Treatment Of Chronic Hepatitis C Virus Infection Research Articles

The efficacy of adding vitamin B12 to pegylated interferon and ribavirin treatment in Hepatitis C virus patients regarding the host and viral prognostic factors

Introduction: Hepatitis C virus (HCV) infection affects almost 180 million people around the world. Even though the development of direct acting antivirals (DAAs) has significantly improved the treatment responses to HCV infection, treatment with pegylated interferon (PegIFN) in combination with ribavirin is considered the standard of care (SOC) for chronic HCV infection treatment in countries with limited medical resources. Considering the inhibitory effect of vitamin B12 on HCV replication, we have evaluated the effect of vitamin B12 supplementation along with SOC on treatment outcomes in patients with chronic HCV infection, who were antiviral treatment-naive.
 Methods: In this regard, seventy-four HCV-infected patients, naïve to antiviral therapy, were randomly assigned to receive SOC or SOC in addition to vitamin B12 (SOC + B12). Viral response was evaluated at 4, 12, 24 and 48 weeks following the initiation of viral treatment and at 24 weeks after completing the treatment. Genotyping of the interleukin 28B (IL28B) polymorphisms was also performed. Demographic characteristics, clinical findings, fibroscan results and drug adverse effects were recorded.
 Results: Our findings showed that rapid viral response was not significantly different between the two groups; however, the rates of complete early viral response (cEVR) (p=0.033), end-of-treatment viral response (ETVR) (p=0.001) and sustained virologic response (SVR) (p=0.0001) were significantly higher in SOC + B12 patients compared to SOC patients. Besides, in SOC + B12 patients, those with a higher baseline viral load and carriers of IL28B CC genotype showed significantly higher rate of SVR.
 Conclusion: In conclusion, the addition of vitamin B12 significantly improved the rate of SVR in HCV-infected patients, who were naïve to antiviral therapy. As this treatment regimen is safe and inexpensive, it proposes an option for improving the effectiveness of the HCV treatment with SOC, particularly in resource-limited settings.

Identification of novel small molecule inhibitors against the NS3/4A protease of hepatitis C virus genotype 4a.

Hepatitis C virus (HCV) infection poses a considerable threat to the public health. The current standard of care treatment with pegylated interferon-alpha in combination with ribavirin (PEG-IFN- α+RBV) is associated with significant side effects, poorly tolerated, and provides limited efficacy. The development of direct-acting antiviral agents (DAAs) targeting key viral enzymes essential for viral replication represents a significant milestone in the treatment of chronic HCV infection. Given its critical role in the viral polyprotein processing and the evasion of the host innate immunity, the NS3/4A protease has emerged as a promising drug target for the development of anti-HCV therapies. Although several potent NS3/4A protease inhibitors (PIs) have been approved or are in clinical development, the majority of currently available PIs have significant limitations related to untoward adverse events and a lack of pan-genotypic activity, indicating a continuing unmet medical need for the development and optimization of novel PIs with improved efficacy and tolerability, convenient dosing schedules, and shorter treatment durations. The inhibitory efficacy of four computer-designed chemically-synthesized compounds was evaluated against in vitro-expressed NS3/4A protease from HCV genotype 4a, the most prevalent genotype in Egypt, using a fluorescence-based enzymatic assay. We successfully identified two non-macrocyclic small molecules, BE113 (7a) and BE114 (7b), which exhibited inhibitory activity against HCV NS3/4A protease from HCV genotype 4a. The two compounds presented in this study may be promising inhibitors against NS3/4A protease of HCV genotype 4a and could be novel lead compounds for developing new therapeutics for the treatment of chronic HCV infection.

Psychometric Validation of the Hepatitis C Symptom and Impact Questionnaire (HCV-SIQv4) in a Diverse Sample of Adults with Chronic Hepatitis C Virus Infection Treated with an Interferon-free Simeprevir-containing Regimen.

