Pangenotypic Regimen Research Articles

Efficacy and safety of glecaprevir/pibrentasvir in patients with chronic hepatitis C virus genotype 5 or 6 infection (ENDURANCE-5,6): an open-label, multicentre, phase 3b trial

The pangenotypic direct-acting antiviral regimen of glecaprevir coformulated with pibrentasvir is approved to treat chronic hepatitis C virus (HCV) genotype 1-6 infection in adults. In registrational studies, 84 (99%) of 85 patients with HCV genotype 5 or 6 infection achieved a sustained virological response (SVR) with glecaprevir/pibrentasvir, with no virological failures. To increase the body of data for these less prevalent genotypes, ENDURANCE-5,6 evaluated the efficacy and safety of glecaprevir/pibrentasvir exclusively in patients infected with HCV genotype 5 or 6. ENDURANCE-5,6 was a phase 3b, single-arm, open-label, multicentre trial done in 24 hospitals or clinics in Europe, Oceania, North America, South Africa, and southeast Asia. Adults with chronic HCV genotype 5 or 6 infection who were previously untreated or treatment-experienced were eligible to be enrolled. Glecaprevir/pibrentasvir (300 mg/120 mg) was given orally once daily for 8 weeks (for patients without cirrhosis) or 12 weeks (for patients with compensated cirrhosis). The primary efficacy endpoint was SVR12 (ie, HCV RNA <15 IU/mL at 12 weeks post-treatment), assessed within each HCV genotype, and analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT02966795. Between Feb 9, 2017, and Aug 28, 2018, 84 patients were enrolled: 23 with genotype 5 infection and 61 with genotype 6 infection. Overall, 82 (97·6%, 95% CI 94·4-100·0) of the 84 patients achieved SVR12. 22 (95·7%, 95% CI 87·3-100·0) of 23 patients with genotype 5 infection achieved SVR12, as did 60 (98·4%, CI 95·2-100·0) of 61 with genotype 6 infection. One patient with an HCV genotype 6f infection and cirrhosis had on-treatment virological failure at treatment week 12, and one patient with HCV genotype 5a without cirrhosis who had achieved SVR at post-treatment week 4 relapsed at post-treatment week 12. Five (6%) patients had serious adverse events, none of which were deemed related to glecaprevir/pibrentsavir or led to discontinuation. Fatigue (11 [13%] patients) and headache (11 [13%]) were the only adverse events that occurred in 10% or more of patients. No post-baseline grade 3 or higher increases in aminotransferase concentrations were reported. Glecaprevir/pibrentasvir achieved high SVR12 rates, comparable with data reported in registrational studies, and was well tolerated in patients with HCV genotype 5 or 6 infection with compensated liver disease. AbbVie.

Profile of the VERSANT HCV genotype 2.0 assay

ABSTRACTIntroduction: Hepatitis C virus (HCV) is divided into 7 genotypes and 67 subtypes. HCV genotype studies reflect the viral transmission patterns as well as human migration routes. In a clinical setting, HCV genotype is a baseline predictor for the sustained virological response (SVR) in chronic hepatitis C patients treated with peginterferon or some direct acting antivirals (DAAs). The Versant HCV genotype 2.0 assay has been globally used for HCV genotyping over a decade.Areas covered: The assay is based on reverse hybridization principle. It is evolved from its former versions, and the accuracy and successful genotyping/subtyping rate are substantially improved. It shows an accuracy of 99–100% for genotypes 1–6. It can also reliably identify subtypes 1a and 1b. However, the assay does not allow a high resolution for many other subtypes. Reasons for indeterminate or inaccurate genotyping/subtyping results are discussed.Expert commentary: Genotyping helps to find the most efficacious and cost-effective treatment regimen. The rapid development of anti-HCV treatment regimens, however, is greatly simplifying laboratory tests. In the near future, the need for HCV genotyping and frequent serial on-treatment HCV RNA tests will decrease along with the wide use of the more potent and pan-genotypic DAA regimens.

The comprehensive outcomes of hepatitis C virus infection: A multi-faceted chronic disease.

