B C Outlines. Child-Pugh scores

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1 B C Outlines Child-Pugh scores

2 CT MRI Fibroscan / ARFI

3 Histologic Scoring Systems for Fibrosis Fibrosis METAVIR Ishak None 0 0 Portal fibrosis (some) 1 1 Portal fibrosis (most) 1 2 Bridging fibrosis (occasional) 2 3 Bridging fibrosis (marked) 3 4 Incomplete cirrhosis 4 5 Cirrhosis 4 6 Fibrosis-4 (FIB-4)

4 AST to Platelet Ratio Index (APRI) Confounders of Fibroscan Tapper EB et al., CGH 2015;13:27 36

5 Cut-off Value of Fibroscan Tapper EB et al., CGH 2015;13:27 36

6 Child-Pugh classification Albumin (g/dl) <2.8 Bilirubin (mg/dl) <2 2-3 >3 Prothrombin time (seconds increased) >6 Ascites Nil Mild moderate Encephalopathy Nil mild moderate A: 5-6, B: 7-9, C: Two-year survival rates of LC D Amico G et al., JH 2006;44:

7 MELD score 3.8 X log e ( [mg/dl]) 11.2 X log e (INR, ) 9.6 X log e (creatinine [mg/dl],, ) 6.4 X ( : 0, 1 ) HEPATOLOGY 2001;33: MELD Calculator

8 MELD and mortality Al Sibae & Cappell. Dig Dis Sci 2011;56: Baveno IV staging of liver cirrhosis Compensated Stage 1: no varices, no ascites Stage 2: varices, no ascites Decompensated Stage 3: ascites varices Stage 4: variceal bleeding ascites Franchis R. JH 2005;43: In Baveno IV, a session was devoted to predictive models in portal hypertension, during which classification stages of cirrhosis were proposed. Prospective validation of this classification is under way. JH 2010;53:

9 1-year outcome probabilities in LC D Amico G et al., JH 2006;44:

10 B (lamivudine, Zeffix) (adefovir, Hepsera) (entecavir, Baraclude) (telbivudine, Sebivo) (tenofovir, Viread) C

11 C +Ribavirin( ) 1b: 50%-60% 1b: > 90% C (Daklinza)+ (Sunvepra) (Viekirax) + (Exviera) (Harvoni) (Sovaldi)

12 B C HBsAg(+) (1) HBsAg (+) HBV DNA 2,000IU/mL + (2) Metavir F4 Ishak F5 ) or / / or / / Zeffix(100mg) / Sebivo(600mg) Baraclude(0.5mg) / Viread (300mg)

13 B C ALT Anti-HCV HCV RNA C

14 ? Child-Pugh scores MELD scores

15 ETV-048: Improvement in MELD/CTP Scores Parameter Mean MELD score change from BL (SE) CTP score improvement or no worsening,* n/n (%) CTP score 2 point reduction,* n/n (%) CTP class improvement, n/n (%) *Noncompleter = failure. CTP class C/B to A only. Wk 24 Wk 48 ETV ADV ETV ADV -2.0 (0.45) -0.9 (0.46) -2.6 (0.62) -1.7 (0.50) 66/100 (66) 32/100 (32) 25/93 (27) 65/91 (71) 22/91 (24) 22/81 (27) 61/100 (61) 35/100 (35) 35/93 (38) 61/91 (67) 25/91 (27) 29/81 (36) Liaw YF, et al. Hepatology. 2011;54: retrospective study from 2005 HBV-associated cirrhosis 18 centers in Turkey 227 patients

16 Changes in CTP scores KÖKLÜ S et al., CGH 2013;11:88 94

17 ETV Long term treatment Distribution of Ishak fibrosis scores at baseline, Year 1 and Years Patients (n) Ishak fibrosis score Missing 0 Baseline Week 48 Long-term* n=57 * Median time of long-term biopsy: 280 weeks (range: weeks). Chang TT et al., HEPATOLOGY 2010;52: Improvement of hepatic fibrosis after 5-year TDF Baseline cirrhosis: N=96 N=384

