Sustained virologic response to therapy of recurrent hepatitis C after liver transplantation is related to early virologic response and dose adherence

Abstract

Sustained virologic response (SVR) after antiviral therapy for recurrent hepatitis C virus (HCV) infection in liver transplant (LT) recipients is consistently lower than that achieved in non-LT patients. We evaluated efficacy and safety of pegylated interferon (IFN) and ribavirin (RBV) therapy in LT recipients with recurrent HCV and factors associated with SVR. All subjects with histologic evidence of recurrent HCV were intended to be treated for 48 weeks with full-dose pegylated IFN; target dose of RBV was 800 mg/day. Thirty-five LT recipients with recurrent HCV, median age 48.5 years, 77% genotype 1, and median pretreatment HCV RNA 6.4 log 10 IU/mL were treated between January 2000 and February 2006. Antiviral therapy was discontinued prematurely in 15 subjects as a result of adverse events. Median overall treatment duration was 46 weeks. Early virologic response at week 12 was seen in 17 (49%) and an end-of-treatment virological response in 19 (54%) patients. SVR was achieved in 13 patients (37%), and all 9 patients followed for Ͼ1 year after treatment had durable response. Patients with SVR had significantly lower pretreatment HCV RNA (5.7 vs. 6.5 log 10 IU/mL, P ϭ 0.003), more likely to have a week 12 virological response (85% vs. 27%, P ϭ 0.0009) and received higher cumulative doses of pegylated IFN (75% vs. 33%, P ϭ 0.029) and RBV (90% vs. 26%, P ϭ 0.016) compared with patients whose disease did not respond to therapy. In conclusion, SVR was achieved in 37% of patients with recurrent hepatitis C after LT. Similar to non-LT patients, those with lower pretreatment HCV RNA, a week 12 virological response, and pegylated IFN and RBV dose adherence were more likely to achieve SVR.

Prevention of hepatitis C recurrence after liver transplantation: An update

“…Sharma et al [141] 2007 Retrospective, uncontrolled Zimmermann et al [107] 2007 Prospective, with recurrence of HCV infection who are not receiving antiviral therapy [109] . A higher risk of developing alloimmune hepatitis is reported, typically after HCV RNA clearance (approximately 5% of cases) [110] .…”

Management of Recurrent HCV and HBV Infections after Liver Transplantation

“…Recent studies suggest that ACR develops due to decreasing levels of immunosuppressive drugs after viral clearance and subsequent improvement of hepatic microsomal function. Reported rejection rates vary in respect to the study design, being lower in randomized controlled trials (0-5%) [Chalasani et al, 2005;Samuel et al, 2003) and as high as 35% in uncontrolled trials (Dumortier et al, 2004;Sharma et al, 2007;Stravitz et al, 2004). Berenguer M et al reported trend towards higher rejection rate on pegylated IFN in comparison with standard treatment (Berenguer et al, 2006b).…”

Managing hepatitis C in liver transplant patients with recurrent infection

“…112 Whether this 12-week stopping rule applies equally to transplant recipients with recurrent hepatitis C has not been conclusively determined, but data from recent studies suggest that the role of EVR in predicting treatment outcome among liver transplant recipients is comparable to that in the nontransplant setting. 104,106,107,110 EVR represents an important predictor of treatment outcome and may be considered a reliable indicator that treatment should be stopped if it is not attained. At present, attainment of EVR is the only factor shown by multivariate analysis to be significantly associated with SVR.…”

“…161 Treatment with PEG-IFN plus ribavirin was administered in most studies over a duration of 12 months. 94,96,98,99,101,[104][105][106][107][108][109][110] The question of whether genotype 2 and 3 can be treated for a shorter time or if it is necessary to prolong therapy in patients with delayed virological response and high baseline viral loads as recommended in the nontransplant setting remains also to be answered. In the transplant setting many studies pool genotype 1 and non-1, resulting in higher overall SVR rates, since genotype 2 and 3 are known to result in better SVR rates.…”

“…104,106,107,109 Thus it is difficult to balance the necessity for high-dose (800 mg/day) ribavirin to attain high SVR rates against its extremely poor tolerability profile in these patients. Weight-based dosing is inadvisable because of the high treatment-related toxicity.…”