BackgroundHepatitis C virus (HCV) infection and its treatments are associated with significant symptoms, side effects and impact on patients functioning. The Hepatitis C Symptom and Impact Questionnaire version 4 (HCV-SIQv4) was developed according to FDA Patient Reported Outcomes (PRO) Guidance, for evaluating chronic HCV infection and its treatment.ObjectivesThis study evaluated the psychometric properties and clinically important change (CIC) thresholds of the measure.MethodsPRO data were pooled from three Phase IIb and III trials evaluating interferon-free simeprevir-containing regimens for treatment of chronic HCV infection. Scale range adequacy, reliability, validity, responsiveness and CIC thresholds were assessed incorporating knowledge of the appropriate measurement model.ResultsData from 437 patients were analyzed. Stage of liver disease was associated with symptom severity and functioning at baseline. Reliability was acceptable (test-retest ICC ≥0.7) for most scores except the Gastrointestinal and Integumentary domains. Convergent validity was observed between HCV-SIQv4 scores and concurrent measures of conceptual similarity. Greater symptom severity and worse impact scores were associated with liver cirrhosis, depression, severe fatigue and health limitations. Patients who achieved SVR12 had better outcomes than those failing to. HCV-SIQv4 symptom and domain scores were responsive to changes in health state (effect sizes ≥0.5). Exploratory thresholds for change in scores indicating a clinically important improvement and worsening were HCV-SIQv4 Overall Body System Score (BSS), 8 and 8; Constitutional BSS, 10 and 10; Gastrointestinal BSS, 5 and 5; Psychiatric BSS, 8 and 8; Neurocognitive BSS, 8 and 8; and Integumentary BSS, 5 and 5.ConclusionsThe HCV-SIQv4 offers reliable, responsive assessments within HCV clinical development. CIC thresholds are now available to aid score interpretation.

Psychometric Validation of the Hepatitis C Symptom and Impact Questionnaire (HCV-SIQv4) in a Diverse Sample of Adults with Chronic Hepatitis C Virus Infection Treated with an Interferon-free Simeprevir-containing Regimen

Background: Hepatitis C virus (HCV) infection and its treatments are associated with significant symptoms, side effects and impact on patients functioning. The Hepatitis C Symptom and Impact Questionnaire version 4 (HCV-SIQv4) was developed according to FDA Patient Reported Outcomes (PRO) Guidance, for evaluating chronic HCV infection and its treatment. Objectives: This study evaluated the psychometric properties and clinically important change (CIC) thresholds of the measure. Methods: PRO data were pooled from three Phase IIb and III trials evaluating interferon-free simeprevircontaining regimens for treatment of chronic HCV infection. Scale range adequacy, reliability, validity, responsiveness and CIC thresholds were assessed incorporating knowledge of the appropriate measurement model. Results: Data from 437 patients were analyzed. Stage of liver disease was associated with symptom severity and functioning at baseline. Reliability was acceptable (test-retest ICC ≥0.7) for most scores except the Gastrointestinal and Integumentary domains. Convergent validity was observed between HCV-SIQv4 scores and concurrent measures of conceptual similarity. Greater symptom severity and worse impact scores were associated with liver cirrhosis, depression, severe fatigue and health limitations. Patients who achieved SVR12 had better outcomes than those failing to. HCV-SIQv4 symptom and domain scores were responsive to changes in health state (effect sizes ≥0.5). Exploratory thresholds for change in scores indicating a clinically important improvement and worsening were HCV-SIQv4 Overall Body System Score (BSS), 8 and 8; Constitutional BSS, 10 and 10; Gastrointestinal BSS, 5 and 5; Psychiatric BSS, 8 and 8; Neurocognitive BSS, 8 and 8; and Integumentary BSS, 5 and 5. Conclusions: The HCV-SIQv4 offers reliable, responsive assessments within HCV clinical development. CIC thresholds are now available to aid score interpretation.

