Hepatitis C virus infection is causing chronic liver disease, cirrhosis, and hepatocellular carcinoma. By combining direct-acting antivirals (DAAs), high sustained virologic response rates (SVRs) can be achieved. Resistance-associated substitutions (RASs) are commonly observed after DAA failure, and especially nonstructural protein 5A (NS5A) RASs may impact retreatment options.1-3 Data on retreatment of DAA failure patients using first-generation DAAs are limited.4-7 Recently, a second-generation protease- and NS5A-inhibitor plus sofosbuvir (voxilaprevir/velpatasvir/sofosbuvir [VOX/VEL/SOF]) was approved for retreatment after DAA failure.8 However, this and other second-generation regimens are not available in many resource-limited countries or are not reimbursed by regular insurance, and recommendations regarding the selection of retreatment regimens using first-generation DAAs are very important. This study aimed to analyze patients who were re-treated with first-generation DAAs after failure of a DAA combination therapy.

Background: The effectiveness of HCV treatment has dramatically improved with the approval of direct-acting antivirals (DAAs). However, a high frequency of clinically relevant DDIs between the regular outpatient medications and DAAs has been reported for HCV treatment with sofosbuvir in combination with simeprevir, daclatasvir or ledipasvir (30%-40%) while patients (pts) treated with ombitasvir/paritaprevir/ritonavir ± dasabuvir had a risk > 60% (Clin Infect Dis 2016;62: 561 – 567). Recently, the NS3/4a protease inhibitor GRZ in combination with the NS5A polymerase inhibitor EBV has been shown to be highly effective and well tolerated in various subgroups of HCV patients. We therefore aimed to assess the clinical relevance of DDIs between the regular outpatient medications and FDA-approved EBV/GRZ therapy in a large German real-world cohort.

Background: Invasive and noninvasive tests in patients (pts) with chronic HCV genotype 1 (G1) infection are aimed to assess the severity of liver disease, in particular the stage of fibrosis, and to detect other potential coexisting liver diseases such as hemochromatosis or diseases which can be aggravated by antiviral treatment such as thyroid dysfunctions. The aim of the present interim analysis of the German NOVUS observational study was to investigate the current clinical evaluation of the patient with chronic HCV G1 infection in German routine clinical practice before antiviral treatment.

Background: Patients (pts) with chronic HCV G1 infection may present with normal or elevated serum ALT or GGT levels. The aim of the present analysis was to investigate the effect of successful treatment of chronic HCV G1 infection with boceprevir (BOC) triple therapy on initially elevated and initially normal ALT and GGT levels.

Background: Renal impairment together with a more pronounced anemia has recently been reported in about 5% of patients (pts) under triple therapy with boceprevir (BOC) or telaprevir (S Mauss et al., Hepatology 2014; 59:46 – 48). In the present interim analysis of the NOVUS observational study we investigated whether renal impairment at baseline or during treatment determines the frequency of anemia in patients undergoing BOC triple therapy.

Background: Since 2011, triple therapy with the HCV protease inhibitor boceprevir (BOC) is widely used as standard of care for patients (pts) with chronic HCV G1 infection. Until now, there is limited information about the efficacy and safety of BOC triple therapy in clinical practice and whether differences occur between female and male pts.

Background: Information about co-morbidities of patients (pts) currently treated for chronic HCV genotype 1 (G1) infection in real-life is scarce. The present interim analysis of the NOVUS observational study was therefore aimed to investigate the frequency of pre-existing and ongoing co-morbidities of pts treated for chronic HCV G1 infection in German real-life and to determine the frequency of co-medications.

BACKGROUND & AIMS:The efficacy and tolerability of faldaprevir, a potent hepatitis C virus (HCV) NS3/4A protease inhibitor, plus peginterferon (PegIFN) and ribavirin (RBV) was assessed in a double-blind, placebo-controlled phase 3 study of treatment-naïve patients with HCV genotype-1 infection. METHODS:Patients were randomly assigned (1:2:2) to PegIFN/RBV plus: placebo (arm 1, n = 132) for 24 weeks; faldaprevir (120 mg, once daily) for 12 or 24 weeks (arm 2, n = 259); or faldaprevir (240 mg, once daily) for 12 weeks (arm 3, n = 261). In arms 2 and 3, patients with early treatment success (HCV-RNA <25 IU/ml at week 4 and undetectable at week 8) stopped all treatment at week 24. Other patients received PegIFN/RBV until week 48 unless they met futility criteria. The primary endpoint was sustained virologic response 12 weeks post-treatment (SVR12). RESULTS:SVR12 was achieved by 52%, 79%, and 80% of patients in arms 1, 2, and 3, respectively (estimated difference for arms 2 and 3 vs. arm 1: 27%, 95% confidence interval 17%-36%; and 29%, 95% confidence interval, 19%-38%, respectively; p < 0.0001 for both). Early treatment success was achieved by 87% (arm 2) and 89% (arm 3) of patients, of whom 86% and 89% achieved SVR12. Adverse event rates were similar among groups; few adverse events led to discontinuation of all regimen components. CONCLUSIONS:Faldaprevir plus PegIFN/RBV significantly increased SVR12, compared with PegIFN/RBV, in treatment-naïve patients with HCV genotype-1 infection. No differences were seen in responses of patients given faldaprevir once daily at 120 or 240 mg.

