Hepatitis C screening in Lithuania: first-year results and scenarios for achieving WHO elimination targets.

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

Integrated Hepatitis C-Opioid Use Disorder Care Through Facilitated Telemedicine: A Randomized Trial.

Importance: Facilitated telemedicine may promote hepatitis C virus elimination by mitigating geographic and temporal barriers. Objective: To compare sustained virologic responses for hepatitis C virus among persons with opioid use disorder treated through facilitated telemedicine integrated into opioid treatment programs compared with off-site hepatitis specialist referral. Design, Setting, and Participants: Prospective, cluster randomized clinical trial using a stepped wedge design. Twelve programs throughout New York State included hepatitis C-infected participants (n = 602) enrolled between March 1, 2017, and February 29, 2020. Data were analyzed from December 1, 2022, through September 1, 2023. Intervention: Hepatitis C treatment with direct-acting antivirals through comanagement with a hepatitis specialist either through facilitated telemedicine integrated into opioid treatment programs (n = 290) or standard-of-care off-site referral (n = 312). Main Outcomes and Measures: The primary outcome was hepatitis C virus cure. Twelve programs began with off-site referral, and every 9 months, 4 randomly selected sites transitioned to facilitated telemedicine during 3 steps without participant crossover. Participants completed 2-year follow-up for reinfection assessment. Inclusion criteria required 6-month enrollment in opioid treatment and insurance coverage of hepatitis C medications. Generalized linear mixed-effects models were used to test for the intervention effect, adjusted for time, clustering, and effect modification in individual-based intention-to-treat analysis. Results: Among 602 participants, 369 were male (61.3%); 296 (49.2%) were American Indian or Alaska Native, Asian, Black or African American, multiracial, or other (ie, no race category was selected, with race data collected according to the 5 standard National Institutes of Health categories); and 306 (50.8%) were White. The mean (SD) age of the enrolled participants in the telemedicine group was 47.1 (13.1) years; that of the referral group was 48.9 (12.8) years. In telemedicine, 268 of 290 participants (92.4%) initiated treatment compared with 126 of 312 participants (40.4%) in referral. Intention-to-treat cure percentages were 90.3% (262 of 290) in telemedicine and 39.4% (123 of 312) in referral, with an estimated logarithmic odds ratio of the study group effect of 2.9 (95% CI, 2.0-3.5; P < .001) with no effect modification. Observed cure percentages were 246 of 290 participants (84.8%) in telemedicine vs 106 of 312 participants (34.0%) in referral. Subgroup effects were not significant, including fibrosis stage, urban or rural participant residence location, or mental health (anxiety or depression) comorbid conditions. Illicit drug use decreased significantly (referral: 95% CI, 1.2-4.8; P = .001; telemedicine: 95% CI, 0.3-1.0; P < .001) among cured participants. Minimal reinfections (n = 13) occurred, with hepatitis C virus reinfection incidence of 2.5 per 100 person-years. Participants in both groups rated health care delivery satisfaction as high or very high. Conclusions and Relevance: Opioid treatment program-integrated facilitated telemedicine resulted in significantly higher hepatitis C virus cure rates compared with off-site referral, with high participant satisfaction. Illicit drug use declined significantly among cured participants with minimal reinfections. Trial Registration: ClinicalTrials.gov Identifier: NCT02933970.

Shear-wave elastography to predict hepatocellular carcinoma after hepatitis C virus eradication: A systematic review and meta-analysis.

