Safety and anti-HCV effect of prolonged intravenous silibinin in HCV genotype 1 subjects in the immediate liver transplant period.

BACKGROUND & AIMS: Reinfection of the graft is the rule in patients with HCV cirrhosis undergoing liver transplantation, and HCV-RNA reaches pre-transplantation levels within the first month. Short-term intravenous silibinin monotherapy is safe and shows a potent in vivo anti-HCV effect. We aimed at evaluating the safety and antiviral effect of prolonged intravenous silibinin, started immediately before liver transplantation. METHODS: Single centre, prospective, pilot study, to assess the safety and effect on HCV-RNA kinetics during at least 21 days of intravenous silibinin monotherapy (20 mg/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 ± 1.3 log(10)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 of them 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 no clinical adverse effects, and silibinin led to asymptomatic transient hyperbilirubinemia (week 2, 4.2 ± 2.2 vs. 2.5 ± 3.6 mg/dl; p=0.02). CONCLUSIONS: Prolonged intravenous silibinin monotherapy was safe in the immediate liver transplantation period, leading to a potent and time dependent 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.

Partial splenic embolization and peg-IFN plus RBV in liver transplanted patients with hepatitis C recurrence: safety, efficacy and long-term outcome.

BACKGROUND: There is limited information on the long-term outcome in liver transplant (LT) subjects undergoing partial splenic embolization (PSE) prior to full dose pegylated interferon/ribavirin (peg-IFN/RBV). METHODS: Retrospective review of eight LT subjects after PSE and antiviral therapy. RESULTS: Baseline platelets and neutrophils were <50 000 cells/mL and <1000 cells/mL in 75% and 50%. Mean splenic infarction volume was 85 +/- 13%. PSE produced major complications in three (37.5%): recurrent sterile netrophilic ascites and renal insufficiency (n = 2), and splenic abscess (n = 1). Full-dose peg-IFN/RBV was started in seven (87.5%), with two early withdrawals (28.6%) despite early virological response (toxicity and infection); both subjects died. Anemia led to RBV dose-adjustment in six (86%), with human recombinant erythropoietin (EPO) use in four (57%). No peg-IFN adjustments or granulocyte-colonies stimulating factor were needed. Two patients reached sustained virological response (SVR) (28.6%). Two non-responders maintained prolonged therapy with biochemical/histological improvement. After a median follow-up of 151 wk, we observed significant improvements in hematological parameters, aspartate aminotransferase, alanine aminotransferase, international normalized ratio, and prothrombin activity. CONCLUSIONS: Extensive PSE after LT produced significant morbidity (37.5%). Peg-IFN/RBV was completed in five out of seven (71%), with SVR in two (28.6%). RBV adjustement due to anemia was high despite EPO use. Only patients able to complete or maintain antiviral therapy survived, with long-term significant benefits in hematological parameters and liver function tests.

HCV clearance and treatment outcome in genotype 1 HCV-monoinfected, HIV-coinfected and liver transplanted patients on peg-IFN-alpha-2b/ribavirin.

BACKGROUND/AIMS: Differences in HCV-RNA clearance during therapy might explain the lower efficacy of peg-IFN/RBV in HIV/HCV-coinfection. There are limited data on HCV-RNA clearance and treatment outcomes in liver transplanted (LT) patients. METHODS: To assess the rates of SVR and baseline predictors of failure after 48 weeks of weight-adjusted peg-IFN-alpha-2b/RBV in 120 patients with HCV genotype 1: 61 HCV-monoinfected, 40 HIV-coinfected and 19 LT-patients. Viral clearance was evaluated in patients completing 24 weeks of therapy (n=112, 93%). RESULTS: SVR was significantly lower in HIV-coinfection than in HCV-monoinfection or LT (18 vs. 39 vs. 42%, P<0.02). By multivariate analysis, HIV-coinfection (OR 3.048, 95% CI 1.133-8.196; P=0.027), baseline HCV-RNA over 800,000 IU/ml (OR 2.800; 95% CI 1.121-6.993, P=0.027) and higher AST values (OR 1.009; 95% CI 1.001-1.018; P=0.028) were significantly associated to failure. Despite similar baseline HCV load (5.67 vs. 5.75 vs. 5.90 log10 IU/ml), HIV-coinfection showed significantly lower HCV-RNA decreases than HCV-monoinfection at weeks 4 (P=0.015), 12 (P=0.015) and 24 (P=0.0003), and than LT at weeks 12 (P=0.003) and 24 (P=0.023). 36/60 subjects (60%) reaching EVR by week 12 obtained SVR vs. 3/60 (5%) who did not. CONCLUSIONS: HIV-coinfection was independently associated to treatment failure, and led to a significantly slower HCV-RNA clearance.