HCV TREATMENT PRE- AND POST TRANSPLANTATION

Transcription

1 HCV TREATMENT PRE- AND POST TRANSPLANTATION Michell L Shiffman, MD Medical Direcor Liver Insiue of Virginia Bon Secours Healh Sysem Richmond and Newpor News, VA, USA Liver Insiue of Virginia Educaion, Research and Treamen for Paiens wih Liver Disease Bon Secours Healh Sysem HCV AND LIVER TRANSPLANTATION SURVIVAL 100 URVIVAL (%) S SRTR daabase YEARS ML Shiffman e al. Am J Transpl 2006; 6: Non-HCV HCV 1

2 HCV AND LIVER TRANSPLANTATION FIBROSIS PROGRESSION % of Paiens Cirrhosis i Bridging Poral YEARS AFTER TRANSPLANTATION N Yilmaz e al. Liver Transpl 2007; 13: HCV AND LIVER TRANSPLANTATION TIMING OF TREATMENT Preven ransplan Afer ransplan Preven recurrence Liver Transplan 2

3 HCV TREATMENT WITH CIRRHOSIS CUPIC COHORT TRV BOC N Relapse Parial Response Null Response 39% 46% 10% 45% 42% 5% Esophageal Varices 35% 38% SVR 40% 41% Relapse 53% 51% Parial response 32% 40% Null Response 29% 11% TPV BOC SAE 49% 38% Premaure DC 26% 24% Infecions 26% 24% Deah 2% 1.3% Decompensaion 4.4% 4.4% Anemia <8.0 gm/dl 10% 10% EPO use 57% 66% Plaeles <25, % 0.6% TPO use 1.7% 1.9% H Fonaine e al. EASL 2013 SOFOSBUVIR/SIMEPREVIR ADVANCED CIRRHOSIS N=120 Cirrhosis Unable o receive PEGINF Prior Ascies, HE, VB (25%) Thrombocyopenia (20%) Age >65 years (20%) CTP B or C (33%) SOF+SMV for 12 weeks No ribavirin SAEs: Sepsis (2); Deah (1) Variceal bleeding (2) HCC: 2 Bilirubin increase 2x baseline: 8 ML Shiffman e al. ACG Annual meeing

4 SOFOSBUVIR/SIMEPREVIR SVR BY SELECTED PARAMETERS Caegory Parameer N SVR Age Prior Treamen IL28B HCV Genoype HCV RNA Tier ML Shiffman e al. ACG Annual meeing 2014 <65 years >65 years None PEGINF/RBV TPVor BOC PEGINF/RBV CC CT TT 1A 1B < 1 million (IU/ml) 1-10 million (IU/ml) >10 million (IU/ml) % 94% 87% 75% 81% 100% 84% 74% 81% 83% 75% 87% 67% SOFOSBUVIR/SIMEPREVIR CIRRHOSIS ML Shiffman e al. Hepaology 2015; (submied) 4

5 SOFOSBUVIR/LEDEPISVIR ADVANCED CIRRHOSIS SOF/LDV/RBV SOF/LDV Weeks of Treamen Male 67% Prior non-response 69% Prior non-response o 67% PI/PEGINF/RBV Genoype 1A 60% IL28B non-cc 79% Plaele coun < 90 18% Albumin < % M Bourliere e al. AASLD 2014; A82 SOFOSBUVIR/LEDEPISVIR ADVANCED CIRRHOSIS 12 weeks 24 weeks Relapsers N 5 Male 5 Genoype 1A 2 IL28B genoype CT/TT 4/1 Plaele coun < 90 1 Albumin < Esophageal varices 3 NS5A RAV 2 M Bourliere e al. AASLD 2014; A82 5

6 LDV-SOF-RBV DECOMPENSATED CIRRHOSIS Chronic HCV genoype 1 N = 108 Child class B and C cirrhosis RBV saring dose 600 mg QD hen increased as oleraed Deah 6 paiens (6%) Underwen liver ransplan 4 (4%) Treamen 12 weeks 24 weeks Child Class B C B C N SVR S Flamm e al. AASLD 2014; A239 TREATMENT OF ADVANCED CIRRHOSIS CHANGE IN MELD SCORE CHILD CLASS B CHILD CLASS C 12 weeks 24 weeks 12 weeks 24 weeks S Flamm e al. AASLD 2014; A239 6

7 HCV AND LIVER TRANSPLANTATION TIMING OF TREATMENT Preven ransplan Afer ransplan Preven recurrence Liver Transplan TREATMENT OF HCV PRIOR TO LT A2ALL STUDY LDLT and MELD excepion for HCC PegINF-2b + RBV LADR schedule No Treamen Conrol = 16, Treamen = 31 No differences in GTs GT Everson e al. Hepaology 2013; 57:

8 TREATMENT OF HCV PRIOR TO LT A2ALL STUDY Overall SAE/P Deah GT Everson e al. Hepaology 2013; 57: Tx % Conrol % Deah 15% 10% Pre-LT SAE/P Infecion % 1.3 0% SBP 5% 0% Liver relaed 14% 15% Pos-LT SAE/P Surgical complicaions % 1.0 0% SOFOSBUVIR AND RBV PRE-LIVER TRANSPLANT SOF+RBV iniiaed prior o undergoing g LT All paiens had HCC wih MELD excepion Treamen coninued up unil he ime of LT MP Curry e al. AASLD 2013 N 61 Age 59 years (46-73) Male 80% Caucasian 90% HCV genoype: 1A, 1B, 2, 3 39%, 34%, 13%, 12% IL28B non-cc 78% Median MELD 8 (6-14) Previous HCV reamen 75% 8

9 SOFOSBUVIR AND RIBAVIRIN PRE-LT TREATMENT MP Curry e al. AASLD 2013 a LT Pos -LT SVR when HCV RNA UD a LT HCV AND LIVER TRANSPLANTATION TIMING OF TREATMENT Preven ransplan Afer ransplan Preven recurrence Liver Transplan 9

10 SOFOSBUVIR AND RBV POST-LT HCV N 40 Age 59 years (49-75) Male 78% Caucasian 85% HCV genoype: 1A, 1B, 2, 3 55%, 28%, 0%, 15% IL28B non-cc 68% HCV RNA (IU/ml) 6.55 Previous HCV reamen 88% Mean ime since LT 4.3 years (6-150 mos) Tacrolimus, Cyclosporin 70%, 25% M Charlon e al. AASLD 2013 SOFOSBUVIR/LEDEPISVIR POST-LT HCV TREATMENT Weeks of Treamen: N=223 Sage 0-3: 112 Cirrhosis: 111 Child A: 52 Child B: 50 Child C: 9 Genoype 1 and 4 Mean HCV RNA Log 6.4 IU/ml Pos-LT mean 4.4 yrs Male 83% KR Reddy e al. AASLD 2014: A8 10

11 PTV/rv/OBV/DSV/RBV POST-LIVER TRANSPLANT N= weeks Abbvie 3D + ribavirin Pos-LT > 12 monhs No HCV reamen since LT Fibrosis < F2 Immune suppression dosing reduced o: Tacrolimus 0.5 mg Q week Cyclosporin 20% of he prereamen dose PS Manry e al. AASLD 2014; A198 NEED FOR LIVER TRANSPLANT IMPACT OF ANTI-VIRAL TREATMENT HBV Addiions Approval of 2000 ani-hbv herapy 200 HBV % HBV wih HCC: 8% 12% HCV WR Kim e al. Hepaology 2007; AASLD absrac 12. YEAR HCV Addions 11