Θεξαπεία γνλνηύπνπ HCV-3

Transcript

1 Θεξαπεία γνλνηύπνπ HCV-3 Ισάλλεο. Κνζθίλαο Καζεγεηήο Παζνινγίαο- Ηπαηνινγίαο Β Παζνινγηθή Κιηληθή Ιαηξηθήο ρνιήο, Ιππνθξάηεην Ννζνθνκείν, Αζήλα 4ε ΤΝΑΝΣΗΗ AIDS -ΗΠΑΣΙΣΙΓΔ Αζήλα 2016

2 ύγθξνπζε ζπκθεξόλησλ (Conflict of interest) Consultant: Gilead, Novartis, Roche, MSD, Bayer, Bristol, Abbvie Talks: Bristol-Myers Squibb, Novartis, Roche, MSD, Bayer, Gilead Grants: Gilead, Roche, MSD, Novartis, Bayer Clinical Trials: Novartis, Roche, MSD, Bayer, Gilead, Janssen, Abbvie

3 Μεηαβνιέο ηξόπνπ κεηάδνζεο ηνπ HCV θαη θαηαλνκήο γνλνηύπσλ ζηελ Διιάδα 434 patients, Savvas, Κoskinas, et al J Viral Hep 2003 G3

4 Molecular epidemiology of HCV in Greece Katsoulidou, J Viral Hepat anti-hcv chronically infected patients ( ) 13x

5 Γονότσποι HCV GT1: 44% (incidence decreasing) GT2: 6% GT3: 35% (incidence increasing due to IVDUs) GT4: 14% Raptopoulou M et al, Hippokratia 2011, 15, 1:26-31 Blood-sample controls since 1992 (mostly warehoused pts) Due to increased number of IDUs (although current estimate puts >20% of IDUs on GT1)

6 Significant epidemiological changes in CHC infection: results of the nationwide HEPNET-GREECE cohort study 2817 patients, 20 hepatology centers, follow up Raptopoulou et al Hippokratia 2011

7 Η ΥΡΟΝΙΑ HCV ΛΟΙΜΩΞΗ ΑΠΟ ΣΟ GT3 ΔΥΔΙ ΞΔΥΩΡΙΣΗ ΠΑΘΟΦΤΙΟΛΟΓΙΑ Accelerated fibrosis Higher mortality Steatosis Burden of disease Higher risk for future event Increased risk for HCC Lower rates of SVR

8 Παξάγνληεο ζπζρεηηδόκελνη κε επηηάρπλζε ηεο επαηηθήο ίλσζεο Αζθενής Ιός Σηάδιο ίνωζης - γονόηυπος 3 Βαρύτητα υλεγμονής - ζυλλοίμωξη με HBV, HIV Μεγάλη ηλικία 1/3 pts: 1 Metavir stage/2.5 y Αρρεν υύλο (Konerman 2014) Μεταμόστεσση ήπατος Ανοζοκαηαζηολή Κατανάλωση αλκοόλης Μη αλκοολική ζηεάηωζη/ζηεαηοηπαηίηιδα Διαβήηης/ αντίσταση στην ινσοσλίνη AASLD/IDSA 2014

9 Υξνλία HCV ινίκσμε

10 HCC-Free Survival GT3 Is Associated With Increased Risk of HCC in Patients With Cirrhosis Probability of HCC-Free Survival According to HCV Genotype 1.0 P= GT4 GT2 GT1 0.2 GT Years Retrospective study of 353 cirrhotic HCV patients in France, prospectively followed and screened for HCC between 1994 and Log-rank test and Cox model were used to compare the actuarial incidence of HCC between genotype subgroups. Nkontchou et al. J Viral Hepat. 2011;18:e516.

11 GT3 Patients Are At Higher Risk for Late-Stage Liver Disease Events and Death Cirrhosis GT1 GT2 Decompensated Cirrhosis GT3 Other Liver-related Hospitalization HCC 0 0,2 0,4 0,6 0,8 1 1,2 1,4 1,6 1,8 Hazard Ratio Observational cohort study of 28,769 HCV patients from the Veterans Affairs (VA) HCV Clinical Registry (CCR), which compiled electronic medical records data from 1999 to the present. McCombs et al. JAMA Intern Med. 2014;172:204.

