAA) therapy. Here, associations of serum triglycerides (TGs) with viral genotype and markers of liver disease severity were evaluated in patients with chronic HCV. Methods The study included the serum of 177 patients with chronic HCV. TGs were quantified by flow injection analysis Fourier transform mass spectrometry. Laboratory values and noninvasive scores for liver fibrosis assessment were determined. The nonparametric Kruskal‒Wallis test, one-way ANOVA, multiple linear regression and Student’s t test were used as appropriate. P values were adjusted for multiple comparisons. Results HCV-infected women had lower serum TGs than men, and thus, a sex-specific analysis was performed. None of the 46 TG species analyzed differed in the serum of female patients with and without liver cirrhosis. In contrast, in the serum of male patients with liver cirrhosis, TGs with 53, 56 and 58 carbon atoms and three to eight double bonds were diminished. These polyunsaturated TGs were also low in males with a high fibrosis-4 score. TGs with 7 or 8 double bonds negatively correlated with the model of end-stage liver disease score in males. In addition, TGs with 49, 51 and 53 carbon atoms were reduced in male patients infected with genotype 3a in comparison to genotype 1a. TGs with 56 carbon atoms were lower in genotype 3a-infected males than in genotype 1b-infected males. TGs did not differ in females by genotype. Genotype 3-related changes disappeared at the end of therapy with DAAs. Overall, the levels of serum TGs did not change during DAA therapy in either sex. Consequently, the serum TGs of males with liver cirrhosis were lower than those of males without cirrhosis at the end of therapy. Such a difference was not apparent in females. Conclusions The decline in TGs observed only in male patients with liver cirrhosis and male patients infected with genotype 3 illustrates sex-specific changes in lipid metabolism in chronic HCV.

Background: Hepatitis C is curable with direct-acting antivirals (DAAs). However, treatment uptake remains low among marginalized populations such as people who inject drugs. We sought to understand challenges to treatment uptake with DAAs among people living with hepatitis C and compare treatment experiences between people who do and do not inject prescription and/or unregulated drugs. Methods: We conducted a qualitative study using focus groups with 23 adults aged 18 years and over who completed DAA treatment or were about to begin such treatment at the time of the study. Participants were recruited from hepatitis C treatment clinics across Toronto, Ontario. We drew upon stigma theory to interpret participants’ accounts. Results: Following analysis and interpretation, we generated five theoretically-informed themes characterizing the experiences of individuals accessing DAAs: “being ‘worthy’ of the cure”, “spatially enacted stigma”, “countering social and structural vulnerability: the importance of peers”, “identity disruption and contagion: attaining a ‘social cure’” and “challenging stigma with population-based screening”. Overall, our findings suggest that structural stigma generated and reproduced through healthcare encounters limits access to DAAs among people who inject drugs. Peer-based programs and population-based screening were proposed by participants as mechanisms for countering stigma within health care settings and ‘normalizing’ hepatitis C among the general population. Conclusions: Despite the availability of curative therapies, access to such treatment for people who inject drugs is limited by stigma enacted in and structured within healthcare encounters. Developing novel, low-threshold delivery programs that remove power differentials and attend to the social and structural determinants of health and reinfection are needed to facilitate further scale up of DAAs and support the goal of eradicating hepatitis C as a public health threat. [ABSTRACT FROM AUTHOR]

