The prediction of immunological dysfunction during antiviral therapy for HCV after liver transplantation: can we improve outcomes?

Abstract

Much research has focused on the incidence and clinical characteristics of recurrent hepatitis C in liver transplantation (LT) patients during and after pegylated-interferon and ribavirin (PEG-IFN/RBV) therapy. These patients are generally characterized by a high prevalence of recurrent hepatitis C, a more aggressive rate of disease progression and low survival rates. Recurrent hepatitis C usually results from repeated therapy using corticosteroid and anti-lymphocyte antibodies [1]. Based on histological evidence, 50-90 % of patients who undergo LT develop recurrent HCV within 12 months, and 20-30 % of patients develop liver cirrhosis within 5 years [2,3]. Patients with recurrent hepatitis C after LT have a 56.7 % of 5-year survival rate, which is significantly lower than that in HCV-negative patients [4,5]. Furthermore, it is difficult to treat recipients with recurrent HCV recurrence [6]. The rate of sustained virological response (SVR) in these patients is frequently lower because of limited therapeutic options and potential immunological complications. Therefore, the treatment for post-LT patients with recurrent hepatitis C remains a significant clinical challenge.Preemptive antiviral treatment and the treatment of established recurrent hepatitis C have been adopted in some clinical settings. Preemptive treatment refers to early antiviral therapy, which is given within days or weeks after LT in all patients, despite histological evidence of recurrence. However, 30 % of patients do not tolerate this treatment well, and half of the patients require drug dose reduction [7]. One randomized trial evaluated the efficacy of preemptive anti-HCV therapy and found that only 9 % of patients achieved SVR [8]. The treatment of established HCV recurrence can involve patients who are most likely to achieve the benefit from antiviral therapy, whereas patients without HCV recurrence can avoid the side effects. A recent study has established that the best treatment results for patients with established HCV recurrence were obtained from PEG-IFN/RBV treatment [9]. Patients who achieved SVR (20-30 %) showed slower disease progression and longer term graft survival compared to non-responders [10][11][12]. A higher proportion of genotype 1 disease, poor adherence to therapy or lower drug doses, and severe complications were responsible to lower SVR rates in these patients.However, the efficacy of PEG-IFN/RBV treatment for post-LT patients with HCV recurrence is negatively affected by immunological dysfunction (ID), which includes acute cellular rejection (ACR), plasma cell/autoimmune hepatitis and chronic rejection [13][14][15][16][17]. ID usually occurs together with LT and recurrent hepatitis C during or after PEG-IFN/RBV therapy, and it is recognized as a unique clinical entity. Patients who develop ID are at risk of lower long-term survival rates, higher re-transplantation rates and fewer increases in the rate of SVR. In a multicenter case-controlled retrospective study, certain risk factors, including no prior PEG-IFN therapy...