Hepatitis C Virus Genotype 1 Patients Research Articles

Safety and efficacy of sofosbuvir-velpatasvir: A meta-analysis.

Introduction:The sofosbuvir-velpatasvir single-tablet regimen (Epclusa) is a newly FDA-approved inhibitor of hepatitis C virus (HCV). This meta-analysis aimed to investigate the safety and efficacy of velpatasvir-sofosbuvir in the treatment of chronic HCV infection.Methods:A comprehensive literature search of PubMed, Cochrane CENTRAL, EMBASE and Web of Science was conducted. Data from eligible studies were pooled in a fixed-effect meta-analysis model, using Open-Meta and RevMan software’s.Results:Pooled data showed that velpatasvir-sofosbuvir achieved sustained virological response (SVR12) rates of 94.2% (95% CI 90.7–97.7%, P < .001) in 1277 patients. The addition of ribavirin did not significantly increase the SVR12 (RR = 1.03, 95%CI [0.95, 1.11]) in HCV genotype-1 patients and the SVR12 (RR = 1.09, 95%CI [0.86, 1.38]) in HCV genotype-2 patients. However, adding ribavirin significantly increased SVR12 (RR = 1.13, 95% CI [1.04, 1.23]) in genotype-3 patients.Conclusion:In conclusion, the 12-week regimen of sofosbuvir-velpatasvir was highly effective in HCV patients. Except for genotype-3, adding ribavirin was not associated with significant improvements in SVR12 rates.

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

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-1β and IL-12p40 were estimated using human anti-MIP-1β and IL-12p40 antibodies in Sandwich ELISA. No difference was observed in the baseline chemokines levels between responders and relapsers, but the later had a significantly higher MIP-1β/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. Baseline MIP-1β/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.

Serum MicroRNAs as predictors for fibrosis progression and response to direct‐acting antivirals treatment in hepatitis C virus genotype‐4 Egyptian patients

MicroRNA (miRNAs) are small non-coding molecules that play an important role in hepatitis C virus (HCV) replication and liver diseases progression. The current study aimed to evaluate serum miRNAs as potential biomarkers for diagnosis, monitoring of fibrosis progression and prediction of responses to direct-acting antivirals (sofosbuvir+daclatasvir + ribavirin) in HCV genotype-4 patients. The serum levels of four miRNAs (miRNA-21, 199, 448 and 181c) were assessed in 150 HCV patients and 50 healthy controls using quantitative real-time PCR. The diagnostic accuracy was determined using receiver operating characteristic (ROC) curve. The four studied miRNAs showed significant upregulation in HCV patients compared with controls. There were significant upregulation of MiR-199 and significant downregulation of miR-448 in late stages of fibrosis with high diagnostic accuracy (area under the curve "AUC" = 0.989%; P<.001) and (AUC=0.0.672; P>.001), respectively. Regarding response to treatment, only miR-199 showed a significant upregulation in non-responder patients with high diagnostic accuracy (AUC=0.968; P<.001). miR-199 and miR-448 could serve as valuable non-invasive biomarkers for assessment of liver fibrosis progression. Additionally, miR-199 could be also a potential biomarker for assessment of treatment efficacy among HCV patients. Therefore, miR-199 and miR-448 serum levels should be considered during the treatment of HCV genotype-4 patients in Egypt and the world.

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

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. 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 12weeks. Data were collected and evaluated at baseline and at weeks 4, 8 and 12. Sustained virologic response 12weeks after the end of treatment (SVR12 ) was evaluated. Cost-minimization analysis (CMA) was performed. 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. The two DAA regimens showed high SVR12 and safety in Egyptian HCV G4 patients. Sofosbuvir plus daclatasvir is the cost-saving regimen.

Direct-acting antivirals in East Asian hepatitis C patients: real-world experience from the REAL-C Consortium.

