1. Hepatocellular Carcinoma Diagnostic and Therapeutic Strategies
Faisal Sanai
Consultant Hepatologist
Riyadh Military Hospital
10th International Advanced Medicine Symposium

2. Tumor Markers for HCC Des3  carboxy prothrombin. Alpha Fetoprotein.
-l-Fucosidase.
5’- nucleotide phosphodiesterase.
Des3  carboxy prothrombin.
CA 19-9, CA 125, ALP.
Alpha Fetoprotein.
Fucosylated AFP.

3. Alpha Fetoprotein Sensitivity and Specificity Issues
GI tumors: 10 – 20%.
Cirrhosis: 40%.
Acute and chronic hepatitis: 20%.
Pregnancy.
Gonadal tumors: 80%.
Ethnicity.
Etiology of liver disease.
Treatment of underlying liver disease.
Tumor staging.
Sensitivity patterns for HCC vary widely: 32 – 93%
Colli A, et al. Am J Gastro 2006.

4. Alpha Fetoprotein Change in HCC Detection by Changing Cut-off Points
Diagnostic Criteria
Sensitivity (%)
Specificity (%)
>615 ng/ml
56.4
96.4
>445 ng/ml
94.5
>100 ng/ml
72.6
70.9
>20 ng/ml
87.1
30.9
Poon TCW, Clin Liv Dis 2001

5. Diagnostic Yield of U/S
Sensitivity in cirrhotic liver: 60%.
Specificity: 97%.
Colli A, et al. Am J Gastro 2006
Sensitivity for lesions cm: 13%.
Sensitivity for lesions cm: 20%.
Dodd G, et al. AJR 1992

6. CT Scan for HCC Diagnosis
Diagnostic procedure of choice.
Arterial phase CT is vastly superior to double phase scanning.
The sensitivity of CT is much greater than ultrasonography (80% vs 60%).
Chalasani N, et al. Am J Gastro 1999

7. The CT Modality of Choice
Recent lipiodol studies have shown reduced sensitivities compared to initial reports.
Reduced sensitivity compared to triple phase CT.
Ngan H. Br J Radiol 1990
Nakayama A, et al. Ann Surg 2001
Earlier Report
Recent Report
Sensitivity
93 – 97%
78%

8. Angiography Does the Route Make Any Difference ?
109 patients with HCC.
Sensitivity of angiographic interventions studied.
CT Lipoidol – 80%.
CT Portography – 84.4%.
CT Angiography – 91.3%.
CT portography revealed additional 15% lesions that had significant therapeutic alterations.
Malagari K & Hadziyannis S. Hepatogastroenterology 1999

9. To Biopsy or Not to Biopsy…
Pre-existing cirrhosis + mass >2 cm:
>95% chance of HCC.
Pre-existing cirrhosis + mass <2 cm:
≈ 75% chance of HCC.
Frazer C J Gastro & Hepat 1999
Horigome H, et al J Gastro & Hepatol 1999
“Only where considerable doubt exists, will a biopsy of the lesion be required.”
BSG Guidelines – Ryder SD, Gut 2003.

10. Needle Track Seeding Incidence of 1 - 2% for each biopsy attempt.
Incidence lower with FNA than tru-cut.
Needle track seeding converts curative resection to palliative.
False-positive clinical/radiological diagnosis about 3%.
20% in HCC <3cm and low AFP
Levy I, et al. Ann Surg 2001

11. Biopsy The Guidelines Lesions <1 cm should not be biopsied.
Lesions cm should have FNA + biopsy.
Conclusions of EASL 2000, J Hepatol 2001
Bruix J, et al. AASLD Guidelines 2005
Lesions >2 cm should not be biopsied in presence of diagnostic clinical criteria.
Abdo A, et al. Saudi Guidelines for HCC, Ann Saudi Med 2006

12. Setting Diagnostic Criteria
Histological diagnosis.
Presence of classic appearance in one imaging modality + AFP >400 µg/L + appropriate clinical setting.
Presence of normal AFP + classic (>2 cm nodule, arterial vascularity) appearance in two imaging modalities + appropriate clinical setting.
Saudi Guidelines for HCC, Ann Saudi Med 2006
Conclusions of EASL 2000, J Hepatol 2001

13. Surveillance and Recall Strategy for HCC
Cirrhotic patients (US + AFP/6 m)
Liver nodule
No nodule
1 cm
<1 cm
Increased AFP*
Normal AFP
<2 cm
>2 cm
US/3m
Spiral CT
FNAB
AFP 400 ng/mL
CT/MRI/Angiography
No HCC
HCC**
Surveillance US + AFP/6 m
*AFP levels to be defined; **Pathological confirmation or non-invasive criteria

14. Decision making in HCC Treatment
The status of the non-tumorous liver:
Underlying cirrhosis.
Non-cirrhotic liver (HBV).
Size and extension of the tumour:
Is it ≤5 cm in size/≤3 lesions ≤ 3 cm ?
Vascular involvement.
General condition of patient, the age and expected life expectancy.

