Clinical Advances in Liver Pancreas and Biliary TractSilibinin Is a Potent Antiviral Agent in Patients With Chronic Hepatitis C Not Responding to Pegylated Interferon/Ribavirin Therapy
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Patients
Patients with previous nonresponse to full dose of PegIFN/RBV combination therapy were selected for these studies (Table 1). Nonresponse was defined by the lack of a >2-log drop of viral load after 12 weeks of therapy and/or by not achieving an end-of-treatment response. Patients were required to have had a liver biopsy within 2 years prior to inclusion into this study. Standard inclusion/exclusion criteria for PegIFN/RBV therapy were applied.
Study Protocol
During a screening phase within 35 days prior to the
Protocol 1
Sixteen pedigreed nonresponders (Table 1) were included. All patients had received full-dose treatment with PegIFN (12 PegIFN-α-2a, 2 PegIFN-α-2b) and RBV (1000–1200 mg/day) for at least 12 weeks. Parameters of oxidative stress measured did not change during silibinin infusions (Figure 1).
Serum HCV RNA declined in all patients on IV silibinin-monotherapy (Figure 2) (baseline: 6.59 ± 0.53, day 8: 5.26 ± 0.81 log IU/mL [mean ± SD], P < .001) with a mean log decline of 1.32 ± 0.55 within 1 week.
Discussion
The unexpected finding of this study was the demonstration that IV silibinin is a potent antiviral agent in patients with chronic hepatitis C not responding to standard antiviral combination therapy. Intravenous silibinin was well tolerated, and no serious adverse effects were observed. The most commonly reported adverse effect was a transient sensation of heat. The antiviral effect was dose dependent but was not maintained after the end of the infusion period by the oral administration of
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Trial registered at: www.clinicaltrials.gov: NCT00684268.
The authors disclose the following: Conflicts of interest: P. Ferenci: Roche, Basel, CH; member of the Global Advisory Board and of the speakers bureau and receives financial support for clinical studies. All other authors have no conflicts of interest.
Supported by an unrestricted research grant by Roche Austria, and silibinin (Legalon Sil) and silimaryin (Legalon) were provided by Rottapharm-Madaus, Köln, Germany. None of the companies was involved in the design, conduct, and evaluation of this protocol.