Hepatitis C epidemiology and treatment outcomes in Italy: Impact of the DAA era and the COVID-19 pandemic.

HCV infection poses a global health threat, with significant morbidity and mortality. This study examines HCV trends in a large Italian region from 2015 to 2022, considering demographic changes, evolving clinical profiles, treatment regimens and outcomes, including the impact of the COVID-19 pandemic. This multicentre retrospective study analysed demographics, clinical histories and risk factors in 6882 HCV patients. The study spanned before and after the direct-acting antiviral (DAA) era, and the COVID-19 period, focusing on treatment outcomes (SVR12, non-SVR12 and patients lost to follow-up). Statistical methods included ANOVA, multinomial logistic regression, Kruskal-Wallis test and chi-square analysis, and were conducted adhering to the intention-to-treat (ITT) principle. The cohort, mainly Italian males (average age 58.88), showed Genotype 1 dominance (56.6%) and a high SVR12 rate (97.5%). The pandemic increased follow-up losses, yet SVR12 rates remained stable, influenced by factors like age, gender, cirrhosis and comorbidities. Despite COVID-19 challenges, the region sustained high SVR12 rates in HCV care, emphasising the importance of sustained efforts in HCV care. Continuous screening and targeted interventions in high-risk populations are crucial for achieving WHO elimination targets. The study highlights the resilience of HCV care during the pandemic and provides insights for future public health strategies.

Efficacy of Sofosbuvir and Velpatasvir Combination in the Treatment of Hepatitis C Virus (HCV) in Chronic Kidney Disease (CKD) Patients.

Background Hepatitis C virus (HCV) infection is still common in patients with chronic renal failure, even those on maintenance dialysis. A bidirectional association exists between HCV infection and chronic renal disease. Objective To assess the efficacy of sofosbuvir and velpatasvir combination in the treatment of chronic HCV in chronic kidney disease (CKD) patients. Methodology This descriptive, cross-sectional study was undertaken at the departments of Gastroenterology and Nephrology Lady Reading Hospital, Peshawar, from April 7, 2021, to October 7, 2021. Patients with chronic HCV and chronic renal disease at stage 4 or 5 were included while patients with decompensated cirrhosis liver, hepatoma, hepatitis B virus/HCV (HBV/HCV) coinfection, and post liver transplant patients were excluded. HCV infection was diagnosed based on detectable HCV ribonucleic acid (HCV RNA) by PCR (polymerase chain reaction). In contrast, CKD was diagnosed based on the Kidney Disease Improving Global Outcomes (KDIGO) criteria for CKD. Sofosbuvir 400 mg orally daily and velpatasvir 100 mg orally with meals were given daily for 12 weeks. Effectiveness was defined as negative HCV RNA by PCR 12 weeks after treatment completion called sustained virological response rate 12 weeks after treatment completion (SVR12). Results A total of 73 patients including 67 (91.78%) males and six (8.22%) females between the ages of 20 years and 70 years were included in this study. The mean age of the participants was 48.77±8.0 years. Twelve weeks after the treatment completion, 69 (94.52%) had negative HCV RNA, whereas four (5.48%) patients had detectable HCV RNA. Conclusion It can be concluded from our study that a fixed-dose combination of sofosbuvir 400 mg and velpatasvir 100 mg is quite effective and recommended for treating chronic hepatitis C infection in patients with chronic renal disease in our local setup.

Updated Clinical Guidelines on the Management of Hepatitis C Infection in Children.

Children represent only a small proportion of those infected with the hepatitis C virus (HCV) compared to adults. Nevertheless, a substantial number of children have chronic HCV infection and are at risk of complications including cirrhosis, portal hypertension, hepatic decompensation with hepatic encephalopathy, and hepatocellular carcinoma in adulthood. The overall prevalence of the HCV in children was estimated to be 0.87% worldwide. The HCV spreads through the blood. Children born to women with chronic hepatitis C should be evaluated and tested for HCV due to the known risk of infection. The course of treatment for hepatitis C depends on the type of HCV. Currently, there are two pan-genotype HCV treatments (Glecaprevir/pibrentasvir and Sofosbuvir/velpatasvir) for children. We aim to review the updated clinical guidelines on the management of HCV infection in children, including screening, diagnosis, and long-term monitoring, as well as currently published clinical trials and ongoing research on direct acting antiviral hepatitis C treatment in children.

