Retrospective Cohort Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 21, 2016; 22(35): 8050-8059
Published online Sep 21, 2016. doi: 10.3748/wjg.v22.i35.8050
Second-generation direct-acting-antiviral hepatitis C virus treatment: Efficacy, safety, and predictors of SVR12
Christoph R Werner, Julia M Schwarz, Daniel P Egetemeyr, Robert Beck, Nisar P Malek, Ulrich M Lauer, Christoph P Berg
Christoph R Werner, Julia M Schwarz, Daniel P Egetemeyr, Nisar P Malek, Ulrich M Lauer, Christoph P Berg, Department of Gastroenterology, Hepatology, and Infectiology, University Hospital Tübingen, 72076 Tübingen, Germany
Robert Beck, Institute of Medical Virology, University Hospital Tübingen, 72076 Tübingen, Germany
Author contributions: Werner CR, Schwarz JM, Egetemeyr DP, Malek NP, Lauer UM and Berg CP designed the research, performed the research, and wrote the paper; Werner CR, Schwarz JM and Berg CP analyzed the data; Beck R contributed the virological analyses.
Institutional review board statement: The retrospective, anonymous analysis of individual patient data, which were obtained during diagnostics and treatment of own patients’ needs no approval by the institutional review board/ethical committee and no informed consent of the patients. No concerns exist against anonymous collection, analysis, and publication of those data.
Informed consent statement: The institutional review board of the Medical Faculty of the University of Tübingen approved this retrospective analysis and waived the need for written informed consent because of the anonymous evaluation of patient data from patient records.
Conflict-of-interest statement: Werner CR received travel grants from Gilead, Bristol-Myers-Squibb, Roche, and Janssen-Cilag, and lecture fees from Roche; Schwarz JM and Beck R declare no conflict; Egetemeyr DP received travel grants, and lecture fees from Roche; Malek NP declares no conflict; Lauer UM received travel grants from Roche; Berg CP received travel grants from Gilead, Bristol-Myers-Squibb, Roche, and Janssen-Cilag, and lecture fees from Gilead, Bristol-Myers-Squibb, Roche, and Janssen-Cilag. The authors received no financial support. No funding source exists.
Data sharing statement: Technical appendix, statistical code, and dataset are available from the corresponding author at Participants consent was not obtained but the presented data are anonymized and risk of identification is low.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Christoph P Berg, MD, Department of Gastroenterology, Hepatology, and Infectiology, University Hospital Tübingen, Otfried-Müller-Str. 10, 72076 Tübingen, Germany.
Telephone: +49-7071-2982723 Fax: +49-7071-294423
Received: June 4, 2016
Peer-review started: June 5, 2016
First decision: June 20, 2016
Revised: July 21, 2016
Accepted: August 10, 2016
Article in press: August 10, 2016
Published online: September 21, 2016

To gather data on the antiviral efficacy and safety of second generation direct acting antiviral (DAA) treatment with respect to sustained virological response (SVR) 12 wk after conclusion of treatment, and to determine predictors of SVR12 in this setting.


Two hundred and sixty patients treated with SOF combination partners PR (n = 51), R (n = 10), SMV (n = 30), DCV (n = 81), LDV (n = 73), or 3D (n = 15). 144/260 were pre-treated, 89/260 had liver cirrhosis, 56/260 had portal hypertension with platelets < 100/nL, 25/260 had a MELD score ≥ 10 and 17/260 were post-liver transplantation patients. 194/260 had HCV GT1, 44/260 HCV GT3.


Two hundred and forty/256 (93.7%) patients achieved SVR12 (mITT); 4/260 were lost to follow-up. SVR12 rates for subgroups were: 92% for SOF/DCV, 93% for each SOF/SMV, SOF/PR, 94% for SOF/LDV, 100% for 3D, 94% for pretreated, 87% for liver cirrhosis, 82% for patients with platelets < 100/nL, 88% post-liver transplantation, 95% for GT1a, 93% for GT1b, 90% for GT3, 100% for GT2, 4, and 6. 12 patients suffered from relapse, 6 prematurely discontinued treatment, of which 4 died. Negative predictors of SVR12 were a platelet count < 100/nL, MELD score ≥ 10 (P < 0.0001), liver cirrhosis (P = 0.005) at baseline. In Interferon-free treatment GT3 had significantly lower SVR rates than GT1 (P = 0.016). Side effects were mild.


Excellent SVR12 rates and the favorable side-effect profile of DAA-combination therapy can be well translated into “real-world”. Patients with advanced liver disease, signs of portal hypertension, especially with platelets < 100/nL and patients with GT3 are in special need for further research efforts to overcome comparatively higher rates of virological failure.

Keywords: Sofosbuvir, Simeprevir, Ledipasvir, Hepatitis C, Liver transplant, Sustained virological response, Liver cirrhosis, Side effects, Resistance, Daclatasvir

Core tip: From 2014 on the second wave of direct acting antiviral agents was available for treatment of chronic hepatitis C infection. Due to the more heterogeneous character of patients in the “real world”, the therapeutic performance of these new drugs outside randomized clinical trials is of interest. Therefore, in this monocentric retrospective cohort study, we analyzed the efficacy, safety, and predictors of sustained virological response 12 for treatment with combinations of second generation direct acting antivirals in a “real-world” setting.