One-third of the global hepatitis C virus (HCV) burden is found in Asia. Real-world data from diverse East Asian cohorts remain limited. This study addressed the real-world status of direct-acting antiviral (DAA) therapy among patients from East Asia. Chronic hepatitis C (CHC) patients from clinical sites in Japan, Taiwan, South Korea, and Hong Kong were recruited in the REAL-C registry, an observational chart review registry. The primary outcome was sustained virologic response (SVR12, HCV RNA PCR < 25IU/mL 12week post-therapy). A total of 6287 CHC patients were enrolled. Compared to other East Asian patients, patients from Japan were older (66.3 vs. 61.5years, p < 0.0001), had lower body mass indices (22.9kg/m2 vs. 24.6kg/m2, p < 0.001), and were more likely to have non-liver malignancy history (12.2% vs. 5.0%, p < 0.001).The overall SVR12 rate was 96.4%, similar to patients both inside and outside Japan (96.6% vs. 96%, p = 0.21). The SVR12 rate ranged from 91.1 to 99.4% except treatment-experienced cirrhotic HCV genotype-1 patients who received daclatasvir/asunaprevir (85.9%) and the treatment-experienced cirrhotic HCV genotype-2 patients treated with sofosbuvir/ribavirin (87%). The overall rate of drug discontinuation was 1.9%, also similar across regions. On multivariate regression analyses, there was no significant association between geographic region and SVR outcomes. In this large multinational CHC cohort from the East Asia, oral DAAs were highly effective and well tolerated across the region. Policies should encourage treatment for all CHC patients with DAAs in Asia with its heavy burden of HCV.

Effectiveness of 8 weeks of ledipasvir/sofosbuvir for hepatitis C in HCV-HIV-coinfected patients.

Data is limited on the use of 8 weeks of therapy with ledipasvir/sofosbuvir (LDV/SOF) for special populations such as HCV-HIV-coinfected patients. The primary objective of this analysis was to compare sustained virological response at 12 weeks after end of therapy (SVR12) rates among HCV-monoinfected and HCV-HIV-coinfected patients in a real-world clinical setting. Additionally, we compared SVR12 rates among patients receiving 8 versus 12 weeks of therapy. This was a single-centre, retrospective study of HCV-infected patients prescribed LDV/SOF at ambulatory clinics associated with the University of Maryland Medical Center (UMMC) from May 2015 to May 2016. Data were obtained from UMMC electronic medical records and outpatient pharmacy claims database. Comparisons between groups were made using χ2 or Fisher's exact test for categorical variables and Student's t-test or Wilcoxon rank-sum for continuous variables. All analyses were per-protocol; patients missing SVR12 data (25.2%) could not be evaluated for our stated objectives. A total of 274 patients were included. Median age was 58 years; 62.8% were male; 82.5% were Black. SVR12 data was available for 65 HCV-HIV-coinfected patients, of which 62 (95.4%) achieved SVR12. There was no difference in SVR12 rate between HCV-HIV-coinfected patients and HCV-monoinfected patients (86/90; 95.6%; P=0.959). Additionally, there was no difference in SVR12 attainment between HIV-HCV-coinfected patients who received 8 versus 12 weeks of therapy (P=0.101). 8 weeks of LDV/SOF was effective for treatment-naive, non-cirrhotic, HCV genotype-1 patients in this real-world setting, regardless of HIV status. Increased uptake of the 8-week regimen can decrease costs for patients and payers without compromising outcomes.

Real-world effectiveness and safety of sofosbuvir and ledipasvir with or without ribavirin for patients with hepatitis C virus genotype 1 infection in Taiwan.

BackgroundThe real-world data for the effectiveness and safety of sofosbuvir/ledipasvir (SOF/LDV) with or without ribavirin (RBV) in patients with hepatitis C virus genotype 1 (HCV-1) infection remain limited in Taiwan.MethodsA total of 273 chronic HCV-1 patients receiving 8, 12, or 24 weeks of SOF/LDV with or without RBV were enrolled. The sustained virologic response rate at week 12 off-therapy (SVR12) by evaluable population (EP) and per-protocol population (PP) were assessed for effectiveness. The treatment discontinuation rate due to adverse events (AEs) and serious AE rate were assessed for safety. Baseline patient characteristics and on-treatment HCV viral kinetics associated with SVR12 were analyzed.ResultsThe SVR12 rates by EP and PP analyses were 96.7% (95% confidence interval [CI]: 93.9%-98.3%) and 97.5% (95% CI: 94.8%-98.8%), respectively. The rates of treatment discontinuation due to AE and serious AE were 0.4% and 4.4%, respectively. Seven patients with true virologic failure were relapsers. In 2 patients who were lost-to follow-up, one expired at treatment week 3 due to pneumonia which was considered not related to treatment, and one declined follow-up at off-therapy week 4. The SVR12 rates were comparable in terms of baseline patient characteristics and viral decline at week 4 of treatment.ConclusionsSOF/LDV with or without RBV for 8–24 weeks is well tolerated and achieves a high SVR12 rate in patients with HCV-1 infection in Taiwan.