12 Κύθινο δσήο ηνπ HCV θαη ζηόρνη ησλ λέσλ αληη-ηηθώλ (DAAs) Receptor binding and endocytosis Fusion and uncoating Transport and release (+) RNA Virion assembly Translation and polyprotein processing NS3/4 protease inhibitors Membranous web NS5A inhibitors replication and assembly RNA replication NS5B polymerase inhibitors Nucleos(t)ide Non-nucleoside Adapted from Manns MP, et al. Nat Rev Drug Discov. 2007;6:

13 Anti-HCV φάρμακα - DAAs 5 UTR - core E1 E2 p7 NS2 NS3 4A NS4B NS5A NS5B - 3 UTR Protease inhibitors - PREVIRS Telaprevir Boceprevir Simeprevir Faldaprevir Asunaprevir Paritaprevir Vaniprevir Sovaprevir MK-5172 ACH-2684 Μέηξην γελεηηθό θξαγκό NS5A inhibitors - ASVIRS Daclatasvir Ledipasvir Ombitasvir Velpatasvir ACH-3102 PPI-668 GSK Samatasvir MK-8742 Υακειό γελεηηθό θξαγκό HOST Cyp Inh Alisporivir Yςειό γελεηηθό θξαγκό NI s Sofosbuvir VX-135 IDX ACH-3422 Yςειό γελεηηθό θξαγκό Polymerase inhibitors - BUVIRS NNI s Dasabuvir Deleobuvir BMS PPI-383 GS-9669 TMC647055l Υακειό γελεηηθό θξαγκό

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15 SVR12 (%) BOSON: SOF Based Regimens in TN/TE NC/CC GT 3 and TE Efficacy Results CC GT 2 Patients SOF + RBV 16 weeks SOF + RBV 24 weeks SOF + PegIFN + RBV 12 weeks /15 17/17 15/16 128/ / /181 GT 2 GT 3. Foster, EASL, 2015, L05 10/11

16 SVR12 (%) BOSON: SOF Based Regimens in TN/TE NC/CC GT 3 and TE CC GT 2 Patients SOF + RBV 16 weeks SOF + RBV 24 weeks SOF + PegIFN + RBV 12 weeks /7 0 65/7 2 68/7 1 12/2 1 18/2 2 21/2 3 41/54 44/54 49/52 94/112 83/100 10/11 17/36 26/34 30/35 TN No no Cirrhosis cirrhosis TN Cirrhosis cirrhosis TE No no Cirrhosis cirrhosis TE Cirrhosis cirrhosis Treatment Naïve Treatment Experienced Higher SVR12 rates with SOF+PegIFN+RBV compared to SOF+RBV for 16 or 24 weeks 86% SVR12 in GT 3 TE with cirrhosis treated with SOF+PegIFN+RBV > 80% in all other subgroups treated with 24 wks SOF+RBV; consistent with Phase 3 studies. Foster, EASL, 2015, L05

17 ALLY-3 : SOF+DCV ζε HCV-3 12 εβδ / RBV - free naive experienced N=101 naïve & 51 exp, SOF: 400mg/d, DCV 60mg/d SVR12: Naïve= 90% Exp= 86% SVR12, % a Κίρρωζη /75 11/ / /32 32/34 9/13 OXI / NAI OXI / NAI OXI / NAI Nelson et al. Hepatology 2015 Γηα αζζελείο γνλόηππνπ 3 θαη θίξξσζε, ε εγθεθξηκέλε δηάξθεηα ζεξαπείαο ηνπ ζπλδπαζκνύ SOF+DCV ± RBVείλαη 24 εβδνκάδεο )

18 SVR12, % Randomized ELECTRON-2 (LDV/SOF±RBV) LDV/SOF + RBV in Genotype 3 Wk 0 Wk 12 Wk 24 SVR12 GT 3; n=51 Treatment naïve, incl. cirrhosis LDV/SOF, n=25 LDV/SOF + RBV, n=26 GT 3; n=50 Treatment experienced, incl. cirrhosis LDV/SOF + RBV, n= RIB effect Gane E, Gastroenterology 2015;149: Treatment naive /50 Overall 16/2 2 41/50 25/28 16/22 No Cirrhosis Cirrhosis Treatment experienced