Efficacy and safety of DAA in children and adolescents with chronic HCV infection: A systematic review and meta-analysis.

BACKGROUND AND AIMS: We evaluated the effectiveness and safety of pan-genotypic regimens, glecaprevir/pibrentasvir (GLE/PIB), sofosbuvir/velpatasvir (SOF/VEL), and sofosbuvir/daclatasvir (SOF/DCV) and other direct-acting antivirals (DAA) regimens for the treatment of hepatitis C virus (HCV)-infected adolescents (12-18 years), older children (6-11 years), and young children (3-5 years). The purpose of this systematic review and meta-analysis was to inform the World Health Organization (WHO) guidelines. METHODS: We included clinical trials and observational studies published up to August 11, 2021, that evaluated DAA regimens in HCV-infected adolescents, older children, and young children. We searched MEDLINE, EMBASE, and CENTRAL databases and key conference abstracts. Sustained virological response 12 weeks after the end of treatment (SVR12), adverse events (AEs), and treatment discontinuation were the outcomes evaluated. Risk of bias was assessed using a modified version of the ROBINS-I tool. Data were pooled using random-effects models, and certainty of the evidence was assessed using the GRADE approach. RESULTS: A total of 49 studies including 1882 adolescents, 436 older children, and 166 young children were considered. The SVR12 was 100% (95% Confidence Interval: 96-100), 96% (90-100), and 96% (83-100) for GLE/PIB in adolescents, older, and young children, respectively; 95% (90-99), 93% (86-98), and 83% (70-93), for SOF/VEL, respectively; and 100% (97-100) and 100% (94-100) for SOF/DCV in adolescent and older children, respectively. There was a clear trend towards a higher rate of any reported AE from adolescents (50%), older children (53%), to young children (72%). Serious AEs and treatment discontinuations were uncommon in adolescents and older children (<1%) but slightly higher in young children (3%). CONCLUSIONS: All three pan-genotypic DAA regimens were highly effective and well-tolerated and are now recommended by the WHO for use in adults, adolescents, and children down to 3 years, which will simplify procurement and supply chain management. The evidence was based largely on single-arm non-randomized controlled studies. Moreover, there were also missing data regarding key variables such as route of HCV acquisition, presence or absence of cirrhosis, or HIV co-infection that precluded evaluation of the impact of these factors on outcomes. PROSPERO RECORD: CRD42020146752.

Higher Hepatitis C Cure Rates in a Patient-Centered Medical Home Compared to Specialist Care.

PURPOSE: The new era of direct-acting antivirals (DAAs) against the hepatitis C virus (HCV) has led many primary care clinicians to begin treating HCV. Nevertheless, many patients are referred to specialists due to comorbidities, care complexities, and knowledge gaps of the primary care provider. We compared clinical outcomes for patients treated within a Family Medicine Residency Program (FMRP) affiliated patient-centered medical home (PCMH) with those referred to a specialist. METHODS: Following didactic education and development of practice resources we conducted a single-center quasi-experimental study of adults with HCV referred for treatment either internally or externally to a specialist between January 2019 and December 2020. The primary outcome was the number of patients with a sustained virologic response at 12 weeks after treatment (SVR12), utilizing an intention-to-treat analysis. RESULTS: During the study period 107 patients were assessed by the PCMH, of whom 24 were deemed not a good candidate for treatment. Of the 83 patients referred for treatment, 36 patients were referred externally and 47 were treated internally. While the rate of SVR12 was 100% for both groups when analyzed per protocol (ie, only patients who completed treatment and attended all follow-ups), the rate of SVR12 was 31% for patients referred externally and 62% for patients treated internally when analyzed by intention to treat (relative risk [RR] 2.02, 95% CI 1.18-3.47, P = .01). This difference was entirely attributable to differences in lost to follow-up rates. CONCLUSIONS: Following education and creation of practice resources, achievement of SVR12 among patients with HCV treated by an internal interdisciplinary family medicine team was superior to those who were externally referred. This was primarily attributable to differences in follow-up rates.

Changes in Components of Metabolic Syndrome after Antiviral Eradication in Hepatitis C Virus Infection.