Effectiveness of sofosbuvir/pegylated-interferon plus ribavirin in treatment of hepatitis C virus genotype 4 patients.

IntroductionNew regimens involving direct-acting antiviral agents (DAAs) have recently been approved for the treatment of hepatitis C virus (HCV) genotype 4 (GT4). The current study aims to assess the efficacy and safety of sofosbuvir (SOF) with pegylated interferon (PegINF)/ribavirin (RBV) for chronic HCV GT4 patients at the beginning of the interferon-free era.Material and methodsBetween March 2015 and November 2015, 99 patients (59 naïve and 40 experienced) infected with HCV GT4 were enrolled in the study. Eligible patients received daily oral 400 mg SOF, RBV (body weight: < 75 kg, 1000 mg; < 75 kg, 1200 mg), the dose modified according to patient tolerability, plus 180 μg PegINFα-2 once weekly for 12 weeks.ResultsAmong the patient cohort, sustained virological response 12 weeks after the end of treatment (SVR12) was achieved by 88% (87/99) of all patients, by 93% (55/59) of naïve patients and by 80% (32/40) of experienced patients. Regarding treatment failure, the data recorded 12% (12/99) of patients (4 null responses and 8 relapsers). Otherwise, the most common adverse events observed during the study included headache, nausea, fatigue, dyspnea, influenza-like illness, anemia, and leukopenia.ConclusionsSOF combination-based therapies were considered promising choice regimens for chronic HCV infection. The present findings suggest that the combination of the SOF/PegINF/RBV regimen was effective for Egyptian patients with HCV GT4. The recorded adverse events and viral outcome revealed the high need for further efforts to minimize the side effects of the current regimen and/or replace PegINF with additional potent DAA(s) to increase SVR12 to achieve 100%.

Safety and efficacy of sofosbuvir plus velpatasvir with or without ribavirin for chronic hepatitis C virus infection: A systematic review and meta-analysis.

Velpatasvir is a newly FDA-approved inhibitor of hepatitis C virus (HCV) NS5A protein. We performed this systematic review and meta-analysis to investigate the safety and efficacy of velpatasvir plus sofosbuvir in the treatment of chronic HCV infection. A computerized literature search of PubMed, SCOPUS, EMBASE, EBSCO, Web of science, and Cochrane CENTRAL was conducted using relevant keywords. Data from eligible studies were pooled in a fixed effect meta-analysis model, using OpenMeta[Analyst] software. Pooled data from six randomized trials (n=1427 patients) showed that velpatasvir plus sofosbuvir achieved sustained virological response (SVR12) rates of 98.2% in genotype-1, 99.4% in genotype-2, 94.7% in genotype-3, 99.6% in genotype-4, 97.1% in genotype-5, and 98.8% in genotype-6 patients. The addition of ribavirin did not significantly increase the SVR12 (RR=0.95, 95%CI [0.88, 1.02]) or decrease relapse rates (RR=2.52, 95% CI [0.49, 12.87]) in HCV genotype-1 patients. However, adding ribavirin significantly increased SVR12 (RR=89.5, 95% CI [80.4, 99.5]) in genotype-3 patients. In conclusion, the 12-week regimen of sofosbuvir plus velpatasvir was highly effective in HCV patients, including those with cirrhosis and former treatment experience. Except for genotype-3, adding ribavirin was not associated with significant improvements in SVR12 rates. Further studies should investigate the effect of adding ribavirin to this regimen, especially in HCV genotype-3 patients.

Efficacy and safety of sofosbuvir-based regimens for treatment in chronic hepatitis C genotype 1 patients with moderately impaired renal function.