BACKGROUND: Direct-acting antiviral agents (DAAs) are highly effective treatment for chronic hepatitis C (CHC) with a significant rate of sustained virologic response (SVR). The achievement of SVR is crucial to prevent additional liver damage and slow down fibrosis progression. The assessment of fibrosis degree can be performed with transient elastography, magnetic resonance elastography or shear-wave elastography (SWE). Liver elastography could function as a predictor for hepatocellular carcinoma (HCC) in CHC patients treated with DAAs. AIM: To explore the predictive value of SWE for HCC development after complete clearance of hepatitis C virus (HCV). METHODS: A comprehensive literature search of clinical studies was performed to identify the ability of SWE to predict HCC occurrence after HCV clearance. In accordance with the study protocol, a qualitative and quantitative analysis of the evidence was planned. RESULTS: At baseline and after 12 wk of follow-up, a trend was shown towards greater liver stiffness (LS) in those who go on to develop HCC compared to those who do not [baseline LS standardized mean difference (SMD): 1.15, 95% confidence interval (95%CI): 020-2.50; LS SMD after 12 wk: 0.83, 95%CI: 0.33-1.98]. The absence of a statistically significant difference between the mean LS in those who developed HCC or not may be related to the inability to correct for confounding factors and the absence of raw source data. There was a statistically significant LS SMD at 24 wk of follow-up between patients who developed HCC vs not (0.64; 95%CI: 0.04-1.24). CONCLUSION: SWE could be a promising tool for prediction of HCC occurrence in patients treated with DAAs. Further studies with larger cohorts and standardized timing of elastographic evaluation are needed to confirm these data.

Changes in Use of Hepatitis C Direct-Acting Antivirals After Access Restrictions Were Eased by State Medicaid Programs.

Importance: Direct-acting antivirals (DAAs) are safe and highly effective for curing hepatitis C virus (HCV) infection, but their high cost led certain state Medicaid programs to impose coverage restrictions. Since 2015, many of these restrictions have been lifted voluntarily in response to advocacy or because of litigation. Objective: To estimate how the prescribing of DAAs to Medicaid patients changed after states eased access restrictions. Design, Setting, and Participants: This modified difference-in-differences analysis of 39 state Medicaid programs included Medicaid beneficiaries who were prescribed a DAA from January 1, 2015, to December 31, 2019. DAA coverage restrictions were measured based on a series of cross-sectional assessments performed from 2014 through 2022 by the US National Viral Hepatitis Roundtable and the Center for Health Law and Policy Innovation. Exposure: Calendar quarter when states eased or eliminated 3 types of DAA coverage restrictions: limiting treatment to patients with severe liver disease, restricting use among patients with active substance use, and requiring prescriptions to be written by or in consultation with specialists. States with none of these restrictions at baseline were excluded. Main Outcomes and Measures: Quarterly number of HCV DAA treatment courses per 100 000 Medicaid beneficiaries. Results: Of 39 states, 7 (18%) eliminated coverage restrictions, 25 (64%) eased restrictions, and 7 (18%) maintained the same restrictions from 2015 to 2019. During this period, the average quarterly use of DAAs increased from 669 to 3601 treatment courses per 100 000 Medicaid beneficiaries. After states eased or eliminated restrictions, the use of DAAs increased by 966 (95% CI, 409-1523) treatment courses per 100 000 Medicaid beneficiaries each quarter compared with states that did not ease or eliminate restrictions. Conclusions and Relevance: The results of this study suggest that there was greater use of DAAs after states relaxed coverage restrictions related to liver disease severity, sobriety, or prescriber specialty. Further reductions or elimination of these rules may improve access to a highly effective public health intervention for patients with HCV.

Hepatitis C prevalence and cascade of care among patients in the decentralised opioid agonist therapy programme of the canton of St Gallen, Switzerland: a cross-sectional study.