Background and Aims Individualization of treatment with peginterferon alfa and ribavirin in patients with chronic hepatitis C showed benefit in controlled trials and was implemented in treatment guidelines to increase response rates and to reduce side effects and costs. However, it is unknown whether individualization was adopted in routine daily practice and whether it translated into improved outcomes. Methods From a large noninterventional cohort study, clinical and virologic response data of 10,262 HCV patients who received peginterferon alfa-2a and ribavirin between 2003-2007 and 2008-2011 were analyzed. To account for treatment individualization, a matched-pair analysis (2,997 matched pairs) was performed. Variation in treatment duration and dosing of ribavirin were analyzed as indicators for individualization. Results Sustained virological response (SVR) rates were similar between 2003-2007 and 2008-2011 (62.0% vs. 63.7%). Patients with comorbidities were more abundant in the later period, (44.3% vs. 57.1%). The subsequent matched-pair analysis demonstrated higher SVR rates in the 2008-2011 period (64.3%) than in the 2003-2007 period (61.2%, p=0.008). More patients received abbreviated or extended treatment regimens in the later than the earlier period as an indicator of treatment individualization. To the same end, ribavirin doses were higher in the later period (12.6 versus 11.6 mg/kg/day). Factors independently associated with SVR included HCV genotype, low baseline viral load, younger age, route of infection, absence of concomitant diseases, lower APRI score, normal gamma-GT, higher ribavirin doses, no substitution for drug abuse, treatment duration, and treatment in the 2008-2011 period. Conclusions Treatment individualization with peginterferon alfa and ribavirin was implemented in daily routine between 2003-2007 and 2008-2011, SVR rates improved in the same period. These findings may be most relevant in resource-limited settings.

Background: Since 2011, triple therapy with the HCV protease inhibitor boceprevir (BOC) is widely used as standard of care for patients (pts) with chronic HCV G1 infection. The present interim analysis of the NOVUS observational study investigated the efficacy and safety of BOC triple therapy in pretreated patients in German real-world according to the previous virologic response to dual therapy with pegylated interferons (PegIFN) and ribavirin (RBV).

Background: Since 2011, triple therapy with the HCV protease inhibitor boceprevir (BOC) is widely used as standard of care for patients (pts) with chronic HCV G1 infection. The present interim analysis of the German NOVUS observational study was aimed to compare the efficacy of BOC triple therapy in previously untreated and previously treated patients in German real-world and, in particular, to compare the virologic outcome of pts who achieve an early virologic response (EVR) at treatment week (TW) 8.

Background: The achievement of early virologic response (EVR) during triple therapy of chronic HCV genotype 1 infection with the HCV protease inhibitor boceprevir has been identified as predictor to shorten treatment to 24 weeks. The present interim analysis of the NOVUS observational study was aimed to determine the frequency of EVR during boceprevir triple therapy in German real-life and to determine the virologic outcome of patients with and without EVR.

Background: The achievement of EVR during triple therapy of chronic HCV genotype 1 (G1) infection with BOC has been identified as predictor of high SVR rates of up to 90% as well as a predictor to shorten triple therapy to 24 weeks. The present interim analysis of the NOVUS observational study was aimed to investigate EVR during BOC triple therapy in German real-life and to identify baseline predictors of EVR.

Background: A considerable number of patients (pts) with chronic HCV G1 infection will present with elevated serum GGT levels. However, the impact of GGT elevation on virologic response to boceprevir (BOC) triple therapy has not been investigated until now and was therefore the aim of the present interim analysis of the German NOVUS observational study.

Background: Information about co-morbidities of patients (pts) currently treated for chronic HCV genotype 1 (G1) infection in real-life is scarce. The present interim analysis of the NOVUS observational study was therefore aimed to investigate the frequency of ongoing co-morbidities of pts with chronic HCV G1 infection in German real-life according to gender and age.

Background: A considerable number of patients (pts) with chronic HCV G1 infection will present with elevated serum gamma-GT levels. However, the impact of gamma-GT elevation on virologic response to boceprevir triple therapy has not been investigated until yet and was therefore the aim of the present interim analysis of the German NOVUS observational study.

Background: The efficacy of sofosbuvir (SOF)-containing regimens in patients who failed to achieve sustained virologic response (SVR) with SOF remains unknown. Given the lack of genotypic or phenotypic resistance to SOF in patients who did not achieve an SVR in the Phase 3 program, we designed an open-label study for relapsers to receive either a longer duration of SOF + RBV (24 weeks) or SOF + RBV with peginterferon (PEG-IFN). Methods: GT-2 and GT-3 HCV infected patients who failed either 12or 16-week regimens of SOF + RBV (Phase 3 studies: FISSION, FUSION, and POSITRON) were offered either 12-weeks of SOF (400 mg once daily) + PEG-IFN (180μg weekly) + RBV (1000-1200 mg daily) or an interferon-free 24-week arm of SOF+RBV. The choice of regimen was based upon investigator discretion. The primary efficacy endpoint is SVR12 and the secondary efficacy endpoint is SVR4. Results: A total of 97 GT-3 and 16 GT-2 patients have been enrolled. The majority of patients were male (80%) with a non-IL28CC genotype (65%) and 33% of patients had cirrhosis. To date, overall SVR4 rates are 96% (27/28) for GT-3 and 100% (6/ 6) for GT-2 infected patients. The table displays these data for patients who have reached the 4-week post-treatment visit. Conclusions: Retreatment with sofosbuvir regimens of longer duration or with the addition of PEG-IFN in prior SOF failures results in high SVR4 rates and appears to offer a viable approach for GT-2 or GT-3 HCV infected patients who fail to achieve an SVR with SOF+RBV regimens.