Chronic hepatitis C infection is a systemic disease that affects over 71 million patients all over the world and it is to be considered nowadays as a new cardiometabolic risk factor. This study aimed to evaluate the weight and metabolic changes after viral eradication in patients with hepatitis C virus (HCV) infection. We conducted a prospective study between October 2017 to December 2021, in a tertiary care center, in which we included 132 patients with HCV or cirrhosis. All patients received treatment with direct antivirals (DAAs) and achieved sustained viral response at 12 weeks (SVR12). During the study, clinical laboratory data and Fibroscan examinations were recorded in all patients. The study group was evaluated at the initiation of antiviral treatment, at SVR12, and within an average follow-up period of 6 months to 12 months after the previous evaluation. Evaluation at SVR12 and the data recorded in the post-SVR surveillance period show a further increase in BMI compared with baseline measurements with a statistically significant difference (27.11 ± 3.22 vs. 27.415 ± 3.03 vs. 28.04 ± 1.11 kg/m2, p = 0.012). The same observation was noticed for waist circumference (WC) at post-SVR evaluation (87.6 ± 13.1 vs. 88.4 ± 13.6 cm, p = 0.031). Moreover, the study population registered an increase in the average total cholesterol (TC) values at post-SVR evaluation (177.01 ± 42.2 mg/dL, p = 0.014) compared to baseline. In addition, the serum level of triglycerides had been modified after viral clearance, with a minimal decrease in the mean values of triglycerides (TGD) at SVR-12 assessment (133.48 ± 41.8 mg/dL, p = 0.78), followed by a significant increase to the mean value of 145.4 ± 47.2 mg/dL (p = 0.026) in the third evaluation. Our study highlights that HCV eradication does not improve the lipid profile in the short term, and these patients still have an additional cardiovascular risk factor due to high levels of TC, TGD, and weight gain.

HCV microelimination in harm reduction centres has benefits beyond HCV cure but is hampered by high reinfection rates.

Background & Aims: Significant scale-up of treatment among people who inject drugs (PWID) is crucial to achieve WHO HCV elimination targets. We explored the impact of on-site HCV diagnosis and treatment on PWID in an externalised hepatology clinic at the biggest harm reduction centre (HRC) in Barcelona attending to a marginalised PWID population with ongoing high-risk practices. Methods: On-site HCV point-of-care testing was performed for diagnosis and treatment delivery. HCV-RNA was assessed at SVR12 (sustained virologic response at 12 weeks) and every 6 months. The programme included behavioural questionnaires at baseline and after treatment. Results: Between 2018 and 2020, 919 individuals were prospectively enrolled. Of these, only 46% accepted HCV screening. HCV-RNA+ prevalence was 55.7% (n = 234). Of the 168 (72%) individuals starting treatment, 48% were foreigners, 32% homeless, 73% unemployed, and 62% had a history of incarceration. At enrolment, 70% injected drugs daily and 30% reported sharing needles or paraphernalia. Intention-to-treat SVR12 was 60%; only 4% were virological failures, the remaining were either early reinfections (20%) or losses to follow-up (16%). The overall reinfection rate during follow-up was 31/100 persons/year. HIV coinfection and daily injection were associated with a higher risk of reinfection. Nonetheless, beyond viral clearance, antiviral therapy was associated with a significant reduction in injection frequency, risk practices, and homelessness. Conclusions: HCV treatment can be successfully delivered to active PWID with high-risk practices and has a significant benefit beyond HCV elimination. However, approaching this difficult spectrum of the PWID population implies significant barriers such as low rate of screening acceptance and high dropout and reinfection rates. Lay summary: People who inject drugs attending harm reduction centres represent the most difficult population to treat for hepatitis C. We show that hepatitis C treatment has a significant benefit beyond viral cure, including improving quality of life, and decreasing injection frequency and risk practices. However, intrinsic barriers and the high reinfection rates hamper the achievement of viral microelimination in this setting.

Cost-Effectiveness of HCV Core Antigen versus PCR for Monitoring Treatment Response in DAAS-Treated Egyptian Patients

PCR is currently the non-debatable proof for diagnosis of HCV infection as well as conclusion of treatment outcomes. HCV core antigen (HCVcAg) testing is a neglected, less expensive and less time consuming test that's presumed to achieve the same aims. The aim of this study is to find the cost-effectiveness of HCV core antigen testing in the monitoring of treatment response as an alternative to the gold-standard PCR test

Circulating macrophage inflammatory protein-1ß/IL-12p40 ratio predicts sofosbuvir-based treatment outcome in HCV- genotype 4 patients.

