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2 Studies on IV Silibinin & Liver Transplants in HCV
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Download the PDF here
Download the PDF here
Article in Press
Intravenous silibinin monotherapy shows significant antiviral activity in HCV-infected patients in the peri-transplantation period
Jnl of Heptology Nov 2012
Ferenci et al [6] have recently shown potent dose-dependent antiviral activity of
intravenous silibinin in patients with chronic hepatitis C not responding to prior
standard antiviral therapy. Moreover, treatment was safe, with only a transient
increase in serum bilirubin levels in accordance to that observed in different
publications [7, 8].
In summary, this proof-of-concept randomized, double-blind, placebo controlled
study in patients in the waiting list for LT treated indicates that daily intravenous silibinin has evident antiviral properties and is well tolerated in the peri-LT period. Thus, a longer treatment regimen with silibinin (alone or in combination with other agents) especially following LT, should be assessed in clinical trials for the prevention of hepatitis C recurrence.
Abstract
Background and Aims
Hepatitis C recurrence after liver transplantation (LT) is the main problem of most transplant programs. We aimed to assess the antiviral activity and safety of intravenous silibinin (SIL) administered daily during the peri-transplant period.
Methods
This was a single-centre, prospective, randomized, double-blind, placebo-controlled study including 14 HCV-infected patients awaiting LT. Eleven patients received SIL and 3 placebo, for a maximum of 21 days before LT and 7 days after LT.
Results
Among the patients who received more than 14 days of pre-LT treatment, the median decrease in viral load (VL) was 2.31 log10 (range 0.6-4.2) in the SIL-treated group (n=9) versus 0.30 log 10 (0.1-0.6) in the placebo group (n=3) (p=0.016). During the post-LT treatment, HCV-RNA levels were consistently and significantly (p=0.002) lower in the SIL group compared to placebo and decreased below the limit of quantification in 2 patients and below the limit of detection in 2 additional patients (all in the SIL-treated group). Peri-transplant treatment with SIL was well tolerated.
Conclusions
This proof-of-concept study in patients in the waiting list for LT indicates that daily intravenous silibinin has evident antiviral properties and is well tolerated in the peri-LT period. A longer treatment regimen with silibinin (alone or in combination with other agents) should be assessed in clinical trials for the prevention of hepatitis C recurrence.
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Article in Press
Safety and anti-HCV Effect of Prolonged Intravenous Silibinin in HCV-Genotype 1 Subjects in the Immediate Liver Transplant Period
In the present study, administration of iv-SIL (20mg/kg/d) monotherapy up to six weeks in patients with HCV genotype 1 undergoing orthotopic LT was safe and showed a potent and sustained antiviral effect, with 44% of subjects reaching undetectable HCVRNA levels during therapy. This is a relevant finding, for to date, any available anti-HCV drug used as monotherapy has been able to achieve similar results, safely and without significant toxicity or interactions with immunosuppresive drugs.
In conclusion, taking into account the unique profile of iv-SIL (lack of toxicity during prolonged administration, no pharmacokinetic interactions with immunosuppressants or other anti-HCV drugs, potent dose- and time-dependent antiviral effect, and specially the absence of HCV-RNA rebound and/or resistance during administration), the results of the present study support further investigation on its use in combination with currently or in the nearest future available anti-HCV combinations in patients with viral
recurrence following LT.
Abstract
Background and aims
Reinfection of the graft is the rule in patients with HCV-cirrhosis undergoing liver transplantation, and HCV-RNA reaches pretransplantation levels within the first month. Short-term intravenous silibinin monotherapy is safe and shows a potent in vivo anti-HCV effect. We aimed to evaluate the safety and antiviral effect of prolonged intravenous silibinin started immediately before liver transplantation.
Methods
single center, prospective, pilot study, to assess the safety and effect on HCV-RNA kinetics during at least 21 days of intravenous silibinin monotherapy (20mg/kg/day) in 9 consecutive HCV genotype 1 subjects, in comparison to a control, non-treated group of 7 consecutive prior transplanted subjects under the same immunosuppressive regimen (basiliximab, steroids, delayed tacrolimus, micophenolate).
Results
intravenous silibinin led to significant, maintained and progressive HCV-RNA decreases (mean HCV-RNA drop at week 3, -4.1±1.3log10 IU/ml), and lack of viral breakthrough during administration. Four patients (44%) reached negative HCV-RNA, maintained during silibinin treatment, vs none in the control group, but HCV-RNA relapsed in all after a median of 21 days (16-28) following silibinin withdrawal. Partial responders to silibinin showed marked decreases in HCV-RNA when compared to controls, but lower than complete responders. There were not clinical adverse effects, and silibinin led to asymptomatic transient hyperbilirubinemia (week 2, 4.2±2.2 vs 2.5±3.6mg/dl; p=0.02).
Conclusions
prolonged intravenous silibinin monotherapy was safe in the immediate liver transplantation period, leading to a potent and timedependent antiviral effect and lack of HCV-RNA breakthrough during administration. However, HCV-RNA rebounded after withdrawal, and silibinin monotherapy did not avoid reinfection of the graft.
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