Hepatitis C virus therapy in liver transplant recipients: Response predictors, effect on fibrosis progression, and importance of the initial stage of fibrosis

Abstract

Antiviral therapy after liver transplantation (LT) using interferon (IFN) and ribavirin (RBV) can achieve a sustained virological response (SVR) rate ranging from 20% to 45%. The aims of our study were to assess efficacy and tolerability of therapy, effect on fibrosis progression and the importance of the initial fibrosis stage to outcome. A total of 113 hepatitis C virus (HCV)-infected LT patients received 133 courses of IFN (standard, n ϭ 29, pegylated IFN [pegIFN], n ϭ 104) and RBV (75% genotype 1). Early virological response (EVR), end-of-treatment (EOT), and SVR were obtained in 74%, 55%, and 38%, respectively. EVR, completion of treatment, viral load before therapy, genotype non-1, and use of pegIFN were predictive of SVR, but only EVR remained in the multivariate analysis. SVR was obtained in 45% patients who received a second course of therapy. Paired biopsies at baseline, at EOT and at long-term were available in 42 patients. The mean fibrosis stage remained stable in patients with SVR and increased in patients without response. Rejection episodes were observed in 6% of patients. Tolerability of therapy decrease in patients with fibrosis stage Ն3 on baseline liver biopsy. A total of 20% of them died or were retransplanted due to liver failure as opposed to 1% of patients who had fibrosis stage Ͻ3. In conclusion, IFN and RBV achieved SVR in 38% of patients. EVR is independently associated with SVR. Fibrosis stage remained stable in patients with SVR and increased in nonresponders. Hepatitis C virus (HCV)-related end-stage cirrhosis is currently the leading indication for liver transplantation (LT) in the United States and Europe. However, recurrent infection with HCV is almost universal, constitutes a significant cause of graft dysfunction and impairs patient and graft survival.1-4 The course of HCV graft disease is accelerated in transplant recipients compared with immunocompetent patients, with 5-year rates of cirrhosis of around 20% reported as leading to graft failure and retransplantation. [1][2][3] Several pilot studies and 1 randomized study of combination antiviral therapy with interferon (IFN) and ribavirin (RBV) achieved rates of sustained virological response (SVR) ranging from 20% to 30% 5-8 and combined pegylated IFN (pegIFN) and RBV was able to attain SVR rates of 25% to 45%. [8][9][10][11][12][13] However, the treatment of recurrent HCV using IFN/RBV-based regimens has been hindered by a high incidence of adverse effects and, in particular, a risk of rejection. Thus identifying the factors associated with an absence of SVR at an early stage of treatment is important to reducing the toxicity of therapy.

Glucocorticosteroids Increase Cell Entry by Hepatitis C Virus

“…PEG-IFNα and ribavirin have also been applied in patients after liver transplantation. However, in this context, efficacy is lower with sustained virological responses ranging from 20% to 45% only 3 .…”

Evidence of Spontaneous Post-transplant HCV Eradication in Two Failed DAA Treatments Awaiting Liver Transplantation

“…Transplant recipients with high levels of HCV-RNA prior to LT are more likely to experience fibrosis progression and poor outcome [1]. It is therefore essential to consider early antiviral therapy in the transplant setting, since achievement of sustained virological response (SVR) improves clinical outcomes and survival rates in LT recipients [2]. The recent introduction of direct-acting antivirals (DAAs) has revolutionized the management of HCV therapy [3].…”

Ledipasvir and sofosbuvir for recurrent hepatitis C after liver transplantation

“…Liver transplant recipients with HCV infection have a poorer prognosis than those without HCV infection (2) when the virological response is not enough (3). Up to 30% of HCV-infected living-donor liver transplantation (LDLT) recipients develop cirrhosis within 5 years after transplantation (4)(5)(6). The interferon-based therapy (pegylated interferon and ribavirin with/without HCV protease inhibitor, such as simeprevir or telaprevir) for recurrent HCV is less effective for inducing an antiviral response in liver transplant recipients.…”