BACKGROUND: To eliminate chronic hepatitis C virus (HCV) infection by 2030, 90% of those infected must be diagnosed and 80% treated. In Switzerland, >40% of the estimated 32,000 infected people are still undiagnosed. In the canton of St Gallen, HCV prevalence and cascade of care have only been studied in the centralised opioid agonist therapy (OAT) setting (institutions), although about 80% of OAT patients are treated decentrally (general practitioner [GP] or pharmacy). AIM: To describe HCV prevalence and cascade of care among patients in the decentralised OAT programme of the canton of St Gallen, Switzerland, and compare it to contemporaneous data from the centralised setting. METHODS: For each patient receiving his/her OAT from a GP or pharmacy on 1 April 2021, the cantonal medical office sent a questionnaire to the prescribing GP. Patient characteristics, HCV antibody (Ab)/RNA screening uptake, HCV Ab/RNA prevalence and HCV treatment uptake were obtained and compared to those of patients of the Medizinisch-soziale Hilfsstelle 1 in St Gallen (centralised setting). RESULTS: Of the 563 OAT patients under the care of 127 GPs, 107 patients from 41 GPs could be analysed (median age: 48 years [IQR: 40-56]; ongoing intravenous drug use: 25%; OAT provider: 66% GP, 34% pharmacy). HCV Ab screening uptake was 68% (73/107) with an HCV Ab prevalence of 68% (50/73) among those tested. Of the HCV Ab-positive patients, 84% (42/50) were HCV RNA-tested, among whom 57% (24/42) were viraemic. HCV treatment uptake was 83% (20/24), with 95% (19/20) achieving a sustained virological response. Non-uptake of HCV screening and treatment tended to be higher among patients receiving OAT at the pharmacy vs at the GP's office: 37% vs 26% (p = 0.245) for screening and 30% vs 7% (p = 0.139) for treatment. The proportion never HCV Ab-tested and the proportion of HCV Ab-positives never HCV RNA-tested was significantly higher in the decentralised compared to the centralised setting: 32% vs 3% (p <0.001) never Ab-tested and 16% vs 0% (p = 0.002) never RNA-tested. In contrast, HCV treatment uptake (83% vs 78%), sustained virological response rate (95% vs 100%) and residual HCV RNA prevalence among the HCV Ab-positive (12% vs 14%) were comparable for both settings. CONCLUSION: In the decentralised OAT setting of the canton of St Gallen, HCV Ab prevalence is high. Since HCV Ab and RNA screening uptake are markedly lower than in the centralised setting, potentially >40% of patients with chronic HCV are not diagnosed yet. HCV screening in the decentralised setting needs improvement, e.g. by increasing awareness and simplifying testing. High HCV treatment uptake and cure rates are possible in centralised and decentralised settings.

Inflammatory Consequences: Hepatitis C Virus-Induced Inflammasome Activation and Pyroptosis.

Hepatitis C virus (HCV), despite the availability of effective direct-acting antivirals (DAAs) that clear the virus from >95% of individuals treated, continues to cause significant health care burden due to disease progression that can lead to fibrosis, cirrhosis, and/or hepatocellular carcinoma. The fact that some people who are treated with DAAs still go on to develop worsening liver disease warrants further study into the immunopathogenesis of HCV. Many viral infections, including HCV, have been associated with activation of the inflammasome/pyroptosis pathway. This inflammatory cell death pathway ultimately results in cell lysis and release of inflammatory cytokines, IL-18 and IL-1ß. This review will report on studies that investigated HCV and inflammasome activation/pyroptosis. This includes clinical in vivo data showing elevated pyroptosis-associated cytokines in the blood of individuals living with HCV, studies of genetic associations of pyroptosis-related genes and development of liver disease, and in vitro studies aimed at understanding the mechanism of pyroptosis induced by HCV. Finally, we discuss major gaps in understanding and outstanding questions that remain in the field of HCV-induced pyroptosis.

The deleterious effects of sofosbuvir and ribavirin (antiviral drugs against hepatitis C virus) on different body systems in male albino rats regarding reproductive, hematological, biochemical, hepatic, and renal profiles and histopathological changes.

