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Pre-liver transplant antiviral therapy reduced risk for HCV recurrence

Patients with chronic hepatitis C who underwent antiviral treatment before liver transplant were less likely to experience recurrence following transplantation in a recent study.

Researchers randomly assigned patients 44 patients with HCV genotype 1, two with genotype 2 and one with genotype 4 to receive either dose-escalated pegylated interferon alpha-2b with ribavirin (Peg-IFN/RBV, n=31) or no treatment (n=16) before undergoing liver transplantation. Peg-IFN/RBV also was administered to 32 patients with HCV genotype 2 or 3 who were not randomly assigned.

Combined virologic response (CVR) was defined as sustained virologic response (SVR) 12 weeks after completing the pretransplant regimen and post-transplant virologic response (pTVR) 12 weeks after transplant. CVR occurred in 19% of treated recipients and 6% of controls in intent-to-treat analysis (P=.29), and 22% of recipients and 0% of controls in per-protocol analysis (P=.03).

Fifty-nine patients received treatment and 20 did not. Transplant was performed in 57 cases, including 44 treated patients and 13 controls. Fifty-nine percent of treated transplant recipients had achieved undetectable HCV RNA beforehand, compared with none of the controls (P<.0001).

Among 30 treated patients with genotypes 1, 4 or 6, 23 underwent transplant, with 22% experiencing pTVR. Among those with genotypes 2 or 3, 21 of 29 treated patients underwent transplant and 29% experienced pTVR (P=.6 compared with genotypes 1, 4 or 6). None of the patients treated for less than 8 weeks experienced pTVR, which occurred in 18% of those who received 8 to 16 weeks and 50% of those treated more than 16 weeks (P<.01).

Sixty-eight percent of treated and 55% of untreated patients experienced serious adverse events (P=.3), and treated patients experienced more events (2.7 per patient compared with 1.3, P=.003). Treatment was not associated with an increased risk for mortality: 15% of treated patients died vs. 10% of controls (P=.81).

“Pretransplant treatment prevented post-transplant recurrence of HCV infection in 25% of transplanted cases,” the researchers wrote. “Despite these potentially significant therapeutic benefits, Peg-IFN and RBV were poorly tolerated in these ‘difficult-to-treat’ and ‘difficult-to-cure’ patients.

“Future treatments incorporating direct-acting antivirals that accelerate and enhance virologic response should improve rates of pTVR, but will require strategies to limit toxicity.”