Antiviral activity and safety profile of silibinin in HCV patients with advanced fibrosis after liver transplantation: a randomized clinical trial.

Response to interferon-based therapies in HCV recurrence after liver transplantation (LT) is unsatisfactory, and major safety issues aroused in preliminary experience with boceprevir and telaprevir. As transplant community identified HCV viral clearance as a critical matter, efficacious and safe anti-HCV therapies are awaited. The aim of this study was to assess efficacy and safety of intravenous silibinin monotherapy in patients with established HCV recurrence after LT, nonresponders to pegylated interferon and ribavirin. This is a single center, prospective, randomized, parallel-group, double-blind, placebo-controlled, phase 2 trial including 20 patients randomly assigned (3:1) to receive daily 20 mg/kg of intravenous silibinin or saline as placebo, for 14 consecutive days. On day 14 of treatment, viral load decreased by 2.30 ± 1.32 in silibinin group versus no change in the placebo group (P = 0.0002). Sixteen days after the end of the treatment, viral load mean values were similar to baseline. Treatment resulted well tolerated apart from a transient and reversible increase in bilirubin. Neither changes in immunosuppressant through levels nor dosage adjustments were necessary. Silibinin monotherapy has a significant antiviral activity in patients with established HCV recurrence on the graft not responding to standard therapy and confirms safety and tolerability without interaction with immunosuppressive drugs (ClinicalTrials.gov number: NCT01518933).

Low molecular weight heparin in portal vein thrombosis of cirrhotic patients: only therapeutic purposes?

Cirrhosis has always been regarded as hemorrhagic coagulopathy caused by the reduction in the hepatic synthesis of procoagulant proteins. However, with the progression of liver disease, the cirrhotic patient undergoes a high rate of thrombotic phenomena in the portal venous system. Although the progression of liver failure produces a reduction in the synthesis of anticoagulant molecules, a test able to detect the patients with hemostatic balance shifting towards hypercoagulability has not yet been elaborated. The need of treatment and/or prophylaxis of cirrhotic patients is demonstrated by the increased mortality, the risk of bleeding from esophageal varices, and the mortality of liver transplantation, when portal vein thrombosis (PVT) occurs even if current guidelines do not give indications about PVT treatment in cirrhosis. In view of the general feeling that the majority of cirrhotic patients at an advanced stage may be in a procoagulant condition (suggested by the sharp increase in the prevalence of PVT), it is presumable that a prophylaxis of this population could be of benefit. The safety and the efficacy of prophylaxis and treatment with enoxaparin in patients with cirrhosis demonstrated by a single paper suggest this option only in controlled trials and, currently, there are no sufficient evidences for a recommendation in the clinical practice.

A Case of Severe Transaminase Elevation Following a Single Ustekinumab Dose with Remission After Drug Withdrawal.

BACKGROUND: Ustekinumab is a fully human monoclonal antibody which binds Interleukin (IL)-12/23. It is indicated for the treatment of moderate-severe psoriasis and active psoriatic arthritis. Few data are available about the possibility of an interaction between ustekinumab and the liver. CASE DESCRIPTION: We reported a case of a 61-year old woman admitted to our Unit for severe transaminase elevation (aspartate transaminase 756 IU/l, alanine transaminase 1212 IU/l) occurred after a single Ustekinumab infusion for psoriasis. All other possible causes of liver damage, including drugs, hepatitis viruses, auto-antibodies and metabolic disorders were excluded. Liver biopsy showed lymphocytic infiltration, biliary duct damage and piecemeal necrosis. On the bases of the nonspecific histological picture and Rucam score, we accomplished the diagnosis of "liver injury of iatrogenic origin". After drug withdrawal, a spontaneous normalization of liver enzymes occurred within six months.

The treatment of chronic hepatitis C with peginterferon alfa-2a (40 kDa) plus ribavirin in haemodialysed patients awaiting renal transplant.

BACKGROUND/AIMS: We undertook a pilot study to investigate the efficacy and safety of peginterferon alfa-2a (40 kDa) plus ribavirin in haemodialysed chronic HCV patients awaiting renal transplant. METHODS: Patients received peginterferon alfa-2a 135 microg/week plus ribavirin 200 mg/day for 24 or 48 weeks (genotype non-1 and 1, respectively). The dose of ribavirin was tailored according to plasma concentrations and to haemoglobin levels. Outcomes in treated patients were compared with those of a matched untreated control group. RESULTS: Thirty-five patients received treatment, while 35 served as untreated controls. Thirty patients completed treatment; patients were withdrawn due to transplantation (n=2), severe anaemia (n=1), dermatitis (n=1) and non-response (n=1) resulting in a drop-out rate of 14%. Overall, 34/35 treated patients were HCV RNA negative at week 4 and had undetectable RNA at the end of treatment, compared with none of the untreated controls (ETR 97% vs 0%; p<0.001). Moreover, all achieved sustained virological response after 24 weeks of treatment-free follow-up versus no control patients (SVR 97% vs 0 %; p<0.001). CONCLUSIONS: In this study, we have shown for the first time in a large cohort of patients that HCV-patients on haemodialysis can be treated successfully with peginterferon alfa-2a (40 kDa) plus ribavirin.