Jong Young Choi, M.D.

Transcription

1 The Liver Week 2014 Jong Young Choi, M.D. Dept. of Internal Medicine The Catholic University of Korea, College of Medicine

2 The clinical study for natural history of LC is not many. Most of them was done 10 years ago. Recent advances in the diagnosis and treatment of chronic liver diseases have changed the natural history of cirrhosis significantly, because regression of fibrosis may take place in cirrhosis.

3 Sub-classification of liver cirrhosis How to predict transition from compensated LC to decompensated cirrhosis Natural History of HBV related cirrhosis Effect of antiviral therapy on natural course of HBV related compensated cirrhosis Clinical course of Decompensated cirrhosis

4 Natural history of liver cirrhosis - A systematic review of 23 studies - Median survival Compensated LC: over 12 years Decompensated LC: ~ 2 years D Amico G, et al. J Hepatol 2006;44: The 5-year survival rate is 84% in patients with compensated HBV-related cirrhosis, but only 14-35% in patients with decompensated cirrhosis. Once decompensation occurs, the prognosis is poor. Peng CY, et al. J Hepatol (review) 2012;57:

5 G.D Amico et al, J Hepatol 2006:44:

6 Zipprich A et al, Liver Intern 2012;34:

7 Clinical sub-classification Invasive /non-invasive Histological sub-classification Combination of both

8 Kim MY et al, J Hep 2011;55: Child Pugh class MELD Eso Variceal grade

9 Albillos et al Dis Marker 2011:31;

10 Albillos et al Dis Marker 2011:31;

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12 Annual progression rate : 6-9% 31% in first year, 5-7% in subsequent year Diseases 4% in hepatitis C LC 6-10% in alcoholic cirrhosis 10% for viral hepatitis B

13 Invasive method : HVPG Non-invasive method Elastography ICG Hepatic vein arrival time

14 An elevated HVPG is strong predictor of decompen Eso. Varices form at HVPG over 10 mmhg 10% reduction of HVPG may prevent eso varices If HVPG<10mmHg, NPV of decompensation is 90% 3% increase in mortality per 1mmHg increase HVPG Reducing HVPG<12 mmhg or decreasing 20% is associated with reduced risk of complication and 60% reduction in mortality. Ripoll C et al, Gastroenterology. 2007;133: Ripoll C et al, Scand J Gastroenterol. 2012;47(2): Poca M et al, Dis Markers. 2011;31(3): Albillos A et al Am J Gastroenterol. 2007;102(5):

15 HVPG<10 mmhg LS<21.1 kpa HVPG>10 mmhg LS>21.1 kpa Robic MA et al, J Hepatol. 2011;55:

16 At a cutoff of 21.1 kpa, TE predicts subsequent development of variceal hemorrhage and ascites (100% sensitivity and 65 % specificity) TE cutoff of 10.5 kpa predicts low risk for clinical decompensation over 2 years Problem Different cut off value for HBV, HCV, NASH, Bias by fatty liver, liver enzyme Robic MA J Hepatol. 2011;55: Klibansky DA J Viral Hepat. 2012;19:

17 60 50 ICG R mmhg HVPG ICG r15 <10% rule out Eso varices (98% sensitivity) ICG r15 >22.9% diagnose Eso varices (90% specificity) Lisotti A et al, Hepatolody 2014;59:

18 Compensated LC Decompensated LC Kim MY et al, Hepatology 2012;56:

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20 Risk score of cirrhosis Risk score of HCC Lee MH et al, hepatology 2013;58:

21 Risk for cirrhosis > <11 Risk for HCC > <9 Lee MH et al, hepatology 2013;58:

22 Hepatic events Control entecavir HCC Liver related mortality All cause mortality Wong GL et al, 2013;58:

23 Hepatic events HCC Liver related mortality All cause mortality Wong GL et al, 2013;58:

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25 Prospective, multicenter, observational, inception cohort study Enrolled at the time of first cirrhosis complication Study duration & participating institutions - Start of patient recruitment between 2005 and 2012 Registration centers and numbers of enrolled patients (Total: 8 centers and 1,515 patients ) The Catholic University of Korea (Seoul & Incheon St. Mary s Hospitals): 403 Pusan University Hospital: 180 Chonnam University Hospital: 255 Daegu Catholic University Hospital: 131 Hanyang University Hospital: 116 Soonchunhyang University Hospital: 257 Kyungpook University Hospital: 173 A total of 707 patients with HBV-related decompensated cirrhosis