19 SVR12, % Zeuzem S, et al. NEJM ; Gane, EASL, 2014, Oral #6; Gane, AASLD, 2014, Poster #LB-11; Foster, EASL, 2015, Oral #L05; Nelson, D., et al. Hepatology 2015;61: Summary of SVR Results from VALENCE, ELECTRON-2, ALLY-3 and BOSON ρήκαηα κε SOF γηα ηνλ HCV-3 87/92 21/21 73/75 68/71 12/13 5/5 11/19 21/23 85/98 25/28 32/34 49/52 29/47 16/22 9/13 30/35 πλνπηηθή παξνπζίαζε δεδνκέλσλ από δηαθνξεηηθέο κε ζπγθξηηηθέο κειέηεο. Γελ πξέπεη λα γίλεηαη ζύγθξηζε κεηαμύ ησλ ζθειώλ ησλ κειεηώλ.

20 ALLY-3+: DCV + SOF + RBV in Pts With GT3 HCV and Advanced Liver Disease Open-label, randomized phase IIIb study Primary endpoint: SVR12 Stratified by F3/F4 fibrosis stage Wk 12 Wk 16 Pts with GT3 HCV and F3/F4 liver disease (N = 50) DCV 60 mg/day + SOF 400 mg/day + RBV (n = 24) DCV 60 mg/day + SOF 400 mg/day + RBV (n = 26) All pts followed for SVR12 Leroy V, et al. AASLD Abstract LB-3.

21 SVR12 (%) ALLY-3+: Virologic Efficacy No virologic failures or AE-related discontinuations 12-wk DCV + SOF + RBV 16-wk DCV + SOF + RBV n/n = 0 21/ 24 All Pts 24/ 26 6/ 6 8/ 8 Advanced Fibrosis (F3) 15/ 18 16/ 18 Cirrhosis 14/ 16 12/ 14 Cirrhosis + Treatment Experienced Leroy V, et al. AASLD Abstract LB-3.

22 SVR4, % DACLATASVIR PLUS SOFOSBUVIR WITH OR WITHOUT RIBAVIRIN IN GENOTYPE 3 A FRENCH MULTICENTER COMPASSIONATE USE PROGRAM Weeks 24 weeks 20 22/29 52/59 11/12 5/6 0 Cirrhotic patients Non-cirrhotic patients EASL 2015 Poster LP05

23 Phase 2, LDV/SOF+RBV in GT3, Canada LDV/SOF+RBV for 12 weeks in TN GT3 patients Feld, EASL 2016, Poster SAT-183 Baseline Demographics LDV/SOF + RBV n=111 Median age, y (range) 47 (26 75) Male, n (%) 68 (61) White, n (%) 78 (70) Asian, n (%) 28 (25) Median BMI, kg/m2 (range) 26 (18 61) IL28B CC, n (%) 40 (36) HCV GT 3a, n (%) 105 (95) Median HCV RNA, log10 IU/mL (range) 6.3 ( ) Median egfr, ml/min (range) 117 (67 327) Cirrhosis, n (%) 39 (35) LDV/SOF + RBV for 12 weeks resulted in high SVR12 rates in treatment-naïve patients with HCV GT 3 without cirrhosis SVR12 99/111 66/70 31/39 Overall No Cirrhosis Cirrhosis Relapse, n LTFU, n Death 1-1 LDV/SOF + RBV (N=111) AE 94 (85) Grade 3 4 AE 8 (7) Serious AE 4 (4) Treatment DC due to AE* 1 (<1) Death* 1 (<1) Grade 3 4 laboratory abnormality 15 (14) 23

