CURRY

CURRY Study: SOF + RBV for HCV with liver cancer before transplantation
Sofosbuvir and Ribavirin Prevent Recurrence of HCV Infection After Liver Transplantation: An Open-Label Study
Curry MP. Gastroenterology 2015;148:100-107

Anti-HCV
Sofosbuvir
Ribavirin
Genotype
1
1a
1b
Special population
Liver transplantation

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Design


Standard post-transplantation immunosuppressive regimen of solumedrol / prednisone, tacrolimus, and/or mycophenolate mofetil (up to 2 g/day) for the first 12W after transplantation

Objective

  • Primary endpoint : post-transplant response 12 weeks after transplantation [pTVR 12] (HCV RNA < 25 IU/ml) in patients with HCV RNA < 25 IU/ml at last assessment before transplantation, by intention to treat, with 2 -sided 90% CI and upper bound of recurrence rate of 65% Baseline characteristics and patient disposition

Baseline characteristics and outcome

Multivariate analysis of factors associated with absence of recurrence post-transplantation

HCV Recurrence and resistance analysis

  • 10 confirmed recurrence after liver transplantation
    • Genotype 1a, N = 2; 1b, N = 7; 3a, N = 1
    • ILB28 non-CC, N = 10
    • Recurrence at W1 (N = 3), W2 (N = 2), W4 (N = 4), or W12 (N = 1) post-transplantation
    • Duration of SOF+ RBV pre-transplantation < 12 weeks , N = 4
  • NS5B sequencing
    • At baseline :
      • 4 patients with L159F variant : 4/4 relapsed
      • 1 patient with N142T : achieved SVR12
    • . 29 patients with failure before transplantation or recurrence after transplantation
      • no S282T mutant
      • 12 patients with other variants as minor subpopulations (< 10%) in 11/12 : N142T (N = 2), L159F (N = 5), S282G (N = 1), L230F
        (N = 3); L159F + S282R + L230F + V321A (N = 1)

Adverse events

  • Median duration of exposure to study regimen : 21 weeks
  • Serious adverse events, N = 11
  • = Grade 3 adverse event, N = 11
  • Discontinuation due to adverse event, N = 2 (pneumonia, sepsis/acute renal failure)
  • Most common adverse events :
    • Fatigue (38%)
    • Headache (23%)
    • Anemia (21%)
    • Nausea (16%)
    • Rash (15%)
    • Dyspnea (11%)
    • Cough (11%)
    • Insomnia (11%)
    • Constipation (10%)
    • Pruritus (10%)
  • Most common grade 3-4 laboratory abnormalities : grade 3 decrease in hemoglobin level, grade 3 hyperglycemia, grade 3-4 bilirubin elevation, lymphopenia < 500/mm3
    • 12 patients with RBV dose reduction, but no transfusion, no epoetin needed

Summary

  • In this pilot study, SOF + RBV before liver transplantation prevented recurrence of HCV infection in 70% of patients with chronic HCV infection and liver cancer who achieved an HCV RNA level < 25 IU/ml before transplantation and in almost half of the total patients in the study
  • The rate of discontinuation owing to adverse events was low, and most adverse events were those associated with RBV therapy-fatigue, anemia, headache, and nausea-as were the laboratory abnormalities of decreased hemoglobin and increased bilirubin
  • Enrichment in minor resistance-associated variants, although rare, may encode for marginal reductions in susceptibility to SOF
  • Limitations
    • Low sample size
    • Exclusion of patients with decompensated liver disease