Baseline Characteristics and Treatment Cost of Hepatitis C at Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam in Direct-Acting Antiviral Treatment Era

Background: Direct-Acting Antivirals (DAAs) are recommended as first-line of drugs for the treatment of chronic hepatitis C virus (HCV) infection in Vietnam in 2016. Since then, Hospital for Tropical Diseases (HTD), Ho Chi Minh City, Vietnam introduced DAAs based treatment for all newly presented chronic HCV patients. Here, we report the sociodemographic, clinical, biochemical, and virologic characteristics of patients and the direct medical cost associated with DAAs treatment. Methods: We conducted a retrospective cross-sectional study among chronic HCV patients attended at HTD from March 2016 to October 2017 and treated with DAAs. We used an extract of the patient’s electronic medical record containing demographics, clinical presentations, laboratory results, drug prescription, and cost of treatment at the hospital for data analysis. Results: 2817 chronic HCV patient received DAAs treatment during the study period. The mean age was 55.0 years, and 54.9% (1546/2817) of the patients were female. HCV genotype 1, 2, 3 and 6 prevalence was 32.1% (904/2817), 12.7% (359/2817), 0.4% (10/2817), and 54.7% (1542/2817) respectively. The mean HCV viral load was 3.1 × 106 copies/ml, including 46.9% (1322/2817) had ≥106 copies/ml. 70.64% (1990/2817) and 16.15% (455/28817) of the patients received Sofosbuvir (SOF)/Ledipasvir (LDV) ± Ribavirin (RBV) and SOF/Daclatasvir (DCV) ± RBV therapy respectively. The average drug cost for a 12-week of SOF/LDV ± RBV and SOF/DCV ± RBV treatment was US$2068 - 2230 and US$2417 - 2472, respectively. Conclusion: Genotype 6 was the most predominant genotype in southern Vietnam. The preferred treatment for chronic HCV infection was SOF/LDV ± RBV for 12 weeks.

Resolved HBV behavior during the treatment of chronic HCV infection with direct-acting antivirals.

This paper aimed to assess and follow up the course of resolved HBV (hepatitis B virus) during and after treatment with direct-acting antiviral drugs (DAAs). Co-infection with hepatitis B and hepatitis C is increasingly recognized in patients with chronic hepatitis. Resolved HBV in patients with chronic HCV (hepatitis C virus) infection has been investigated during interferon therapy, and the investigators suggest a possible correlation with a lower response to anti-viral treatment, higher grades of liver histological changes, and development of hepatocellular carcinoma. Three hundred and thirteen patients were included in our observational and prospective study; two hundred and fifty-three patients had chronic hepatitis C (CHC) (group I), and sixty patients had both CHC and resolved HBV-infection (group II). They all were eligible for treatment with DAAs therapy for chronic HCV in our hepatology unit, Internal Medicine Department, Zagazig University Hospitals from December 2017 to September 2018. They were subjected to thorough history taking, full clinical examination, routine laboratory investigations, HCV antibody, HCV RNA, HBV surface antigen (HBsAg), HBV surface antibody (anti-HBs) HBV core antibody (anti-HBc), and HBV-DNA quantitative levels. All patients were followed up at baseline, at the end of week 4 of anti-viral therapy, at the end of treatment and 12 weeks after treatment. Assessment at 28 days showed significant decreases in ALT and AST levels in both groups, with stabilization of these levels on follow-up at 12 and 24 weeks. The efficacy of treatment was comparable in both groups. No case of ALT flare was observed in either group. Similar outcomes regarding AST and ALT levels were found in patients with diseases associated with immune derangement. The risk of resolved HBV reactivation during or after treatment with DAAs is low.

Treatment of HCV Infection with Direct-Acting Antiviral Agents in Patients with HIV/HCV Co-Infection: A Systematic Review

