Session Title: Category 5g. VIRAL HEPATITIS: g. HEPATITIS C - CLINICAL (THERAPY)
Presentation Date: Apr 15, 2010
PREDICTIVE FACTORS FOR SILIBININ MONOTHERAPY IN PATIENTS WITH CHRONIC HEPATITIS C AND NONRESPONSE TO PEG-IFN/RBV THERAPY
K. Rutter1*, A. Stättermayer1, T. Reiberger1, J. Aberle2, K. Zinober1, T.-M. Scherzer1, S. Beinhardt1, H. Holzmann2, P. Steindl-Munda1, H. Hofer1, P. Ferenci1
1Gastroenterology and Hepatology, 2Clinical Virology, Medical University of Vienna, Vienna, Austria. *email@example.com
Introduction: Silibinin (SIL) is a potent antiviral agent for treatment of chronic hepatitis C (CHC) patients not responding to PEGIFN+RBV treatment. The predictive value of liver histology, IP-10 levels, and the polymorphism in the IL-28B gene (all are useful predictors of SVR in treatment-naive CHC patients) was studied in PEGIFN/RBV nonresponders receiving SIL monotherapy.
Methods: 47 patients (m/f: 31/16; mean age: 50.2±9.3; BMI: 25.7±3.7; baseline viral load 5.91±5.54 IU/ml, HCV-1: 37; HCV-3: 2, HCV-4: 8) with previous nonresponse to PEGIFN+RBV were treated with either 15mg/kg/SIL/day (n=5) or 20mg/kg/SIL/day (n=42) for 7 days as monotherapy. Liver biopsy (n=36) (F1/2: 20; F3/4: 16), IP-10 measurement at BL and D8 (n=19) as well as the rs12979860 polymorphism of the IL28B-gene (n=28) were investigated. For IP10 an enzyme-linked immunosorbent assay (BD OptEIA Set Human IP10; San Diego, CA; USA) and for the rs1297980 region of the IL28B-gene the StepOnePlus Real time PCR System (Applied Biosystems, Foster City, USA) was used.
Results: HCV decline after seven days of iv. SIL monotherapy was 2.32±1.46 (log drop; mean+SD). Patients with pre-treatment IP-10 levels < 450pg/ml tended to have a better response to SIL monotherapy (log-drop at day 8: 2.7(±1.4) vs. 2.1(±0.65) IU/mL; p=0.267). On iv. SIL monotherapy IP-10 decreased from baseline (522±403pg/mL) to D8 (337±346pg/mL p=0.092). The predominant genotype of IL-28B was T/C (n=21), 2 pts had a C/C and 5 patients a T/T genotype. Despite the predominant T allele SIL showed potent antiviral activity. By multiple step linear regression analysis only the stage of fibrosis appeared as a predictive factor of response at day 8 (p< 0.05).
Conclusions: Stage of fibrosis is a strong predictor of the antiviral efficacy of SIL. In this cohort the T-allele was highly prevalent but had no impact on the magnitude of virus decline suggesting that SIL has a different mode of action than interferon. Baseline IP-10 levels give further information on the likelihood of response to SIL monotherapy in PEGIFN/RBV nonresponders.