Background/AimsTreatment of chronic hepatitis C virus (HCV) infection in patients with chronic kidney disease (CKD) is essential. The availability of sofosbuvir (SOF) has dramatically improved overall HCV cure rates, however there is insufficient data regarding its use in patients with CKD. We evaluated SOF in patients with hepatitis C genotype 1 (G1) and moderately impaired renal function.MethodsWe retrospectively reviewed all patients treated with a SOF-based regimen from December 2013 through September 2015 at Virginia Mason Medical Center. Data was then collected for HCV G1 patients with stage 3 CKD.ResultsA total of 28 patients with HCV G1 and stage 3 CKD were treated with a SOF-based regimen. Twenty-one patients had stage 3A CKD (estimated glomerular filtration rate [eGFR] 45–60 mL/min/1.73m2) and 7 patients had stage 3B CKD (eGFR 30–45 mL/min/1.73m2). The overall rate of sustained virologic response (SVR) 12 weeks after completion of therapy (SVR12) was 85.7% (24/28). SVR12 in stage 3A CKD patients was 81.0% (17/21) and in stage 3B CKD patients, SVR12 was 100% (7/7). Based on the treatment regimen used, the SVR12 was 81.8% (9/11), 92.3% (12/13), and 75.0% (3/4) for SOF/ledipasvir (LDV), SOF/simeprevir (SIM), and SOF/pegylated interferon (PEG)/ribavirin (RBV), respectively. Greater than 30% reduction eGFR was observed in 4 out of 28 patients.ConclusionsSOF-based regimens resulted in high SVR12 rates in patients with moderately impaired renal function. During therapy, HCV patients with CKD should be carefully monitored for worsening renal function.

Response Tailored Protocol Versus the Fixed 12 Weeks Course of Dual Sofosbuvir/Daclatasvir Treatment in Egyptian Patients With Chronic Hepatitis C Genotype-4 Infection: A Randomized, Open-label, Non-inferiority Trial

BackgroundThe most recent European Association for the Study of the Liver (EASL) 2016 Guidelines on treatment of hepatitis C (HCV), allowed for shortening the course of treatment for some subsets of patients with sofosbuvir/ledipasvir and with grazoprevir/elbasvir based on cutoff baseline HCV RNA values. We hypothesized that it would be prudent to also consider an objectively assuring very rapid, on-treatment, virologic response to therapy at week 2 (vRVR) before taking the decision of shortening the treatment duration. So we planned this study to test whether a dual sofosbuvir/daclatasvir (SOF/DCV) treatment duration tailored according to achieving vRVR to 8 or 12weeks is non-inferior to the recommended fixed 12weeks course in non-cirrhotic Egyptian chronic HCV genotype-4 patients. MethodsThe study was conducted in an outpatient setting according to a prospective, randomized, open-label, comparative, non-inferiority study design. A hundred twenty eligible, non-cirrhotic, chronic HCV patients were randomly assigned (1:1) to receive daily doses in the form of one Gratisovir 400mg table (generic sofosbuvir produced by Pharco Pharmaceuticals, Alexandria, Egypt) plus one Daktavira 60mg tablet (generic daclatasvir produced by Dawood Pharm, Egypt) for either a fixed 12weeks duration (reference group) or a response tailored duration (test group). In the test group the treatment duration was tailored according to the virus load tested by real time PCR into 8weeks for patients who had undetectable HCV RNA level in their serum by the end of the second week of treatment (vRVR)), or 12weeks for those who did not show vRVR. The primary outcome of the trial was the proportions of patients achieving SVR12 (HCV RNA below lower level of quantification at week 12 after end of treatment). The comparison between groups was based on testing the null hypothesis of inferiority of the response-tailored group with a pre-specified margin of non-inferiority (NI-m) of 0.1 (10%).The protocol was registered with a WHO Clinical Trial Registration ID: ACTRN12617000263392. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372041 FindingsStarting from Jun, 5 2016, a hundred twenty eligible patients from 4 outpatient clinics in Alexandria, Egypt were randomized to either a fixed duration group (reference group: n=60 patients) or a response tailored duration group (test group: n=60 patients). During the whole period of the study, only 1 patient dropped-out from each group. Both were lost to follow-up after the 4th week's visit. Baseline characteristics in both groups were almost matching. Fifty eight out of the total 60 intention-to-treat (ITT) patients in the reference group achieved SVR12 (96.67% (95% confidence interval (CI): 88.64–99%). Whereas, 59 out of the total 60 (ITT) patients in the test group achieved SVR12 (98.33% (CI: 91.14–99.71%). The per-protocol (PP) analysis, excluding patients who dropped-out before collecting their final result, showed that 58/59 (98.31% (CI: 91–99.7%)) of patients in the reference group and 59/59 (100% (CI: 93.89–100%) of the test group achieved SVR12. Non-inferiority was declared since the upper bound of the two-sided 95% CI for the difference in proportions of SVR12 between groups (P(reference)−P(test)) did not exceed the specified non-inferiority margin of +0.1 (10%), both in ITT population (−1.67%, CI: −9.8%–+5.9%), and in the PP population (−1.69%, CI: −9%–+4.58%). No fatalities or serious adverse events were reported during the period of the study. Similar rates of non-serious adverse events were reported in both groups with a trend of higher incidence rate in the fixed 12weeks group; all were mild in severity. InterpretationShortening the duration of therapy based on observed vRVR could provide a prudent basis to avoid unnecessary long treatment courses. This could not only reduce the drug exposure and the risk of adverse drug reactions, but also cut the cost of full treatment course with such expensive medications by one third. This could economize the treatment budget at the individual out-of-pocket level as well as the public health services and insurance levels and allow for better utilization of public health resources.