Context: Hepatitis C virus (HCV) infection is a significant cause of chronic liver disease in patients with human immunodeficiency virus (HIV) infection. Introduction of HCV direct-acting antiviral agents (DAAs) revolutionized the treatment of hepatitis C in patients with HIV/HCV co-infection. In this study, we systematically reviewed the treatment of chronic HCV infection in patients with HIV/HCV co-infection. Evidence Acquisition: In this systematic review, electronic databases including PubMed, Scopus, ScienceDirect, and Web of Science were comprehensively searched using appropriate strategies containing all related keywords of “HCV”, “HIV” and “DAA”. Studies assessed the effectiveness of interferon-free HCV antiviral therapies in patients with HIV/HCV co-infection were evaluated for inclusion in the systematic review. Results: After the screening of 728 records, we included 33 articles in our study, and seven different HCV antiviral regimens were evaluated. Ten studies for sofosbuvir plus simeprevir (SVR ranged from 72.2% to 100%), eight studies for sofosbuvir plus ribavirin (SVR ranged from 51.6% to 91.6%), 12 studies for sofosbuvir/ledipasvir (SVR ranged from 88.8% to 100%), eight studies for sofosbuvir plus daclatasvir (SVR ranged between 84.6% and 100%), two studies for grazoprevir/elbasvir (SVR ranged from 86.6% to 96.5%), six studies for ombitasvir/paritaprevir/ritonavir plus dasabuvir (SVR ranged from 90.6% to 100%), and just one study for sofosbuvir/velpatasvir with 95.2% SVR rate. Conclusions: This study found that treatment of HCV infection with DAAs can result in high SVR rate in patients with HIV/HCV co-infection.

Characterization of changes in intrahepatic immune cell populations during HCV treatment with sofosbuvir and ribavirin.

Treatment of chronic hepatitis C virus (HCV) infection with direct-acting antivirals (DAAs) results in a sustained virologic response (SVR) in most patients. While highly efficacious, ~3%-5% of patients do not achieve SVR despite having virus that appears susceptible. It is unclear whether host factors contribute to treatment failures, although innate and adaptive immunity may play a role. Previous studies showed that after DAA treatment, the composition of intrahepatic immune cells does not normalize relative to healthy volunteers, even in cases where SVR is achieved. We used paired pre- and post-treatment liver biopsies from 13 patients treated with sofosbuvir and ribavirin, 4 of whom relapsed, to analyse intracellular immune changes during DAA treatment and explore correlations with inflammation and treatment outcome. We performed single marker immunohistochemistry followed by electronic image capture, manual annotation of parenchymal and non-parenchymal regions, and quantitative image analysis. The predominant cellular change during treatment was a decrease in CD8+ cellular density in both parenchymal and non-parenchymal regions. CD68+ Kupffer cell density correlated with hepatic inflammation (AST, ALT) pre-treatment, but did not change during treatment. CD4+ cellular density decreased in non-parenchymal regions and, intriguingly, was lower pre-treatment in subjects who eventually relapsed. Other cellular markers (CD56, CD20), as well as markers of apoptosis (TIA-1) and activated stellate cells, did not change significantly during treatment or differ by treatment outcome. The predominant intrahepatic cellular change during DAA treatment of chronic HCV infection is a reduction in CD8+ cellular density, but this did not correlate with treatment outcome.

Efficacy and safety of sofosbuvir and daclatasvir with or without ribavirin in elderly patients with chronic hepatitis C virus infection.

Hepatitis C virus (HCV) infection is considered as a major public health problem that, worldwide, chronically affects 170 million people. Elderly patients are more likely than younger patients to have increased duration of infection, increased rate of disease progression, and subsequently increased incidence of advanced liver disease. Natural history models predicted that the prevalence of HCV infection and its chronic sequelae as well as extrahepatic manifestations will eventually increase through the next decade and will mostly affect those who are greater than 60 years of age. Moreover, polytherapy and polypharmacy are frequent in elderly patients due to associated comorbidities. As advanced age is associated with increasing risk of development of cirrhosis and hepatocellular carcinoma, elderly patients are in special need of safe and effective antiviral therapies. Achievement of sustained viral responses (SVR) is associated with reduced liver-related complications and overall mortality in such patients with the advanced liver disease. With the recent introduction of interferon-free direct-acting antivirals, successful treatment for chronic HCV infection had dramatically improved, with overall cure rates that exceed 90% SVR. In our study, we aimed to study the efficacy and safety of combined sofosbuvir and daclatasvir, with or without ribavirin, in management of chronically infected HCV elderly patients who are more than 60 years old.

