7. • The major risk factor for HCC :
– HBV chronic infection (52% of all HCC)
– Followed by chronic HCV infection and alcohol intake
• Other HCC risk factors : male, aflatoxin, obesity, type
II DM, hereditary hemochromatosis, primary biliary
cirrhosis, several hereditary metabolic conditions
Risk factors of HCC
de Lope CR, Tremosini S, Forner A, et al. J Hepatol 2012;56 Suppl:S75-87.
11. 台灣 B 型肝炎與肝癌相關之危險性
Yang HI, et al NEJM, 2002; 347:168-74. This article has been cited for 805 times till Sep. 2012
HBsAg HBeAg ALT Risk
- - Normal 1 (23/71,105 person/yr)
- - Elevated 5.4
+ - Normal 10.3
+ - Elevated 29.3
+ + Normal 61.3
+ + Elevated 109
12. REVEAL: Relationship Between Baseline HBV DNA Levels and
HCC Incidence Entire Cohort, N = 3653
14
12
10
8
6
4
2
0
0 1 2 3 4 5 6 7 8 9 10 11 12 13
Year of Follow-up
Cumulative Incidence of HCC (%)
Baseline HBV DNA Level (copies/mL)
1 Million
100,000-999,999
10,000-99,999
300-9,999
<300
No. at Risk
Baseline HBV DNA Level (copies/mL)
1 Million
100,000-999,999
10,000-99,999
300-9,999
<300
627 621 611 604 593 582 571 561 550 541 528 513 499 414
349 346 342 338 333 327 321 317 310 304 302 294 288 228
643 637 633 633 627 625 622 615 609 606 597 588 586 490
1161 1155 1146 1139 1137 1131 1129 1123 1119 1113 1102 1091 1082 879
873 865 862 854 850 845 836 826 823 819 814 807 802 720
Chen CJ et al. JAMA. 2006;295:65-73. This article has been cited for 1362 times till Sep. 2012
13. Nomogram for risk of HCC
Yang HI, et al. J Clin Oncol 2010;28:2437-44
14. Serum HCV RNA and ALT levels predict
HCV outcomes
High HCV RNA levels: > 3.5 x 105 U/ML
Lee MH, et al. J Clin Oncol 2010;28:4587-93
15. Diagnostic accuracies of four thresholds of ULN of ALT
for predicting unhealthy status in male
Sensitivity (%)
(95% CI)
Specificity (%)
(95% CI)
Youden’s index AUROC
(95% CI)
Training set
Current 20.3(19.5-21.0) 96.4(95.3-97.4) 0.167 0.583(0.575-0.592)
Kang 34.8(33.9-35.7) 91.0(89.3-92.6) 0.258 0.629(0.620-0.638)
Prati 36.9(36.0-37.8) 89.4(87.6-91.1) 0.263 0.632(0.623-0.640)
Wu (this study) 65.1(64.2-66.0) 67.7(65.1-70.3) 0.328 0.664(0.656-0.673)
Validation set
Current 25.1(24.0-26.2) 96.9(95.2-98.0) 0.220 0.610(0.598-0.621)
Kang 41.7(40.4-42.9) 90.3(87.7-92.4) 0.320 0.660(0.648-0.671)
Prati 44.2(43.0-45.5) 89.2(86.6-91.5) 0.334 0.667(0.656-0.678)
Wu (this study) 74.5(73.4-75.6) 63.6(59.8-67.2) 0.381 0.690(0.679-0.701)
ULN threshold of ALT: current 40 IU/L; Kang: 31 IU/L for male and 23 IU/L for female;
Prati: 30 IU/L for male and 19 IU/L for female; Wu: 21 IU/L for male and 17 IU/L for female
Wu WC, Wu CY, Wang YJ, Su CW, et al. Aliment Pharmacol Ther 2012;36:560-568
16. 2012 EASL recommendation for HCC
surveillance
Cirrhotic patients, Child-Pugh stage A and B
Cirrhotic patients, Child-Pugh stage C awaiting liver
transplantation
Non-cirrhotic HBV carriers with active hepatitis or
family history of HCC
Non-cirrhotic patients with chronic hepatitis C and
advanced liver fibrosis F3
2012 J Hepatol 2012:56:908-43
18. Diagnostic criteria for HCC in Barcelona-
2000 EASL conference
• Cyto-histological criteria
• Non-invasive criteria (restricted to cirrhotic patients)
– Radiological criteria: two coincident imaging techniques
• Focal lesion > 2cm with arterial hypervascularization
– Combined criteria: one imaging technique associated
with AFP
• Focal lesion > 2cm with arterial hypervascularization
• AFP levels > 400 ng/mL
• Four techniques considered: US, spiral CT, MRI and