26 - Cumulative proportion after the 1 st onset of decompensation Median survival Decompensated LC: months Analysis of 1515 patients N = months Mean FU months No at risk

27 Ascites Vx bled HE SBP HRS Ascites Vx bled 1st complication Ascites Vx bled HE SBP HRS HE 36.6 Vx bled 2nd complication 31 SBP HE HE SBP HRS 3rd complication 4th complication

28 Time to other complications Mean SD Time intervals (days) Median (range) 1st ~ 2nd complications (1-7,667) 2nd ~ 3rd complications (0-3,114) 3rd ~ 4th complications (0-1,605) Accelerated disease progression with multiple types of complications

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30 Patients presenting with 1st onset of decompensated complications (n = 707) Untreated patients (n = 284, 40.2%) Treated patients (n = 423, 59.8%) Previous treatment (n = 58, 13.4%) Immediate treatment (n = 253, 59.8%) Delayed treatment (n = 112, 26.5%) Lamivudine (n = 203) Entecavir (n = 198) Adefovir (n = 7) Clevudine (n = 10) Telbivudine (n = 5) (47.9%) (46.8%) (1.7%) (2.4%) (1.2%)

31 LT-free Survival (%) - Early treatment (n = 253) vs. untreated group (n = 284) P = No at risk Time (months) treated untreated Time LT-free Survival Treated Untreated 6 mo 85.8% 79.6% 1 yr 83.3% 73.2% 5 yrs 59.5% 46.0% treated untreated yrs 52.0% 36.5%

32 Survival (%) Survival (%) Survival (%) Childs A Childs C Treated Untreated Treated Untreated Time (months) P = Time (months) P < Childs B Time (months) P = Treated Untreated Survival gain: more apparent in patients with advanced diseases (Childs B or C)

33 Survival (%) P = Low viremia - - High viremia - Treated Untreated P < Time (months) Treated Untreated Better survival in the treated group than untreated group Significance: high > low viremia group High viremia: defined as HBeAg(+) or HBV DNA > 2000 IU/mL Low viremia: defined as HBeAg(-) and HBV DNA < 2000 IU/mL

34 Survival (%) - Comparison of 7-year survival rate among each group Sustained % Non-sustained % 30 Untreated % Time (months) Treatment response was analyzed in patients surviving 6 months Groups P value SVR vs. untreated P< SVR vs. non-svr P= Non-SVR vs. untreated P= VR = virological remission Sustained VR Non-sustained VR Untreated Sustained VR was defined as a decrease in HBV DNA levels < 400 IU/mL which was maintained till the last visit.

35 After potent antiviral therapy, some of cirrhosis can be reversible. The natural history of cirrhosis continue to change. Especially, the proportion of HBV related liver transplantation gradually decrease in western country, and korea. With advance of non-invasive methods such as liver stiffness and ICG, HVAT, clinician can sub-classify compensated cirrhosis and predict the risk of transition to decompensated cirrhosis.

36 Adequate treatment with antiviral drugs changes the natural history of decompensated cirrhosis even after the onset of major cirrhosis complication. Sustained viral remission under antiviral therapy in decompenstaed patients leads to improved long-term survival, compared with non-sustained responders or untreated patients. In decompensated LC patients, potent antiviral drugs with low resistance rate should be promptly and adequately administered under consideration for liver transplantation.

37 Research project supported by Liver Cirrhosis Clinical Research Center (LCCRC) Thank you to all who took part in this study The Catholic University of Korea: J.Y. Choi, J.W. Jang, C.W. Kim Pusan University Hospital: H. Y. Woo, J. Heo Chonnam University Hospital: S.K, Choi, H. Y. Hwang Daegu Catholic University Hospital: C. H. Lee Hanyang University Guri Hospital: T.Y. Kim, J.H. Son Soonchunhyang University Hospital: Y.S. Kim, S.G. Kim Kyungpook University Hospital: Y.D. Park, S.J. Yoon, W.Y. Tak

38 Thank you..