Design and evaluation of novel tetracyclic benzofurans as palm site allosteric inhibitors of HCV NS5B polymerase.

Hepatitis C virus (HCV) NS5B polymerase is a prime target for the development of direct-acting antiviral drugs for the treatment of chronic HCV infection. Several novel and potent HCV NS5B non-nucleoside inhibitors with unique tetracyclic bezonfuran-based structures were prepared and evaluated. Similar to clinical developmental compound MK-8876, N-linked (compounds 1 and 2) and C-linked (compounds 3 and 4) tetracyclic structures maintained broad spectrum anti-replicon potency profiles and demonstrated moderate to excellent oral bioavailability and pharmacokinetic parameters across the three preclinical animal species. To better understand the importance of tetracyclic structures related to pan genotypic potency profiles especially against clinically relevant GT1a variants, the teracycles with different ring size were prepared and in vitro evaluations suggested compounds with six number ring have better overall potency profiles.

Hepatitis C virus infection in chronic kidney disease: paradigm shift in management.

Hepatitis C virus (HCV) infection in chronic kidney disease (CKD) is associated with increased liver-related morbidity and mortality rates, accelerated progression to end-stage renal disease, and risk of cardiovascular events. CKD patients with HCV infection require antiviral therapy. Pegylated interferon (peg-IFN) plus ribavirin was the standard of care for HCV-infected CKD patients before the introduction of first-generation direct-acting antiviral (DAA) oral anti-HCV agents. Peg-IFN-based treatment has a low virologic response rate and poor compliance, resulting in a high dropout rate. Recently, several clinical trials of all-DAA combination regimens have reported excellent antiviral efficacy and few adverse drug reactions in HCV-infected patients with CKD. These positive results have revolutionized the treatment of chronic HCV infection in this population. In this review, we address the impact of chronic HCV infection in CKD patients, and discuss their management using next-generation DAAs.

Deferred treatment with sofosbuvir–velpatasvir–voxilaprevir for patients with chronic hepatitis C virus who were previously treated with an NS5A inhibitor: an open-label substudy of POLARIS-1

Direct-acting antiviral regimens containing NS5A inhibitors are highly effective treatments for chronic hepatitis C virus (HCV) infection, but are not always successful. In the POLARIS-1 phase 3 study, sofosbuvir-velpatasvir-voxilaprevir for 12 weeks was highly effective in the treatment of chronic HCV infection in patients previously treated with a direct-acting antiviral regimen containing an NS5A inhibitor. We aimed to assess the efficacy and safety of sofosbuvir-velpatasvir-voxilaprevir in patients from the deferred treatment group of POLARIS-1, who were initially assigned to masked placebo treatment. This open-label, deferred treatment substudy was done at 73 clinical sites (hospitals and clinics) in the USA, France, Canada, the UK, Germany, Australia, and New Zealand. Patients who received placebo in the primary study and who did not have a new clinically significant illness at the post-treatment week 4 assessment were eligible to enter this substudy. Participants received a combination tablet of sofosbuvir (400 mg), velpatasvir (100 mg), and voxilaprevir (100 mg) once daily for 12 weeks. The primary efficacy outcome was achievement of sustained virological response (defined as HCV RNA concentration below the lower limit of quantification) 12 weeks after the end of treatment (SVR12). The primary safety outcome was the proportion of patients who discontinued treatment due to adverse events. This study is registered with ClinicalTrials.gov, number NCT02607735, and the EU Clinical Trials Register, number 2015-003455-21. 152 patients received placebo in the primary study and were potentially eligible for participation in the open-label substudy, of whom 147 were enrolled from March 30, 2016, to Oct 12, 2016. All 147 patients completed treatment, and 143 (97%; 95% CI 93-99) achieved SVR12. Four (3%) patients had virological relapse; all had HCV genotype 1a infection and one also had compensated cirrhosis. The most common adverse events were fatigue (31 [21%]), headache (29 [20%]), diarrhoea (28 [19%]), and nausea (21 [14%]). No deaths, treatment discontinuations, or treatment-related serious adverse events occurred. Supporting the results from the blinded portion of the phase 3 primary study, the single-tablet regimen of sofosbuvir-velpatasvir-voxilaprevir for 12 weeks was safe, well tolerated, and highly effective in patients with chronic HCV infection who had previous treatment failure with NS5A inhibitor-containing regimens. A salvage regimen for this population represents an important advance for patients with limited retreatment options. Gilead Sciences.