Treatment of hepatitis C virus (HCV) infection has been revolutionized with the introduction of pangenotypic, interferon- and ribavirin-free regimens associated with high cure rates and a low side effect profile. Additionally, there is evidence that HCV cure reduces HCV complications, improves patient-reported outcomes and is cost-saving in most western countries in the long term. This is a review of the comprehensive burden of HCV and the value of eliminating HCV infection. With the introduction of the interferon-free all-oral, once a day pill treatment regimen for the cure of HCV, the potential to eliminate HCV by 2030 has become a possibility for some regions of the world. Nevertheless, there are barriers to screening, linkage to care, and treatment in many countries that must be overcome in order to reach this goal. In conclusion, globally, work must continue to ensure national policies are in place to support screening, linkage to care and affordable treatment in order to eliminate HCV.

Review article: novel antivirals for hepatitis C-sofosbuvir/velpatasvir/voxilaprevir, glecaprevir/pibrentasvir.

In 2017, the hepatitis C treatment regimens sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) and glecaprevir/pibrentasvir (G/P) received approval from the U.S. Food and Drug Administration. Although both SOF/VEL/VOX (NS5B polymerase inhibitor/NS5A inhibitor/NS3/4A protease inhibitor) and G/P (NS3/4A protease inhibitor/NS5A inhibitor) are pangenotypic regimens, they are indicated for distinct subsets of patients with hepatitis C. To compare and contrast available safety and efficacy data for SOF/VEL/VOX and G/P and outline their clinical utility. For each of the regimens, this review outlines the indications, safety information, and the major clinical studies in which SOF/VEL/VOX and G/P were evaluated. SOF/VEL/VOX is positioned as a salvage regimen for patients previously treated with NS5A inhibitors and for genotype 1a- and 3-infected patients who had failed other sofosbuvir-containing regimens. G/P is the first pangenotypic regimen with an 8-week duration for treatment-naïve, non-cirrhotic patients, and it is indicated for patients with any genotype who have advanced kidney disease, including those on dialysis. The addition of SOF/VEL/VOX and G/P to existing hepatitis C treatment options will expand the number of patients who are eligible for and responsive to treatment, thus increasing the possibility of eliminating hepatitis C as a public health issue.

Cost Effectiveness of Universal Screening for Hepatitis C Virus Infection in the Era of Direct-Acting, Pangenotypic Treatment Regimens

Most persons infected with hepatitis C virus (HCV) in the United States were born from 1945 through 1965; testing is recommended for this cohort. However, HCV incidence is increasing among younger persons in many parts of the country and treatment is recommended for all adults with HCV infection. We aimed to estimate the cost effectiveness of universal 1-time screening for HCV infection in all adults living in the United States and to determine the prevalence of HCV antibody above which HCV testing is cost effective. We developed a Markov state transition model to estimate the effects of universal 1-time screening of adults 18 years or older in the United States, compared with the current guideline-based strategy of screening adults born from 1945 through 1965. We compared potential outcomes of 1-time universal screening of adults or birth cohort screening followed by antiviral treatment of those with HCV infection vs no screening. We measured effectiveness with quality-adjusted life-years (QALY), and costs with 2017 US dollars. Based on our model, universal 1-time screening of US residents with a general population prevalence of HCV antibody greater than 0.07% cost less than $50,000/QALY compared with a strategy of no screening. Compared with 1-time birth cohort screening, universal 1-time screening and treatment cost $11,378/QALY gained. Universal screening was cost effective compared with birth cohort screening when the prevalence of HCV antibody positivity was greater than 0.07% among adults not in the cohort born from 1945 through1965. Using a Markov state transition model, we found a strategy of universal 1-time screening for chronic HCV infection to be cost effective compared with either no screening or birth cohort-based screening alone.

Hepatitis C Management Simplification From Test to Cure: A Framework for Primary Care Providers

This article proposes a strategy for primary care providers to begin treating patients with hepatitis C virus (HCV). We are motivated by the need to expand HCV treatment and by developments that have simplified treatment for most patients. This article presents 5 steps to achieving quality HCV treatment in the primary care setting: (1) accurate diagnosis via reflex testing; (2) risk stratification and identifying comorbidities via pretreatment evaluation; (3) simple, once-daily, pan-genotypic HCV treatment regimens; (4) minimized on-treatment monitoring: and (5) posttreatment monitoring and high-quality care for comorbidities such as cirrhosis and injection drug use. We provide indications for referral to specialists: notably children, patients with genotype 3 and cirrhosis, advanced liver or kidney disease, previous treatment failures, drug interactions with recommended regimens, and hepatitis B co-infection. Finally, potential barriers for providers are discussed, as well as further research findings and policy interventions that can promote HCV treatment in the primary care setting. We believe that a substantial portion of patients with HCV can be treated safely and effectively by nonspecialists and that the engagement of primary care providers is critical to efforts to end the HCV epidemic.