Sofosbuvir is one of the crucial drugs used in the treatment of chronic hepatitis C virus (HCV) in adults and children with compensated liver disease, including cirrhosis. It may be used alone or with other drugs. Ribavirin is an antiviral medication used to treat HCV infection. It is not effective when used alone and must be used in combination with other medications, such as sofosbuvir. This study pertains to a comprehensive assessment of the deleterious effects of sofosbuvir (an antiviral drug against chronic HCV) or sofosbuvir combined with ribavirin (an antiviral drug against RNA and DNA viruses) on several biological activities of the body, including hematological, hormonal, biochemical, histological, and immunohistochemical examinations during a long-standing period on male healthy rats. In addition, fertility assessments were performed, including sperm collections and semen parameter investigations. This study was conducted on 21 male rats divided into three equal groups. Group I (control group) received distilled water; group II (sofosbuvir group) received sofosbuvir (4 mg/kg); and group III (sofosbuvir + ribavirin) received sofosbuvir (4 mg/kg) plus ribavirin (30 ml/kg). All groups received the specific drug for six months. Blood and tissue samples were collected for hematological, hormonal, biochemical, histological, and immunohistochemical examinations. In addition, sperm collection and assessments of semen parameters were performed. Results revealed that sofosbuvir causes a highly significant decrease in the mean of most hematological, immunological, hormonal, and biochemical parameters, except for a few numbers of parameters such as neutrophils, monocytes, basophils, cortisol, GOT, and lipase, which exhibit a significant increase. The same occurred in the sofosbuvir + ribavirin group, but at much higher levels, as most hematological, immunological, hormonal, and biochemical parameters exhibit a highly significant decrease except for monocytes, triglyceride, and lipase, which exhibit a significant increase. When compared to the sofosbuvir group alone, the sofosbuvir + ribavirin group demonstrated a highly significant decline in the mean of most hematological, immunological, hormonal, and biochemical parameters except lymphocytes and triglycerides, which exhibit a substantial increase. For the reproductive parameters, both groups exhibit a significant decrease in the total sperm motility percentage. Finally, it can be concluded that sofosbuvir causes acute pancreatitis and combined immunodeficiency. Ribavirin is associated with hormonal deficiency, which indicates the occurrence of hypopituitarism. Moreover, sofosbuvir and ribavirin synergistically affect myelosuppression and cause iron-deficiency anemia. However, sofosbuvir, or its combination with ribavirin, is associated with a reduced risk of hepatocellular carcinoma. Besides, adding ribavirin to be combined with sofosbuvir improved the immunodeficiency caused by sofosbuvir; this confirms that using ribavirin with sofosbuvir reduces the side effects of both alone.

Effects of sustained viral response on lipid in Hepatitis C: a systematic review and meta-analysis.

BACKGROUND: Direct-acting Antiviral Agents (DAAs) influence serum lipids of patients with Hepatitis C virus (HCV). This paper presents an analysis of the relevant literature to investigate the effects of DAAs in treating hepatitis C to achieve a sustained viral response (SVR) on lipid parameters. METHODS: PubMed,Web of science, Embase and Central databases were searched, with a deadline of September 2023. Studies on the effects of sustained viral response on lipid parameters after DAAs treatment for hepatitis C were selected. The required information was extracted from the included studies, and then the Stata 12.0 was used to analyze the data quantitatively. RESULTS: Of 32 studies, the results showed that total cholesterol (TC) levels increased from the end of treatment (WMD = 20.144, 95%CI = 3.404, 36.884,P = 0.018) to one year after treatment (WMD = 24.900, 95%CI = 13.669, 36.131, P < 0.001). From the end of treatment (WMD = 17.728, 95%CI = 4.375, 31.082, P = 0.009) to one year after treatment (WMD = 18.528, 95%CI = 7.622, 29.433, P < 0.001), the levels of low-density lipoprotein (LDL) were also increased. High-density lipoprotein (HDL) levels were elevated from 4 weeks after treatment (WMD = 6.665, 95%CI = 3.906, 9.424, P < 0.001) to 24 weeks after treatment (WMD = 3.159,95% CI = 0.176, 6.142, P = 0.038). Triglyceride (TG) levels showed no significant change after the treatment. CONCLUSIONS: Hepatitis C patients who achieved SVR on DAAs showed the increase of lipid levels and the improvement of hepatic inflammation indicators AST and ALT. This may provide evidence-based medical evidence for the follow-up and monitoring of blood lipids and hyperlipidemia treatment. REGISTRATION: PROSPERO CRD42020180793.

