Treatment Of HCV Genotype Research Articles

Predictive Potential Of Il28b Gene In Hcv Patients, Resistant To Daclatasvir And Sofosbuvir In KPK Population.

Recently various combinations of direct acting antivirals (DAAs) have been tried successfully. The Sofosbuvir + Daclatasvir combination has been used with promising results. Recently, resistance has been noticed against DAAs. Therefore, polymorphism at particular sites in the interleukin 28B gene are under study to find possible association with resistance. This study was aimed at finding out any association of SNPs rs8099917 and rs12979860 (IL28B gene) with response and resistance to treatment in HCV genotype 3 patients in Khyber Pakhtunkhwa. This cross sectional, Analytical study was conducted at Gastroenterology/hepatology OPD of Prime Teaching Hospital, Peshawar Medical College. Collected Samples were stored at -20o C in PCR Lab of the College. DNA extraction and genotyping was carried out at BJ Molecular Biology Lab in Rawalpindi. Data was analyzed by using SPSS version 21. Chi-Square Test was used to see the statistically significant differences between rs8099917 T/G and rs12979860 T/C model. In the IL28-B gene, single nucleotide polymorphism at rs12979860 T/C model, we observed that there are 37.5% CC homozygous, 12.5% TT homozygous and 50% CT heterozygous genotypes in resistant patients and 42.85% CC homozygous, 28.57% TT and 28.57% CT genotype in responder group. In rs12979860 T/C model, genotype of IL28-B in the responder and resistant group significantly varies at p-value =0.00572. We conclude that in SNP at rs12979860, CC genotype is associated with clearance of HCV, while CT genotype was more prevalent in the resistant group and associated with chronicity.

Pangenotypic and Genotype-Specific Antivirals in the Treatment of HCV Genotype 4 Infected Patients with HCV Monoinfection and HIV/HCV Coinfection.

The introduction of the direct-acting antivirals (DAA) has substantially improved the effectiveness of the therapy in patients with chronic hepatitis C. We aimed to compare the efficacy of pangenotypic and genotype-specific DAA in the cohort of genotype (GT) four patients with HCV monoinfection and HIV coinfection. A total of 662 GT4-infected patients treated in 2015–2020—of whom 168 (25.3%) were coinfected with HIV, selected from the retrospective EpiTer-2 database—were enrolled in the analysis. Among HIV-coinfected patients, 54% (90) were treated with genotype-specific regimens and 46% (78) with pangenotypic options, while among HCV-monoinfected patients, the rates were 72% and 28%, respectively. Significantly higher rate of males (67.9% vs. 57.7%, p = 0.01), a lower rate of liver cirrhosis (10.2% vs. 18.1%, p = 0.02), and higher of treatment-naïve patients (87.5% vs. 76.7%, p = 0.003) were documented in the HIV coinfected population. The overall sustained virologic response after exclusion of non-virologic failures was achieved in 98% with no significant difference between HIV-positive and HIV-negative patients, 96.2% vs. 98.5%, respectively. While the genotype-specific regimens resulted in a similar cure rate regardless of the HIV status, the pangenotypic options were more efficacious in patients with HCV monoinfection (99.3% vs. 94.4%, p = 0.05). Hereby, we demonstrated the high effectiveness and good safety profile of the DAA therapy in the population of HCV GT4 infected patients with HIV coinfection supporting the current recommendations to treat HCV/HIV coinfected patients with the same options as those with HCV monoinfection.

Daclatasvir Plus Sofosbuvir With and Without Ribavirin for Previously Treated or Untreated Chronic HCV Infection Genotype 1, 2 and 4 in Togo