Liver disease burden and required treatment expenditures for hepatitis C virus (HCV) infection in Thailand: Implications for HCV elimination in the new therapeutic era, a population-based study.

The prevalence of hepatitis C virus (HCV) infection has been decreasing globally, but the growing effects of HCV-related morbidity and mortality remain of concern. Advances in curative medicine, involving direct-acting antivirals (DAAs), have led many countries to aim to eradicate HCV. Information on epidemiology and disease burden is essential for national policy development. Thus, this study aimed to determine the HCV-related hepatic disease burden in areas of Thailand with high and average HCV prevalence in order to extrapolate the viral burden across Thailand. Patients previously diagnosed as positive for anti-HCV antibodies were recruited to assess chronic HCV infection (CHC) status, liver function, HCV-RNA level and hepatic fibrosis. The number of patients eligible for Universal Health Coverage (UC) scheme and the approximately required expenditure on interferon (IFN)-based treatment were estimated. In areas of both high (12%) and average (2%) HCV viremic prevalence, over half of the patients (52.2% to 62.5%) had advanced liver fibrosis (F3 and F4). A striking percentage of patients with F4 (38.9%) were found in the high-prevalence area, while comparable proportions of advanced liver fibrosis presented in the two areas and disease burden peaked at 50–59 years. Under the current UC program treatment scenario, 78–83% of CHC patients with stage F2–F4 fibrosis were eligible for treatment. The estimated expenditure required for overall CHC treatment across the whole country was 1,240 million USD at this current status, but the declining cost of generic DAA-based therapy may reduce the requirement to <90 million USD. This study provides information on the estimated number of CHC patients, liver disease burden and expenditure requirements for Thailand. To eliminate HCV by 2030, proactive government strategies raising public health to minimize transmission and emphasizing targeted screen-and-treatment programs, novel therapeutic guideline development for decentralizing treatment, and effective budget allocation are urgently needed.

Demonstration of Near-Elimination of Hepatitis C Virus Among a Prison Population: The Lotus Glen Correctional Centre Hepatitis C Treatment Project.

Micro-elimination of hepatitis C virus (HCV) infection through rapid uptake of government-funded direct-acting antiviral therapy within an Australian prison setting is demonstrated. During a 22-month period, 119 patients initiated treatment for chronic HCV infection, with HCV in-prison viremic prevalence declining from 12% to 1%.

Interleukin-7 augments CD8+ T cells function and promotes viral clearance in chronic hepatitis C virus infection

Interleukin (IL)-7 is a potent proliferation, activation, and survival cytokine for CD8+ T cells to improve viral and tumor specific CD8+ T cell responses. However, the role of IL-7 in regulation of dysfunctional hepatitis C virus (HCV)-specific CD8+ T cells was not fully elucidated. Thus, a total of 53 patients with chronic hepatitis C and 24 healthy individuals were enrolled in the current study. Serum IL-7 and its receptor α chain CD127 expression was measured. The modulatory function of IL-7 to CD8+ T cells was investigated in both direct and indirect contact co-culture with HCVcc-infected Huh7.5 cells. Both serum IL-7 and CD127 expression on CD8+ T cells was significantly reduced in chronic HCV-infected patients, which was negatively correlated with HCV RNA. Stimulation of IL-7 promoted both cytotoxicity and cytokines (interferon-γ, tumor necrosis factor-α, and IL-2) production of CD8+ T cells from patients with chronic hepatitis C. Moreover, IL-7 increased proliferation of CD8+ T cells, while downregulated a critical repressor of cytokine signaling, suppressor of cytokine signaling 3 (SOCS3). The IL-7-mediated enhancement effects to CD8+ T cells were dependent on IL-6 production. The current data suggested that IL-7 induced both cytolytic and noncytolytic functions of CD8+ T cells probably via repression of SOCS3. IL-7 might be considered as one of the therapeutic candidates for treatment of chronic HCV infection.