This study aimed to evaluate the prognostic value of baseline macrophage inflammatory protein (MIP)-1ß/IL12p40 ratio for antiviral treatment outcome in HCV genotype 4 patients. METHODS: Sera of 450 treatment-naïve chronic HCV patients and 50 healthy individuals were collected. Liver transaminases, total bilirubin and albumin were biochemically tested, viral RNA was quantified, and circulating MIP-1ß and IL-12p40 were estimated using human anti-MIP-1ß and IL-12p40 antibodies in Sandwich ELISA. RESULTS: No difference was observed in the baseline chemokines levels between responders and relapsers, but the later had a significantly higher MIP-1ß/IL-12p40 ratio (P< 0.0001). Multivariate regression analysis of baseline characteristics showed that gender, age, viral load, albumin level and chemokine ratios can significantly predict treatment outcome (P= 0.0114, 0.0095, 0.042, 0.0004 and < 0.0001; respectively). Accordingly, a predictive threshold of baseline chemokine ratio was calculated and it showed an AUC of 0.6917 (P= 0.0108; 95% CI: 0.5566 to 0.8268). The calculated threshold for predicting virologic response was 8.245, with positive and negative predictive values of 92.98% and 100%; respectively. The chemokine ratios had significant correlations with liver transaminases in treated groups whether pre or post-treatment. CONCLUSION: Baseline MIP-1ß/IL-12p40 ratio represents a non-invasive prognostic biomarker that would provide shorter treatment duration and minimizes the emergence of drug-resistant variants in HCV genotype 4-patients.

Efficacy and safety of ledipasvir/sofosbuvir for hepatitis C among drug users: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Limited data is available on the efficacy of direct acting anti-viral drugs on hepatitis C in drug users. The aim of this meta-analysis was to comprehensively analyze the efficacy and safety of LDV/SOF in drug users infected with the hepatitis C virus (HCV). METHODS: The PubMed, Cochrane library, Embase and Web of Science databases were searched for articles published till April 2021 on HCV-positive drug users who were treated with ledipasvir/sofosbuvir (LDV/SOF). The primary endpoint was pooled sustained virological response at 12 weeks (SVR12) with 95% confidence interval (95% CI). Funnel plots and Egger's test were used to assess the publication bias. RESULTS: A total of 12 studies and 711 subjects treated with LDV/SOF-based regimen for HCV were included, and the pooled SVR12 rate was 89.8% (95% CI 85.9-92.7). The pooled SVR12 rate of genotype 1 drug users was 92.4% (95% CI 88.6-95.0). Subgroup analysis showed that pooled SVR12 rates of patients treated with LDV/SOF and LDV/SOF ± RBV were 89.2% (95% CI 83.4-93.1), 90.4% (95% CI 83.6-94.5) respectively. In addition, the SVR12 rates were 88% (95% CI 70.7-95.7) for 8 weeks, 89.9% (95% CI 81.0-94.9) for 12 weeks and 82.2% (95% CI 24.9-98.5) for 24 weeks of treatment. CONCLUSION: LDV/SOF is a safe and relatively effective treatment for hepatitis C in drug users.

An evaluation of ledipasvir + sofosbuvir for the treatment of chronic hepatitis C infection.

Introduction: Hepatitis C (HCV) is viral disease with a global impact. Over the last 10 years, the treatment of this disease has evolved. Treatment guidelines have evolved to adopt new medications for HCV. These drugs have shown efficacy over 90% throughout the class as well as a better safety profile than the previous recommended pharmacotherapy. Dual-therapy DAAs emerged with FDA approval of Ledipasvir/Sofosbuvir (LDV/SOF) in 2014.Areas Covered: LDV/SOF is a dual-therapy option for chronic HCV patients (>6 months of infection) in select genotypes. This article reviews the studies relevant to the pharmacokinetic/pharmacodynamic properties of these drugs as well as its trials leading to approval.Expert opinion: LDV/SOF is included in the AASLD/IDSA guidelines for the treatment of HCV genotypes 1a and 1b with or without cirrhosis and genotype 4 without cirrhosis with an evidence and recommendation rating of IA. Genotype 4 with cirrhosis and genotypes 5 and 6 carry a Class IIa level B recommendation. The combination is not FDA approved for genotypes 2 and 3. Single-pill regimens, like LDV/SOF, are important to maintain the quality of life of children and other special populations infected with HCV by shortening treatment regimens, avoiding complex pill regimens, and eliminating injection therapies.