Background: We aimed to investigate the factors associated with improvement of liver functional reserve after sustained virological response using interferon‐free, direct‐acting antiviral combination treatment in patients with compensated, severe fibrosis. Methods: Between September 2014 and April 2020, 492 patients received direct‐acting antiviral combination treatment in our hospital. Among them, 173 patients who had severe fibrosis based on a fibrosis‐4 index ≥3.25, showed sustained virological response after treatment. We investigated the dynamic change in albumin‐bilirubin score and the baseline factors associated with its improvement, 48 weeks after treatment. Results: The baseline significant factors associated with albumin‐bilirubin ≦ −0.5 were lower albumin (HR: 15.625, 95% CI: 4.273–58.824, P <.001), higher hepatitis C virus RNA (HR: 4.995, 95% CI: 1.882–13.260, P =.001), and higher alpha‐fetoprotein (HR: 1.033, 95% CI: 1.011–1.055, P =.003). Patients with alpha‐fetoprotein ≧10 ng/mL showed significant improvement of albumin‐bilirubin score from baseline to 48 weeks after treatment compared to those with alpha‐fetoprotein <10 ng/mL (P <.001). Conclusions: Baseline serum alpha‐fetoprotein might be a predictive factor for improvement of liver function after sustained virological response in patients with severe fibrosis. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C virus (HCV) transmission is primarily driven by injection drug use, and acute HCV infection rates are increased in rural communities with substantial barriers to care. Treatment of HCV in persons who use drugs (PWUD) is cost effective, decreases high risk behaviors and HCV transmission, and achieves high rates of treatment completion and sustained viral response. Adapting HCV care delivery to utilize peer support specialists, telemedicine technology, and streamlined testing and treatment strategies can better reach rural populations living with HCV. Methods: This is an open label, two-arm, non-blinded, randomized controlled trial designed to test the superiority of peer-facilitated and streamlined telemedicine HCV care (peer tele-HCV) compared to enhanced usual care (EUC) among PWUD in rural Oregon. In the intervention arm, peers conduct HCV screening in the community, facilitate pretreatment evaluation and linkage to telemedicine hepatitis C treatment providers, and support participants in HCV medication adherence. For participants assigned to EUC, peers facilitate pretreatment evaluation and referral to community-based treatment providers. The primary outcome is sustained virologic response at 12 weeks post treatment (SVR12). Secondary outcomes include: (1) HCV treatment initiation, (2) HCV treatment completion, (3) engagement with harm reduction resources, (4) rates of substance use, and (5) engagement in addiction treatment resources. The primary and secondary outcomes are analyzed using intention-to-treat (ITT) comparisons between telemedicine and EUC. A qualitative analysis will assess patient, peer, and clinician experiences of peer-facilitated telemedicine hepatitis C treatment. Discussion: This study uses a novel peer-based telemedicine delivery model with streamlined testing protocols to improve access to HCV treatment in rural communities with high rates of injection drug use and ongoing disease transmission. We hypothesize that the peer tele-HCV model will increase treatment initiation, treatment completion, SVR12 rates, and engagement with harm reduction services compared to EUC. Trial registration This trial has been registered with ClinicalTrials.gov (clinicaltrials.gov NCT04798521) [ABSTRACT FROM AUTHOR]

Chronic hepatitis C is a major health concern with high morbidity and mortality rates. The introduction of direct acting antivirals (DAAs) as a first-line treatment for hepatitis C virus (HCV) has significantly enhanced HCV eradication. However, DAA therapy is facing rising concerns regarding long-term safety, viral resistance, and reinfection. HCV is associated with different immune alteration mechanisms that can evade immunity and establish persistent infection. One of these suggested mechanisms is the accumulation of myeloid-derived suppressor cells (MDSCs), which is known to accumulate in chronic inflammatory conditions. Moreover, the role of DAA in restoring immunity after successful viral eradication is still unclear and needs further investigations. Thus, we aimed to investigate the role of MDSCs in chronic HCV Egyptian patients and its response to DAA in treated compared with untreated patients. Fifty untreated chronic hepatitis C (CHC) patients, 50 DAA-treated CHC patients, and 30 healthy individuals were recruited. We used flow cytometer analysis to measure MDSCs frequency and enzyme-linked immunosorbent assay analysis to evaluate the serum level of interferon (IFN)-γ. We found a significant elevation in MDSC% among the untreated group (34.5 ± 12.4%) compared with the DAA-treated group (18.3 ± 6.7%), while the control group had a mean of (3.8 ± 1.6%). IFN-γ concentration was higher in treated patients compared with untreated. We also found a significant negative correlation (rs −0.662) (p < 0.001) between MDSC% and IFN-γ concentration among treated HCV patients. Our results revealed important evidence of MDSCs accumulation in CHC patients and partial retrieval of the immune system regulatory function after DAA therapy. [ABSTRACT FROM AUTHOR]