Real-World Experiences with the Combination Treatment of Ledipasvir plus Sofosbuvir for 12 Weeks in HCV Genotype 1-Infected Japanese Patients: Achievement of a Sustained Virological Response in Previous Users of Peginterferon plus Ribavirin with HCV NS3/4A Inhibitors.

The aim of this study was to characterize the treatment response and serious adverse events of ledipasvir plus sofosbuvir therapies in Japanese patients infected with hepatitis C virus (HCV) genotype 1 (GT1). This retrospective study analyzed 240 Japanese HCV GT1 patients treated for 12 weeks with 90 mg of ledipasvir plus 400 mg of sofosbuvir daily. Sustained virological response at 12 weeks post-treatment (SVR12) was achieved in 236 of 240 (98.3%) patients. Among treatment-naïve patients, SVR12 was achieved in 136 of 138 (98.6%) patients, and among treatment-experienced patients, SVR12 was achieved in 100 of 102 (98.0%) patients. In patients previously treated with peginterferon plus ribavirin with various HCV NS3/4A inhibitors, 100% SVR rates (25/25) were achieved. Two relapsers had HCV NS5A resistance-associated variants (RAVs), but no HCV NS5B-S282 was observed after they relapsed. We experienced two patients with cardiac events during treatment. In conclusion, combination of ledipasvir plus sofosbuvir for 12 weeks is a potential therapy for HCV GT1 patients. Caution is needed for HCV NS5A RAVs, which were selected by HCV NS5A inhibitors and cardiac adverse events.

Detection of MicroRNA in Hepatic Cirrhosis and Hepatocellular Carcinoma in Hepatitis C Genotype-4 in Egyptian Patients.

Background In Egypt, the prevalence of chronic hepatitis C (CHC) infection is 13.8% of whole population and about 80% of the patients with hepatocellular carcinoma have underling hepatitis C. Aim This study was designed to assess the diagnostic value of plasma miR-122 and miR-21 in patients with CHC, genotype-4, to detect fibrosis progression versus noninvasive indices and their diagnostic value in detection of early stages of hepatocellular carcinoma (HCC). Methodology A prospective study that included 180 patients, divided into 3 groups: healthy controls (group I), CHC patients (group II), and hepatitis C patients with HCC (group III); all cases were subjected to thorough clinical, radiological, and laboratory investigations. Selected biomarkers were evaluated and correlated with degree of liver damage. Results revealed that miR-122 followed by miR-21 had the highest efficiency in prediction of liver cell damage. Also, miR-21 was strongly correlated with vascular endothelial growth factor (VEGF) and alpha fetoprotein (α-FP) in HCC patients. Conclusions Plasma miR-122 and miR-21 had strong correlation with degree fibrosis in HCV genotype-4 patients; consequently they can be considered as potential biomarker for early detection of hepatic fibrosis. Moreover, miR-21 can be used as a potential biomarker, for early detection of HCC combined with VEGF and α-FP.

Incremental cost-effectiveness pharmacoeconomic assessment of hepatitis C virus therapy: an approach for less wealthy members of the common market.