24 NHS England Early Access Program (EAP) SOF+NS5A ± RBV for 12 Weeks in 467 Patients with History of Decompensated Cirrhosis GT 1 N=235 GT 3 N=189 Other GTs N=43 Total N=467 Mean age, years (range) 56.1 (29-76) 54 (36-75) 59 (36-81) 55.6 (29-81) Male gender, n (%) 174 (74.0) 131 (69.3) 32 (74.4) 337 (72.2) Treatment experienced, n (%) 107 (45.5) 88 (46.6) 25 (58.1) 220 (47.1) Liver transplanted, n (%) 27 (11.5) 15 (7.9) 5 (11.6) 47 (10.1) Past or present decompensated cirrhosis, n (%) 223 (94.9) 179 (94.7) 39 (90.7) 441 (94.4) CTP B, n (%) 161 (68.5) 121 (64.0) 27 (62.8) 309 (66.2) CTP C, n (%) 19 (8.1) 24 (12.7) 3 (7.0) 46 (9.9) MELD mean (range) 11.9 (6-36) 11.3 (6-24) 12.6 (6-36) 11.9 (6-36) Active ascites, n (%) 97 (41.3) 67 (35.4) 14 (32.6) 178 (38.1) Previous variceal bleed, n (%) 61 (26.0) 55 (29.1) 11 (25.6) 127 (27.2) Active encephalopathy, n (%) 41 (17.4) 34 (18.0) 5 (11.6) 80 (17.1) Treatment, n (%)* LDV/SOF+RBV SOF+DCV+RBV SOF+NS5A without RBV *Choice of therapy was at clinician's discretion 164 (35.1) 45 (9.6) 26 (5.6) 61 (13.1) 114 (24.4) 14 (3.0) 27 (5.8) 13 (2.8) 3 (0.6) Foster GR, et al. EASL Abstract O (54) 172 (36.8) 43 (9.2) 24

25 SVR12, % (ITT) SOF + NS5A Inhibitors ± RBV in Pts With GT1/3 HCV and Decompensated Cirrhosis Observational cohort study of National Health Service of England (N = 467) At physician s discretion, pts received 12 wks of SOF + LDV or DCV ± RBV 12-wk SOF + LDV + RBV 12-wk SOF + LDV 12-wk SOF + DCV + RBV 12-wk SOF + DCV P < n = All GT1 GT3 SVR12 among pts with other HCV GTs: 89% (n = 27) with SOF + LDV + RBV; 85% (n = 13) with SOF + DCV + RBV; 100% (n = 3) SOF + DCV Foster GR, et al. EASL Abstract O002.

26 SVR12, % NHS England EAP: SOF+NS5A±RBV for 12 Weeks GT 3 Patients with History of Decompensated Cirrhosis /7 36/61 5/7 LDV/SOF LDV/SOF +RBV Majority of patients received RBV SOF+DCV 80/114 SOF+DCV +RBV SVR rates were comparable to those seen in other studies of SOF+NS5A±RBV for 12 weeks in decompensated cirrhotics Foster GR, et al. EASL Abstract O

27 SVR12 (%) Interim Analysis: Daclatasvir + Sofosbuvir ± RBV in GT3 HCV in European CUP Pts treated with DCV 60 mg + SOF 400 mg QD for 24 wks; RBV added or duration shortened to 12 wks per physician discretion Most common AEs: fatigue, nausea, anemia Tx-related serious AEs (n = 1 each): pancytopenia, HE, HCC, circulatory collapse DCV + SOF DCV + SOF + RBV n/n = 0 42/ 49 29/ 33 All Pts 37/ 42 25/ 29 Cirrhosis 19/ 19 11/ 13 12/ 15 12/ 14 6/ 8 A B C Naive Exp d 12 wks 24 wks Child-Pugh Class 2/ 2 19/ 21 12/ 12 23/2 8 Tx History 17/ 21 6/ 7 5/ 7 36/ 42 Tx Duration 24/ 26 Welzel TM, et al. AASLD Abstract 37.

