Successful combination of direct antiviral agents in liver-transplanted patients with recurrent hepatitis C virus

Abstract

AIMTo analyze the safety and efficiency of direct-acting antiviral (DAA) regimens in liver-transplanted patients with hepatitis C virus (HCV) reinfection.METHODSBetween 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.RESULTSThe 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)5A and NS5B 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.CONCLUSIONOur cohort of liver-transplanted patients achieved high rates of SVR12 after a 24-wk course of treatment, especially with combination of NS5A and NS5B inhibitors.

Liver Grafts with Major Extended Donor Criteria May Expand the Organ Pool for Patients with Hepatocellular Carcinoma

“…The number of transplant candidates with HCV-induced cirrhosis at our center peaked in 2011 and declined steadily until 2018. The interaction between advanced donor age and HCV recurrence may have been eradicated by DAA that cure HCV either before or after transplantation [29,35]. Although DAA medications were not available during most of the study period, HCV recurrence caused graft failure in only three patients and death in only one patient in the first year after transplantation.…”

Recurrent hepatitis C treatment with direct acting antivirals – a real life study at a Brazilian liver transplant center

“…All treatment failures were genotype 3-infected patients, similar to the present study. A German real-life study including ten patients treated with SOF and DCV, with or without RBV, achieved 100% SVR (20).…”

“…Favorable results can also be obtained with other DAA combinations, such as ombitasvir/paritaprevir/ritonavir and dasabuvir/ledipasvir/SOF or simeprevir and SOF, with or without RBV. The SVR rates achieved in clinical studies range from 80 to 100% (10–14,20).…”

Consensus on management of hepatitis C virus infection in resource-limited Ukraine and Commonwealth of Independent States regions

“…In real-world settings and large-scale, multicentric studies, an optimal duration of 12 wk and 24 wk has been suggested with this regimen in noncirrhotic and cirrhotic HCV GT1-infected patients, respectively, for achieving favorable SVR rates[47,88]. The efficacy and safety of this regimen have also been proven in other clinical and real-world studies and meta-analyses that enrolled HCV GT1-infected patients, including treatment-experienced patients, patients with cirrhosis or advanced liver disease, and liver transplant recipients[46,49,57,89-95]. The SVR rates in a few studies were found to be lower in cirrhotic versus noncirrhotic HCV GT1-infected patients treated with this regimen[46,96].…”

“…The regimen was well-tolerated[133]. In real-world settings, treatment of HCV GT3-infected patients, including cirrhotic and treatment-experienced patients, and liver transplant recipients (with a history of HCC prior to transplantation) with recurrent cirrhosis, with this regimen has been found to result in high SVR rates[46,56,57,91,112,134-144].…”