Abstract

Background: Treatment of recurrent HCV after liver transplant (LT) with interferon (PEG) and ribavirin (RBV) is complicated by poor tolerance, risk of rejection, low SVR (15−35%), and high relapse (18−50%). Ability to predict relapse may prompt extended therapy. Tissue PCR may be useful in identifying residual hepatic HCVRNA when unable to detect in serum. We postulated that negative tissue PCR during PEG/RBV would predict low risk of relapse. Methods: Patients with recurrent HCV following LT were given PEG/RBV for a minimum 48 weeks. In 14 patients that achieved serum PCR negativity, treatment was extended until serum TMA negative, tissue PCR negative, and absence of moderate necroinflammation on biopsy. Tissue PCR (NGI, Los Angeles, CA) was performed on liver biopsy specimens frozen in liquid nitrogen at bedside. Results: 11/14 patients eventually achieved SVR (79%) while 3/14 patients had relapse or breakthrough on treatment. One patient required 2 treatment courses for SVR (initially relapsed), and another patient received 2 treatment courses, with one relapse and one breakthrough, for a total of 16 treatment courses for 14 patients. SVR was noted in 11/16 courses; relapse or breakthrough were noted in 5/16 courses. The baseline viral load, HAI, stage, duration of PEG, and duration of PCR or TMA negativity on treatment were no different between the groups. The Delta HAI trended toward more improved in those with SVR (p = 0.07). 20 biopsies for tissue PCR from 14 patients were obtained. 18/20 biopsy PCRs were negative while 2 were positive. All patients with negative serum PCR/TMA at time of biopsy also had negative tissue PCR, including the 3 patients that relapsed. The only 2 positive tissue PCRs had viremia (breakthrough) at time of biopsy. Positive tissue PCR identified breakthrough, but not relapse. Conclusions: Treatment of HCV recurrence following LT appears to require protracted treatment courses with prolonged negative molecular testing and a decrease in necroinflammation before sustained response is likely. Tissue PCR does not appear to add additional information regarding risk of relapse in post-transplant patients undergoing treatment for HCV.

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