28 Background SOF Nucleotide NS5B polymerase inhibitor Sofosbuvir (SOF) 1,2 Potent antiviral activity against HCV GT 1 6 Once-daily, oral, 400-mg tablet VEL NS5A inhibitor Velpatasvir (VEL; GS-5816) 3-5 Picomolar potency against GT nd -generation inhibitor with improved resistance profile SOF VEL SOF/VEL Single Tablet Regimen (STR) Once daily, oral, STR (400/100 mg) 1. Jacobson IM, et al. N Engl J Med 2013;368: ; 2. Lawitz E, et al. N Engl J Med 2013;368: ; 3. Cheng G, et al. EASL 2013, poster 1191; 4. German P, et al. EASL 2013, poster 1195; 5. Lawitz E, et al. EASL 2013, poster 1082.

29 ASTRAL-3 SOF/VEL STR for 12 Weeks Compared to SOF+RBV for 24 Weeks in GT 3 HCV-Infected Patients Week n=277 SOF/VEL SVR12 n=275 SOF + RBV SVR12 SOF/VEL 12 Weeks n=277 Mangia, AASLD, 2015, 249. Foster GR, et al. New Engl J Med DOI: /NEJMoa SOF + RBV 24 Weeks n=275 Mean age, y (range) 49 (21 76) 50 (19 74) Male, n (%) 170 (61) 174 (63) White, n (%) 250 (90) 239 (87) Mean BMI, kg/m 2 (range) 26.4 ( ) 26.6 ( ) Cirrhosis, n (%) 80 (29) 83 (30) Treatment experienced, n (%) 71 (26) 71 (26) IL28B CC, n (%) 105 (38) 111 (40) HCV RNA, log 10 IU/mL (SD) 6.2 (0.7) 6.3 (0.7)

30 SVR12 (%) ASTRAL-3: SOF/VEL STR for 12 Weeks in GT 3 HCV-Infected Patients P< / /275 0 SOF/VEL SOF + RBV 12 Weeks 24 Weeks Error bars represent 95% confidence intervals. Mangia, AASLD, 2015, 249. Foster GR, et al. New Engl J Med DOI: /NEJMoa

31 SVR12 (%) ASTRAL-3: SOF/VEL STR for 12 Weeks in GT 3 HCV-Infected Patients SVR12 by Cirrhosis Status and Treatment History SOF/VEL SOF + RBV / /156 40/43 33/45 31/34 22/31 33/37 22/38 Non-Cirrhotic Cirrhotic Non-Cirrhotic Cirrhotic Treatment Naïve Treatment Experienced Mangia, AASLD, 2015, 249. Foster GR, et al. New Engl J Med DOI: /NEJMoa

32 ASTRAL-3: SOF/VEL STR for 12 Weeks in GT 3 HCV-Infected Patients Safety Adverse Events Laboratory Abnormalities Patients, n (%) SOF/VEL 12 Weeks n=277 SOF + RBV 24 Weeks n=275 AE 245 (88) 260 (95) Grade 3 4 AE 12 (4) 23 (8) Serious AE 6 (2) 15 (6) D/C due to AE 0 9 (3) Death 0 3 (1) Grade (7) 47 (17) Hb <10 g/dl 0 10 (4) Hb <8.5 g/dl 0 0 Mangia, AASLD, 2015, 249. Foster GR, et al. New Engl J Med DOI: /NEJMoa

33 SVR12 (%) ASTRAL-4: Sofosbuvir/Velpatasvir in Decompensated Cirrhosis Open-label trial; HCC and liver transplantation excluded In pts with BL MELD > 15, SVR12, score improved in 84%, worsened in 8%; in pts with BL MELD < 15, SVR12, score improved in 52%, worsened in 27% AEs consistent with advanced liver disease and RBV toxicity SOF/VEL 12 wks SOF/VEL + RBV 12 wks SOF/VEL 24 wks n/n = 0 75/90 82/8 7 77/9 0 60/6 8 65/6 8 65/7 1 7/ 14 All Pts / 13 6/ 12 2, 4, and 6 HCV Genotype Charlton MR, et al. AASLD Abstract LB-13. Curry MP, et al. N Engl J Med. 2015;[Epub ahead of print]. 8/ 8 6/ 6 6/ 7

