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BROWSE SLIDES

Design

Baseline characteristics, median or %

SVR₁₂ (HCV RNA < 15 IU/ml), % (90% CI)

• 7 subjects who were transplanted before day 70 after start of treatment with HCV RNA < 15 IU/ml and 3 subjects who did not meet study criteria are excluded

SVR₁₂ (HCV RNA < 15 IU/ml)

Fibrosing cholestatic hepatitis

• Patients transplanted 0.2 to 1.5 years before
• All 5 (3 with 12W and 2 with 24W) achieved SVR₁₂

SVR₁₂ (HCV RNA < 15 IU/ml) in Genotype 1

• 7 subjects who were transplanted and 3 subjects who did not meet inclusion criteria are excluded

Relapse and resistance

• Pretreatment resistance analysis using a 1% deep sequencing cutoff
  • Genotype 1
    • NS5A RAVs in 59/276 (21%) : 2/59 (3%) relapsed vs 5/217 (2.3%) with no RAVs (no relapse in the 32 patients with baseline NS5A RAVs with LDV/SOF + RBV 24W)
  • Genotype 4
    • NS5A RAVs in 24/32 (75%) : 3/24 relapsed vs 0/8 with no RAVs
• Overall, 10 relapses (decompensated cirrhosis in 9/10)
  • Genotype 1 = 7 : genotype 1a = 5; genotype 1b = 2
  • Genotype 4 = 3
• NS5A RAVs in genotype 1
  • At pretreatment : 2/7 (positions Q30, L31, Y93I)
  • At virologic failure : 7/7 (K24R, M28T, Q30H/K/T, L31M/V, Y93H/C)
• NS5A RAVs in genotype 4
  • At virologic failure : 3/3 (L30H/R, M31V, P58L, Y93C)
• NS5B at relapse : 2 patients (genotype 1 and 4d) with E237G, no S282T

MELD score change from baseline to follow-up W12 in patients achieving SVR

*Missing follow-up: N = 7

Improvements in MELD score:

• 58/81 (72%) of non-transplanted patients
• 25/43 (58%) of transplanted patients

Liver function change from baseline to follow-up W4

Change in Child-Pugh Class, n (%)

Adverse events, n (%)

*Fall, anemia (5), vomiting, diarrhea, dyspnea, hyperbilirubinemia
† edema, dehydration, HCC (2), type 2 diabetes mellitus, hyperbilirubinemia

• No deaths were considered treatment related

Grade 3 or 4 laboratory abnormalities

• Most common : decreases in hemoglobin and lymphocytes, increases in total bilirubin and glucose
• Median creatinine concentrations remained stable in all groups

Ribavirin

• A verage daily dose
  • Decompensated cirrhosis (transplanted or not) : 600 mg
  • No cirrhosis or compensated cirrhosis : 800 mg
• Dose modification
  • Reduction : 134 patients (40%)
  • Interruption : 26 patients (8%)
  • Discontinuation : 40 patients (12%)
  • No association with relapse

Summary

• LDV/SOF + RBV resulted in high SVR₁₂ rates in HCV patients with advanced liver disease, irrespective of transplantation status
  • For genotype 1, SVR₁₂ were similar between 12 and 24 weeks
  • 12 weeks of treatment should become the standard of care for this group of patients
• Rates of relapse were low and were most frequently seen in non-transplanted patients with decompensated cirrhosis
• Similar SVR rates were recorded in patients with and without baseline NS5A resistance-associated variants whether using a 1% cutoff or 15% cutoff for both genotype 1 and genotype 4
• Among patients with cirrhosis, virologic response was associated with improvements in MELD and Child-Pugh scores largely due to decreases in bilirubin and improvement in synthetic function (e.g. albumin)
• LDV/SOF + RBV for 12-24 weeks was generally safe and well tolerated in patients with advanced liver disease, pre and post liver transplantation
• Limitations
  • Few genotype 4