Glecaprevir + pibrentasvir (ABT493 + ABT-530) for the treatment of Hepatitis C

ABSTRACTIntroduction: Glecaprevir (formerly ABT-493, pangenotypic NS3/4A protease inhibitor) and pibrentasvir (formerly ABT-530, pangenotypic NS5A inhibitor) are second generation direct acting antivirals (DAA) for the treatment of chronic Hepatitis C (HCV). It is a fixed dose ribavirin (RBV)-free regimen with activity against genotypes (GT) 1–6. In vitro the two antivirals have synergistic activity with a high barrier to resistance and potent activity against common polymorphisms. It is once daily oral dosing with minimal absorption, primary biliary excretion, and negligible renal excretion, making it safe for patients with renal impairment. This regimen is being reviewed because it is the first pangenotypic regimen suitable for those with renal impairment and prior DAA failure.Areas covered: The key phase 2 and 3 trials which investigated the efficacy and safety of glecaprevir/pibrentasvir are reviewed by methodology, primary end point, baseline demographic data, response rates, and adverse events. Literature search methodology involved reviewing key abstracts presented at the American Association for the Study of Liver Disease and European Association for the Study of Liver.Expert commentary: The advantages and limitations of glecaprevir/pibrentasvir will be reviewed in comparison to its competitor drug on the market.

Sofosbuvir and velpatasvir with or without voxilaprevir in direct-acting antiviral-naïve chronic hepatitis C: patient-reported outcomes from POLARIS 2 and 3.

Chronic hepatitis C infection leads to impairment of patient-reported outcomes (PROs). Treatment with direct-acting antiviral regimens results in short- and long-term improvement of these outcomes. To assess PROs in patients treated with a newly developed direct-acting antiviral, a fixed-dose combination of sofosbuvir/velpatasvir (SOF/VEL) with/without voxilaprevir (VOX). The PRO data were collected from participants of POLARIS-2 and POLARIS-3 clinical trials (DAA-naïve, all HCV genotypes). Participants self-administered SF-36v2, FACIT-F, CLDQ-HCV and WPAI:SHP instruments at baseline, during treatment, and in follow-up. Of 1160 patients, 611 received SOF/VEL/VOX and 549 received SOF/VEL (52.8±11.0years, 55.9% male, 75.4% treatment-naïve, 33.9% cirrhotic). The sustained viral response at 12 weeks (SVR12) rates were 95%-98%. During treatment, improvements in most PRO scores were significant (all but one P<.01) and ranged from, on average, +2.3 to +15.0 points (on a 0-100 scale) by the end of treatment. These improvements were similar between SOF/VEL/VOX and SOF/VEL arms (all P>.05). After treatment discontinuation, patients treated with both regimens achieved significant and clinically meaningful PRO gains (+2.7 to +16.7 by post-treatment week 12, +3.9 to +20.1 by post-treatment week 24; all but one P<.001). Multivariate analysis showed that depression, anxiety and cirrhosis were the most consistent independent predictors of PRO impairment while no association of PROs with the treatment regimen choice was found (all P>.05). The pan-genotypic regimens with SOF/VEL with or without VOX not only have excellent efficacy and safety, but also significantly positively impact patients' experience both during treatment and after achieving sustained virologic response in DAA-naïve patients with HCV.