34 Efficacy and safety of direct acting antiviral(s) (DAA) containing regimens in the treatment of chronic hepatitis C (CHC) patients with genotype 3. A real life experience John Koskinas, Melani Deutsch, Panagiota Ioannidou, Spilios Manolakopoulos, Evangelos Cholongitas, Eirini Rigopoulou, Maria Schina, Vassilios A. Sevastianos, Ioannis S. Elefsiniotis, John Goulis, John Vlachogiannakos, Christos Triantos, Andreas Kapatais, Ioannis Ketikoglou, Emanuel Manesis, Stylianos Karatapanis, Maria-Vasiliki Papageorgiou, Maria Tampaki, Anastasia Kourikou, Emanuel Sinakos, Theodoros A. Voulgaris, Georgia Barla, Argyro Koukoufiki, Dimitrios Karagiannakis, Chrysostomos Tsolias, Theofanie Karaoulani, Georgios Ntetskas, George Dalekos, Evangelos Akriviadis, George V. Papatheodoridis

35 HCV-3 patients/ Greek cohort 149 HCV-3 out of 648 patients treated with DAAs M/F: 107/42 Age: mean 53 yrs (29-88) 46.3% history of IVDU, 25% transfusion, unknown 26% BMI: mean 27, % diabetes 87/149 (58.4%) TE 9/87 DAAs failures: 6 SOF/RIB, 2 SOF/LDV, 1 SOF/DCV

36 HCV-3 patients/ Greek cohort HCV-RNA: mean Hb: 13,14 ( ) WBC: ( ) PLT: ( ) ALT: 87 ( ) AST: 84 ( (13-308) Albumin: 3,8 ( ) 97/149 (65%) cirrhosis 22/149 (14.8%) decompensated cirrhosis 6/149 (4%) OLT

37 HCV-3 patients/ Greek cohort Rx: PR/SOF (12wks): 17 (11.4%) SOF/RIB (12, 24wks): 16 (10.7%) SOF/DCV+/- RIB (12,24 wks): 105 (70%)- 43.6% RIB SOF/LDV/RIB (12, 24wks): 11 (7.4%)

38 HCV-3 patients/ Greek cohort ,8 EFFICACY BASED ON RX COMBINATION AVAILABLE DATA: 72/91 (79%) SVR ,3 13/14 7/14 28/31 20/24 PR/SOF SOF/RIB SOF/DCV SOF/DCV/RIB SOF/LDV/RIB 50 4/8 4/8

39 HCV-3 patients/ Greek cohort In SOF/DCV combination addition of RIB: 83% vs 90.3% 12 vs 24 wks: 84% vs 100% Rx SOF+DCV: 30 pts 12wks, 10 pts 24 wks SOF+ DCV+ R: 59 pts 12 wk, 6 pts 24 wks

40 HCV-3 patients/ Greek cohort SVR ACCORDING TO FIBROSIS 85,7 85,7 78,6 0 FO-2 F3 F4 DEC.CIR

41 HCV-3 patients/ Greek cohort 7/91 patients SAEs 1 encephalopathy epilepsia (decomp cirrhosis - stop Rx) 1 decompensation (F4, SOF+R 24 wks - SVR) 1 encepalopathy, cellulitis (Dec. Cirrhosis, SOF+R 24 wks, SVR) 1 HCC (F4, Rx: SOF/DCV/R 12 wks, No SVR) 2 severe cytopenia (F4 and dec. cirrhosis, P/R +SOF 12 wks both had SVR) 1 renal injury (F4, CKD/dialysis, SOF+DCV+R 12 wks, No SVR )

42 HCV-3 patients/ Greek cohort HCV-3 difficult to treat with the current DAAs SOF/DCV for 24 wks seems to be the best choice P/R + SOF good alternative if IFN is not contraindicated