Changing epidemiology of patients treated with direct acting antivirals for HCV and persistently high SVR12 in an endemic area for HCV infection in Italy: real-life 'LIver Network Activity' (LINA) cohort update results.

BACKGROUND: Second generation direct acting antivirals (DAAs) drastically changed the landscape of chronic HCV (CHCV). Aim of this paper was to assess the effectiveness of DAAs, also looking at the demographic characteristics of subjects enrolled. RESEARCH DESIGN AND METHODS: Ambispective multi-center real-life study conducted among patients with CHCV treated with DAAs in Campania Region (Southern Italy). Patient were enrolled in two cohorts according to time of enrolment. RESULTS: 1,479 patients were enrolled. Patients aged ≥60 years were 74.7% in the historic cohort (953 patients) and 70.2% in the prospective cohort (526 patients. Patients aged ≥ 60 years showed a higher prevalence of genotype 1b (p<0.001) and 2 (p<0.001), while patients aged < 60 years showed a higher prevalence of genotype 1a (p<0.001), 3 (p<0.001) and 4 (p<0.05). SVR12 was 98.5% in both cohorts. SVR12 was similar among patients of the prospective cohort aged < and ≥ 60 years (99.4% vs 98.1%). SVR12 among patients with and without cirrhosis was 96.0% and 98.9%, respectively. CONCLUSIONS: DAAs provide high efficacy also in harder to treat patients. The effectiveness of DAAs is leading to a shift in patients characteristics with a greater prevalence of younger subjects and persons with mild liver disease.

Efficacy and safety of sofosbuvir-containing regimens in patients with chronic hepatitis C virus infection after liver transplantation: a meta-analysis.

BACKGROUND: This meta-analysis evaluated the efficacy and safety of a sofosbuvir (SOF)-containing regimen in patients with hepatitis C virus (HCV) infection after liver transplantation (LT). METHODS: We performed a systematic search for relevant published data on the PubMed, EMBASE, and Cochrane Library databases. Studies that evaluated any regimen in which SOF was used to treat patients with HCV infection after LT and reported the sustained virologic response 12 weeks (SVR12) after therapy were included. RESULTS: A total of 12 studies, involving 892 patients, were included in this analysis. The pooled estimate of SVR12 (sustained virologic response 12 weeks) was 88.1%. Subgroup analysis showed that patients who received SOF plus other DAAs had higher SVR12 than those treated with SOF plus ribavirin or peg-IFN. The pooled incidence of any adverse events (AEs) was 73.7%. CONCLUSIONS: The results of this study showed that the treatment response of SOF-containing regimens in patients with HCV infection after LT was satisfactory. However, more attention needs to be paid to the high rate of AEs associated with such regimens.

High sustained viral response rate in patients with hepatitis C using generic sofosbuvir and daclatasvir in Phnom Penh, Cambodia.

Safe and efficacious pan-genotypic direct-acting antiviral (DAA) regimens, such as sofosbuvir and daclatasvir (SOF + DCV), facilitate simplified models of care for hepatitis C virus (HCV). However, in Cambodia access to HCV testing and treatment has typically been low. In response, Médecins Sans Frontières (MSF) implemented a HCV testing and treatment pilot project in Phnom Penh, Cambodia in 2016. This project provides the first real-world evidence of SOF + DCV effectiveness across a large patient cohort using a simplified care model in Cambodia. Patients treated with SOF + DCV from September 2016 to June 2019 were included in the analysis. Medical standard operational procedures (SOPs) were simplified significantly across the study period. Treatment effectiveness was assessed by sustained viral response at 12 weeks post-treatment (SVR12) according to a modified intention-to-treat methodology. Treatment safety was assessed by clinical outcome and occurrence of serious and nonserious adverse events (S/AE). Of 9158 patients, median age was 57 years and 39.6% were male. At baseline assessment, 27.2% of patients had compensated cirrhosis and 2.9% had decompensated cirrhosis. Genotype 6 was predominant (53.0%). Among patients analysed according to modified intention to treat (n = 8525), treatment effectiveness was high, with 97.2% of patients achieving SVR12. Occurrence of SAE was low (0.7%). Treatment effectiveness and safety was not affected by the iterative simplification to treatment modality. In conclusion, in this large treatment cohort in Phnom Penh, Cambodia, the SOF + DCV regimen showed high rates of treatment effectiveness and safety across patient sub-groups and during progressive simplification.

