Successful combination of direct antiviral agents in livertransplanted patients with recurrent hepatitis C virus

AIM To analyze the safety and efficiency of direct-actingantiviral(DAA) regimens in liver-transplanted patients with hepatitis C virus(HCV) reinfection.METHODS Between January 2014 and December 2016, 39 patients with HCV reinfection after liver transplantation were treated at our tertiary referral center with sofosbuvir(SOF)-based regimens, including various combinations with interferon(IFN), daclatasvir(DAC), simeprivir(SIM) and/or ledipasvir(LDV). Thirteen patients were treated with SOF + IFN ± RBV. Ten patients were treated with SOF + DAC ± RBV. Fiveteen patients were treated with fixed-dose combination of SOF + LDV ± RBV. One patient was treated with SOF + SIM + RBV. Three patients with relapse were retreated with SOF + LDV + RBV. The treatment duration was 12-24 wk in all cases. The decision about the HCV treatment was made by specialists at our transplant center, according to current available or recommended medications.RESULTS The majority of patients were IFN-experienced(29/39, 74.4%) and had a history of hepatocellular carcinoma(26/39, 66.7%) before liver transplantation. Sustained virological response at 12 wk(SVR12) was achieved in 10/13(76.9%) of patients treated with SOF + IFN ± RBV. All patients with relapse were treated with fixed-dose combination of SOF + LDV + RBV. Patients treated with SOF + DAC + RBV or SOF + LDV + RBV achieved 100% SVR12. SVR rates after combination treatment with inhibitors of the HCV nonstructural protein(NS)5 A and NS5 B for 24 wk were significantly higher, as compared to all other therapy regimens(P = 0.007). Liver function was stable or even improved in the majority of patients during treatment. All antiviral therapies were safe and well-tolerated, without need of discontinuation of treatment or dose adjustment of immunosuppression. No serious adverse events or any harm to the liver graft became overt. No patient experienced acute cellular rejection during the study period. CONCLUSION Our cohort of liver-transplanted patients achieved high rates of SVR12 after a 24-wk course of treatment, especially with combination of NS5 A and NS5 B inhibitors.

Comparative effectiveness of medical treatment vs.metabolic surgery for histologically proven non-alcoholic steatohepatitis and fibrosis:a matched network meta-analysis

Background:Non-alcoholic steatohepatitis(NASH)comprises a major healthcare problem affecting up to 30%of patients with obesity and the associated risk for cardiovascular and liver-related mortality.Several new drugs for NASH-treatment are currently investigated.No study thus far directly compared surgical and non-surgical therapies for NASH.This network meta-analysis compares for the first time the effectiveness of different therapies for NASH using a novel statistical approach.Methods:The study was conducted according to the PRISMA guidelines for network meta-analysis.PubMed,CENTRAL and Web of Science were searched without restriction of time or language using a validated search strategy.Studies investigating therapies for NASH in adults with liver biopsies at baseline and after at least 12 months were selected.Patients with liver cirrhosis were excluded.Risk of bias was assessed with ROB-2 and ROBINS-I-tools.A novel method for population-adjusted indirect comparison to include and compare single-arm trials was applied.Main outcomes were NASH-resolution and improvement of fibrosis.Results:Out of 7,913 studies,twelve randomized non-surgical studies and twelve non-randomized surgical trials were included.NASH-resolution after non-surgical intervention was 29%[95%confidence interval(CI):23-40%]and 79%(95%CI:72-88%)after surgery.The network meta-analysis showed that surgery had a higher chance of NASH-resolution than medication[odds ratio(OR)=2.68;95%CI:1.44-4.97]while drug treatment was superior to placebo(OR=2.24;95%CI:1.55-3.24).Surgery(OR=2.18;95%CI:1.34-3.56)and medication(OR=1.79;95%CI:1.39-2.31)were equally effective to treat fibrosis compared to placebo without difference between them.The results did not change when only new drugs specifically developed for the treatment of NASH were included.Conclusions:Metabolic surgery has a higher effectiveness for NASH-therapy than medical therapy while both were equally effective regarding improvement of fibrosis.Trials directly comparing surgery with medication must be urgently conducted.Patients with NASH should be informed about surgical treatment options.