Impact of ITPA gene polymorphism for predicting anemia and treatment outcome in HCV infected patients taking Sofosbuvir Ribavirin therapy.

BACKGROUND: Globally, 80 million people are suffering from chronic Hepatitis C virus (HCV) infection. Sofosbuvir ribavirin-based anti-HCV therapy is associated with anemia and other adverse effects. Polymorphisms of Inosine triphosphatase (ITPA) gene may cause functional impairment in the Inosine triphosphate pyrophosphatase enzyme, resulting in enhanced sustained viral response (SVR) and protection from ribavirin-associated anemia in patients on therapy. The study objective was to investigate the effect of Inosine triphosphatase gene polymorphism on SVR achievement, hemoglobin decline and ribavirin dose reduction in patients on therapy. METHODS: This prospective cohort study was of 170 hepatitis C infected patients received 6-month sofosbuvir ribavirin therapy. Patient viral load, reduction in ribavirin amount, liver function test, and complete blood count were noted monthly. Inosine triphosphatase variants rs1127354 and rs7270101 were assessed through the restriction fragment length polymorphism and confirmed using Sanger sequencing. The impact of polymorphism on cumulative reduction of ribavirin, and anti-HCV therapy outcome were studied. RESULTS: A total of 74.3% of patients had ITPA rs1127354 CC genotype, 25.7% were CA and AA 0%. The frequency of ITPA genotype rs7270101-AA was 95%, AC 5%, and CC was 0%. ITPA rs1127354-CA had a notably positive impact on SVR achievement with a zero-relapse rate. ITPA rs1127354-CA genotype was significantly (P ˂0.05) protective against ≥ 2 g/dl Hb reduction from baseline to 1st, 2nd and 6th months of therapy. During treatment, Hb reduction ≥ 10 g/dl was frequently observed in rs1127354-CC genotype and rs7270101-AA genotype patients. Ribavirin dose reduction was significantly (P ˂0.05) high in rs1127354-CC genotype as compared to genotype CA whereas no significant difference was observed in ribavirin dose reduction in rs7270101 AA and non-AA genotype. Patient baseline characteristics such as age, body mass index, rs1127354-CC genotype, and baseline Hb were significantly associated with significant Hb reduction. CONCLUSION: Pretreatment evaluation of ITPA polymorphism can be a diagnostic tool to find out patients at risk of anemia and improve treatment adherence. ITPA genotype rs1127354-CA contributes to improved compliance with ribavirin dose and protects against hemoglobin decline in HCV patients while taking ribavirin-based therapy. However, ITPA rs1127354, rs7270101 polymorphism have no significant impact on SVR achievement.

No gender differences in the 24-month course of non-invasive liver fibrosis markers after DAA therapy in HCV-mono and HCV/HIV-coinfected patients.

Untreated HCV mono and HCV/HIV coinfected women have lower degrees of liver fibrosis (LF) compared to men. Direct acting antiviral (DAA) therapy attains viral eradication in > 90% of patients with progressive LF decline in parallel. Gender-related differences in LF regression in the long term assessed by non-invasive liver fibrosis markers (NILFM) in HCV mono and HCV/HIV coinfected after DAA treatment have not been explored so far. 374 HCV-infected adult patients, 214 of them HCV/HIV coinfected, were followed-up for 24 months after starting DAA therapy. LF was assessed by NILFM: transient elastometry (TE) and several biochemical indexes (APRI, Forns, FIB-4). Men had significantly more advanced LF at baseline than women assessed by NILFM. No LF differences at baseline in age, HIV coinfection course (CD4, HIV viral load), and HCV features (HCV viral load, genotype) were detected. No significant gender differences in LF decline after comparing 24-month and baseline LF values were observed. LF changes after DAA therapy were similar in HCV mono and HCV/HIV coinfected patients and in both sexes. Gender did not influence the course of LF decline after DAA assessed by NILFM: TE (P = 0.8), APRI (P = 0.9), Forns (P = 0.4) and FIB-4 (P = 0.7) by multivariate analysis. No gender differences in the 24 month LF decline after DAA with independence of having HCV mono or HCV/HIV coinfection were found.