Patient-Reported Outcomes Following Treatment of Chronic Hepatitis C Virus Infection With Sofosbuvir and Velpatasvir, With or Without Voxilaprevir

Chronic infection with hepatitis C virus (HCV) has many hepatic and extrahepatic manifestations, measured by patient-reported outcomes (PROs). We measured changes in PROs during HCV treatment with recently developed pangenotypic regimens and from a sustained virologic response 12 weeks after treatment ended (SVR12). We collected PRO data from 2 multi-center, blinded, international phase 3 trials of sofosbuvir, velpatasvir, and voxilaprevir, from 748 patients previously treated with direct-acting antivirals for chronic infection with HCV of any genotype (59% HCV genotype 1, 43% with compensated cirrhosis) (POLARIS-1 and POLARIS-4). The combination of sofosbuvir, velpatasvir, and voxilaprevir was given to 445 patients, the combination of sofosbuvir and velpatasvir to 151 patients, and placebo to 152 patients. Patients completed the SF-36, FACIT-F, CLDQ-HCV, and WPAI:SHP questionnaires at baseline, during treatment, and during the follow-up period. There was no difference in baseline clinical or demographic features or PRO scores among the groups (all P > .05). The group that received the combination of sofosbuvir, velpatasvir, and voxilaprevir had more gastrointestinal symptoms than the groups that received sofosbuvir and velpatasvir or placebo (P = .0001). An SVR12 was achieved by 90.1% of patients who received sofosbuvir and velpatasvir vs 96.9% of patients who received sofosbuvir, velpatasvir, and voxilaprevir (P=.0008). After 12 weeks of treatment, some PRO scores improved in both treatment groups (by 2.5 or by 9.1 points, on a 0-100 scale; P < .05) but not in the placebo group. All increases in PRO scores were sustained or increased after treatment ended (an increase of up to 11.1 points at 12 weeks after treatment and an increase of up to 16.6 points at 24 weeks after treatment ended) (P < .05 for all but 2 PROs). There were no differences in PROs between the sofosbuvir and velpatasvir group vs the sofosbuvir, velpatasvir, and voxilaprevir group (all P > .05). In multivariate analysis, after adjustment for clinical and demographic factors and baseline PRO scores, receiving treatment was associated with higher PROs scores than receiving placebo (beta as high as 5.1) (P < .05). In an analysis of data from 2 phase 3 clinical trials of patients with chronic HCV infection of any genotype, we found the combination of sofosbuvir, velpatasvir, with or without voxilaprevir, to increase PRO scores compared with placebo. These findings indicate the comprehensive benefit of these regimens during treatment and after SVR.

Integrated Efficacy and Safety of Glecaprevir/Pibrentasvir in Patients Taking Concomitant Proton Pump Inhibitors: 2017 Presidential Poster Award

Introduction: Proton pump inhibitors (PPIs) are commonly used medications in both the general population and hepatitis C virus (HCV)-infected patients. Co-administration of PPIs is not recommended with some direct-acting antivirals (DAAs) as PPIs may compromise their efficacy. We assessed the efficacy and safety of the pangenotypic DAA combination regimen of glecaprevir (NS3/4A protease inhibitor developed by AbbVie and Enanta) and pibrentasvir (NS5A inhibitor) in patients receiving concomitant PPIs at baseline in nine phase 2 and 3 studies. Methods: Data were pooled from the SURVEYOR-I and -II and MAGELLAN-1 and ENDUR-ANCE-1, -2, -3, and -4, and EXPEDITION-1 and -4 studies. Patients in the analysis had chronic HCV infection (all genotypes; GT1-6) and received glecaprevir/pibrentasvir (G/P) for 8, 12, or 16 weeks. Patients without decompensated cirrhosis were either treatment-naïve or treatment-experienced (DAA NS5A and/or PI failures were enrolled in the MAGELLAN-1 study; all other studies enrolled patients experienced with prior treatment with interferon/peginterferon ± ribavirin or sofosbuvir + ribavirin ± interferon/peginterferon). Efficacy was evaluated as the rate of sustained virologic response (HCV RNA < lower limit of quantification) at 12 weeks post-treatment (SVR12). Safety was assessed in all patients. Results: In total, 2369 chronic HCV patients were included in the analysis. Table 1 lists key baseline patient characteristics. In the intent-to-treat (ITT) population, 2307/2369 (97%) achieved SVR12. The SVR12 rate was not impacted by concomitant PPI use (SVR12: 97% with concomitant PPI use versus 97% without concomitant PPI use). Figure 1 shows SVR12 rates by concomitant PPI use as well as by HCV genotype for all patients. G/P was well-tolerated, with few serious adverse events (SAEs; 3.1%), discontinuations due to AEs (0.5%), and grade ≥3 adverse events (3.8%).Figure: Efficacy of G/P in patients with and without concomitant PPI use.Table: Table. Baseline CharacteristicsConclusion: Results from this integrated analysis demonstrate that G/P is highly efficacious in HCV GT1-6-infected patients receiving concomitant PPIs regardless of other baseline patient or viral characteristics. Overall, the safety profile of G/P was favorable in both non-cirrhotic and compensated cirrhotic patients.