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.

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Position Paper on Treatment of Hepatitis C in Romania 2017. Part Two.

Hepatitis C virus (HCV) infection is a common condition with endemic prevalence in some areas of the world. In Romania, the mean prevalence is about 3%. New treatments have become available on the market in recent years and new drugs are in the pipeline. A re-evaluation of HCV therapy was considered mandatory. The Romanian Society of Gastroenterology and Hepatology undertook this task for the practitioners of this country. A group of recognized experts was created who screened the available literature and the major available guidelines. A list of items requiring attention was created and these were discussed and rated. Decisions were taken by consensus. We present here the second part of the Society's recommendations for chronic HCV infection treatment. An agreement between experts was reached regarding the therapy of the special categories of patients infected with HCV, complications and monitoring of the therapy, follow-up of the patients who reached sustained virologic response and re-treatment of the patients with therapy failure. This Position Paper represents a guide for the assessment and the therapy of HCV infection. The recommendations are in concordance with other guidelines but are applied to real-life conditions in Romania.

Sofosbuvir, velpatasvir and voxilaprevir combination for the treatment of hepatitis C

ABSTRACTIntroduction: The advent of direct-acting antiviral (DAA) treatments for chronic hepatitis C virus (HCV) infection has dramatically increased rates of cure. However, there remain difficult-to-treat populations, including patients with genotype 3 infection and cirrhosis, and limited salvage treatment options for those that have failed first-line DAA therapy.Areas covered: This is a review of the preclinical and clinical development of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX), an interferon-free, oral, once daily, pangenotypic treatment for chronic HCV infection. All relevant literature from 2015 through June of 2017 is included.Expert commentary: Voxilaprevir, a second-generation HCV protease inhibitor, in combination with the already approved combination of sofosbuvir and velpatasvir, was evaluated in the POLARIS trials and found to be a safe and effective regimen. Patients with prior DAA treatment failure, genotype 3, cirrhosis and/or unfavorable resistance profiles all achieved cure rates of 96% or greater. The most distinctive role for this potent regimen may prove to be as a salvage regimen for patients who have failed previous DAA therapy.

Chronic Hepatitis C Treatment in Patients with Drug Injection History: Findings of the INTEGRATE Prospective, Observational Study.

IntroductionPeople who inject drugs represent an under-treated chronic hepatitis C virus (HCV)-infected patient population.MethodsINTEGRATE was a prospective, observational study investigating the effectiveness, safety, and adherence in routine clinical practice to telaprevir in combination with peg-interferon and ribavirin (Peg-IFN/RBV) in patients with history of injecting drug use chronically infected with genotype 1 HCV.ResultsA total of 46 patients were enrolled and included in the intent-to-treat (ITT) population. Among heroin and/or cocaine users (n = 37; 80%), 22% reported use in the past month; 74% (34/46) of patients were on opioid substitution therapy in the pre-treatment phase, and 43% (20/46) discontinued HCV treatment prematurely. Sustained virologic response rate was 54% (25/46) in the ITT population and 74% (25/34) in the per protocol (evaluable-for-effectiveness) population. The main reason for failure in the ITT analysis was loss to follow-up (n = 8; 17%). Adverse events occurred in 91% (42/46) of patients. Mean patient-reported adherence to study drugs was >89% at Week 4, Week 12 and end of treatment.ConclusionDespite a high rate of treatment discontinuation (including loss to follow-up), self-reported adherence to treatment was good and virologic cure rates were similar to those reported in large real-world cohorts. Our findings suggest that people with a history of injecting drug use should be considered for treatment of chronic HCV infection, and highlight the need for improvements in patient support to boost retention in care and, in turn, help to prevent reinfection and transmission.Clinical trial registrationClinicaltrials.gov identifier, NCT01980290.FundingJanssen Pharmaceuticals.