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The Hong Kong Association for the Study of Liver Diseases What are the remaining questions in The Hong Kong Association for the Study of Liver Diseases Hepatitis C management? The Hong Kong Association for the Study of Liver Diseases The Hong Kong Association for the Study of Liver Diseases The Hong Kong Association for the Study of Liver Diseases The Hong Kong Association for the Study of Liver Diseases Prof.Teerha Piratvisuth MD. NKC Institute of Gastroenterology and Hepatology The Hong Kong Association for the Study of Liver Diseases Prince of Songkla University, Thailand

The Hong Kong Association for the Study of Liver Diseases The Hong Kong Association for the Study of Liver Diseases What is the Optimal management for CHC decompensated cirrhosis? The Hong Kong Association for the Study of Liver Diseases The Hong Kong Association for the Study of Liver Diseases The Hong Kong Association for the Study of Liver Diseases The Hong Kong Association for the Study of Liver Diseases The Hong Kong Association for the Study of Liver Diseases

The Hong Kong Association for the Study of Liver Diseases Key Considerations for CHC Decompensated Cirrhosis The Hong Kong Association for the Study of Liver Diseases ▪ Treatment options are more limited than for patients The Hong Kong Association for the Study of Liver Diseases without cirrhosis or with compensated cirrhosis – SVR rates are generally lower The Hong Kong Association for the Study of Liver Diseases ▪ Protease inhibitors are not recommended for CTP B or C The Hong Kong Association for the Study of Liver Diseases ▪ Continuing role for ribavirin – Initial low dose The Hong Kong Association for the Study of Liver Diseases ▪ Extend duration to 24 wks if RBV ineligible The Hong Kong Association for the Study of Liver Diseases

The Hong Kong Association for the Study of Liver Diseases SOF/VEL/VOX and G/P and not recommended in patients with decompensated cirrhosis The Hong Kong Association for the Study of Liver Diseases Exposure Level (relative to The Hong Kong Association for the Study of Liver Diseases DAA patients with normal hepatic function) The Hong Kong Association for the Study of Liver Diseases Voxilaprevir 5-fold The Hong Kong Association for the Study of Liver Diseases Pibrentasvir 11-fold The Hong Kong Association for the Study of Liver Diseases The Hong Kong Association for the Study of Liver Diseases Pearlman BL. Aliment Pharmacol Ther. 2018;48:914-923

The Hong Kong Association for the Study of Liver Diseases SVR12 by Baseline Disease Severity ALLY-1 SOF/DCV+RBV: SVR12 by Child-Pugh Class Cirrhosis Cohort Advanced cirrhosis cohort, all genotypes The Hong Kong Association for the Study of Liver Diseases The Hong Kong Association for the Study of Liver Diseases SVR12, % The Hong Kong Association for the Study of Liver Diseases The Hong Kong Association for the Study of Liver Diseases No Yes No Yes >3.5 2.8 <2.8 <1.7 1.7 >2.3 <2.0 2.0 >3.0 A B C to to to 3.5 2.3 3.0 The Hong Kong Association for the Study of Liver Diseases Child-Pugh class Ascites HE Albumin, g/dL INR T bili, mg/dL The Hong Kong Association for the Study of Liver Diseases HE = hepatic encephalopathy

The Hong Kong Association for the Study of Liver Diseases ALLY-3+ The SOLAR-1 STUDY: LDV/SOF+RBV Treatment in HCV genotype 1 or 4 with decompensated cirrhosis The Hong Kong Association for the Study of Liver Diseases RBV: initial dose of 600mg daily SVR 12 (%) 100 87 89 86 87 The Hong Kong Association for the Study of Liver Diseases 80 60 The Hong Kong Association for the Study of Liver Diseases 40 20 48 52 43 56 35 The Hong Kong Association for the Study of Liver Diseases 0 12 W 24 W 12 W 24 W Treatment CTP class B CTP class C duration Serious Adverse event The Hong Kong Association for the Study of Liver Diseases CTP 12W 24 treatment duration Class B 10% 34% Class C 26% 42% The Hong Kong Association for the Study of Liver Diseases Rookstroh JK. etal. Lancet HIV 2015; 2: e319 – 27.

The Hong Kong Association for the Study of Liver Diseases ASTRAL-4: SOF/VEL ± RBV in HCV Patients with Decompensated Liver Disease SVR12 The Hong Kong Association for the Study of Liver Diseases SOF/VEL 12 wk SOF/VEL+RBV 12 wk SOF/VEL 24 wk 100 85 96 94 100 92 100 88 86 86 83 The Hong Kong Association for the Study of Liver Diseases 50 50 80 The Hong Kong Association for the Study of Liver Diseases SVR12 (%) 60 40 The Hong Kong Association for the Study of Liver Diseases 20 GT2 3/4 GT2 4/4 GT2 4/4 GT4 2/2 GT6 1/1 75/90 82/87 77/90 60/68 65/68 65/71 7/14 11/13 6/12 GT4 4/4 GT4 2/2 0 The Hong Kong Association for the Study of Liver Diseases Overall GT 1 GT 3 GT 2, 4, and 6 Breakthrough, n ― 1 1 ― ― ― ― 1* 1 ― ― ― Relapse, n 11 2 7 5 1 3 6 1* 4 ― ― ― Lost to follow up, n 1 ― 3 1 ― 3 ― ― ― ― ― ― Death, n 3 2 2 2 2 ― 1 ― 1 ― ― 1 SOF/VEL + RBV resulted in highest SVR12 in patients with decompensated liver disease The Hong Kong Association for the Study of Liver Diseases *Patient with nondetectable drug levels at time of virologic failure. Charlton M, et al., AASLD, 2015, #LB-13