43 Θεξαπεία κε ζρήκαηα ρσξίο ΙΦΝ θαηά πξνηεξαηόηεηα ζε αζζελείο αλεμαξηήησο γνλνηύπνπ (ΔEMH/ΚΔΔΛΠΝΟ) 1) κε αληηξξνπνύκελε θίξξσζε ζηαδίνπ Child B ή C 2) αληηξξνπνύκελε θίξξσζε (ζηαδην Ishak: 5-6, METAVIR: F4, ειαζηνγξαθία: >12 kpa) πνπ δελ κπνξνύλ λα ιάβνπλ ζρήκαηα κε ΙΦΝ 3) αληηξξνπνύκελε θίξξσζε (ζηάδην Ishak: 5-6, METAVIR: F4, ειαζηνγξαθία: >12 kpa ) πνπ δελ έρνπλ αληαπνθξηζεί ζε ζρήκαηα κε ΙΦΝ 4) αληηξξνπνύκελε θίξξσζε (ζηάδην Ishak: 5-6, METAVIR: F4, ειαζηνγξαθία: >12 kpa ) πνπ είλαη πξσηνζεξαπεπόκελνη. 5) ππνηξνπή ηεο HCV ινίκσμεο κεηά από κεηακόζρεπζε ήπαηνο αλεμαξηήησο ζηαδίνπ ίλσζεο 6) ζνβαξή εμσεπαηηθή εθδήισζε ηεο HCV ινίκσμεο αλεμαξηήησο ζηαδίνπ ίλσζεο (ζπκπηωκαηηθή θξπνζθαηξηλαηκία: λεθξωηηθή αγγεηίηηδα, ζπεηξακαηνλεθξίηηδα, λεθξωζηθό ζύλδξνκν, αηζζεηηθνθηλεηηθή αμνληθή πνιπλεπξνπάζεηα) 7) ζνβαξή ίλσζε (ζηάδην Ishak: 4, METAVIR: F3, ειαζηνγξαθία: >9 kpa ) θαη αληέλδεημε ζηε ΙΦΝ θαη/ε πξνεγνύκελε απνηπρία ζε ζρήκαηα κε ΙΦΝ 8) ζνβαξή ίλσζε [(ζηάδην Ishak: 4, METAVIR: F3, ειαζηνγξαθία: >9 kpa ) πξσηνζεξαπεπόκελνη ρσξίο αληέλδεημε γηα ΙΦΝ 9) HCV θαη HIV ζπιινίκσμε αλεμαξηήησο ζηαδίνπ ίλσζεο

44 Γηαηί Θεξαπεία ζε αζζελείο κε ήπηα ίλσζε? Πξόιεςε αλάπηπμεο ζνβαξήο ίλσζεο/θίξξσζεο Ρπζκόο εμέιημεο? (αμηνιόγεζε?) άιινη παξάγνληεο? (ΣΔ/ιίπωζή/αιθνόι/Fe) Πξόιεςε/κείσζε θηλδύλνπ γηα ΗΚΚ Μεηαδνηηθόηεηα (λενγλό, νκάδα, ζύληξνθν) Αίζζεκα επεμίαο Αβεβαηόηεηα γηα ην κέιινλ

45 Αιιειεπίδξαζε θαξκάθσλ Drug-Drug Interactions πνιιέο θαη ελίνηε πεξίπινθεο κε ην ζπλδπαζκό ηωλ DAAs έιεγρνο ηωλ θαξκάθωλ πνπ ιακβάλεη ν αζζελήο αλαδήηεζε αιιειεπηδξάζεωλ παξέκβαζε

46 HCV-3 NAÏVE OR TE NO CIRRHOSIS EASL recommendations 2016

47 HCV-3 NAÏVE OR TE COMPENSATED CIRRHOSIS EASL recommendations 2016

48 HCV-3 FAILURES ON SOF BASED (Sof, Sof+Rib, Sof+P/R) EASL recommendations 2016

49 HCV-3 FAILURES ON SOF + NS5A INH EASL recommendations 2016

50 Θεξαπεία HCV ινίκσμεο Η επαλάζηαζε Πνηέ δελ είρακε ηόζν απνηειεζκαηηθά θάξκαθα κε επλντθό πξνθίι αζθάιεηαο γηα ηόζν κεγάιν αξηζκό αζζελώλ ηόρνο ε ζεξαπεία κε ηα DAAs όισλ ησλ αζζελώλ Αλεμαξηήησο ζηαδίνπ επαηηθήο λόζνπ

51 EASL recommendations 2016