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Aim: To determine the safety profile of new hepatitis C virus (HCV) treatments in liver transplant (LT) recipients with recurrent HCV infection., Methods: Forty-two patients were identified with recurrent HCV infection that underwent LT at least 12 mo prior to initiating treatment with a Sofosbuvir-based regimen during December 2013-June 2014. Cases were patients who experienced hepatic decompensation and/or serious adverse events (SAE) during or within one month of completing treatment. Controls had no evidence of hepatic decompensation and/or SAE. HIV-infected patients were excluded. Cumulative incidence of decompensation/SAE was calculated using the Kaplan Meier method. Exact logistic regression analysis was used to identify factors associated with the composite outcome., Results: Median age of the 42 patients was 60 years [Interquartile Range (IQR): 56-65 years], 33% (14/42) were female, 21% (9/42) were Hispanic, and 9% (4/42) were Black. The median time from transplant to treatment initiation was 5.4 years (IQR: 2.1-8.8 years). Thirteen patients experienced one or more episodes of hepatic decompensation and/or SAE. Anemia requiring transfusion, the most common event, occurred in 62% (8/13) patients, while 54% (7/13) decompensated. The cumulative incidence of hepatic decompensation/SAE was 31% (95%CI: 16%-41%). Risk factors for decompensation/SAE included lower pre-treatment hemoglobin (OR = 0.61 per g/dL, 95%CI: 0.40-0.88, P < 0.01), estimated glomerular filtration rate (OR = 0.95 per mL/min per 1.73 m(2), 95%CI: 0.90-0.99, P = 0.01), and higher baseline serum total bilirubin (OR = 2.43 per mg/dL, 95%CI: 1.17-8.65, P < 0.01). The sustained virological response rate for the cohort of 42 patients was 45%, while it was 31% for cases., Conclusion: Sofosbuvir/ribavirin will continue to be used in the post-transplant population, including those with HCV genotypes 2 and 3. Management of anemia remains an important clinical challenge.

Aim: To describe our experience using a low-accelerating-dose regimen (LADR) with pegylated interferon alpha-2a and ribavirin in treatment of hepatitis C virus (HCV) recurrence., Methods: From 2003, a protocolized LADR strategy was employed to treat liver transplant (LT) recipients with recurrent HCV at our institution. Medical records of 182 adult patients with recurrent HCV treated with LADR between 1/2003 and 1/2011 were reviewed. Histopathology from all post-LT liver biopsies were reviewed in a blinded fashion. Paired recipient and donor IL28B status were assessed. A novel technique was employed to ascertain recipient and donor IL28B (rs12979860) Gt data using DNA extracted from archival FFPE tissue from explanted native livers and donor gallbladders respectively. The primary endpoint was SVR; secondary endpoints examined include (1) patient and graft survival; (2) effect of anti-viral therapy on liver histology (fibrosis and inflammation); (3) incidence of on-treatment development of ACR, CDR, or PCH; (4) association of recipient and donor IL28B genotype with SVR; and (5) incidence of anti-viral therapy-associated adverse events (anemia, leukopenia, thrombocytopenia, depression) and hepatic decompensation., Results: The overall SVR rate was 38% (29% Gt1, 67% Gt2, 86% Gt3 and 58% Gt4). HCV Gt (P < 0.0001), donor age (P = 0.003), cytomegalovirus mismatch (P = 0.001), baseline serum bilirubin (P = 0.002), and baseline viral load (P = 0.04) were independent predictors for SVR. SVR rates were significantly higher in the recipient-CC/donor-non CC pairs (P = 0.007). Neither baseline fibrosis nor change in fibrosis stage after anti-viral therapy were associated with SVR. Fibrosis progressed in 72% of patients despite SVR. Median graft survival was 91 mo. Five-year patient survival was superior in patients who achieved SVR (97% vs 82%, P = 0.001). Pre-treatment ALP ≥ 150 U/L (P = 0.01), total bilirubin ≥ 1.5 mg/dL (P = 0.001) and creatinine ≥ 2 mg/dL (P = 0.001) were independently associated with patient survival. Only 13% of patients achieving SVR died during the follow-up period. Treatment discontinuation and treatment-related mortality occurred in 35% and 2.2% of patients, respectively. EPO, G-CSF and blood transfusion were needed in 89%, 40% and 23% of patients, respectively. Overall hospitalization rate for treatment-related serious adverse events was 21%. Forty-six (25%) of the patients were deceased; among those who died, 25 (54%) were due to liver-related complications, and 4 deaths (9%) occurred while receiving therapy (2 patients experienced hepatic decompensation and 2 sepsis)., Conclusion: LADR strategy remains relevant in managing post-LT recurrent HCV where access to DAAs is limited. SVR is associated with improved survival, but fibrosis progression still occurs.