The Hong Kong Association for the Study of Liver Diseases ALLY-3+ Treatment of HCV genotype 1 or 4,6 with decompensated cirrhosis CTP class B or C The Hong Kong Association for the Study of Liver Diseases Regimens Ribavirin Treatment duration The Hong Kong Association for the Study of Liver Diseases Ledipasvir (60mg)/ With low initial dose of RBV 12-24 week Sofosbuvir (400mg) The Hong Kong Association for the Study of Liver Diseases Sofosbuvir (400mg) / 12 week With low initial dose of RBV Velpatasvir (100mg) The Hong Kong Association for the Study of Liver Diseases The Hong Kong Association for the Study of Liver Diseases Daclatasvir (60mg) + With low initial dose of RBV 12 week Sofosbuvir (400mg) The Hong Kong Association for the Study of Liver Diseases

The Hong Kong Association for the Study of Liver Diseases ALLY-3+ Treatment of HCV genotype 2, 3 The Hong Kong Association for the Study of Liver Diseases decompensated cirrhosis The Hong Kong Association for the Study of Liver Diseases Treatment Regimens Ribavirin duration The Hong Kong Association for the Study of Liver Diseases Sofosbuvir (400mg) / Low initial dose of RBV 12 week Velpatasvir (100mg) The Hong Kong Association for the Study of Liver Diseases Daclatasvir (60mg) + Low initial dose of RBV 12 week The Hong Kong Association for the Study of Liver Diseases Sofosbuvir (400mg) The Hong Kong Association for the Study of Liver Diseases

The Hong Kong Association for the Study of Liver Diseases Treatment of CHC decompensated cirrhosis: considering risk and benefit The Hong Kong Association for the Study of Liver Diseases Improving MELD The Hong Kong Association for the Study of Liver Diseases Non-use HCV score and improve positive donor survival Delay liver The Hong Kong Association for the Study of Liver Diseases Delisting from transplantation Liver transplantation MELD purgatory The Hong Kong Association for the Study of Liver Diseases The Hong Kong Association for the Study of Liver Diseases Benefit Risk The Hong Kong Association for the Study of Liver Diseases

The Hong Kong Association for the Study of Liver Diseases Long term clin linic ical benefits of DAAs treatment in in decompensated cir irrhosis is The Hong Kong Association for the Study of Liver Diseases • 454 cirrhotic patients with either CP (B) or decompensated cirrhosis • Treated with DAAs 12weeks or 24 weeks : 386 SVR+ 66 no SVR and 5 LFU The Hong Kong Association for the Study of Liver Diseases Transplant free survival Novo HCC development SVR (50 HCC/383) SVR (56 deaths/370) No SVR (17 HCC/66) No SVR (20 deaths/64) The Hong Kong Association for the Study of Liver Diseases 100 100 % without HCC % Survival 80 80 p = 0,002 p = 0,001 60 60 The Hong Kong Association for the Study of Liver Diseases 0 10 20 30 40 0 10 20 30 40 Months since DAA start Months since DAA start Hazard ratio 0,44 (IC 95 % : 0,23-0,84) Hazard ratio 0,42 (IC 95 % : 0,21-0,88) The Hong Kong Association for the Study of Liver Diseases � Successful HCV treatment was associated with significantly fewer deaths and liver cancer development The Hong Kong Association for the Study of Liver Diseases Cheung MCM, Royaume-Uni, EASL 2018, Abs. LBP-009 actualisé

The Hong Kong Association for the Study of Liver Diseases Long term clin linic ical benefits of DAAs treatment in in decompensated cir irrhosis is The Hong Kong Association for the Study of Liver Diseases Patients outcome according to pre-treatment baseline MELD score 70 The Hong Kong Association for the Study of Liver Diseases 60 50 Patients (%) 40 The Hong Kong Association for the Study of Liver Diseases MELD < 16 (n = 391) MELD 16-20 (n = 42) 30 MELD > 20 (n = 14) 20 The Hong Kong Association for the Study of Liver Diseases 10 0 Died Transplanted or Alive without on waitlist transplant need The Hong Kong Association for the Study of Liver Diseases � 2/3 of patients alive with a baseline MELD score < 16 avoid liver transplantation. The Hong Kong Association for the Study of Liver Diseases Cheung MCM et al. EASL 2018, Abs. LBP-009