Background: Daclatasvir (DCV) is a potent, pangenotypic nonstructural protein 5A inhibitor with demonstrated antiviral efficacy when combined with sofosbuvir (SOF) with or without ribavirin (RBV) in patients with chronic hepatitis C virus (HCV) infection. We are using SOF-DCV combination for large scale treatment. Objectives: The aim of the current study was designed to investigate the efficacy and safety of sofosbuvir/daclatasvir, with or without ribavirin for previously treated or untreated in treatment of HCV genotype 1, 2 and 4, as well as their effect on the liver fibrosis. Methods: One hundred twenty-seven patients with chronic HCV infection were categorized into 2 groups. The group 1 comprised treatment naïve patients, with total serum bilirubin ≤ 1.2mg/10-1L, serum albumin ≥ 3,5g/10-1L, ALAT ≥ 3N, ASAT≤ 2N and platelets count 150 x 109 /L. The group 2 included Peg-INF-alpha or sofosbuvir treatment-experienced patients or patients having at least 2 of the following characteristics: total bilirubin ≤ 1.2mg/10-1L, serum albumin ≥ 3,5g/10-1L, ALAT ≥ 3N, ASAT ≤ 2N and platelets count 150 x 109 /L. The first group was treated with sofosbuvir/daclatasvir for 12 weeks except sofosbuvir treatment experienced patients, who were treated with sofosbuvir/daclatasvir + ribavirin for 24 weeks, with generic medications: DCV 60 mg plus SOF 400 mg ± ribavirin (RBV) within the treatment of hepatitis C virus infection. Efficacy and safety were assessed, and baseline factors associated with sustained virological response at post-treatment week 12 (SVR12) were explored. Results: Sustained virological response (SVR12), was 95,8% in group 1 and 93,8% in group 2. Such high efficacy was accompanied with tolerable adverse effects as well as with significant improvement in liver fibrosis. Conclusion: SOF plus DCV with or without ribavirin achieved high efficacy and safety in HCV genotypes 1,2 and 4 patients. Their effect was accompanied with attenuation of liver fibrosis. Further wider-scale studies are needed to evaluate the actual role of IL 18 polymorphism in treatment response with Sofosbuvir/Daclatasvir.

Outcomes of Treatment and Predictors of Response to Sofosbuvir Plus Simeprevir in Hepatitis C Virus with Genotype-4 Infection.

Treatment plan of chronic HCV infection has dramatically improved after the introduction of different groups of Direct-Acting Antiviral (DAA) drugs. These drugs have been found to be safe and effective. Sofosbuvir (SOF) plus simeprevir (SMV) regimen has been shown to be tolerable and effective in treatment of patients with HCV genotype 1. The aim of the study was to evaluate the safety and the efficacy of combined sofosbuvir plus simeprevir treatment in genotype 4 chronic HCV patients. This open-label multicenter prospective study was carried out on 381 Egyptian patients with chronic hepatitis C virus- infection. Treatment experienced and treatment-naive patients were included. Subjects administrated a regimen of sofosbuvir (400 mg/ day) plus semiprevir (150 mg /day) for twelve weeks. Sustained Virological Response (SVR) was confirmed by undetectable HCV RNA by quantitative PCR 3 months after the end of the treatment. 97.6% (372 /381) of patients had SVR. None of the studied clinical and demographic characteristics were associated with the SVR status. However, patients who failed to achieve SVR showed low albumin level and high total leucocyte. The most common side effects of the studied regimen were headache, fatigue, itching, photosensitivity, and cough. Twelve weeks' regimen of sofosbuvir plus simeprevir was considered to be safe and tolerable in the treatment of HCV genotype 4; also it was associated with high SVR (97.6%).

Hepatocellular carcinoma occurs frequently and early after treatment in HCV genotype 3 infected persons treated with DAA regimens

BackgroundThere are conflicting data regarding the risk of hepatocellular carcinoma (HCC) after direct-acting antiviral agent (DAA) treatment. Risk of HCC in HCV genotype-3 infected persons after DAA therapy is not well known.MethodsWe prospectively studied HCV infected persons initiated on a DAA regimen between October 2014 and March 2017 at two centers in Pakistan. All persons were free of HCC at study initiation. HCC was confirmed based on characteristic CT scan findings. Patients were followed for 12 months after the completion of therapy.ResultsA total of 662 persons initiated treatment. Median age (IQR) was 50 (41, 57) years and 48.8% were male. At baseline, 49.4% were cirrhotic, 91% were genotype 3 and 91.9% attained SVR. Treatment regimens used were: Sofosbuvir (SOF)/ribavirin (RBV)/pegylated interferon (PEG-IFN), 25.2%; SOF/RBV, 62.4%; SOF/RBV/daclatasavir (DCV), 10.6%; SOF/DCV, 2.0%. Incident HCC was detected in 42 patients (12.8%) in the 12-month period after treatment completion and was exclusively observed in those with cirrhosis. In multivariable Cox regression analysis, SVR was associated with a reduction in HCC risk (HR, 95% CI: 0.35, 0.14,0.85). In Kaplan-Meier plots by treatment regimen, those treated with SOF/RBV, SOF/RBV/DCV, or SOF/DCV regimens had a shorter HCC-free survival compared with those treated with a SOF/RBV/PEG-IFN regimen.ConclusionIn a predominantly genotype 3 cohort, incident HCC occurred frequently and early after treatment completion, and exclusively in those with pre-treatment cirrhosis. SVR reduced the risk of HCC. Treating HCV infected persons before development of cirrhosis may reduce risk of HCC.

