2015-01-28 B (HBV-LC) C (HCV-LC)
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 B (HBV-LC)
Goals of chronic hepatitis B therapy Su TH & Kao JH. Expert Rev Gastroenterol Hepatol 2015;9:141-54 B (lamivudine, Zeffix) (adefovir, Hepsera) (entecavir, Baraclude) (telbivudine, Sebivo) (tenofovir, Viread)
B 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)
B? B Child-Pugh scores in HBV-LC
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;54:91-100. retrospective study from 2005 HBV-associated cirrhosis 18 centers in Turkey 227 patients
Changes in CTP scores KÖKLÜ S et al., CGH 2013;11:88 94 B
ETV Long term treatment Distribution of Ishak fibrosis scores at baseline, Year 1 and Years 3 7 60 Patients (n) 50 40 30 20 10 Ishak fibrosis score 6 5 4 3 2 1 0 Missing 0 Baseline Week 48 Long-term* n=57 * Median time of long-term biopsy: 280 weeks (range: 144 316 weeks). Chang TT et al., HEPATOLOGY 2010;52:886-893 Improvement of hepatic fibrosis after 5-year TDF Baseline cirrhosis: N=96 N=384
Tenofovir for Chronic Hepatitis B Tsai NC et al., Dig Dis Sci 2015;60:260-8 Yun-Fan Liaw. Clin Liver Dis 2013;17:413-23
B NA increases survival rate in HBV-LC NA Historical control Kim et al. JGH 2012;27:1589 1595
NA increases survival rate in HBV-LC Kim et al. JGH 2012;27:1589 1595 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;58:1537-1547
B 50 ETV reduced HCC incidence compared with control Cumulative HCC rate (%) 40 30 20 10 Log-rank test: P < 0.001 7.2% 13.7% Control ETV therapy reduced the 5-year HCC risk by > 60% compared with control group Multivariate Cox regression analysis:* HR 0.37 (95% CI 0.15 0.91) P = 0.030 0 1.2% 3.7% ETV 0 1 3 5 7 Treatment duration (years) No. at risk ETV 316 316 264 185 101 44 2 2 Control 316 316 277 246 223 200 187 170 * Adjusted for age, sex, alcohol, smoking, cirrhosis, HBV genotype, HBeAg status, HBV DNA, ALT, albumin, γgtp, total bilirubin and platelet count. CI, confidence interval; HR, hazard ratio. Hosaka T et al. Hepatology 2013;58:98-107
Reduction in HCC incidence with ETV greater among cirrhotic patients Cirrhosis No Cirrhosis 50 50 Cumulative HCC rate (%) 40 30 20 10 Log-rank test: P < 0.001 20.9% 4.3% 38.9% 7.0% Control ETV Cumulative HCC rate (%) 40 30 20 10 Log-rank test: P = 0.440 1.6% 3.6% Control 0 0 0% 2.5% ETV 0 1 3 5 Treatment duration (years) 0 1 3 5 Treatment duration (years) No. at risk ETV Control 79 79 72 53 35 17 85 85 76 65 54 47 No. at risk ETV Control 237 237 192 132 66 27 231 231 201 181 169 143 Hosaka T et al. Hepatology 2013;58:98-107 Cumulative probability of HCC in cirrhotic patients Wong GL et al. HEPATOLOGY 2013;58:1537-1547
Cumulative incidences of HCC 22.7% 7.32% Chun-Ying Wu et al. Gastroenterology 2014;147:143 151 B
Wu CY et al. JAMA 2012;308(18):1906-1913
C (HCV-LC) C + ribavirin
Peg-Intron Pegasys Rebetol Robetrol C
B C ALT Anti-HCV HCV RNA C?
IFN treatment regress HCV-related fibrosis 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;135:821 829
Post-SVR Cirrhosis Regression Rates According to the METAVIR Score D Ambrosio & Aghemo. Hepat Mon 2012;12:361-368 IFN treatment decreases mortality in patients with CHC
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 2011. (The Ishak fibrosis score was 4 in 143 patients (27%), 5 in 101 patients (19%), and 6 in 286 patients (54%).) SVR and Liver-related mortality Van der Meer AJ et al., JAMA 2012-;308:2584-2593
SVR and Liver failure Van der Meer AJ et al., JAMA 2012-;308:2584-2593 C
HCC in HCV-related liver cirrhosis (SVR vs no SVR) Singal et al. CGH 2010;8:192 199
HCC in HCV-related liver cirrhosis (treated vs untreated) Singal et al. CGH 2010;8:192 199 Cumulative incidence of HCC in HALT-C Trial Lok AS et al., GASTROENTEROLOGY 2011;140:840 849
SVR and HCC Van der Meer AJ et al., JAMA 2012;308:2584-2593 1013 Japanese Chronic hepatitis C (non-cirrhosis, n = 863, cirrhosis, n = 150) SVR (sustained virological response) TVR (transient virological response): ETVR+, no SVR NVR (non-virological response): decrease in the HCV RNA < 2 log10 IU/ml at week 12 Ogawa E et al., JH 2013;58:495 501
Cumulative incidence of HCC after PegIFNa2b and RBV treatment Ogawa E et al., JH 2013;58:495 501 Free from HCC and any liver-related complication 351 patients with HCV-related cirrhosis Soo Aleman et al. Clinical Infectious Diseases 2013;57(2):230 6
Eradication of HCV Infection and the Development of HCC Rebecca L. Morgan et al. Ann Intern Med 2013;158:329-337 C
Recurrence of resected HCC in chronic hepatitis C Yao-Chun Hsu et al. HEPATOLOGY 2013;58:150-157 Postoperative Peg-Interferon Plus Ribavirin Is Associated With Reduced Recurrence of HCV-Related HCC? Yao-Chun Hsu et al. HEPATOLOGY 2013;58:150-157
Direct antiviral agent for HCV-related liver cirrhosis Long-term? Mission impossible? Tom Cruise Mission possible
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