Safety, efficacy and cost of two direct-acting antiviral regimens: A comparative study in chronic hepatitis C Egyptian patients.

WHAT IS KNOWN AND OBJECTIVE: Direct-acting antivirals (DAAs) have become the most widely used treatment of chronic hepatitis C infection. Comparative studies on DAAs regimens approved by the Egyptian Ministry of Health for easy-to-treat genotype 4 (G4) Egyptian patients are still deficient. In this prospective study, we compared the efficacy and cost of two DAA regimens that are used in the treatment of Egyptian chronic hepatitis C virus (HCV) G4. The cost-saving regimen is determined. METHODS: Eligible patients were randomized into 2 groups. Group 1 (Gp 1) received sofosbuvir plus daclatasvir, and group 2 (Gp 2) received ombitasvir, paritaprevir and ritonavir plus ribavirin (RBV) for 12 weeks. Data were collected and evaluated at baseline and at weeks 4, 8 and 12. Sustained virologic response 12 weeks after the end of treatment (SVR12 ) was evaluated. Cost-minimization analysis (CMA) was performed. RESULTS AND DISCUSSION: Eligibility was achieved in 107 patients, Gp1 included 57 patients, and Gp 2 included 50 patients. Two patients dropped out from Gp 2 due to non-compliance. All patients in the two groups showed negative HCV blood levels at the end of treatment. At the 24th week, 3 relapsers (5.2%) were detected in Gp1 and 2 relapsers (4.1%) were detected in Gp 2. SVR12 was 54/57 (94.7%) and 46/48 (95.8%) for Gp 1 and Gp 2, respectively. After the 12th week of treatment, a significant decrease in aspartate aminotransferase (AST), alanine aminotransferase (ALT) and haemoglobin levels were observed in both groups. Albumin levels declined in Gp 2 only. CMA showed higher cost in Gp 2 than Gp 1, although similar efficacy and safety. WHAT IS NEW AND CONCLUSION: The two DAA regimens showed high SVR12 and safety in Egyptian HCV G4 patients. Sofosbuvir plus daclatasvir is the cost-saving regimen.

Pangenotypic direct acting antivirals for the treatment of chronic hepatitis C virus infection: A systematic literature review and meta-analysis.

BACKGROUND: Recent approval and adoption of pangenotypic direct acting antivirals (DAAs) necessitated a revision of the 2015 World Health Organization guidelines for the management of persons with hepatitis C virus (HCV) infection. METHODS: We searched MEDLINE, EMBASE, CENTRAL, and relevant conference proceedings to identify randomized and non-randomized trials, as well as prospective observational studies of DAAs. The proportions of persons with events were pooled for sustained virological response at 12 weeks post-treatment (SVR12), discontinuations due to adverse events (DAEs), serious adverse events (SAEs), and all-cause mortality. Analyses were stratified by HCV genotype and antiviral treatment experience, with subgroup analyses based on presence of cirrhosis and HIV-HCV coinfection. FINDINGS: The evidence base consisted of 238 publications describing 142 studies. In the overall analysis, which included all persons irrespective of treatment experience or comorbidities, the pooled proportion achieving SVR12 exceeded 0.94 for all pangenotypic regimens across genotypes 1, 2, and 4. Some heterogeneity may have led to lower SVR rates in persons with genotype 3 infection. High SVR12 (>0.90) was observed in persons with genotype 1 infection with cirrhosis, though evidence varied and was limited for genotypes 2-4. Evidence was sparse for persons with HIV-HCV coinfection. All regimens were associated with small proportions of persons with DAEs, SAEs, or all-cause mortality. INTERPRETATION: Based on this and other supporting evidence, the WHO issued updated guidelines with a conditional recommendation, based on moderate quality evidence, for the use of pangenotypic DAA regimens for persons with chronic HCV infection aged 18 years and older (July 2018). FUNDING: This study was funded by the World Health Organization.

