Predictors of sustained virological response after antiviral treatment for hepatitis C recurrence following liver transplantation

Abstract

Factors associated with sustained virological response (SVR) in patients treated for hepatitis C virus (HCV) recurrence after liver transplantation (LT) are unclear. Ninety-nine HCV-positive/hepatitis B surface antigen-negative patients received antiviral treatment (AVT) with interferon/peginterferon plus ribavirin for HCV recurrence after LT. Cyclosporine (CyA) or tacrolimus (TAC) was used as the main immunosuppressor in 37 (37%) and 62 (63%) patients, respectively. Twenty-five patients (25%) achieved an SVR. Twenty-seven donor-related, recipient-related, HCV-related, and immunosuppression-related variables were investigated for their association with SVR. In logistic regression analysis, donor age Ͻ 60 years (odds ratio ϭ 4.45, 95% confidence interval ϭ 1.39-14.19, P ϭ 0.01), viral genotype other than 1 (odds ratio ϭ 4.97, 95% confidence interval ϭ 1.59-15.48, P ϭ 0.006), and the use of CyA during treatment (odds ratio ϭ 6.85, 95% confidence interval ϭ 2.15-21.73, P ϭ 0.001) were predictors of SVR. Patients treated with CyA (SVR rate: 43%) and those treated with TAC (SVR rate: 14%) were comparable for all variables, except for a shorter ischemia time and shorter timing of AVT initiation in the TAC group (P ϭ 0.02 and P ϭ 0.005, respectively) and a greater use of anti-CD25 antibodies, azathioprine, and mycophenolate mofetil in the CyA group (P ϭ 0.03, P Ͻ 0.001, and P ϭ 0.001, respectively). The rate of AVT discontinuation due to side effects was similar between groups (16% versus 8%, P ϭ 0.3). In conclusion, the type of immunosuppression during AVT may predict SVR in patients treated for HCV recurrence after LT. Hepatitis C virus (HCV)-related cirrhosis is the leading indication for liver transplantation (LT) in both theUnited States and Europe.1,2 Hepatitis C recurrence is almost universal, leading to severe liver damage in 30% of patients within 5 years of transplant. 3,4 In patients with posttransplant HCV recurrence, antiviral treatment (AVT) with interferon (IFN) and ribavirin is the only way to prevent severe reinfection of the graft, even though sustained virological response (SVR) is achieved in a minority of cases. 5Although predictors of severe HCV recurrence have been identified in recent years, 5-11 factors associated with the probability of SVR are much less clear. In fact, the effectiveness of AVT may be partly influenced by the same factors determining the natural course of HCV recurrence-donor age, quality of the graft, HCV-RNA level, viral genotype, type of immunosuppression, occurrence of rejection, and occurrence of cytomegalovirus (CMV) infection-and partly linked to other variables, such as the type of AVT, patient conditions, and grading and staging of reinfection at the time of initiation of antiviral drugs. 5,12Primary immunosuppression and particularly the use of cyclosporine (CyA) or tacrolimus (TAC) have been

Liver Transplantation for Hepatitis C: Disease Management

“…They found no effect. Factors associated with sustained viral response (SVR) in patients treated for HCV recurrence after LT were evaluated in 99 patients by Cescon et al [46]. TAC was the main immunosuppressor in 63% and CSA in 37%.…”

10.5937/mckg48-5925 = Therapy of chronic HCV infection: Association between virological response and predictive factors

“…616.36-002-085 Med čas (Krag) / Med J (Krag) 2014; 48(3): 113-121. bolesnicima s nepovoljnim odgovorom na terapiju (rr/nr). Ovakav nalaz potvrđen je i u drugim studijama koje su se bavile istraživanjem prediktora terapijskog odgovora (43,53,54). u skladu s ovim podacima, serumske vrednosti aminotransferaza, koje se smatraju vrlo osetljivim indeksom nekroze ćelija jetre, odnosno specifičnim parametrom hepatocelularnog oštećenja, niže su u grupi pacijenata sa nižim stepenom fibroze, a to su pacijenti sa pozitivnim odgovorom na terapiju (SVr i ETr) u odnosu na grupu bolesnika sa višim stepenom fibroze koja je karakteristična za pacijente sa negativnim odgovorom na terapiju (nr/rr).…”

HCV-Recurrence After Liver Transplantation

“…The indication for HCV-treatment after LT depends on the individual clinical and biochemical condition after a definitive stabilization of the graft function, which is usually achieved within six post-operative months [69]. Analogously to the natural setting, therapy regimen is based on the administration of pegylated interferon-α2a (Peg-IFN-α2a) and ribavirin (RBV) for 12-18 months.…”

“…Therefore, unnecessary exposition to adverse therapy events in non-responders could be avoided by improved predictability. HCV-genotype and early viral kinetics are predominantly considered to be important for therapy performance and its potential modification [69,76]. Apart from the identified factors (high levels of immunosuppression, corticosteroid-based ACR-treatment and HCV-genotype-1b), unfavorable host-and donorrelated genetic confounders are suspected to exert a negative influence on the course and success of antiviral treatment [22,69,77].…”

“…HCV-genotype and early viral kinetics are predominantly considered to be important for therapy performance and its potential modification [69,76]. Apart from the identified factors (high levels of immunosuppression, corticosteroid-based ACR-treatment and HCV-genotype-1b), unfavorable host-and donorrelated genetic confounders are suspected to exert a negative influence on the course and success of antiviral treatment [22,69,77]. According to several studies, genetic variants of IL-28B are strongly considered to affect the antiviral therapy results [64,78,79].…”