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THERAPY OF CHRONIC HCV IN PATIENTS WITH LIVER CIRRHOSIS DIRK - - PowerPoint PPT Presentation
THERAPY OF CHRONIC HCV IN PATIENTS WITH LIVER CIRRHOSIS DIRK - - PowerPoint PPT Presentation
THERAPY OF CHRONIC HCV IN PATIENTS WITH LIVER CIRRHOSIS DIRK NIERHOFF, PD DR. MED. UNIKLINIK KLN Natural disease course in liver cirrhosis Optimist-2: SOF + SIM
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Optimist-2: SOF + SIM
Lawitz E, et al. EASL 2015. Abstract LP04. Published 19.02.2016
- FIG. 2. SVR12 by baseline NS5A and Q80K polymorphisms
(intent-to-treat population).
- SAEs in 5% of patients
- 1 patient died in traffic accident
- No hepatic decompensation
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ALLY-1: DAC + SOF + RBV
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Phase 2/3 integrated Analysis of LDV/SOF +/- RBV
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TURQUOISE-II: OBV/PTV/r+DSV+RBV
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TURQUOISE-III: OBV/PTV/r+DSV+RBV
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FDA Drug Safety Communication: FDA warns of serious liver injury risk with HCV treatments Viekira Pak and Technivie
Reported cases typically occurred within one to four weeks of initiating therapy and were characterized by the acute onset of rising direct serum bilirubin levels without ALT [alanine aminotransferase] elevations in association with clinical signs and symptoms of hepatic decompensation.
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Pooled safety analysis: OBV/PTV/r+DSV+RBV
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Jacobson et al., AASLD 2015; O#42+LB22
SVR12 (%)
98 90 No RBV RBV 135/ 138 28/ 31 Treatment Naive (n=169); 12 Wks n/N = 80 100 60 40 20
SVR12 (%)
89 91 94 100 48/ 54 74/ 81 46/ 49 49/ 49 No RBV RBV No RBV RBV 12 wks 16 or 18 wks n/N = 80 100 60 40 20 Treatment Experienced (n=233) Advantage for Non-Responder with RBV and 16w.
Phase 2/3 integrated Analysis Grazoprevir + Elbasvir
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ASTRAL-1: Sofosbuvir + Velpatasvir
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Decompensated liver cirrhosis
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Open-label, ~90% Child B, ~80% Aszites, ~60% HE, MELD Median 10; HCC/LTx excluded MELD>15: 84% better, 8% worse after SVR; MELD <15: 52% better, 27% worse after SVR AEs konsistent with liver cirrhosis und ribavirin toxicity
Charlton MR, et al. AASLD 2015. Abstract LB-13. Curry MP, et al. N Engl J Med. 2015;[Epub ahead of print].
All Pts 1 3 HCV Genotype n/N = SVR12 (%) SOF/VEL 12 wks SOF/VEL + RBV 12 wks SOF/VEL 24 wks 2, 4, and 6 100 80 60 40 20 83 94 86 88 96 92 50 85 50 100 100 86 75/90 82/87 77/90 60/68 65/68 65/71 7/ 14 11/ 13 6/ 12 8/ 8 6/ 6 6/ 7
Astral-4: Decomp. liver cirrhosis Sofosbuvir + Velpatasvir
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Conclusion I
DAA therapy in compensated liver cirrhosis is safe. SVR12 in all combinations > 90 - 100%. In decompensated liver cirrhosis protease inhibitors should be avoided. SVR12 rates are significantly lower.
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And what happens to liver cirrhosis after SVR12? But what about safety in the real world?
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Hepa-C-Registry (Spanien)
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UK EAP Advanced liver cirrhosis
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UK EAP Advanced liver cirrhosis
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UK EAP Advanced liver cirrhosis
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UK EAP Advanced liver cirrhosis
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Hepa-C-Registry (Spanien)
MELD 18: 3 M-Mortality 11%!
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Final conclusion
In compensated cirrhosis DAA therapy is safe with high SVR12-rates. In decompensated cirrhosis SVR12 rates are significantly lower Severe AEs more common with higher MELD. Consider listing before start of therapy! Only a minority of patients with CP-C achieve long-term benefit. Consider therapy after liver transplantation!
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Hepa-C-Registry (Spanien)
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- Komp. LCI und Real-
World?
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- Dekomp. LCI und Real-
World?
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