Background: Sofosbuvir-Velpatasvir has a high efficacy in adult patients with chronic hepatitis C infection .In this study, we reported treatment outcome with this drug in children and younger adults in Pakistani population. Objective: To assess the efficacy and safety of Sofosbuvir-velpatasvir in treating HCV-infected children and young adults. Methods: This Interventional(Clinical trial) was done in Hepatitis clinic Jinnah Hospital, Lahore from April 10, 2021 to January 9, 2022.A total of 45 patients aged 6 to 18 years with detectable HCV RNA by PCR were registered. They were evaluated clinically. HCV genotyping was not done as Sofosbuvir -- Velpatasvir is pangenotypic. All of the patients were given a single oral dose of Sofosbuvir-velpatasvir per day. Ribavirin was included for patients with compensated cirrhosis and for those who were treatment-experienced .Clinical assessment, CBC, LFT, RFT, and PT were performed monthly to determine side effects and safety. To evaluate treatment efficacy, HCV RNA was measured by PCR at 12 weeks (end of treatment) and 12 weeks post-treatment (sustained virological response). Treatment lasted for 24weeks for those with compensated cirrhosis. (Child Turcotte Pugh score 5 and 6; Child class A) or those who were treatment experienced. SPSS 24 was used for data analysis. Results: Non cirrhotic patients had a mean age of 13.6±1.45 years, while those with compensated cirrhosis had 14.1±2.15 years. There were 63.6% males (28) and 36.4% female (17). 41 patients (91.11%) had undetectable HCV RNA by PCR, 12 weeks after treatment (Sustained virological response), indicating treatment effectiveness. Nine patients had HBV co-infection and took HBV medications as well during HCV treatment. At 12 weeks post-treatment, all HBV-coinfected patients had undetectable HCV RNA by PCR and lower HBV titers. Some of the patients experience minor side effects. However, none of the patients stopped their treatment due to these side effects Thus, this treatment was safe and effective. Conclusion: Sofosbuvir/velpatasvir has effectiveness and safety in treating HCV in children and young adults. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C virus is the underlying cause of chronic hepatitis which frequently progresses to cirrhosis and hepatocellular carcinoma. In addition, HCV is thought to cause steatosis, dyslipidemia, insulin resistance, diabetes, obesity, and cardiovascular events. The aim of this study is to evaluate the role of serum RBP-4 in the prediction of fibrosis regression and the response of treatment among chronic HCV patients receiving direct-acting antiviral agents. Methods: This study included 40 chronic HCV Egyptian patients, divided into two groups: Naive cases, 20 chronic HCV patients before starting first line of treatment; Relapser cases, 20 chronic HCV patients who were non-responders before starting second line treatment; and 10 healthy subjects as control. Laboratory investigations including complete blood count, full hepatic profile, fibroscan assessment, and retinol-binding protein-4 level at baseline and re-assessed 12 weeks after the end of treatment [sustained virological response SVR12]. Student T test, analysis of variance, chi-square, Tukey's test, and Pearson correlation coefficient tests were used for statistical analysis. Results: Baseline retinol-binding protein-4 level was significantly higher in the naïve case group than in the relapser and control groups with a P value of P value of < 0.001. All the naïve patients had 100% SVR12, only 90% of the relapser group achieved SVR12. A significant reduction in retinol-binding protein-4 and fibrosis staging and measurements by fibroscan among all studied patients were noted after receiving direct acting antivirals (P value < 0.001). Retinol-binding protein-4 levels before and after treatment were significantly lower among F4 patients in comparison to those of F1–F3 patients (P value 0.002, 0.009, respectively). The best cutoff value of retinol-binding protein-4 in the prediction of liver cirrhosis (F4) was ≤ 46 pg/ml with sensitivity of 100% and specificity of 66.67%. Conclusion: Serum retinol-binding protein-4 was found to be higher in chronic HCV infection with a significant reduction after successful eradication. Its level is much lower in cirrhotic patients [F4]. As a result, retinol-binding protein-4 may have a promising role in assessing direct acting antivirals response, as well as a prognostic value in predicting liver cirrhosis. [ABSTRACT FROM AUTHOR]

