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Despite the availability of highly effective and well-tolerated direct-acting antivirals, not all patients with chronic hepatitis C virus infection receive treatment. This retrospective, multi-centre, noninterventional, case-control study identified patients with chronic hepatitis C virus infection initiating (control) or not initiating (case) treatment at 43 sites in Germany from September 2017 to June 2018. It aimed to compare characteristics of the two patient populations and to identify factors involved in patient/physician decision to initiate/not initiate chronic hepatitis C virus treatment, with a particular focus on historical barriers. Overall, 793 patients were identified: 573 (72%) who received treatment and 220 (28%) who did not. In 42% of patients, the reason for not initiating treatment was patient wish, particularly due to fear of treatment (17%) or adverse events (13%). Other frequently observed reasons for not initiating treatment were in accordance with known historical barriers for physicians to initiate therapy, including perceived or expected lack of compliance (14.5%), high patient age (10.9%), comorbidities (15.0%), alcohol abuse (9.1%), hard drug use (7.7%), and opioid substitution therapy (4.5%). Patient wish against therapy was also a frequently reported reason for not initiating treatment in the postponed (35.2%) and not planned (47.0%) subgroups; of note, known historical factors were also common reasons for postponing treatment. Real-world and clinical trial evidence is accumulating, which suggests that such historical barriers do not negatively impact treatment effectiveness. Improved education is key to facilitate progress towards the World Health Organization target of eliminating viral hepatitis as a major public health threat by 2030. [ABSTRACT FROM AUTHOR]

Background & Aims: The presence of baseline resistance‐associated substitutions (RASs) reduced sustained virologic response (SVR) rates in chronic hepatitis C virus (HCV) genotype 1a infected patients treated with Elbasvir/Grazoprevir (EBR/GZR). This study aimed to evaluate the frequency of NS5A RASs and treatment outcomes in patients for whom EBR/GZR was intended. Methods: We sequenced NS5A in 832 samples from German genotype1a‐infected DAA‐naïve patients population‐based, which were collected in the European Resistance Database. Treatment outcomes and clinical parameters were evaluated in 519 of such patients retrospectively. Results: Overall, 6.5% of patients harboured EBR‐specific NS5A RASs at baseline, including Q30H/R (3.3%), L31M (1.8%), Y93H (1.6%) and other individual variants. Antiviral treatment, including EBR/GZR, was initiated in 88% of the patients. In the absence of RASs, the majority of patients received EBR/GZR for 12 weeks (57%) and the SVR rate was 97% compared to 99% SVR achieved using other DAA regimens (LDV/SOF ± RBV, G/P, PrOD + RBV, VEL/SOF). Various regimens were used in the presence of RASs and SVR rates were high following treatment with LDV/SOF (100%), G/P (83%), PrOD/RBV (100%), VEL/SOF (100%), SMV/SOF (100%) and EBR/GZR + RBV for 16 weeks (100%). However, two patients received EBR/GZR for 16 weeks without RBV and one relapsed. Conclusions: EBR/GZR treatment with or without RBV for 12 or 16 weeks according to a baseline RAS analysis was highly effective with ≥97% SVR in patients with genotype 1a. EBR/GZR without RBV should be avoided in patients with RASs. High SVR rates were also achieved using other 8‐ or 12‐week DAA regimens. [ABSTRACT FROM AUTHOR]