Efficacy and safety of glecaprevir/pibrentasvir in Japanese patients with chronic genotype 1 hepatitis C virus infection with and without cirrhosis

BackgroundThe once-daily, all oral, RBV-free, pangenotypic direct-acting anti-viral regimen consisting of co-formulated NS3/4A protease inhibitor glecaprevir and NS5A inhibitor pibrentasvir (G/P), demonstrated high rates of sustained virologic response (SVR) in phase 2 and 3 studies outside Japan.MethodsCERTAIN-1 is a phase 3, open-label, multicenter study assessing the safety and efficacy of G/P (300/120 mg) once daily in Japanese patients with chronic HCV GT1 infection. Patients without cirrhosis received 8 weeks of G/P or 12 weeks of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r, 25/150/100 mg); patients with cirrhosis received G/P for 12 weeks. The primary efficacy endpoint was non-inferiority of G/P compared to OBV/PTV/r by assessing SVR at post-treatment week 12 (SVR12) among non-cirrhotic patients without the NS5A Y93H polymorphism.ResultsSVR12 was achieved by 128/129 (99.2%; one patient lost to follow-up) non-cirrhotic patients in the 8-week G/P Arm (including 23/23 patients with the NS5A Y93H polymorphism) and 52/52 (100%) patients in the 12-week OBV/PTV/r Arm. No patients from the G/P Arm prematurely discontinued the study drug or experienced a treatment-emergent serious adverse event (TESAE). Three patients from the OBV/PTV/r Arm experienced five TESAEs and one of these patients discontinued the study drug due to TESAEs. All 38 (100%) patients with compensated cirrhosis achieved SVR12; in this group, no TESAEs were reported and one patient discontinued treatment due to an AE.ConclusionsCERTAIN-1 study results demonstrate high efficacy and favorable tolerability of G/P in GT1-infected Japanese patients including those with the NS5A Y93H polymorphism, with no virologic failures observed.

Treatment of hepatitis C virus in advanced renal disease.

Treatment of hepatitis C virus in advanced renal disease.

Natural NS5A inhibitor resistance associated substitutions in hepatitis C virus genotype 1 infected patients from Italy

ObjectivesGenetic variability in NS5A is associated with different levels of resistance to the currently licensed NS5A inhibitors. The aim of this study was to detect NS5A inhibitor resistance associated substitutions (RASs) in hepatitis C virus (HCV) genotype 1 (GT1) patients who are naive to direct-acting HCV antivirals. MethodsAmplification, Sanger sequencing and phylogenetic analysis of the HCV NS5A region were performed on plasma obtained from 122 consecutive patients with HCV chronic infection attending four different clinics in Italy. ResultsNS5A inhibitor RASs were detected in 14/61 (23.0%) HCV GT1b and 3/61 (4.9%) HCV GT1a infected patients (p 0.007). The pan-genotypic RAS Y93H was detected in 1 (1.6%) GT1a and 4 (6.6%) GT1b patients. GT1a sequences clustered into two different clades with RASs detected in 1/34 (2.9%) clade I and 2/27 (7.4%) clade II sequences. ConclusionsAlthough the impact of naturally occurring NS5A RASs might be limited with upcoming pan-genotypic treatment regimens, this information is still useful to map naturally occurring HCV variants in different geographic areas in the context of current HCV therapy.

Pangenotypic regimens and the next generation hepatitis C virus therapy.

Pangenotypic regimens and the next generation hepatitis C virus therapy.

Combination of sofosbuvir and daclatasvir in the treatment of genotype 3 chronic hepatitis C virus infection in patients on maintenance hemodialysis.