High rate of sustained virological response with direct-acting antivirals in haemophiliacs with HCV infection: A multicenter study.

BACKGROUND AND AIMS: Chronic hepatitis C is the main co-morbidity in adult patients with haemophilia (PwH). It causes progressive liver damage leading to end-stage liver disease and/or hepatocellular carcinoma. Eradication of HCV was possible with interferon (IFN)-based regimens in the past and direct-acting antivirals (DAAs) more recently. PwH have been considered "difficult-to-treat" because of several bad predictors of response. The advent of DAAs has provided high rates of sustained virological response (SVR) despite bad prognostic factors. Here, we present the results of antiviral treatment with DAAs in PwH treated in 2 large Italian Hemophilia Treatment Centers. METHODS: PwH and chronic hepatitis C sustained by any HCV genotype were eligible for therapy with DAAs, including those with compensated cirrhosis, HIV infection and/or previous failure to IFN-based antiviral therapy. Patients received DAAs for 8-24 weeks according to existing guidelines. SVR was defined as persistent negative serum HCV-RNA at 12 weeks after treatment completion (SVR12). RESULTS: Between January 2015 and November 2018, 200 patients aged 21-84 years (median: 50.5) received DAAs. HCV genotype 1 was the most prevalent (158, 79%). Forty patients (20%) were HIV positive, 56 (28%) had cirrhosis and 91 (46%) previously failed interferon-based treatment. Ribavirin was used in 70 (35%). HCV-RNA was undetectable at week 4 in 124/192 (65%) and SVR12 was achieved in 193/195 (99%). No patient had serious side effects related to DAAs. CONCLUSIONS: DAAs were safe and highly effective in PwH irrespective of HIV status, stage of liver disease severity and/or previous failure to IFN-based therapy.

Efficacy of direct-acting antivirals: UK real-world data from a well-characterised predominantly cirrhotic HCV cohort.

Direct-acting antivirals (DAAs) have revolutionised the management of chronic hepatitis C virus (HCV) infection. We describe UK real-world DAA experience. Individuals commencing HCV treatment containing a DAA regimen (Mar 2014-Nov 2016), participating in the National HCV Research UK (HCVRUK) Cohort Study were recruited from 33 UK HCV centers. The data were prospectively entered at sites onto a centralised database. The data were reported as median (Q1-Q3). Of the 1448 treated patients, 1054 (73%) were males, the median age being 54 years (47-60), 900 (62%) being genotype 1 and 455 (31%) genotype 3. The majority, 887 (61%) had cirrhosis, and 590 (41%) were treatment-experienced. DAA regimens utilised: genotype1 sofosbuvir (SOF)/Ledipasvir/±Ribavirin (625/900, 69%) and Ombitasvir/Paritaprevir/Dasabuvir/±RBV (220/900, 24%), and in genotype 3 SOF/Daclatasvir + RBV (256/455, 56%) and SOF/pegylated interferon/RBV (157/455, 35%). Overall, 1321 (91%) achieved sustained virological response (SVR12), genotype 1 vs 3, 93% vs 87%, P < .001. Prior treatment, presence of cirrhosis and treatment regimen did not impact SVR12. Predictors of treatment failure were genotype 3 infection, OR, 2.015 (95% CI: 1.279-3.176, P = .003), and male sex, OR, 1.878 (95% CI: 1.071-3.291, P = .028). Of those with hepatic decompensation at baseline (n = 39), 51% (n = 20) recompensated post-treatment, lower baseline serum creatinine being associated with recompensation (P = .029). There were two liver-related deaths, both having decompensated disease. This real-world UK data, comprising of a predominantly cirrhotic HCV genotype 1/3 cohort, confirms DAA efficacy with an overall 91% SVR12, with 51% recompensating post-treatment. Genotype 3 infection was a predictor of treatment failure.

Sofosbuvir/velpatasvir for 12 weeks in hepatitis C virus-infected patients with end-stage renal disease undergoing dialysis.