Background Depression is common in people with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), with biological and psychosocial mechanisms at play. Direct acting antivirals (DAA) result in high rates of sustained virologic response (SVR), with minimal side-effects. We assessed the impact of SVR on presence of depressive symptoms in the HIV-HCV coinfected population in Canada during the second-generation DAA era (2013–2020). Methods We used data from the Canadian CoInfection Cohort (CCC), a multicenter prospective cohort of people with a HIV and HCV coinfection, and its associated sub-study on food security. Because depression screening was performed only in the sub-study, we predicted Center for Epidemiologic Studies Depression Scale-10 classes in the CCC using a random forest classifier and corrected for misclassification. We included participants who achieved SVR and fit a segmented modified Poisson model using an interrupted time series design, adjusting for time-varying confounders. Results We included 470 participants; 58% had predicted depressive symptoms at baseline. The median follow-up was 2.4 years (interquartile range [IQR]: 1.0–4.5.) pre-SVR and 1.4 years (IQR: 0.6–2.5) post-SVR. The pre-SVR trend suggested depressive symptoms changed little over time, with no immediate level change at SVR. However, post-SVR trends showed a reduction of 5% per year (risk ratio: 0.95 (95% confidence interval [CI]:.94–.96)) in the prevalence of depressive symptoms. Conclusions In the DAA era, predicted depressive symptoms declined over time following SVR. These improvements reflect possible changes in biological pathways and/or better general health. If such improvements in depression symptoms are durable, this provides an additional reason for treatment and early cure of HCV. [ABSTRACT FROM AUTHOR]

Copyright of Brazilian Journal of Biology is the property of Instituto Internacional de Ecologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background and Aim: Management of genotype 4 hepatitis C virus (HCV) has shifted to interferon‐free regimens with a high sustained virological response (SVR‐12), especially with NS5B/NS5A inhibitor combinations such as sofosbuvir and ledipasvir (Sof‐Led). The guidelines have recommended the combination of sofosbuvir and another NS5A inhibitor, daclatasvir, to manage HCV genotypes 1–3. However, its use was extended to genotype 4 HCV based on extrapolating evidence. Our aim is to assess the efficacy of generic sofosbuvir + branded daclatasvir (Sof‐Dac) compared to the Sof‐Led combination in treating genotype 4 HCV. Methods: This study is an open‐label, 2‐period, noninferiority study that compared patients receiving a combination of generic sofosbuvir 400 mg and daclatasvir 60 mg orally daily (Group 2) prospectively to a historical control (Group 1) that included patients who received a combination of sofosbuvir/ledipasvir 400/90 mg orally daily. The primary endpoint is the proportion of patients who achieved SVR‐12. Results: The study included 111 patients in the (Sof‐Led) Group 1 and 109 patients (Sof‐Dac) Group 2. For the primary outcome, SVR‐12 was achieved in 106 (95.5%) of the patients in Group 1 versus 108 (99.1%) in Group 2 (p = 0.2). In addition, all patients who achieved SVR‐12 also achieved SVR‐24. Conclusion: Generic sofosbuvir combined with branded daclatasvir was safe and effective for treating genotype 4 HCV compared to Sof‐Led. This combination may significantly reduce the cost burden, enabling a larger pool of treated patients. Office of research affairs at KFSHRC RAC# 2171 036. [ABSTRACT FROM AUTHOR]

Abstract Background and Aim Management of genotype 4 hepatitis C virus (HCV) has shifted to interferon‐free regimens with a high sustained virological response (SVR‐12), especially with NS5B/NS5A inhibitor combinations such as sofosbuvir and ledipasvir (Sof‐Led). The guidelines have recommended the combination of sofosbuvir and another NS5A inhibitor, daclatasvir, to manage HCV genotypes 1–3. However, its use was extended to genotype 4 HCV based on extrapolating evidence. Our aim is to assess the efficacy of generic sofosbuvir + branded daclatasvir (Sof‐Dac) compared to the Sof‐Led combination in treating genotype 4 HCV. Methods This study is an open‐label, 2‐period, noninferiority study that compared patients receiving a combination of generic sofosbuvir 400 mg and daclatasvir 60 mg orally daily (Group 2) prospectively to a historical control (Group 1) that included patients who received a combination of sofosbuvir/ledipasvir 400/90 mg orally daily. The primary endpoint is the proportion of patients who achieved SVR‐12. Results The study included 111 patients in the (Sof‐Led) Group 1 and 109 patients (Sof‐Dac) Group 2. For the primary outcome, SVR‐12 was achieved in 106 (95.5%) of the patients in Group 1 versus 108 (99.1%) in Group 2 (p = 0.2). In addition, all patients who achieved SVR‐12 also achieved SVR‐24. Conclusion Generic sofosbuvir combined with branded daclatasvir was safe and effective for treating genotype 4 HCV compared to Sof‐Led. This combination may significantly reduce the cost burden, enabling a larger pool of treated patients. Office of research affairs at KFSHRC RAC# 2171 036.