Utilising organs from hepatitis C virus PCR-positive donors in Western Australia.

We transplanted six solid organs from three hepatitis C virus (HCV) polymerase chain reaction (PCR)-positive donors during 2018-2023. Recipients were treated with glecaprevir/pibrentasvir or sofosbuvir/velpatasvir for 4-12 weeks, with all six achieving sustained virological response without significant adverse events. As occurs in other jurisdictions, solid organ transplants from HCR PCR-positive donors can be safely utilised in Australia.

Personalized care approaches to hepatitis C therapy: recent advances and future directions.

INTRODUCTION: The introduction of direct-acting antivirals (DAAs) has significantly transformed the therapeutic landscape for chronic C hepatitis virus (HCV) infection. However, there is still room for further improvement in optimizing therapy efficacy and minimizing adverse effects. AREAS COVERED: This review is devoted to the rationale for adopting a personalized approach to HCV therapy. Specifically, we explore the role of host-related factors, such as sex or the presence of comorbidities. We thoroughly examine the implications of commonly encountered comorbidities, including HIV infection, chronic renal disease, liver cirrhosis, and other chronic viral hepatitis infections. Additionally, we discuss the prevalent drug-to-drug interactions between DAAs and other medications, while providing guidance on their management. Finally, we investigate viral-related issues that can influence treatment outcomes, such as viral genotype, quasi-species, and the presence of resistance-associated mutations. EXPERT OPINION: Despite pivotal trials demonstrating efficacy rates exceeding 90% for currently available DAA regimens, there are still opportunities to optimize therapy outcomes and tailor treatment to each patient. This can be achieved through a meticulous evaluation of the patient's specific clinical conditions and comorbidities, a vigilant approach to manage potential drug interactions, and diligent patient follow-up.

Impact of direct-acting antiviral on subclinical atherosclerosis in chronic hepatitis C infected patients.

INTRODUCTION: The impact of direct antiviral drugs (DAAs) on extrahepatic manifestations in chronic hepatitis C (CHC) has been poorly studied. AIM: To assess the prevalence of subclinical atherosclerosis in patients with CHC and the impact of DAAs on atherosclerotic lesions. Methods A 5-year prospective evaluative study, including patients followed for CHC at hepato-gastroenterology department. The subclinical atherosclerosis was assessed by ultrasound measurement of carotid intima-media thickness (IMTc) and the highest IMTc measurements from the left and right side defined the IMTc maximum (IMTc max). IMTc>75th percentile (IMTc75) define subclinical atherosclerosis with high cardiovascular risk. Patients were evaluated before (T0) and one year after DAAs therapy achievement (T1). RESULTS: At time T0, forty patients (median age: 55 y.; sex ratio M / F = 0.48), were included. Average value of IMTc max was 0.68 ± 0.16 mm. Subclinical atherosclerosis was noted in 82.5 %. At time T1, 28 patients were evaluated, all of whom completed sustained virological response (SVR). Compared to time T0, there was a significant increase in cholesterol (p = 0.001) and triglyceride (p = 0.009) levels. IMTc max was significantly higher at time T1 compared to T0 (0.75 Vs 0.67 mm, p = 0.04). Prevalence of IMTc75 was 82.1% at time T0 and 75% at time T1 (p=0.5). CONCLUSIONS: SVR, in CHC patients treated with DAA, was associated with worsening of carotid atherosclerotic lesions.