Corrigendum.

Journal of Medical VirologyVolume 92, Issue 8 p. 1369-1369 CORRIGENDUMFree Access Corrigendum This article corrects the following: The efficacy and safety of elbasvir/grazoprevir treatment in HCV genotype 1 patients in Taiwan Tzu-Cheng Tsai, Shin-Tarng Deng, Chao-Wei Hsu, Volume 92Issue 2Journal of Medical Virology pages: 219-226 First Published online: October 22, 2019 First published: 12 February 2020 https://doi.org/10.1002/jmv.25687AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat The efficacy and safety of elbasvir/grazoprevir treatment in HCV genotype 1 patients in Taiwan Tzu-Cheng Tsai, Shin-Tarng Deng, Chao-Wei Hsu The article to which this Corrigendum refers was published in Journal of Medical Virology 92(2): 219-226 (https://doi.org/10.1002/jmv.25605). The corrigendum corrects the institute title "Department of Long Term Care, Hsin Sheng College of Medical Care and Management" to "Hsin Sheng Junior College of Medical Care and Management." Authors apologize for the error. REFERENCE Tsai T-C, Deng S-T, Hsu C-W. The efficacy and safety of elbasvir/grazoprevir treatment in HCV genotype 1 patients in Taiwan. J Med Virol. 2020; 92: 219- 226. https://doi.org/10.1002/jmv.25605 Volume92, Issue8August 2020Pages 1369-1369 ReferencesRelatedInformation

Real life application of FIB-4 & APRI during mass treatment of HCV genotype 4 with directly acting anti-viral agents in Egyptian patients, an observational study

ABSTRACTBackground: Non-invasive prediction of significant liver fibrosis and gastro-esophageal varices during mass treatment for HCV is crucial.The aim is to validate the accuracy of FIB-4 & APRI for predicting significant fibrosis in chronic HCV patients during mass treatment with directly acting anti-viral agents (DAAs) & their validity for predicting varices.Methods: We did a search in a database of 21,617 patients with chronic HCV infection recruited to one of the national HCV treatment centers to find out those with fibrosis assessment by recent liver biopsies &/or liver stiffness to serve as a gold standard. The diagnostic accuracy of FIB-4 and APRI values were assessed against the gold standard. Demographics and relevant laboratory data of 3144 patients (14.5%) were retrieved.Results: Significant fibrosis (F3-F4) was detected in 1585 (50.4%). AUROCs for detecting significant fibrosis (F3-F4) were 0.76 (0.75–0.78) for FIB-4 and 0.72 (0.72–0.75) for APRI. To diagnose liver cirrhosis, AUROCs were higher; 0.82 (0.80–0.83) for FIB-4 and 0.78 (0.76–0.79) for APRI, p < 0.001. Prediction of gastro-oesophageal varices; AUROC for FIB-4 and APRI, were 0.65 and 0.62 respectively.Conclusion: FIB-4 and APRI are reliable methods in predicting cirrhosis during mass HCV treatment. Their role in predicting gastro-oesophageal varices is less remarkable.

A Phase III Study to Evaluate Efficacy and Safety of TG-2349 in Combination With DAG181 and Ribavirin for 12 Weeks of Treatment in HCV Genotype I Infected Patients

A Phase III Study to Evaluate Efficacy and Safety of TG-2349 in Combination With DAG181 and Ribavirin for 12 Weeks of Treatment in HCV Genotype I Infected Patients

304. Hepatocellular Carcinoma Occurs Frequently and Early After Treatment in HCV Genotype 3 Infected Persons Treated with DAA Regimens