Background: Hepatitis C virus (HCV) infection is associated with serum lipid abnormalities, which partly normalize following direct-acting antiviral (DAA) therapy. Here, associations of serum triglycerides (TGs) with viral genotype and markers of liver disease severity were evaluated in patients with chronic HCV. Methods: The study included the serum of 177 patients with chronic HCV. TGs were quantified by flow injection analysis Fourier transform mass spectrometry. Laboratory values and noninvasive scores for liver fibrosis assessment were determined. The nonparametric Kruskal‒Wallis test, one-way ANOVA, multiple linear regression and Student’s t test were used as appropriate. P values were adjusted for multiple comparisons. Results: HCV-infected women had lower serum TGs than men, and thus, a sex-specific analysis was performed. None of the 46 TG species analyzed differed in the serum of female patients with and without liver cirrhosis. In contrast, in the serum of male patients with liver cirrhosis, TGs with 53, 56 and 58 carbon atoms and three to eight double bonds were diminished. These polyunsaturated TGs were also low in males with a high fibrosis-4 score. TGs with 7 or 8 double bonds negatively correlated with the model of end-stage liver disease score in males. In addition, TGs with 49, 51 and 53 carbon atoms were reduced in male patients infected with genotype 3a in comparison to genotype 1a. TGs with 56 carbon atoms were lower in genotype 3a-infected males than in genotype 1b-infected males. TGs did not differ in females by genotype. Genotype 3-related changes disappeared at the end of therapy with DAAs. Overall, the levels of serum TGs did not change during DAA therapy in either sex. Consequently, the serum TGs of males with liver cirrhosis were lower than those of males without cirrhosis at the end of therapy. Such a difference was not apparent in females. Conclusions: The decline in TGs observed only in male patients with liver cirrhosis and male patients infected with genotype 3 illustrates sex-specific changes in lipid metabolism in chronic HCV. [ABSTRACT FROM AUTHOR]

Background: Chronic hepatitis C (CHC) is associated with hepatic and extrahepatic complications, including cardiovascular disease (CVD). The effects of sustained virological response (SVR) and liver fibrosis on CVD risk are not well established. Aims: We aim to assess the dynamics of Fibrosis-4 (FIB-4) and Atherosclerotic Cardiovascular Disease 2013 (ASCVD) scores up to three years after direct acting antivirals (DAA) treatment and explore the time-dependent association between the two scores. Methods: We included consecutive CHC patients treated with DAA and followed up with them for three years. Outcomes were changes from baseline (before DAA) in ASCVD and FIB-4 scores, measured at the end of treatment, 12-, 24-, and 36-months follow-up. Results: In total, 91 patients with CHC were finally included (median age: 66 years (IQR = 58–72 years); 43% females). Median follow-up was 2 years (1–3 years) and all patients reached SVR. The ASCVD score did not significantly change from baseline (Mean = 17.2%, 95% CI 14.1, 20.3), but the FIB-4 score significantly decreased at any time-point by an average of 0.8 (95% CI 0.78, 0.82, p < 0.001). Elevated FIB-4 scores at one (β = 1.16, p < 0.001) and three years (β = 2.52, p < 0.001) were associated with an increased ASCVD score. Clinically, two participants- with non-decreasing FIB-4 scores after treatment- had acute coronary syndrome at the end of treatment and one year follow-up, respectively. Conclusions: In our study, we found that FIB-4 and ASCVD scores exhibited a positive correlation irrespective of time-point after treatment. Larger studies are essential to further investigate the utility of FIB-4 scores in cardiovascular risk assessment. [ABSTRACT FROM AUTHOR]