Integration of Hepatitis C and Addiction Treatment in People Who Inject Drugs: The San Patrignano HCV-Free and Drug-Free Experience.

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

Ongoing Gaps in the Hepatitis C Care Cascade during the Direct-Acting Antiviral Era in a Large Retrospective Cohort in Canada: A Population-Based Study.

To achieve hepatitis C virus (HCV) elimination, high uptake along the care cascade steps for all will be necessary. We mapped engagement with the care cascade overall and among priority groups in the post-direct-acting antivirals (DAAs) period and assessed if this changed relative to pre-DAAs. We created a population-based cohort of all reported HCV diagnoses in Quebec (1990-2018) and constructed the care cascade [antibody diagnosed, RNA tested, RNA positive, genotyped, treated, sustained virologic response (SVR)] in 2013 and 2018. Characteristics associated with RNA testing and treatment initiation were investigated using marginal logistic models via generalized estimating equations. Of the 31,439 individuals HCV-diagnosed in Quebec since 1990 and alive as of 2018, there was significant progress in engagement with the care cascade post- vs. pre-DAAs; 86% vs. 77% were RNA-tested, and 64% vs. 40% initiated treatment. As of 2018, a higher risk of not being RNA-tested or treated was observed among individuals born <1945 vs. >1965 [hazard ratio (HR); 95% CI; 1.35 (1.16-1.57)], those with material and social deprivation [1.21 (1.06-1.38)], and those with alcohol use disorder [1.21 (1.08-1.360]. Overall, non-immigrants had lower rates of RNA testing [0.76 (0.67-0.85)] and treatment initiation [0.63 (0.57-0.70)] than immigrants. As of 2018, PWID had a lower risk of not being RNA tested [0.67 (0.61-0.85)] but a similar risk of not being treated, compared to non-PWID. Engagement in the HCV care cascade have improved in the post-DAA era, but inequities remain. Vulnerable subgroups, including certain older immigrants, were less likely to have received RNA testing or treatment as of 2018 and would benefit from focused interventions to strengthen these steps.

Evaluating hepatitis C cascade of care surveillance system in Tuscany, Italy, through a population retrospective data-linkage study, 2015-2021.

This comprehensive retrospective data-linkage study aimed at evaluating the impact of Direct-Acting Antivirals (DAAs) on Hepatitis C Virus (HCV) testing, treatment trends, and access to care in Tuscany over six years following their introduction. Utilizing administrative healthcare records, our work reveals a substantial increase in HCV tests in 2017, attributed to the decision to provide universal access to treatment. However, despite efforts to eradicate chronic HCV through a government-led plan, the target of treating 6,221 patients annually was not met, and services contracted after 2018, exacerbated by the COVID-19 pandemic. Key findings indicate a higher prevalence of HCV screening among females in the 33-53 age group, influenced by pregnancy-related recommendations, while diagnostic tests and treatment uptake were more common among males. Problematic substance users constituted a significant proportion of those tested and treated, emphasizing their priority in HCV screening. Our paper underscores the need for decentralized HCV models and alternative testing strategies, such as point-of-care assays, especially in populations accessing harm reduction services, communities, and prisons. The study acknowledges limitations in relying solely on administrative records, advocating for improved data access and timely linkages to accurately monitor HCV care cascades and inform regional plans. Despite challenges, the paper demonstrates the value of administrative record linkages in understanding the access to care pathway for hard-to-reach populations. The findings emphasize the importance of the national HCV elimination strategy and the need for enhanced data collection to assess progress accurately, providing insights for future regional and national interventions.

Hemophilia and hepatology, back to the future.