BackgroundTreatment of HCV with directly acting antiviral agents (DAAs) is associated with a significant reduction in cardiovascular, metabolic and cancer risk. However, there are conflicting data regarding the risk of hepatocellular carcinoma (HCC) after DAA treatment. Risk of HCC in HCV genotype 3 infected persons after DAA therapy is not well known.MethodsWe prospectively studied HCV-infected persons initiated on treatment between October 2014 and March 2017 at two centers in Pakistan. All persons were free of HCC at study initiation. The occurrence of HCC was confirmed based on radiologic findings on a triphasic CT on 64 slice MDCT scanner. The treatment regimen was at the discretion of clinical care providers, taking into account the national guidelines and patient preferences. Patients were followed for 24 weeks after the completion of therapy. Informed consent was obtained from all participants.ResultsA total of 662 persons were initiated on treatment. Median age (IQR) was 50 (41, 57) years and 48.8% were male. At baseline, 49.4% were cirrhotic with 90% of cirrhotics having compensated cirrhosis. 91% were genotype 3 and SVR was attained in 91.9%. Treatment regimens used were: Sofosbuvir (SOF)/ribavirin (RBV)/pegylated interferon (PEG-IFN), 25.2%; SOF/RBV, 62.4%; SOF/RBV/daclatasavir (DCL), 10.6%; SOF/DCL, 2.0%. Incident HCC was detected in 42 patients (12.8%) in the six month period after treatment completion, and was exclusively observed in those with cirrhosis. In multivariable Cox regression analysis, SVR was associated with a reduction in HCC risk (HR, 95% CI: 0.35, 0.14,0.85) while SOF/RBV/DCL regimen (compared with SOF/RBV/PEG-IFN) was associated with an increased risk of HCC (HR, 95% CI: 17.32, 2.14,140.36). In K-M plots by treatment regimen, those treated with SOF/RBV, SOF/RBV/DCL, or SOF/DCL regimens had shorter HCC-free survival compared with those treated with a SOF/RBV/PEG-IFN regimen. (See figure)ConclusionIn a predominantly genotype 3 cohort, incident HCC occurs commonly and early after treatment completion, and exclusively in those with pretreatment cirrhosis. SVR reduces but does not completely eliminate the risk of HCC. Treating HCV-infected persons before the development of cirrhosis may reduce future risk of HCC. Disclosures All authors: No reported disclosures.

956 – Safety and Efficacy of Glecaprevir/Pibrentasvir for the Treatment of Hcv Genotype 1-6: Results of the Hcv-Target Study

956 – Safety and Efficacy of Glecaprevir/Pibrentasvir for the Treatment of Hcv Genotype 1-6: Results of the Hcv-Target Study

THU-181-Safety and efficacy of glecaprevir/pibrentasvir for the treatment of HCV genotype 1-6: Results of the HCV-TARGET study

THU-181-Safety and efficacy of glecaprevir/pibrentasvir for the treatment of HCV genotype 1-6: Results of the HCV-TARGET study

Utilization of elbasvir/grazoprevir (EBR/GZR) and adoption of resistance associated substitutions (RAS) testing in real-world treatment of HCV genotype 1 (GT1) infection: results from the German Hepatitis C Registry (DHC-R)

Utilization of elbasvir/grazoprevir (EBR/GZR) and adoption of resistance associated substitutions (RAS) testing in real-world treatment of HCV genotype 1 (GT1) infection: results from the German Hepatitis C Registry (DHC-R)

Efficacy of an 8-week course of sofosbuvir and ledipasvir for the treatment of HCV infection in selected HIV-infected patients.

Background: With the availability of direct acting antiviral treatment for hepatitis C (HCV), HIV and HCV co-infected patients show comparable treatment responses to HCV-monoinfected patients. An 8-week course of sofosbuvir/ledipasvir (SOF/LDV) is highly effective for the treatment of HCV genotype 1 infection in treatment-naïve mono-infected patients with HCV viral loads <6 million IU/ml. There is limited data on the efficacy of this 8-week HCV treatment regimen in HIV-infected individuals with similar viral loads. Methods: The study was a retrospective review of HIV-infected adults coinfected with HCV genotype 1 for whom an 8-week course of SOF/LDV was prescribed by providers at two clinics in the Yale-New Haven health system from November 1, 2014 until April 30, 2016. Treatment efficacy was assessed as the proportion of treatment initiators who achieved a sustained virologic response 12 weeks after completion of therapy (SVR 12). Results: Nineteen patients met study eligibility criteria and included 14 men (74%); and 12 African-Americans (63%). All patients were on antiretroviral therapy with fully suppressed HIV viral loads and were HCV treatment-naïve. All patients had pre-treatment HCV viral loads <6 million IU/mL. Eighteen patients (95%) completed HCV treatment. Overall, SVR 12 was 95%, with 1 treament failure occurring due to suboptimal adherence. Conclusion: Among our HIV-infected patient cohort with HCV genotype 1 infection, 95% of those treated with an 8 week course of SOF/LDV achieved SVR 12. This is comparable to the efficacy of the same treatment regimen in patients without HIV infection. This study lends proof of concept to the use of shorter course SOF/LDV treatment for HIV-HCV genotype 1 coinfected patients with viral loads <6 million IU/ml. Larger studies are indicated to validate our findings.