angiography
Bruix J, et al. J hepatol 2001;35:421-30
19. Diagnosis accuracy of CEUS and MRI
Diagnosis accuracy of combined CEUS and MRI
Forner A, Bruix J, et al. Hepatology 2008:47:97-104
20. Algorithm for investigation of a nodule found on ultrasound
Bruix J, Sherman M. Management of hepatocellular carcinoma. AASLD practice guideline. Hepatology 2005;42:1208-1236
Image:
CEUS
CT
MRI
21. Diagnosis accuracy of single imaging
Scan Sensitivity Specificity Positive predictive
value
Negative predictive
value
Accuracy
CEUS 53% 91% 75% 79% 78%
CT 53% 99% 95% 80% 83%
MRI 62% 100% 100% 84% 87%
Khalili K, Sherman M, et al. J Hepatol 2011;54:723-8
22. The sensitivity of HCC diagnosis by imaging is
not influenced by the cirrhotic background
Imaging Liver cirrhosis Non-cirrhotic liver P
Liver CT (typical/atypical) (n=204) 81/14 (85.3%) 86/23(78.9%) 0.239
Tumor 1-2 cm (n=38) 15/6 (71.4%) 12/5 (70.6%) 1.000
Tumor > 2cm (n=166) 66/8 (89.2%) 74/18 (80.4%) 0.123
MRI (typical/atypical) (n=80) 48/12 (80%) 13/7 (65%) 0.226
Tumor 1-2cm (n=26) 19/5 (79.2%) 2/0 (100%) 1.000
Tumor >2cm (n=54) 29/7 (80.6%) 11/7 (61.1%) 0.188
Lin MT, Chen CL, Hu TH, et al. J Gastroenterol Hepatol 2011;26;745-50
25. HCC staging
• At least 10 systems have been raised
– Okuda (Japan)
– TNM/ AJCC (US)
– BCLC (Spain)
– CLIP (Italy)
– French
– CUPI (Hong Kong)
– JIS (Japan)
– NATURE scoring system (Taiwan)
– Taipei Integrated Scoring system (Taiwan)
26. • To best assess the prognosis of HCC patients it is
recommended that the staging system take into
account tumor stage, liver function and physical
status. The impact of treatment should also be
considered when estimating life expectancy.
• Currently, the BCLC system is the only staging
system that accomplishes these aims (level II).
AASLD 2010
Staging system
27. Selecting an optimal staging system for HCC
Hsu CY, Huo TI, et al. Cancer 2010;116:3006-14
28. The Cancer of the Liver Italian Program (CLIP) scoring system
Variable Score
Child-Pugh stage
A
B
C
0
1
2
Tumor morphology
Uninodular & extension 50%
Multinodular & extension 50%
Massive or extension > 50%
0
1
2
AFP
< 400
400
0
1
Portal vein thrombosis
No
Yes
0
1
Hepatology 1998;28:751
35. Patients in the RFA group had lower overall survival rate and higher
recurrence rate than those in the SR group
Hung HH, Chiou YY, Hsia CY, et al. Clin Gastroenterol Hepatol 2011;9:79-86
36. Comparison of demographic data between HCC patients underwent RFA or SR
Parameter RFA group (n=190) SR group (n=229) P
Patient demographics
Age (years) (mean±SD) 67.42±11.45 60.07±12.56 < 0.001
Sex (M: F) (%) 121/69 (63.7%/36.3%) 184/45 (80.3%/19.7%) < 0.001
Viral factors
HBsAg positive/negative 88/97(46.3%/51.1%) 137/81(59.8%/35.4%) 0.004
Anit-HCV positive/negative 85/101(44.7%/53.2%) 61/151(26.6%/65.9%) < 0.001
Serum biochemistry tests and liver function tests
Albumin (g/dL) (mean±SD) 3.85±0.55 4.09±0.40 < 0.001
Total bilirubin (mg/dL) (mean±SD) 0.99±0.60 0.81±0.48 0.001
ALT (U/L) (mean±SD) 71.84±56.08 59.83±49.75 0.022
AST (U/L) (mean±SD) 71.43±56.55 50.58±37.67 < 0.001
Alk-P(U/L) (mean±SD) 114.08±56.02 91.25±42.06 < 0.001
Creatinine (mg/dL) (mean±SD) 1.20±1.05 1.08±0.51 0.159
Glucose (mg/dL) (mean±SD) 117.40±57.83 105.91±40.47 0.026
ICG-15R (%) (median; 25 and 75 percentiles) 19.50;8.00-29.00 11.50;7.00-16.00 0.002
PT/ INR (mean±SD) 1.06±0.12 1.03±0.06 0.002
Platelet (/mm3) (mean±SD) 128889±62029 162078±61612 < 0.001
