A Randomized Controlled Trial of Pretransplant Antiviral Therapy to Prevent Recurrence of Hepatitis C after Liver Transplantation

摘要

Hepatitis C virus (HCV) infection recurs in liver recipients who are viremic at transplantation. We conducted a randomized controlled trial to test the efficacy and safety of pre-transplant pegylated interferon alpha-2b plus ribavirin (Peg-IFN-a2b/RBV) for prevention of post-transplant HCV recurrence. Enrollees had HCV and were listed for liver transplantation, with either potential living donors or MELD upgrade for hepatocellular carcinoma. Patients with HCV genotypes (G) 1/4/6 (n=44/2/1) were randomized 2:1 to treatment (n=31) or untreated control (n=16); HCV G2/3 (n=32) were assigned to treatment. Overall, 59 were treated and 20 were not. PEGIFN alfa-2b, starting at 0.75 μg/kg/wk, and ribavirin (RBV), starting at 600 mg/d, were escalated as tolerated. Patients assigned to treatment versus control had similar baseline characteristics. Combined virologic response (CVR) included pre-transplant sustained VR (SVR12) and post-transplant VR (pTVR), defined as undetectable HCV RNA 12 weeks after end of treatment or transplant, respectively. In intent-to-treat analyses, 12 (19%) assigned to treatment and 1 (6%) assigned to control achieved CVR (p=0.29); per-protocol values were 13 (22%) and 0 (0%) (p=0.03). Among treated G1/4/6 patients, 23/30 received transplant of whom 22% had pTVR; among treated G2/3 patients 21/29 received transplant, of whom 29% had pTVR. pTVR was 0%, 18%, and 50% in patients treated for <8, 8–16, and >16 weeks, respectively (p=0.01). Serious adverse events (SAEs) occurred with similar frequency in treated versus untreated patients (68% vs. 55%, p=0.30) but the number of SAEs per patient was higher in the treated group (2.7 vs. 1.3, p=0.003).ConclusionPretransplant treatment with PEGIFN/RBV prevents post-transplant recurrence of HCV in selected patients. Efficacy is higher with >16 weeks of treatment, but treatment is associated with increased risk of potentially serious complications.