AimTo develop a new method of health-economic analysis based on a marginal approach.MethodsWe tested the research hypothesis that a detailed comparative a priori incremental cost-effectiveness analysis provides the necessary input for budget impact analysis about the proper order of introduction of new therapies, and thus maximizes the cost-effectiveness bounded by the total budget constraint. For the analysis we chose a combination therapy for the treatment of hepatitis C virus (HCV) genotype 1 (GT1) infection, which was approved by the European Medicine Agency in 2015. We used the incremental cost-effective approach to assess the increase in the percentage of patients achieving sustained virological response (SVR) and the expenditure per additional SVR modulated by the new therapy's market entrance dynamics. Patient subpopulations were differentiated by their response to previous treatment, presence of cirrhosis, and HCV GT1 subtype. Final parameters were estimated by Monte Carlo simulations.ResultsThe new combination therapy had high efficacy, shorter duration, and was better tolerated than alternative interventions. The research hypothesis was confirmed: gradual introduction of the new therapy on the market, based on a priori incremental cost-effectiveness analysis, would result in average increase in successfully treated patients by 20%-40%, while additional costs would approximately be between 8%-40%, ie, €21,000-52 000 per additional patient achieving SVR.ConclusionWe showed the new combination therapy to be cost-effective for certain patient subpopulations, especially for experienced cirrhotic HCV GT1 patients. Results of the analysis are in agreement with the latest recommendations for HCV patients’ treatment in Croatia. This economic evaluation could serve as a starting point for negotiations between pharmaceutical industry and insurance companies.

The value of cure associated with treating treatment-naïve chronic hepatitis C genotype 1: Are the new all-oral regimens good value to society?

All-oral regimens are associated with high cure rates in hepatitis C virus-genotype 1 (HCV-GT1) patients. Our aim was to assess the value of cure to the society for treating HCV infection. Markov model for HCV-GT1 projected long-term health outcomes, life years, and quality-adjusted life years (QALYs) gained. The model compared second-generation triple (sofosbuvir+pegylated interferon+ribavirin [PR] and simeprevir+PR) and all-oral (ledipasvir/sofosbuvir and ombitasvir+paritaprevir/ritonavir+dasabuvir±ribavirin) therapies with no treatment. Sustained virological response rates were based on Phase III RCTs. We assumed that 80% and 95% of HCV-GT1 patients were eligible for second-generation triple and all-oral regimens. Transition probabilities, utility and mortality were based on literature review. The value of cure was calculated by the difference in the savings from the economic gains associated with additional QALYs. Model estimated 1.52 million treatment-naïve HCV-GT1 patients in the US. Treating all eligible HCV-GT1 patients with second-generation triple and all-oral therapies resulted in 3.2 million and 4.8 million additional QALYs gained compared to no treatment respectively. Using $50,000 as value of QALY, these regimens lead to savings of $185 billion and $299 billion; costs of these regimens were $109 billion and $128 billion. The value of cure with second-generation triple and all-oral regimens was $55 billion and $111 billion, when we conservatively assumed only drug costs. Cost savings were greater for HCV-GT1 patient cured with cirrhosis compared to patients without cirrhosis. The recent evolution of regimens for HCV GT1 has increased efficacy and value of cure.

Pharmacogenetics of ribavirin-induced anemia in HCV patients.

Dual therapy (pegylated interferon plus ribavirin) was considered the standard of care for hepatitis C virus (HCV) treatment until 2011, when the first-wave direct-acting antivirals were added to this regimen for HCV genotype-1 patients to increase the sustained virological response rate. The second-wave direct-acting antivirals entered the clinical use also in some ribavirin (RBV)- and/or interferon-free combinations. Nevertheless, since some of the new therapeutic regimens also include RBV and its use results still associated with hemolytic anemia, this requires countermeasures to be prevented. These include the identification of several host predictive factors involved in RBV absorption, distribution, metabolism, elimination and many others that might influence this toxic effect. For this reason, we provided an overview of the potential role of pharmacogenomics in predisposing RBV-treated HCV patients to anemia.