Tumor factors
Tumor size (cm) (median; 25 and 75 percentiles) 2.20;1.70-2.90 2.70;2.00-3.70 < 0.001
Single tumor/multinodularity (%) 152/38 (80.0%/20.0%) 181/48 (79.0%/21.0%) 0.904
AFP (ng/ml) (median; 25 and 75 percentiles) 17.86;7.30-49.87 17.88;6.59-190.25 0.043
37. Multivariate analysis to determine factors associated with
poor outcomes after curative therapy for HCC
Hazard ratio (95% confidence interval) P
Poor overall survival
Age > 65 years 1.988 (1.266-3.121) 0.003
Albumin ≦4 g/dL 1.751 (1.073-2.857) 0.025
Bilirubin > 1.6mg/dL 2.032 (1.033-3.998) 0.040
PT/INR > 1.1 2.114 (1.275-3.506) 0.004
AFP> 20 ng/mL 1.680 (1.079-2.617) 0.022
Multiple tumor 1.851 (1.139-3.007) 0.013
Recurrence
RFA/SR 1.949 (1.479-2.571) < 0.001
Platelet ≦105/mm3 1.420 (1.033-1.949) 0.031
Multiple tumor 1.798 (1.344-2.405) <0.001
38. After propensity score matching, RFA was not inferior to SR in overall
survival, but SR had lower incidence of developing recurrence than RFA
A B
39. There was no statistical significance between RFA and SR in
overall survival and recurrence for BCLC stage 0 HCC patients
A B
40. Survival of patients with HCC within Milan criteria
Lee YH, Hsu CY, Huo TI, et al. Aliment Pharmacol Ther 2012;36:551-59
41. Conclusions
• Patients with small HCCs (5 cm) have a higher rate
of tumor recurrence following RFA than surgery,
but overall survival rates are comparable between
therapies.
• RFA is as effective as surgery in patients BCLC stage
0 HCC.
46. Viral etiology does not impact on the outcome of
small HCC patients who undergo RFA
Overall Survival
Disease-free Survival
Propensity score matching analysis
Chen PH, Kao WY, Chiou YY, et al. Ann Hepatol (in press)
48. Minimal fibrosis
Advanced fibrosisP=0.018
P=0.018
Minimal fibrosis
Advanced fibrosis
Survival 1 yr 3yr 5yr 10yr
Mininal 100% 92.9% 92.9% 78.6%
Advanced 91.9% 71.0% 59.7% 29.2%
Recurrence 1 yr 3yr 5yr 10yr
Mininal 7.1% 21.4% 21.4% 28.6%
Advanced 24.4% 49.6% 60.3% 72.6%
Hung HH, Su CW, Chau GY, Huo TI, Wu JC, et al.
Hepatol Int 2010;4:691-699
The degree of liver fibrosis is critical in determining post-surgery
outcomes for patients with small HCC
49. APRI could predict prognosis of HCC
patients undergoing resection
APRI could serve as a feasible marker for predicting the
prognosis of patients with small HCC undergoing resection surgery
Hung HH, Su CW, Chau GY, Huo TI, Wu JC, et al. Hepatol Int 2010;4:691-699
51. Patients with splenomegaly had poorer overall
survival rate than those with normal splenic volume
Wu WC, Chiou YY, Hung HH. J Clin Gastroenterol 2012; 46;789-95
56. Resection is superior to TACE in patients
with HCC beyond Milan criteria
Hsu CY, Huo TI, et al. Ann Surg Oncol 2012;19:842-9
Propensity score matching analysis
57. Resection is superior to TACE in patients
with HCC beyond Milan criteria
Chang WC, Kao WY, Chau GY, et al. Surgery (in press)
Variable HR 95%CI p
Overall survival
Albumin 4 / > 4 g/dL 1.570 1.225-2.012 <0.001
ICGR-15 >10%/ 10% 1.290 1.009-1.650 0.042
Creatinine > 1.2 / 1.2 mg/dL 1.462 1.029-2.077 0.034
Multiple tumor (yes/no) 1.517 1.154-1.994 0.003
Edmondson stage III or IV / I or II 1.485 1.164-1.895 0.001
Macroscopic vascular invasion (yes) 1.585 1.217-2.064 0.001
58. The impact of poor respond to TACE on
overall survival
Tsai YJ, Hsu CY, Huo TI, et al. Hepatol Int 2011;5:975-84
59. Liver failure after TACE
Hsin IF, Hsu CY, Huo TI, et al. J Clin Gastroenterol 2011;45:556-62