BACKGROUND & AIMS: Although off-label use of sofosbuvir-containing regimens occurs regularly in patients with hepatitis C virus (HCV) infection undergoing dialysis for severe renal impairment or end-stage renal disease (ESRD), these regimens are not licensed for this indication, and there is an absence of dosing recommendations in this population. This study evaluated the safety and efficacy of sofosbuvir/velpatasvir in patients with HCV infection with ESRD undergoing dialysis. METHODS: In this phase II, single-arm study, 59 patients with genotype 1-6 HCV infection with ESRD undergoing hemodialysis or peritoneal dialysis received open-label sofosbuvir/velpatasvir (400 mg/100 mg) once daily for 12 weeks. Patients were HCV treatment naive or treatment experienced without cirrhosis or with compensated cirrhosis. Patients previously treated with any HCV NS5A inhibitor were not eligible. The primary efficacy endpoint was the proportion of patients achieving sustained virologic response (SVR) 12 weeks after discontinuation of treatment (SVR12). The primary safety endpoint was the proportion of patients who discontinued study drug due to adverse events. RESULTS: Overall, 56 of 59 patients achieved SVR12 (95%; 95% CI 86-99%). Of the 3 patients who did not achieve SVR12, 2 patients had virologic relapse determined at post-treatment Week 4 (including 1 who prematurely discontinued study treatment), and 1 patient died from suicide after achieving SVR through post-treatment Week 4. The most common adverse events were headache (17%), fatigue (14%), nausea (14%), and vomiting (14%). Serious adverse events were reported for 11 patients (19%), and all were deemed to be unrelated to sofosbuvir/velpatasvir. CONCLUSIONS: Treatment with sofosbuvir/velpatasvir for 12 weeks was safe and effective in patients with ESRD undergoing dialysis. LAY SUMMARY: Sofosbuvir/velpatasvir is a combination direct-acting antiviral that is approved for treatment of patients with hepatitis C virus (HCV) infection. Despite the lack of dosing recommendations, sofosbuvir-containing regimens (including sofosbuvir/velpatasvir) are frequently used for HCV-infected patients undergoing dialysis. This study evaluated the safety and efficacy of sofosbuvir/velpatasvir for 12 weeks in patients with HCV infection who were undergoing dialysis. Treatment with sofosbuvir/velpatasvir was safe and well tolerated, resulting in a cure rate of 95% in patients with HCV infection and end-stage renal disease. Clinical Trial Number: NCT03036852.

Therapy with Oral Directly Acting Agents in Hepatitis C Infection Is Associated with Reduction in Fibrosis and Increase in Hepatic Steatosis on Transient Elastography.

BACKGROUND/AIMS: Direct-Acting Antivirals (DAAs) are now the standard of care for management of Chronic Hepatitis C (CHC) infection. The aim of this study was to evaluate change in Liver Stiffness Measurement (LSM) and Controlled Attenuation Parameter (CAP) by transient elastography (FibroScan®) after completion of DAA therapy. METHODS: LSM and CAP were measured serially (baseline pre-treatment, at 12 weeks post therapy, and one year after completion of therapy) in a prospective cohort of 372 CHC patients treated with DAAs. Patients with at least two FibroScan measurements were included. RESULTS: The mean age was 38.1 ± 12.6 years; 58.3% males. Cirrhosis as defined by biopsy or fibroscan measurement (≥12.5) kPa was found in 25.5%. On paired analysis (n = 317), LSM (IQR) decreased from a baseline value 7.1 (5.3-13.8) kPa to 6.2 (4.8-11.2) kPa 12 weeks post therapy with a median decline 0.7 (-0.6-2.6) kPa, P < 0.001. Similarly, on paired analysis (n = 160), LSM decreased from baseline 6.9 (5.1-12.7) kPa to 6.1 (4.8-9.4) kPa after one year of treatment with median decline 0.9 (-0.6-3.2) kPa, P < 0.001. In contrast, on paired analysis (n = 317), CAP increased from baseline of 213.0 (180.0-254.5) dB/m to 225.0 (190.0-269.0) dB/m at 12 weeks post therapy with median increase 7.0 (-23.5-45.5), P = 0.001. Similarly, on paired analysis (n = 160), CAP increased from baseline of 210.0 (180.3-260.8) dB/m to 234.0 (204.0-282.0) dB/m at one year post therapy with median increase 25.0 (-12.5-61.5) dB/m, P < 0.001. On multivariate linear regression analysis, low baseline CAP value and low albumin were significantly associated with increase in CAP values. CONCLUSION: Treatment with DAAs reduces liver stiffness, but is associated with increase in hepatic steatosis.