Second-generation direct-acting-antiviral hepatitis C virus treatment: Efficacy, safety, and predictors of SVR12.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
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.
Christoph R
CR
Werner
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.
Julia M
JM
Schwarz
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.
Daniel P
DP
Egetemeyr
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
R
Beck
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.
Nisar P
NP
Malek
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.
Ulrich M
UM
Lauer
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.
Christoph P
CP
Berg
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use; D002219:Carbamates; D004359:Drug Therapy, Combination; D005260:Female; D005449:Fluorenes / Q000627:therapeutic use; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D006975:Hypertension, Portal / Q000150:complications; D007093:Imidazoles / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000150:complications; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D000069616:Simeprevir / Q000627:therapeutic use; D000069474:Sofosbuvir / Q000627:therapeutic use; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives
D000998:Antiviral Agents; D001562:Benzimidazoles; D002219:Carbamates; D005449:Fluorenes; D007093:Imidazoles; D011759:Pyrrolidines; C586541:ledipasvir; D012254:Ribavirin; D000069616:Simeprevir; D014633:Valine; C549273:daclatasvir; D000069474:Sofosbuvir
Daclatasvir; Hepatitis C; Ledipasvir; Liver cirrhosis; Liver transplant; Resistance; Side effects; Simeprevir; Sofosbuvir; Sustained virological response
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