Background: One of the most significant threats to public health is hepatitis C virus infection (HCV). Pegylated interferon alpha (Peg-IFNα) and ribavirin (RBV) had been the main stay of treatment for hepatitis C until recently. This combination often causes systemic and ocular side effects. More effective and safer than IFN therapy is direct acting antiviral agents (DAAs). Objective: The objective of the current study was to assess the impact of sofosbuvir (SOF) and daclatasvir (DAC) on choroidal and macular thickness among HCV cases. Patients and methods: Between June 2018 and February 2019, 30 HCV cases were included and treated using RBV-free SOF/DAC regimen for 12 weeks. They were referred to the ophthalmology department where full ophthalmological assessment was done before and at the end of treatment. Furthermore, macular and choroidal thicknesses were assessed by optical coherence tomography (OCT). Results: 60 eyes of 30 HCV cases (aged from 24-56 years, males: 18 [60%], females: 12 [40%]) received RBV-free SOF/DAC regimen for 12 weeks. During the 3 months of follow-up, no ocular complications were reported. Best corrected visual acuity (BCVA) was not changed. OCT showed increase in macular thickness from baseline. Although there was an increase, it didn’t show statistical significance (p=0.743). The choroidal thickness measurements showed no statistically significant difference. Conclusion: There are no observable ophthalmic sequelae among patients treated with DAAs, and this includes the RBV-free SOF/DAC regimen. There appears to be a decreased need for routine ophthalmic follow-up among patients treated with DAAs in comparison to INF. [ABSTRACT FROM AUTHOR]

• Limited data exists about treatment outcomes in nationwide HCV elimination programs where injection drug use is the main mode of transmission. • In 2016 Iceland initiated the HCV elimination program known as treatment as prevention for Hepatitis C (TraP HepC). • History of injection drug use was reported by 84 % and 33 % had injected recently. • By reengagement in care and prompt retreatment when needed, a cure rate of 95.5 % was achieved. • Unstable housing was the only independent factor associated with not achieving cure. Limited data exists about treatment outcomes in nationwide hepatitis C virus (HCV) elimination programs where injection drug use (IDU) is the main mode of transmission. In 2016 Iceland initiated the HCV elimination program known as Treatment as Prevention for Hepatitis C (TraP HepC). Factors associated with HCV cure in this population are examined. Unrestricted access was offered to direct acting antiviral agents (DAAs). Testing and harm reduction was scaled up and re-treatments were offered for those who did not attain cure. Cure rates for the first 36 months were assessed and factors associated with failure to achieve cure analysed using multivariable logistic regression. Treatment was initiated for 718; 705 consented for the study. Median age was 44 years (IQR 35–56), history of IDU reported by 593 (84.1 %), recent IDU by 234 (33.2 %); 48 (6.8 %) were homeless. Of 705 patients, 635 achieved cure (90.1 %) during the first treatment. A total of 70 (9.9 %) patients initiated two or more treatments, resulting in 673 participants cured (95.5 %). By multivariable analysis, homelessness was the only statistically significant independent factor associated with not achieving cure (OR 2.67, 95 % CI 1.32–5.41) after first treatment attempt. By reengagement in care and prompt retreatment when needed, a cure rate of 95.5 % was achieved. Unstable housing, a potentially actionable factor is associated with poor outcome. [ABSTRACT FROM AUTHOR]

We report a quantification of the decrease of effectiveness of antiviral agents directed to hepatitis C virus, when the agents are added during an ongoing infection in cell culture vs. when they are added at the beginning of the infection. Major determinants of the decrease of inhibitory activity are the time post-infection of inhibitor administration and viral replicative fitness. The efficacy decrease has been documented with antiviral assays involving the combination of the direct-acting antiviral agents, daclatasvir and sofosbuvir, and with the combination of the lethal mutagens, favipiravir and ribavirin. The results suggest that strict antiviral effectiveness assays in preclinical trials may involve the use of high fitness viral populations and the delayed administration of the agents, relative to infection onset. [ABSTRACT FROM AUTHOR]