Chronic hepatitis C virus infection (HCV) has a negative impact on the long-term survival of recipients of kidney transplants. HCV should be treated in hemodialyzed patients before their enlistment for kidney transplantation in order to avoid the reactivation of virus after transplantation. Direct-acting antivirals represent the current standard of care in hemodialyzed patients with HCV genotypes 1 and 4; in patients with genotypes 2 or 3, the optimal regimen is yet to be established. Sofosbuvir (SOF) and daclatasvir (DCV) represent an antiviral pangenotypic regimen with favorable pharmacokinetics in hemodialyzed patients. We retrospectively evaluated safety and efficacy of the combination of SOF and DCV in the treatment of genotype 3a chronic HCV in six male patients (mean age of 39 years, range 25–53 years) with end-stage renal disease on maintenance hemodialysis; these patients were treated with a reduced dose of SOF (one half of a 400 mg tablet) and 60 mg of DCV once daily. The anticipated treatment duration was 12 weeks. Initial HCV RNA ranged from 120,000 to 11,000,000 IU/mL. Two of the six patients had compensated liver cirrhosis based on shear-wave elastography result. All of the patients completed a 12-week treatment. Viremia became negative on treatment and remained negative 12 weeks after the end of therapy in all the patients. All of them (6/6, 100%) achieved sustained virological response, including two with cirrhosis and two with HCV RNA >6,000,000 IU/mL. The treatment was well tolerated: none of the patients presented with a serious adverse event requiring hospital admission and none had anemia or any significant changes in blood count. One patient had a short period of diarrhea, which was resolved with antibiotic treatment. The combination of reduced-dose SOF and full-dose DCV, daily, was a safe and effective treatment in our group of hemodialyzed patients infected with HCV genotype 3.

Sofosbuvir and velpatasvir for the treatment of hepatitis C

ABSTRACTIntroduction: Direct acting antivirals are revolutionizing the treatment of chronic hepatitis C. Specifically, the combination therapy sofosbuvir and velpatasvir offers a pangenotypic regimen with high sustained viral response (SVR).Areas covered: Reviewed here are the clinical trials that led to the FDA approval of sofosbuvir and velpatasvir combination therapy, the adverse events during registration trials, and drug-drug interactions. Sofosbuvir and velpatasvir is a fixed dose regimen that is both interferon- and ribavirin-free. It is administered for 12 weeks as a once-a-day pill, covers all genotypes of hepatitis C, and achieves SVR >95% in non-cirrhotic patients and patients with compensated cirrhosis. Addition of ribavirin is recommended for patients with decompensated cirrhosis (CTP B or C). Baseline resistance-associated substitutions do not appear to impair ability to achieve SVR with an initial course of treatment.Expert commentary: Availability of this highly efficacious, well tolerated, all oral regimen formulated as a single pill, can potentially simplify hepatitis C treatment. Its utility as a pangenotypic regimen additionally limits resource utilization.

HCV Antiviral Therapy in Liver Transplant Candidates and Recipients With Renal Insufficiency.

Hepatitis C virus (HCV) remains the leading indication for liver transplant in much of the world and has traditionally been associated with diminished posttransplant survival due to recurrent HCV-related liver disease. This field has been dramatically changed by the advent of safe and effective direct-acting antiviral therapy, such that most patients can be cured in the pretransplant or posttransplant setting. In addition, there are now direct-acting antiviral regimens specifically approved for use in patients with severe renal insufficiency. However, patients with pre or posttransplant severe renal insufficiency remain more difficult to treat, due to mechanisms of drug metabolism in hepatic and renal failure, as well as posttransplant drug-drug interactions. Treatment options are even more restricted in non-1 HCV genotypes. Because renal insufficiency is common among patients with HCV, with decompensated cirrhosis, and in the posttransplant setting, this difficult scenario is relatively common. However, ongoing development of pangenotypic regimens with improved safety profiles, as well as additional data on dosing and safety among patients with severe renal insufficiency, will continue to expand options for cure even in these most difficult to treat patients.

Efficacy and safety outcomes of sofosbuvir-based treatment regimens for hepatitis C virus-infected patients with or without cirrhosis from phase III clinical trials.

