Slow achievement of HCV-RNA undetectability in cirrhotic patients treated with sofosbuvir+ribavirin: possible clinical implications in the liver transplant list management

Sofosbuvir (SOF) treatment ± ribavirin (RBV) prior to LT has the potential to change the HCV recurrence after Liver Transplantation (LT). This approach has been reported to avoid graft reinfection in compensated patients with hepatocellular carcinoma (HCC), but only among those who reached and maintained undetectable HCV-RNA (TND) before LT. Since the time to obtain this result in decompensated cirrhotics is unknown, we sought to investigate the early HCV-RNA decay in this setting. Sixteen decompensated patients (M/F 12/4, median age 55.3, CPT score>=B7), infected by HCV genotype 1a, 1b, 3 and 4 (2-8- 4-2), 4 of whom with HCC, were treated with SOF 400mg/day and RBV (200-1000 mg/day), except 2 who received SOF alone, for a median(IQR) of 12(11-16) weeks awaiting LT. HCV-RNA levels were measured weekly and safety and clinical parameters were analyzed. No serious adverse events were reported. The median(IQR) RBV dose was 600(400-800). Despite 11/16 patients had low baseline viremia (<600.000 IU/ml), HCV-RNA decay in the first 4 weeks of treatment was suboptimal (median[IQR] = -3.7[-4.3;-3.3] LogIU/ml). Only 3/16 (18.7%) patients reached TND HCV-RNA at week 4 (rapid virological response, RVR), and 5/10 (50%) evalu- able patients were still viremic at week-12. Median(IQR) MELD decreased from 15(13-16) at baseline to 13(12-15) at week 4, when 14/16 (87.5%) patients returned in a compensated stage. One patient underwent LT after 6 weeks of treatment, while HCV-RNA was still positive (26 UI/mL). SOF was interrupted only during the first 4 perioperative days, obtaining TND HCV-RNA at week 10 of therapy. The kinetics of HCV-RNA decay in decompensated cirrhotic patients are slower compared to those obtained in non cirrhotic patients. As a practical implication, pre-LT treatment may need to be longer and/or based on more effective antiviral strategies. Alter- natively, MELD-based prioritization to LT should be reassessed in light of the results of antiviral therapy.