Molecular epidemiology of hepatitis C virus (HCV) is exceptionally complex due to the highly diverse HCV genome. Genetic diversity, transmission dynamics, and epidemic history of the most common HCV genotypes were inferred by population sequencing of the HCV NS3, NS5A, and NS5B region followed by phylogenetic and phylodynamic analysis. The results of this research suggest high overall prevalence of baseline NS3 resistance associate substitutions (RAS) (33.0%), moderate prevalence of NS5A RAS (13.7%), and low prevalence of nucleoside inhibitor NS5B RAS (8.3%). Prevalence of RAS significantly differed according to HCV genotype, with the highest prevalence of baseline resistance to NS3 inhibitors and NS5A inhibitors observed in HCV subtype 1a (68.8%) and subtype 1b (21.3%), respectively. Phylogenetic tree reconstructions showed two distinct clades within the subtype 1a, clade I (62.4%) and clade II (37.6%). NS3 RAS were preferentially associated with clade I. Phylogenetic analysis demonstrated that 27 (9.0%) HCV sequences had a presumed epidemiological link with another sequence and classified into 13 transmission pairs or clusters which were predominantly comprised of subtype 3a viruses and commonly detected among intravenous drug users (IDU). Phylodynamic analyses highlighted an exponential increase in subtype 1a and 3a effective population size in the late 20th century, which is a period associated with an explosive increase in the number of IDU in Croatia. [ABSTRACT FROM AUTHOR]

Fatih Karbeyaz,1 Seraphina Kissling,2 Paul Julius Jaklin,1 Jaqueline Bachofner,1 Barbara Brunner,1 Beat Müllhaupt,1 Thomas Winder,3 Joachim C Mertens,1 Benjamin Misselwitz,1,4 Stefanie von Felten,5 Alexander R Siebenhüner6,7 1Division of Gastroenterology and Hepatology, University Hospital Zurich and Zurich University, Zurich, Switzerland; 2Master Program in Biostatistics, University of Zurich, Zurich, Switzerland; 3Division of Oncology, Landeskrankenhaus Feldkirch, Feldkirch, Austria; 4Department of Visceral Surgery and Medicine, Inselspital Bern and Bern University, Bern, Switzerland; 5Department of Biostatistics, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland; 6Department of Medical Oncology and Hematology, University Hospital Zurich and University of Zurich, Zurich, Switzerland; 7Department of Medical Oncology, Cantonal Hospital Schaffhausen, Schaffhausen, SwitzerlandCorrespondence: Alexander R SiebenhünerKlinik für Medizinische Onkologie und Hämatologie, Universitätsspital Zürich, Rämistrasse 100, Zürich, CH-8091, SwitzerlandEmail alexander.siebenhuener@usz.chBackground: Direct-acting antivirals (DAA) have revolutionized the therapy of chronic hepatitis C (CHC) and have replaced previous PEG-interferon/ribavirin (PEG-IFN/RBV) treatment. Patients with CHC and advanced liver disease are at increased risk for hepatocellular carcinoma (HCC). However, the effects of DAA-based CHC treatment on subsequent HCC incidence remain poorly understood.Patients and Methods: This retrospective single-institution cohort study included 243 consecutive patients after PEG-IFN/RBV and 263 patients after DAA treatment. Multivariable cause-specific Cox proportional hazards models were used to compare time to HCC between treatment types, censoring patients who died or had an orthotopic liver transplantation (OLT) at the time of the competing event. Age, gender, BMI, viral load, cirrhosis, fibrosis stage, diabetes, virus genotype and previous PEG-IFN/RBV (before DAA) were used as covariates. In addition, we performed a propensity score-matched analysis.Results: Nineteen HCC cases were observed after DAA therapy compared to 18 cases after PEG-IFN/RBV treatment. Patients were followed for a median of 4.1 years (IQR: 3.5– 4.7) for DAA and 9.3 years (IQR: 6.6– 12.4) for the PEG-IFN/RBV group. In an unadjusted Cox model, a hazard ratio (HR) of 6.40 (CI: 2.20– 18.61, p=0.006) for HCC following DAA vs PEG-IFN/RBV was estimated. In multivariable Cox proportional hazard models, age and liver cirrhosis were identified as further HCC risk factors but the HR estimates for DAA vs PEG-IFN/RBV still indicate a considerably increased hazard associated with DAA treatment (HR between 7.23 and 11.52, p≤ 0.001, depending on covariates). A HR of 6.62 (CI: 2.01– 21.84, p=0.002) for DAA vs PEG-IFN/RBV was estimated in the propensity score-matched analysis. The secondary outcomes death and OLT did not differ between treatment groups.Conclusion: In a cohort study from a tertiary care hospital rates of HCC after the start of DAA treatment were higher compared to PEG-IFN/RBV treatment. Our data reinforce the recommendation that surveillance should be continued after successful CHC treatment.Keywords: hepatocellular carcinoma, chronic hepatitis C, direct-acting antivirals, PEG-interferon and ribavirin, viral load, liver transplantation, sustained virological response

