P0783 : Viral kinetics during interferon-free sofosbuvir containing treatment regimens in a real-life cohort of chronic hepatitis C patients with advanced liver disease

POSTERS P0783 VIRAL KINETICS DURING INTERFERON-FREE SOFOSBUVIR CONTAINING TREATMENT REGIMENS IN A REAL-LIFE COHORT OF CHRONIC HEPATITIS C PATIENTS WITH ADVANCED LIVER DISEASE K. Kozbial1 , C. Freissmuth1 , R. Strassl2 , R. Al-Zoairy3 , A. Maieron4 , R. Stauber5 , M. Gschwantler6 , M. Strasser7 , H. Laferl8 , T. Bamberger9 , S. Moser6 , M. Eder1 , S. Beinhardt1 , A.F. Staettermayer1 , M. Mandorfer1 , A. Ferlitsch1 , H. Zoller10 , P. Knoflach11 , K. Staufer12 , M. Peck-Radosavljevic1 , P. Munda1 , W. Vogel10 , P. Ferenci1 , H. Hofer1 . 1 Department of Internal Medicine III, Division of Gastroenterology and Hepatology, 2 Department of Laboratory Medicine, Div. of Clinical Virology, Medical University of Vienna, Vienna, 3 Department of Medicine II, Gastroenterology and Hepatology, Medical University of Innsbruck, Innsbruck, 4 Department of Gastroenterology, Elisabethinen Hospital, Linz, 5 Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, 6 Department of Gastroenterology, Wilhelminenspital Wien, Vienna, 7 Department of Gastroenterology and Hepatology, Paracelsus Medical University Salzburg, Salzburg, 8 Department of Internal Medicine, Kaiser-Franz-Josef-Spital, Vienna, 9 Department of Internal Medicine II, Allgemeines Krankenhaus Linz, Linz, 10 Department of Internal Medicine II, Medical University of Innsbruck, Innsbruck, 11 Department of Internal Medicine, Klinikum Wels-Grieskirchen, Wels, 12 Department of Transplant Surgery, Medical University of Vienna, Vienna, Austria E-mail: [email protected] Background and Aims: Sofosbuvir (SOF), Simeprevir (SMV) and Daclatasvir (DCV) are reimbursed for chronic hepatitis C patients with advanced liver disease (F3, F4) and posttransplant patients in Austria. Real-life data in these patients are scarce and the optimal duration of treatment is still under debate. The aim of this study was to evaluate viral kinetics in patients with advanced liver disease receiving interferon-free treatment regimens. Methods: We included 181 patients (mean age: 55.8±10.1 years, m/f: 117/64, treatment experienced: 109 [60%], prior failure to protease inhibitors: 23 [13%]) with advanced fibrosis (Metavir score F3: n = 13, F4: n = 168; median platelet count: 98 G/l) who were treated with Sofosbuvir (SOF) 400 mg/day combined with 60 mg/day Daclatasvir (DCV) (GT 1, 3, 4; n = 86) or with Simeprevir (SMV) 150 mg/d (GT1 and 4; n = 49) or weight based ribavirin (RBV; GT 1–4; n = 46). Duration of treatment was at the discretion of the investigator. Viral load was measured after 48 hours, at weeks 1, 2, 3, 4 and then every 4 weeks until the end of treatment by Abbott RealTime HCV quantitative assay (lower limit of quantification [LLOQ]: 12 IU/ml) or by Roche COBAS AmpliPrep/ COBAS TaqMan HCV quantitative assay, Version 2 (LLOQ: 15 IU/ml). Results: HCV-RNA dropped by a mean log of 2.91 and 3.54 after 48 hours and 7 days, respectively. At weeks 4, 8, 12, and 16 of treatment, 23%, 60%, 84%, and 93% of patients with advanced liver disease had undetectable HCV RNA (TND, target not detected), respectively. Currently 54 patients have reached end of treatment after a treatment duration of 12 weeks (n = 16), 16 weeks (n = 2) or 24 weeks (n = 36). 5 patients discontinued therapy due to psychiatric adverse events (n = 2), death (n = 2, sepsis and multiple organ failure due to decompensation), and non-adherence (n = 1). 29 patients reached follow-up week 4 (23 SVR4, 6 relapsed) and 4 reached follow-up week 12 (all SVR12). All relapsers received SOF/RBV treatment. Conclusions: Determination of on-treatment response may help to optimize treatment regimen in patients with advanced liver disease. Patients with detectable HCV RNA at treatment week 12 (16%) may need a treatment of 24 weeks.