HCV core antigen as an alternate test to HCV RNA for assessment of virologic responses to all-oral, interferon-free treatment in HCV genotype 1 infected patients

In light of the advances in HCV therapy, simplification of diagnosis confirmation, pre- treatment diagnostic workup and treatment monitoring is required to ensure broad access to interferon-free therapies. HCV core antigen (HCV cAg) testing is rapid, giving results in approximately 60min, and less expensive than HCV RNA methods. While extensive data on the analytical performance of HCV cAg relative to RNA or comparisons in longitudinal studies of patients on interferon based (response guided) therapy there is very limited data on the relative performance of HCV cAg in diagnosis and monitoring patients receiving all-oral interferon free regimens. Furthermore, there is no data in the literature that describes the specificity of HCV cAg in patients with resolved HCV infection i.e. anti-HCV positive/HCV RNA negative. In this study a total of 1201 plasma samples from the 411 HCV genotype 1 subjects with a HCV RNA viral load >50,000IU/ml who enrolled in a clinical trial with ombitasvir, ritonavir-boosted paritaprevir and dasabuvir, with or without ribavirin were retrospectively tested in a blinded fashion with HCV cAg test and results were compared to HCV RNA levels. The specificity of the HCV cAg test was also evaluated in anti-HCV positive but HCV RNA negative samples. Overall concordance between HCV cAg and HCV RNA was 98.6% while concordance in pre-treatment samples was 99.5% (409/411; n=2 HCV RNA pos. with viral loads>3 Mill IU/ml but HCV cAg neg.) and 99.24% in post treatment week 12 samples (391/394; n=2 HCV RNA pos.<25IU/ml and n=1 HCV RNA pos. 2180IU/ml). Specificity in anti-HCV positive HCV RNA negative samples tested was 100%.

Effect of Obesity on Disease Progression and Response to Antiviral Treatment in HCV Genotype 4 Patients

Effect of Obesity on Disease Progression and Response to Antiviral Treatment in HCV Genotype 4 Patients

Dasabuvir (ABT333) for the treatment of chronic HCV genotype I: a new face of cure, an expert review

ABSTRACTHepatitis C virus (HCV) affects nearly 1.3% of US population and around 2% of people worldwide. It is associated with serious complication of Cirrhosis and Hepatocellular carcinoma leading to significant morbidity and mortality. Until now the only treatment option for this serious disease was interferon based therapy which had poor tolerance and at best SVR (Sustained virological response) in only 50% of cases. With the introduction of other direct – acting antiviral agents the treatment of HCV has been revolutionized with significantly high rates of cure. Among novel Direct acting antivirals are non-nucleoside inhibitor NS5B which is highly effective in treatment of HCV genotype 1 a and 1b including those with compensated cirrhosis achieving high cure rates with SVR more than 97 % in pooled analysis from six different phase 3 trials. This review will discuss the DAA – Dasabuvir, a non – nucleoside NS5B inhibitor, its mechanism of action, efficacy, safety & tolerance, and drug resistance. Dasabuvir is approved by FDA in combination with other DAA agents called as the 3D(Viekira Pak) in various interferon free regimens achieving high cure rates (SVR >95%) with low adverse effects. In Europe, it is approved by European medicines agency for use in combination with Ombitasvir, Paritaprevir, and ritonavir with or without ribavirin. The drug is used in treatment naive as well as previously treated patient with high success rates. It is also approved in patients with compensated cirrhosis, patients with HIV co-infection and liver transplant recipients which were in the past were excluded from treatment with interferon based therapy. Dasabuvir is extensively evaluated in large clinical trials and shown excellent SVR among HCV genotype1 patient population in combination with other oral DAAs, with good safety profile and tolerance. Its drawback is its genotype restriction, need for ribavirin (RBV) for 1a genotype, low resistance barrier and high cost. It is well tolerated with less than 1 % of patients permanently discontinuing treatment and 2% of patient experiencing a serious adverse reaction. It is contraindicated in patients with known hypersensitivity to ritonavir (e.g. Steven – Johnson syndrome) and strong inducers of CYP3A and CYP2CB.