Years ago, patients with hemophilia were often cared for because of liver issues. The use of hemoderivatives in the 1970s and 1980s, and the natural history of chronic hepatitis B and C, led to a surge of patients with cirrhosis and related complications after two or three decades. It was not until the approval of entecavir and tenofovir (2005-2008) against the B virus, and of direct-acting antiviral agents (2015) against the C virus, that a truly effective treatment became available for liver disease. Since then, patients with hemophilia disappeared from hepatology clinics and wards, apart from specific isolated problems.

Comparison of Glecaprevir/Pibrentasvir and Sofosbuvir/Ledipasvir in Patients with Hepatitis C Virus Genotype 1 and 2 in South Korea.

Background/Aims: This study compared the effectiveness and safety of glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/ledipasvir (SOF/LDV) in real-life clinical practice. Methods: The data from genotype 1 or 2 chronic hepatitis C patients treated with GLE/PIB or sofosbuvir + ribavirin or SOF/LDV in South Korea were collected retrospectively. The analysis included the treatment completion rate, sustained virologic response at 12 weeks (SVR12) test rate, treatment effectiveness, and adverse events. Results: Seven hundred and eighty-two patients with genotype 1 or 2 chronic hepatitis C who were treated with GLE/PIB (n=575) or SOF/LDV (n=207) were included in this retrospective study. The baseline demographic and clinical characteristics revealed significant statistical differences in age, genotype, ascites, liver cirrhosis, and hepatocellular carcinoma between the GLE/PIB and SOF/LDV groups. Twenty-two patients did not complete the treatment protocol. The treatment completion rate was high for both regimens without statistical significance (97.7% vs. 95.7%, p=0.08). The overall SVR12 of intention-to-treat analysis was 81.2% vs. 80.7% without statistical significance (p=0.87). The overall SVR12 of per protocol analysis was 98.7% vs. 100% without statistical significance (p=0.14). Six patients treated with GLE/PIB experienced treatment failure. They were all male, genotype 2, and showed a negative hepatitis C virus RNA level at the end of treatment. Two patients treated with GLE/PIB stopped medication because of fever and abdominal discomfort. Conclusions: Both regimens had similar treatment completion rates, effectiveness, and safety profiles. Therefore, the SOF/LDV regimen can also be considered a viable DAA for the treatment of patients with genotype 1 or 2 chronic hepatitis C.

Non-liver-related mortality in the DAA era: Insights from post-SVR patients with and without previous HCC history.

BACKGROUND AND AIMS: Mortality after sustained virological response (SVR) with interferon-free direct-acting antiviral (IFN-free DAA) therapy is crucial for optimizing post-SVR patient care, but it remains unclear, especially regarding non-liver-related mortality. METHODS: Consecutive post-SVR patients from 14 institutions were stratified into three cohorts: A (without advanced fibrosis and without prior HCC), B (with advanced fibrosis and without prior HCC), and C (curative HCC treatment). We assessed mortality (per 1000 person-years [/1000PY]) post-SVR. Mortality rates were compared between cohorts A and B and the general population using age- and sex-adjusted standardized mortality ratio (SMR). Comparison of survival between each cohort was performed using propensity-score (PS) matching with sex, age, and comorbidity. RESULTS: In cohort A (n = 762; median age, 65 years), 22 patients died (median follow-up, 36 months); all-cause mortality was 10.0/1000PY, with 86.4% non-liver-related deaths. In cohort B (n = 519; median age, 73 years), 27 patients died (median follow-up, 39 months); all-cause mortality was 16.7/1000PY, with 88.9% non-liver-related deaths. In both cohorts, malignant neoplasm was the most common cause of death; all-cause mortality was comparable to that of the general population (SMR: 0.96 and 0.92). In cohort C (n = 108; median age, 75 years), 15 patients died (median follow-up, 51 months); all-cause mortality was 36.0/1000PY, with 53.3% liver-related deaths. PS matching showed no significant survival differences between cohorts A and B, both of which had better survival than cohort C. CONCLUSIONS: Mortality varies based on HCC history in the DAA era; nevertheless, attention should be paid to non-liver-related deaths in all post-SVR patients.