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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