Daclatasvir plus Sofosbuvir with or without Ribavirin in patients infected with HCV genotype 3: Interim results of a multicenter compassionate use program in Europe

Einleitung: Treatment of HCV genotype 3 (GT3) infection remains a high medical need. Compared to HCV non-GT3, pts with HCV GT3 have faster rates of fibrosis progression, higher prevalence of severe steatosis, and a higher incidence of hepatocellular carcinoma. Treatment options for HCV GT3 pts are limited, and debate continues on the optimal regimen and duration of treatment, especially in those with cirrhosis. This analysis reports interim findings from a compassionate use program (CUP) of Daclastavir (DCV) plus Sofosbuvir (SOF) with or without Ribavirin (RBV) opened in 5 European countries.

Protease inhibitor-induced acute pancreatitis in post liver transplant hepatitis C Patients

Drug induced pancreatitis (DIP) is a serious adverse effect of many commonly used drugs. Pegylated interferon (peg- IFN) and ribavirin used for treatment of chronic hepatitis C (CHC) infection and various protease inhibitors (PIs) such as indinavir, nelfinavir, ritonavir and saquinavir used for HIV infection have been reported to cause DIP; although the mechanism of pancreatitis is not well known. Recently, telaprevir and boceprevir are introduced for treatment of HCV genotype 1 infection along with peg-IFN and ribavirin. There are no reports of acute pancreatitis due to telaprevir and boceprevir in liver transplant setting. We managed two such cases; both were male with HCV genotype 1 infection, had living donor liver transplantation for hepatocellular cancer few years ago and stable on cyclosporine. Both developed AP a month after adding one of PI to their combination therapy. First patient had past history of partial response with peg-IFN and ribavirin and retreated with addition of telaprevir to combination therapy. Second patient received peg-IFN and ribavirin for 4 months and then boceprevir was added. Patients were managed conservatively, the culprit PI was stopped and they recovered. We used the Naranjo Probability Scale for Adverse Drug Events to estimate the probability that a drug was the cause of the acute pancreatitis. A score of 7 was calculated in both patients, indicating a probable adverse drug reaction. The algorithm devised by Trivedi et al to diagnose drug-induced pancreatitis was also used and confirmed that this was likely to be a drug reaction. There is adequate circumstantial evidence pointing to telaprevir and boceprevir as the cause of their acute pancreatitis. Further evidence is needed but in the meantime we would recommend routine monitoring of amylase levels for all patients on triple therapy and advise patients of potential symptoms for which they should seek medical advice.

P1346 : Study protocol for a partly randomised, open-label phase IIA trial of once-daily simeprevir combined with sofosbuvir for the treatment of HCV genotype 4 infected patients with or without cirrhosis (OSIRIS)

P1346 : Study protocol for a partly randomised, open-label phase IIA trial of once-daily simeprevir combined with sofosbuvir for the treatment of HCV genotype 4 infected patients with or without cirrhosis (OSIRIS)

Optimal Management of HCV Genotype 4

The optimal treatment for HCV genotype 4 (HCV-G4)-infected patients is still evolving. Pegylated interferon (PEG)-ribavirin (RBV) therapy was the standard of care but provides moderate response rates and adverse events. Sofosbuvir (SOF) and simeprevir (SIM) allow for shorter duration and higher cure rates when added to PEG-RBV. The recommended treatment depends on interferon eligibility and previous treatment status. Currently, the optimal therapy for HCV-G4 interferon-eligible is a 12-week course of SOF plus PEG-RBV or SIM plus PEG-RBV. The combination of PEG-RBV may still be appropriate where no other treatment option is available, especially for treatment-naive patients with baseline predictors of a high likelihood of response. For interferon-ineligible patients, the optimal regimen is a 24-week course of SOF plus RBV or a 12-week course of SOF-SIM combination with or without RBV. These recommendations will be very short-lived. The combination of ABT-450/r plus ombitasvir and the SOF-ledipasvir combination for 12 weeks may become an optimal therapy when approved. Next generation therapies that allow high cure rates with shorter duration of treatment with will shortly become available.