We report a quantification of the decrease of effectiveness of antiviral agents directed to hepatitis C virus, when the agents are added during an ongoing infection in cell culture vs. when they are added at the beginning of the infection. Major determinants of the decrease of inhibitory activity are the time post-infection of inhibitor administration and viral replicative fitness. The efficacy decrease has been documented with antiviral assays involving the combination of the direct-acting antiviral agents, daclatasvir and sofosbuvir, and with the combination of the lethal mutagens, favipiravir and ribavirin. The results suggest that strict antiviral effectiveness assays in preclinical trials may involve the use of high fitness viral populations and the delayed administration of the agents, relative to infection onset.

Several key areas in gastroenterology pharmacotherapy are rapidly evolving, including the treatment of hepatitis C virus (HCV), irritable bowel syndrome, gastroesophageal reflux disease (GERD) and peptic ulcer disease. HCV treatment has radically changed in the past 2 years and now most patients are treatment candidates and have a high likelihood of permanent cure. Pharmacotherapy is now first-line treatment for patients with moderate to severe symptoms of irritable bowel syndrome. Proton pump inhibitors (PPIs) are the mainstay of therapy in gastric and duodenal ulcers and GERD, although long-term use carries the risk of several side effects that should be considered.

Background. The development of direct acting antivirals (DAAs) has spurred a revolution in treatment of patients with chronic hepatitis C. However, there are cases showing no response to treatment. In 5% of cases, the viral breakthrough is most likely caused by DAA resistance mutations in the hepatitis C virus genome.The purpose of the study is to detect drug resistance mutations of hepatitis C virus in patients with DAA treatment failure.Materials and methods. The study was performed on plasma samples from 3 patients diagnosed with chronic hepatitis C virus infection and demonstrating DAA virological treatment failure. All isolates had genotype 1b. Drug resistance mutations were detected by using direct sequencing of NS3, NS5A, and NS5B genome regions. The detection technique was developed at the Pasteur Research Institute of Epidemiology and Microbiology.Results. Drug resistance mutations were detected in all cases. By using the Geno2pheno [hcv] 0.92 tool, nucleotide substitutions were detected in different viral genome regions and presumably caused resistance or decreased sensitivity to antivirals both present and absent in the sofosbuvir + daclatasvir combination therapy. Antiviral treatment failure in patients with chronic hepatitis C is caused by drug resistance mutations.Conclusions. The developed technique is efficient for detection of drug resistance mutations in NS3, NS5A, and NS5B regions in cases of virological failure of DAA treatment.

Abstract Whether patients with advanced hepatocellular carcinoma (aHCC) benefit from hepatitis C virus (HCV) eradication is uncertain. We aimed to investigate whether a survival benefit was conferred by HCV eradication in aHCC patients. This retrospective cohort study enrolled 168 HCV‐infected aHCC patients from April 2013 to January 2019. All patients were treated with sorafenib. Endpoints included overall survival (OS), progression free survival (PFS), and time to liver decompensation. Patients with undetectable HCV RNA exhibited reduced aspartate aminotransferase and alpha fetoprotein levels, as well as an attenuated proportion of aHCC at initial diagnosis but increased albumin and mean sorafenib daily dosing. Patients with undetectable HCV RNA exhibited significantly longer OS compared to patients with detectable or unknown HCV RNA, which was an independent factor of OS (HR: 0.56, 95% CI: 0.350‐0.903, P = .017). Patients with undetectable HCV RNA also presented a trend for longer PFS (HR 0.68, 95% CI: 0.46‐1.00, P = .053). The survival benefit was considered with respect to the significantly prolonged time to Child‐Pugh B scores in patients with undetectable HCV RNA (HR 0.59, 95% CI: 0.38‐0.92, P = .020). Patients with detectable HCV RNA at sorafenib initiation who further received direct acting antiviral therapy also had significantly longer OS (HR 0.11, 95% CI: 0.02‐0.81, P = .030) and PFS (HR 0.23, 95% CI: 0.06‐0.99, P = .048). In conclusion, abolishing HCV viremia preserves liver function and confers a survival benefit in advanced HCC patients on sorafenib treatment.