PGI14 - TREATMENT OF CHRONIC HEPATITIS C VIRUS GENOTYPE 1 INFECTION: COMPARISON OF HEALTH-ECONOMIC OUTCOMES FOR NAÏVE PATIENTS

Objectives: During the past couple of years very effective direct acting antiviral (DAA) therapies for treating hepatitis C virus (HCV) infection appeared on the market. Beside high efficacy, these therapies are also designated by high prices in comparison to the therapy with pegylated interferon (pegIFN). The objective of presented work was to compare the cost-effectiveness of the therapies for HCV genotype 1 (GT1) naive patients currently available on Croatian market. Methods: Costs of therapies were calculated according to publicly available medication pricing list and information found in Summary of Product Characteristics (SmPC) documents. The main health-economic outcome was defined as cost per cure i.e. therapy cost per achieved sustained viral response (SVR). Final parameters were estimated by Monte Carlo simulations. ANOVA and Tukey post-hoc test were used to test differences between mean therapies’ costs per SVR. Results: Currently on the Croatian market, there are five different treatments of HCV GT1 naive patients. Those therapies are therapies with pegIFN that have SVR rates 30-55% as well as DAAs therapies with SVR range 60-100 % for naive HCV GT1 patients. There is statistically significant difference (p < 0.001) among average treatment costs per SVR of the therapies and those are as low as €14, 800 for pegIFN and for new therapies reach €79, 600 in case of patients without cirrhosis. For cirrhotic patients prices are in range from €23, 400 for pegIFN, up to €91, 500 for DAA therapies. Conclusions: Due to the low costs per achieved SVR we can expect that in future there will still remain certain portion of naive HCV GT1 patients who will receive pegIFN therapy. “Pay per cure” policy in which pharmaceutical company is not being paid for the drugs in cases in which patient does not achieve SVR, seems to be good solution for health providers and appropriate answer to high prices of the new therapies.

Lower response to simeprevir and sofosbuvir in HCV genotype 1 in routine practice compared with clinical trials

BackgroundHigh sustained virological response at 12 weeks after end of treatment (SVR12) with 12 weeks of simeprevir and sofosbuvir±ribavirin (SMV+SOF±RBV) has been demonstrated in hepatitis C virus genotype 1 (HCV-1)...

SAT-161 - Final Results of the Pyramid 1 Study, a Phase 3 Registrational Trial of Ravidasvir (PPI-668) and Sofosbuvir in HCV Genotype-4 Patients: High Rates of Sustained Viral Clearance in Cirrhotic and Non-Cirrhotic Patients

SAT-161 - Final Results of the Pyramid 1 Study, a Phase 3 Registrational Trial of Ravidasvir (PPI-668) and Sofosbuvir in HCV Genotype-4 Patients: High Rates of Sustained Viral Clearance in Cirrhotic and Non-Cirrhotic Patients

P-B11 Retreatment of HCV GT-1 in patients who failed previous short course combination DAA therapy with 12 weeks of LDV/SOF is highly effective

Introduction: Directly-acting antivirals (DAAs) revolutionized HCV therapy, but retreatment options for patients failing combination DAA therapy remain unstudied. Our aim is to determine if HCV genotype-1 patients who failed short course therapy with 3 or 4 DAAs, including LDV/SOF, can be retreated with 12 weeks of LDV/SOF. Methods: In this single- center, open-label, phase 2a trial, patients with HCV gt-1, early stage (F0-F2) liver fibrosis and previous exposure to combination DAA therapy (LDV/SOF with GS-9451 ± GS-9669) were eligible for treatment with 12 weeks of LDV/SOF. HCV RNA was measured by the Abbott assay, lower level of quantitation (LLOQ) 12 IU/mL. The primary endpoint was HCV viral load (VL) less than LLOQ 12 weeks after end of therapy (SVR12). Deep sequencing of NS5B and NS5A regions was performed at baseline by Illumina next generation sequencing technology. Results: The study enrolled 34 persons; 32 (94%) completed 12 weeks of LDV/SOF. Two patients withdrew consent after Day 0. Participants were predominantly male (82%) and black (82%), mean age 58.9 years, and BMI 27.3 kg/m2. Baseline HCV VL was 1.3 × 106 IU/mL (IQR: 5.8 × 105 − 3.9 × 106), 76.5% (26/34) were infected with HCV gt 1a, and median Metavir fibrosis stage was 1. Time from relapse to retreatment was 22 weeks (±8 weeks). SVR12 rates were 91% (31/34; ITT). At baseline, 29/34 patients (85%) had resistance-associated variants (RAVs) consistent with greater than 25 fold resistance in NS5A. Of all patients completing therapy, 1 patient with NS5A RAVs relapsed. Conclusions: For the first time, we demonstrate a high SVR rate following retreatment with DAAs in patients who have previously failed DAA-only therapy.