Lecture on hepatocellular carcinoma for medical students. Encompasses basic sciences, pathophysiology, classification, principles and tips on management.

1. Hepatocellular carcinoma
Chea Chan Hooi
Surgeon
Department of Surgery
Sibu Hospital

2. Content
• Introduction
• Etiology
• Pathophysiology
• Work-up
• Treatment options
• Screening
• Q&A

3. Introduction
• Primary malignancy of liver
• Highest incidence in Asia and Africa
– Hepatitis infection
• Incidence in developing nations is >2x
developed countries
• Increases with age
• Predominantly in patients with underlying
chronic liver disease and cirrhosis

4. Etiology
• Modifiable
– Hepatitis C & B
– Alcoholism
– NASH
– Aflatoxin
• Non-modifiable
– Alpha-1-antitrypsin deficiency
– Haemachromatosis
Epidemic of HCC predicted with emergence of NASH, aging population & more survivors of
cirrhosis

5. Pathophysiology

6. Work-up
• Confirm diagnosis (cirrhosis + characteristic
imaging studies + elevated AFP)
– Multiphase liver CT scan/MRI
– AFP
– Biopsy?
• Staging
• Disease severity
• Etiology of HCC

7. • Multiphase liver CT scan
– Accurate diagnosis, staging & surgical planning
– Plain, early & late arterial, portal venous &
delayed phases
– Hypervascular pattern with arterial enhancement
and rapid washout during portal venous phase
– Tumor capsule, internal mosaic from variable
attenuation within the tumor and PV
thrombosis/invasion

9. • Hepatic MRI
– Hepato-specific paramagnetic gadolinium-based
contrast (Primovisttm)
– Arterial, portal venous, late dynamic &
hepatobiliary phases
– HCC appears darker than background liver on T1-
weighted images
– Superior sensitivity & specificity vs. CT for lesions
<1cm3

10. • Biopsy
– Controversial
– Depending on lesion size & institutional practice
<1cm <50% malignant, high false-negative. For
conservative management with close
follow-up and no biopsy
1 – 2cm Imaging usually inconclusive, need to biopsy
or MRI with gadoxetate contrast
>2cm Usually can be diagnosed without biopsy.
Risk of tumour seeding must be taken into
account

11. • Staging
– CT scan/PET scan
• Disease severity
– FBC – anaemia, leucocytosis (infected HCC),
thrombocytopenia (portal HPT)
– RP – dilutional hyponatraemia, hepatorenal syndrome
– LFT – metabolic & synthetic functions of liver
– PT/PTT – synthetic function of liver
– AST/ALT – active hepatitis
– Hypogycaemia – end-stage liver disease (no glycogen)
• Etiology
– HBV/HCV serology

12. Treatment options
• Surgery
– Resection
– Liver transplant
• Ablative therapy
– Thermal
– Chemical
– Electrical
• Regional liver therapy
– TACE
– SIRT
• Radiotherapy
– Stereotactic radiosurgery
• Systemic
– Multikinase inhibitors

13. Surgery
• Irresectable
– Child-Pugh score C
– Distant metastases
– Extrahepatic disease present – e.g. extensive
lymphadenopathy or peritoneal deposits
– Extensive bilobar disease
– Hilar tumour involving major blood vessels not
amenable to repair
– Inadequate functional liver residue predicted post-
operatively (FLR < 40% if cirrhotic, <30% if non-
cirrhotic, ICG15 >14%)

14. • Resections
– Non-anatomic (wedge)
• Limited resections of a small portion of liver without adhering to
segmental biliary ducts & vascular supply
– Anatomic
• Removing 1 or more of the 8 segments of the liver
• To improve resectability
– Contralateral portal vein embolization (for parenchymal
hypertrophy) ± TACE (minimise resected parenchymal mass)
– To increase FLR
• Liver transplantation
– Significant cirrhosis and limited tumour burden
– Milan criteria (determines candidacy for transplantation)

15. Ablative therapy
• Best for tumours <3cm
• Indications
– Bridge to transplant by reducing the risk of tumor progression
– Palliative procedure to extend DFS
• Percutaneous, laparoscopic or open surgery
• Options
– Thermal
• Radiofrequency ablation
• Microwave ablation
• High intensity focused ultrasonography (HIFU)
• Cryoablation
– Chemical
• Ethanol – obsolete
– Electrical
• Irreversible electroporation aka nanoknife
– DC pulses across 2 electrodes causing actively dividing cells’ membrane to rupture

16. Regional liver therapy
• Generally considered non-curative
• Options
– Transarterial chemoembolization (TACE)
– Selective internal radiotherapy (SIRT)

17. Radiotherapy
• Stereotactic radiosurgery
• EBRT is obsolete

18. Systemic therapy
• Multikinase inhibitors
• Indications
– Child’s A
– Metastatic disease
– Irresectable but failed/unsuitable for regional
therapy
• Sorafenib, sunitinib

19. Screening
• All cirrhotic patients
• 6 monthly USG & AFP*
– No extra benefit with 3 monthly screen
• Reason
– Increased detection of early HCC
– Increased detection of single HCC <5cm
– Increased surgery for HCC
– Increased survival
– Increased cost effectiveness

20. • USG
– Low cost, low risk, non-invasive, acceptable to patient
– Have a range of echogenicity
– Significant arterial blood supply and neovascularization
– Might miss nodules on cirrhotic background & SVII or VIII small lesions
near diaphragm
– Does not provide sufficient anatomic detail for planning surgical
resection or ablation
– No data to support CT/MRI for screening
• AFP
– The result of production by the tumor or regenerating hepatocytes
– Suboptimal as a screening tool, therefore never performed alone
– Only 40-64% sensitive
– Only 20% of early HCC have abnormal AFP
– Fluctuates in flares of hepatitis or exacerbations of liver disease

22. Thank you!
Q&A?