P0784 SOFOSBUVIR IN COMBINATION WITH PEGINTERFERON AND RIBAVIRIN FOR PATIENTS CHRONICALLY INFECTED WITH HEPATITIS C VIRUS GENOTYPE 4: “REAL-LIFE” EXPERIENCE OF TWO LARGE VIRAL HEPATITIS CENTERS IN NORTHERN GERMANY M.H. Wehmeyer1 , S. Jordan1 , C. Eißing1 , J. Hartl1 , A. Stohr ¨ 2, J. Petersen2 , A.W. Lohse1 , S. Luth ¨ 1 , P. Buggisch2 , J. Schulze zur Wiesch1 . 1 I. Department of Medicine, University Medical Center Hamburg-Eppendorf, 2 IfI-Institute for Interdisciplinary Medicine, Hamburg, Germany E-mail: [email protected] Background and Aims: Sofosbuvir (SOF)-based triple therapy has been approved for all hepatitis C virus (HCV) genotypes. However, real life efficacy data of SOF in patients with genotypes 4 to 6 are limited. Furthermore, SOF-based triple therapy was never directly compared to dual therapy with peginterferon (IFN) and ribavirin (RBV). Methods: Every patient with HCV genotype 4, 5 or 6 infection who received IFN/RBV/SOF between January and June 2014 at our two centers was included, and patients’ data were compared with historical HCV genotype 4 patients treated with IFN/RBV from 01/2001 to 12/2007. IFN/RBV/SOF

IFN/RBV

N (%)

N (%)

Mean (±SD)

Mean (±SD)

P-value

Median (range)

Median (range)

Male sex

21 (80.8%)

41 (83.7%)

0.757

Age [years]

47.00 (± 11.02)

42.33 (± 9.29)

0.072

13 (50%)

36 (73.5%)

Stage of fibrosis [METAVIR] F0–2 F3–4

0.073 13 (50%)

13 (26.5%)

Cirrhosis (F4)

6 (23.1%)

6 (12.2%)

0.321

Treatment naïve

13 (50%)

39 (79.6%)

0.017*

Treatment experienced Relapse

7 (26.9%)

3 (6.1%)

0.017*

Non-response

5 (19.2%)

6 (12.2%)

0.498

Breakthrough

1 (3.8%)

1 (2.0%)

1

Viral load [U/mL]

645×103 (102 to 7×106 )

70×103 (0.5×103 to 2×106 )

<0.001*

Haemoglobin [g/dL]

14.9 (11.8–17.2)

15.2 (11.5–18.3)

0.691

Baseline laboratory

Platelets [billion/L]

200.5 (104–350)

220 (59–392)

0.589

Leucocytes [billion/L]

6 (2.5–10.6)

6.5 (2.9–15.6)

0.853

ALT [U/L]

56 (25–290)

63 (11–346)

0.997

Ribavirin dose reduction

7 (26.9%)

14 (28.6%)

1

Peginterferon dose reduction

1 (3.8%)

11 (22.4%)

0.048*

RVR (N = 66)

17/24 (70.1%)

16/42 (38.1%)

0.020*

EOTR

25/26 (96.2%)

30/49 (61.2%)

0.002*

SVR12

19/22 (86.4%)

21/49 (42.9%)

0.001*

Results: We included 75 patients in our study. 26 patients received SOF-based triple therapy and 49 patients were treated with IFN/RBV. Baseline characteristics of both groups are provided in the accompanying table. Sustained virological response (SVR12) was achieved in 19/22 (86.4%) patients who received IFN/RBV/SOF and in 21/49 patients (42.9%) of the control group (P = 0.001). Rapid virological response (RVR) was a predictor of SVR12 in the control group (13/16 with RVR compared to 4/26 patients without RVR achieved SVR12; P < 0.001), whilst patients with SOF-based therapy achieved SVR12 regardless of reaching RVR (SVR12 in 6/6 patients with RVR and in 13/15 patients without RVR; P = 1). All cirrhotic patients with SOF-based triple therapy achieved SVR12. Notably, adverse events (AEs) of any kind more frequently occurred in the control group than in the SOF group (95.9% vs. 69.2%; P = 0.002). Particularly gastrointestinal (P < 0.001), dermatologic (P = 0.003) and psychiatric (P = 0.030) AEs were more frequent in IFN/RBV patients than in patients receiving IFN/RBV/SOF. SVR data of 4 patients are pending, but will be provided in April 2015. Conclusions: A 12 week course of IFN/RBV/SOF was significantly more effective than dual therapy for 48 weeks. Furthermore,

Journal of Hepatology 2015 vol. 62 | S263–S864

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