Background: This Phase 3, open-label, rollover study (NCT01323244) investigated the efficacy and safety of simeprevir plus peginterferon α-2a (PegIFNα-2a) and ribavirin (RBV) in a well-characterized population of HCV genotype 1 (GT1)-infected treatment-experienced patients.Methods: Patients who had failed PegIFNα/RBV treatment in the placebo arm of a previous Phase 2/3 simeprevir study (Phase 2/3 group, n = 125), or had been exposed to HCV direct-acting antivirals (simeprevir or other) for up to 14 days in a selected Phase 1 study (Phase 1 group, n = 16), were eligible. Phase 2/3 group patients were classified according to prior relapse, breakthrough, or non-response (null response, partial response, non-classifiable non-response) to PegIFNα/RBV. Eight patients in the Phase 1 group received short-term (≤14 days) simeprevir. Treatment comprised simeprevir 150 mg once daily (QD) plus PegIFNα-2a/RBV for 12 weeks followed by PegIFNα-2a/RBV for 12 or 36 weeks (using response-guided therapy [RGT] to determine total treatment duration in Phase 2/3 prior relapsers or breakthrough) or 36 weeks fixed (Phase 2/3 group non-responders and Phase 1 group). The primary endpoint was sustained virologic response 12 weeks after planned end of treatment (SVR12).Results: Phase 2/3 group: SVR12 rate was 69.6% (87/125) overall; 92.7% (51/55), 60.0% (6/10), 64.3% (18/28), and 36.7% (11/30) in patients with prior relapse, viral breakthrough, partial response, or null response, respectively. SVR12 rates were similar for patients with HCV GT1a (66.0% [33/50]) and GT1b infection (72.0% [54/75]) and among HCV GT1a-infected patients with/without a baseline Q80K polymorphism (66.7% [8/12] and 65.8% [25/38], respectively). The majority of RGT-eligible patients (prior viral relapse or breakthrough) met RGT criteria (89.2% [58/65]); of these, 89.7% (52/58) achieved SVR12. Overall, 16.0% (20/125) of patients experienced on-treatment failure and 14.4% (18/125) experienced post-treatment failure (15 relapses, 3 missing data). Phase 1 group (simeprevir-naïve and -experienced patients combined): SVR12 rate was 37.5% (6/16). Safety and tolerability findings were comparable to those of the feeder studies.Conclusions: The majority of RGT-eligible patients met criteria for shortening treatment to 24 weeks in total. Simeprevir 150 mg QD with PegIFNα-2a/RBV led to a high SVR rate among prior relapsers with HCV GT1 infection. No new safety signals were noted.Trial Registration: NCT01323244 . (date of registration: March 24, 2011). [ABSTRACT FROM AUTHOR]

Evidence based clinical guidelines are implemented to treat patients efficiently that include efficacy, tolerability but also health economic considerations. This is of particular relevance to the new direct acting antiviral agents that have revolutionized treatment of chronic hepatitis C. For hepatitis C genotypes 2/3 interferon free treatment is already available with sofosbuvir plus ribavirin. However, treatment with sofosbuvir-based regimens is 10–20 times more expensive compared to pegylated interferon alfa and ribavirin (PegIFN/RBV). It has to be discussed if PegIFN/RBV is still an option for easy to treat patients. We assessed the treatment of patients with chronic hepatitis C genotypes 2/3 with PegIFN/RBV in a real world setting according to the latest German guidelines. Overall, 1006 patients were recruited into a prospective patient registry with 959 having started treatment. The intention-to-treat analysis showed poor SVR (GT2 61%, GT3 47%) while patients with adherence had excellent SVR in the per protocol analysis (GT2 96%, GT3 90%). According to guidelines, 283 patients were candidates for shorter treatment duration, namely a treatment of 16 weeks (baseline HCV-RNA <800.000 IU/mL, no cirrhosis and RVR). However, 65% of these easy to treat patients have been treated longer than recommended that resulted in higher costs but not higher SVR rates. In conclusion, treatment with PegIFN/RBV in a real world setting can be highly effective yet similar effective than PegIFN± sofosbuvir/RBV in well-selected naïve G2/3 patients. Full adherence to guidelines could be further improved, because it would be important in the new era with DAA, especially to safe resources. [ABSTRACT FROM AUTHOR]

Background/Aims: Since ribavirin was able to improve the antiviral efficacy of interferon alfa in patients with chronic hepatitis C, several other adjuncts have been studied. It has been shown that mycophenolate mofetil (MMF) is a more potent inhibitor of the inosine 5′-monophosphate-dehydrogenase (IMPDH) than ribavirin. The present study is a pilot study evaluating the efficacy and safety of combination therapy with interferon alfa-2a and MMF in interferon alfa nonresponder patients.Methods: Thirty-eight adult patients with chronic hepatitis C who did not respond to a previous interferon alfa monotherapy were enrolled to receive 6 million units of interferon alfa-2a tiw in combination with MMF (1 week 500 mg/day, 1 week 1000 mg/day, 22 weeks 2000 mg/day).Results: An interim analysis of 29 patients after 12 weeks of therapy showed that only one patient had negative hepatitis C virus-RNA at this time point. There was no significant reduction of the viral load during therapy. Due to inefficacy the study was discontinued.Conclusions: Combination therapy of interferon alfa-2a and MMF is ineffective in improving virological response rates in nonresponder patients with chronic hepatitis C. These data suggest that inhibition of the IMPDH seems not to be the major mechanism of ribavirin in enhancing the antiviral effect of interferon alfa in chronic hepatitis C. [Copyright &y& Elsevier]