18 Comparison of Liver Fibrosis Stage in patients of CHC reaching SVR Fibrosis improved in 56%, stable in 32%, Deteriorated in 12% Regression of cirrhosis in 9/14 patients Maylin S. et al., GASTROENTEROLOGY 2008;135:

19 NA increases survival rate in HBV-LC NA Historical control Kim et al. JGH 2012;27: NA increases survival rate in HBV-LC Kim et al. JGH 2012;27:

20 Cumulative probability of liver-related mortality in cirrhotic patients Liver-related mortality: death related to cirrhosis complications and/or HCC Wong GL et al. HEPATOLOGY 2013;58: Design, Setting, and Patients An international, multicenter, long-term follow-up study from 5 large tertiary care hospitals in Europe and Canada of 530 patients with chronic HCV infection who started an interferon-based treatment regimen between 1990 and 2003, following histological proof of advanced hepatic fibrosis or cirrhosis (Ishak score 4-6). Complete followup ranged between January 2010 and October (The Ishak fibrosis score was 4 in 143 patients (27%), 5 in 101 patients (19%), and 6 in 286 patients (54%).)

21 SVR and Liver-related mortality Van der Meer AJ et al., JAMA 2012-;308: SVR and Liver failure Van der Meer AJ et al., JAMA 2012-;308:

22 Reduction in HCC incidence with ETV greater among cirrhotic patients Cumulative HCC rate (%) Cirrhosis Log-rank test: P < % 4.3% Treatment duration (years) No. at risk ETV Control Control 38.9% 7.0% ETV Hosaka T et al. Hepatology 2013;58:98-107

23 Cumulative probability of HCC in cirrhotic patients Wong GL et al. HEPATOLOGY 2013;58:

24 HCC in HCV-related liver cirrhosis (SVR vs no SVR) Singal et al. CGH 2010;8: SVR and HCC Van der Meer AJ et al., JAMA 2012;308:

25 Eradication of HCV Infection and the Development of HCC Rebecca L. Morgan et al. Ann Intern Med 2013;158:

26 Wu CY et al. JAMA 2012;308(18): Recurrence of resected HCC in chronic hepatitis C Yao-Chun Hsu et al. HEPATOLOGY 2013;58:

27 French study 1323 patients 35 clinical centers 2006 ~ 2012 All patients biopsy-proven cirrhosis Child Pugh class A SVR decreases incidence of HCC and hepatic decompensation in HCV-LC HCC Hepatic decompensation Nahon P et al., Gastroenterology 2016 in press

28 SVR decreases incidence of cardiovascular event and bacterial infection in HCV-LC CV event Baterial infection Nahon P et al., Gastroenterology 2016 in press SVR did not decrease incidence of extrahepatic cancer in HCV-LC Extrahepatic cancer Nahon P et al., Gastroenterology 2016 in press

29 SVR improves survival in HCV-LC Overall survival Liver mortality Extrahepatic mortality Nahon P et al., Gastroenterology 2016 in press Impact of Portal HTN on death or LT because of HCC EV+ Marco et al., Gastroenterology 2016;151:

30 DAA C VA real world data Ioannou GN. et al., Gastroenterology 2016;151:

31 VA Real world data (ERCHIVES study) Butt AA. et al., APT 2016;44: Child Pugh A (N=319), SVR: 85.9% Child Pugh B/C (N=114), SVR: 82.2%

32 Occurrence of hepatic decompensation from the start of therapy to SVR12 Straight lines: first event; dotted :subsequent events Maan R. et al., CGH 2016;14: Management of decompensated HCV-LC Bunchorntavakul & Reddy. JVH 2016;23:

33 JH 2016;65: JH 2016;65: in press Cumulative HCC development rate in patients with SVR NO difference between the two groups

34 (in the past) Mission impossible (now) Mission impossible? Tom Cruise Mission possible

35 B C Thanks

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