BackgroundWith the appearance of oral direct-acting antivirals (DAAs), the field of hepatitis C virus (HCV) treatment has been dramatically changed. This evolution makes possible for all oral treatments to be available for the treatment of HCV-infected patients. The aims of this review were to report the efficacy and safety of sofosbuvir (SOF)-based regimens for the treatment of patients with chronic HCV infection and to provide our clinical perspectives on these regimens.MethodsA literature search of clinical studies published in PubMed and posted on ClinicalTrials.gov website was performed to identify studies evaluating the efficacy or safety of SOF-containing treatment regimens.ResultsA total of 23 clinical trials were examined in the review. The evaluated SOF-based regimens are as follows: SOF/daclatasvir (DCV) ± ribavirin (RBV), SOF/ledipasvir (LDV) ± RBV, SOF/simeprevir (SMV), SOF/velpatasvir (VEL) ± RBV, and SOF/RBV ± peginterferon (peg-IFN). These SOF-based regimens were at least effective and safe for HCV-infected patients with or without cirrhosis. The SOF/VEL ± RBV regimen, a pan-genotypic DAA regimen, was effective for the treatment of patients with HCV genotype 1, 2, 3, 4, 5, or 6 infection. The 24-week SOF/RBV regimen was as effective as the 12-week SOF/RBV/peg-IFN regimen. Patients with HCV genotype 3 infection could have benefits from the use of the 24-week SOF/RBV regimen. For cirrhotic patients with HCV genotype 3 infection, the 12-week SOF/RBV/peg-IFN regimen could be considered as an alternative treatment option when access to SOF-based regimens with other DAAs is limited. In the included studies, significant adverse events due to SOF-based regimens were not reported.ConclusionThe clinical trials suggest that SOF-based treatment regimens for HCV-infected patients with or without cirrhosis can be at least effective and safe patient-convenient medications. However, it is necessary to monitor HCV-infected patients, since rare adverse events, drug–drug interactions, and drug–disease interactions can occur in real clinical settings.

Recent advances in the treatment of hepatitis C in 2016

It has been rapidly developed in treatment of chronic hepatitis C from the past few years. Here we summarize the progress in chronic hepatitis C treatment in 2016. We introduce the pan-genotypic regimens with short-duration, the efficacy of DAA regimens in difficult-to-treat population, the influence on hepatocellular carcinoma, decompensation of liver cirrhosis, liver fibrosis and liver transplantation, the safety of DAA regimens in special population, information from real-world studies and data from China.

Chronic hepatitis C and chronic kidney disease: Advances, limitations and unchartered territories.

Over the past few years, treatment options for chronic hepatitis C virus (HCV) infection have evolved dramatically. The current approved interferon-free direct-acting antiviral (DAA) regimens have been shown to be safe and effective with sustained virologic response (SVR) rates of >90% in most patients. Unique issues yet remain such as the challenges in patients with impaired renal function or decompensated cirrhosis. Patients with stages 4-5 chronic kidney disease (CKD) have a higher prevalence of HCV infection compared with the general population. Chronic HCV in those on dialysis and in kidney transplant recipients is associated with higher morbidity and mortality than uninfected patients. The HCV-infected population is also at risk of developing extrahepatic manifestations associated with altered immune system function and chronic inflammation with cryoglobulinaemic vasculitis being the most common of these manifestations. Therefore, patients with CKD stages 4-5 have to be considered priority patients for HCV therapy. New antiviral therapies have the potential to improve outcomes in this vulnerable patient population, including those on haemodialysis. Recently published studies conducted in kidney transplant recipients have demonstrated successful outcomes. It is thus essential that we carefully select the most appropriate DAA regimen and the best time for treatment in the context of kidney transplantation or cryoglobulinaemic vasculitis. While sofosbuvir, the only approved nucleotide NS5B inhibitor, has been the backbone of most pangenotypic therapeutic regimens, it has a limitation in those with advanced kidney disease. The currently approved regimens for those with stage 4/5 CKD, while effective, have challenges in that they apply to genotype 1/4 and may require RBV for genotype 1a. Globally, genotype 3 is a common infection, and thus, this group with CKD presents a huge unmet need for effective therapies. As therapy of HCV in renal transplant recipients has been highly successful, it provides an opportunity to expand the use of HCV-infected organs in solid organ transplantation.