15. Liver Transplantation for HCC
HCC is the curative intervention of choice
Survival: 75% at 5 years.
Data comparable to non-HCC LT.
HCC require priority listing for LT.
Living Donor LT can be offered.
Milan Criteria serve as threshold for LT option (single lesion < 5 cm; ≤ 3 in number, < 3 cm).
Conclusions of EASL 2000, J Hepatol 2001
Saudi Guidelines for HCC, Ann Saudi Med 2006
Bruix J, et al. AASLD Guidelines 2005

16. Liver Transplantation for HCC Expanding the Milan Criteria
UCSF Criteria: (single lesion < 6.5 cm; ≤ 3 in number, < 4.5 cm; combined diameter < 8cm)
Survival
Milan Criteria
94%
88%
UCSF Criteria
90%
Yao et al. Hepatology 2005, 197A

17. The Optimal Resection Candidate
All non-cirrhotic patients with no extrahepatic spread (Western 5%, Asian 40%).
When cirrhosis present - 30%:
Child-Pugh class ‘A’.
No portal HTN.
Pr. gradient >10 mmHg
Oesophageal varices
Splenomegaly  plats <105
Patient is not a candidate for LT treatment.
Solitary lesions <5 cm.

18. Resections Outcome Recurrence: Survival: Decompensation:
5 years >70%.
Survival:
3 years: %.
5 years: %.
Decompensation:
50%.
Song TJ, et al. Gastroenterology 2004

19. Survival: 3 years, 391 patients, 1 lesion, <5 cm
Local Ablative Therapies for HCC PEI: Livraghi T, et al., J Hepatol 1995
Survival: 3 years, 391 patients, 1 lesion, <5 cm
Child - A
Resection
79% (p <0.001)
P E I
71% (p <0.001)
No Treatment
26%
Child - B
40% (p <0.01)
41% (p <0.001)
13%

20. Local Ablative Therapies for HCC
Radiofrequency Ablation (Lencioni R et al, Radiology 2003)
Randomized trial: RFA vs PEI.
Child A or B in accordance with Milan criteria.
Survival
1 year
2 years
RFA
100%
98%
p = 0.138
PEI
96%
88%
1 Year
89%
3 years
62%
5 years
33%
Buscarini L et al., Eur Radiol 2001

21. Rationale for Embolization Therapy
HCC blood supply >90% from hepatic artery.
Normal liver % blood supply from portal vein.
Breedis et al, Am J Pathol 1954
Occlusion of blood supply may cause tumor necrosis in up to 95% of lesion.
Higuchi et al, Cancer 1994

22. Improved Survival with TACE
Systematic review of 7 RCT comprising 545 patients.
Llovet & Bruix, Hepatology 2003
(Chemo)embolization vs no treatment.
Significant improvement in 2 year survival.
Subanalysis showed significant benefit with chemoembolization but not with bland emolization.
Small tumors, good liver reserve:
TACE: 63%
Bland: 50%
Control: 27%
Llovet et al, Lancet 2002

23. Guidelines Recommendation for TACE
“The evidence for a survival benefit with TACE is sound and that this useful procedure should be used more often in the right clinical setting.”
Saudi Guidelines for HCC, Ann Saudi Med 2006
“TACE is recommended as first line non-curative therapy for non-surgical patients with large/multifocal HCC who do not have vascular invasion or extrahepatic spread”.
AASLD Practice Guidelines: HCC; Hepatology 2005

24. Approach in Non-Cirrhotic Patient
No Cirrhosis
Resection candidate
Normal bilirubin
No portal HTN
No extra-hepatic spread
Technically resectable
Not Resection candidate
Multifocal (>3)
Lesion >4 cm
Less than 3 lesions
Smaller than 3 cm
Resection
TACE
TACE
Local ablation
Saudi HCC Guidelines. Ann Saudi Med 2006

25. Approach in Child-Pugh ‘A’ Cirrhotic
Child-Pugh Class A
Timely transplant available
Yes No
≤3 lesions each <3 cm
1 lesion <5 cm
No extra hepatic spread
Resection candidate
Normal bilirubin
No portal HTN
No extra-hepatic spread
Technically resectable
Not Resection
candidate
Transplant
Multifocal (>3)
Lesion >4 cm
Less than 3 lesions
Smaller than 3 cm
Resection
TACE
TACE
Local ablation
Local ablative therapy or TACE may be used while awaiting liver transplant
Saudi HCC Guidelines. Ann Saudi Med 2006

26. Approach in Child-Pugh ‘B’ Cirrhotic
Child-Pugh Class B
Timely transplant available
Yes No
≤3 lesions each <3 cm
1 lesion <5 cm
No extra hepatic spread
Multifocal (>3)
Lesion >4 cm
Less than 3 lesions
Smaller than 3 cm
Transplant
TACE
TACE
Local ablation
therapy
Saudi HCC Guidelines. Ann Saudi Med 2006

27. Approach in Child-Pugh ‘C’ Cirrhotic
Child-Pugh Class C
Timely transplant available
Yes No
≤3 lesions each <3 cm
1 lesion <5 cm
No extra hepatic spread
Good performance
status
<50 years old
Poor performance
status
>50 years old
Transplant
Cirrhosis complication
management
Consider enrollment in
systemic chemotherapy
trials
Cirrhosis complication
management
Palliative symptomatic
treatment
Saudi HCC Guidelines. Ann Saudi Med 2006

28. Summary
HCC is essentially diagnosed by non-invasive criteria which is a combination of serology and imaging means.
Liver biopsy is to be performed only where considerable doubt exists for the diagnosis
Recent advances in ablative therapy (RFA) and improved survival with TACE are encouraging; that these should be used more frequently.
LT remains the curative treatment of choice.

29. Saudi Gastroenterology Association Guidelines Diagnosis & Management of HCC Technical Review & Practice Recommendations