HCC

Question 1

risk factors for HCC

Answer 1

1) chronic Hep B
- increase risk of cirrhosis & HCC
2) chronic Hep C
. increase risk for cirrhosis & HCC
- but lesser risk for patient with sustained serologic viral response to HCV therapy
. increased in “baby boom” gen
- exposed to blood transfusion, clotting factors, dialysis prior to 1992
3) NAFLD
- hepatic manifestation of metabolic disease
- higher in countries with higher obesity & diabetes
- associated with late onset & high tumour burden
- don’t check when asymptomatic then too late when they check
4) alcohol
- alteration in hepatic metabolism, cause progressive steatosis, fibrosis/cirrhosis, HCC
- promote hepatocarcinogenesis by increasing mutagenic acetaldehyde, oxidative stress, DNA damage -> create carcinogenic tissue environment
5) cirrhosis
- repeated damage -> scarring -> fibrosis -> liver cell destruction -> malignant transformation -> HCC
6) smoking & environmental carcinogens (fungal toxin)
7) genetic predisposition
- alpha-1 antitrypsin deficiency, alpha-1 antitrypsin protein protect liver & lung, deficiency = destruction

Question 2

primary prevention for HCC

Answer 2

. identify patients with risk factors
. prevent progression
. vaccination, lifestyle mod, blood screening before transfusion

Question 3

secondary prevention for HCC

Answer 3

. patient with hepatitis, fibrosis/cirrhosis
. screening (early detection) for high risk patients
. chemoprevention for patients exposed to aetiologic agents & treat underlying disease

Question 4

tertiary prevention for HCC

Answer 4

. patient alr has HCC
. prevent recurrence

Question 5

diagnosis of HCC

Answer 5

. LFT
. CT, MRI
. start with surveillance ultrasound
- -ve: repeat 6 month
- subthreshold: repeat 3-6 months
- +ve: imaging test

Question 6

treatment for early stage cancer - surgical

Answer 6

• mainstay, best outcome
• resection/transplant

Question 7

treatment for early stage cancer - ablation

Answer 7

• modify liver temperature using radio waves/microwaves
• minimum invasiveness
• not enough for large tumour cells, require resection

Question 8

treatment for early stage cancer - arterially directed therapies

Answer 8

. liver highly vascularised, good for cancer cells to grow
. transarterial chemo embolism (TACE)
- drug released, beads form “embolism”, drug trapped with cancer
. transarterial radio embolism (TARE)
- Ytrium-90 microsphere directly release radiation to tumour

Question 9

treatment for advanced stage - chemotherapy

Answer 9

• kill proliferating cancer cells
• BUT also kill your own cells

Question 10

treatment for advanced stage - targeted therapy

Answer 10

. monoclonal antibodies (-mab)
- identify antigens that target growth factors (VEGF) that promote cancer cell growth
- inhibit VEGF = lesser blood vessels formed = cut off blood supply to tumour
- lower systemic effects
- but can affect normal cell VEGF as well = increased risk for bleeding so need to hold off 28 days before and after surgery

. small molecules (-nib)
- target kinases/enzymes part of signalling cascade

. ideal targets & outcomes
- inhibit VEGFR: inhibit angiogenesis
- inhibit RAF, KIT, PDGFR: inhibit oncogenesis
- inhibit PDGFR, FGFR: inhibit proliferation, angiogenesis

Question 11

treatment for advanced stage - immuno therapy

Answer 11

. why is there a problem?
- immune checkpoints holds T cells & prevent release (for autoimmune purposes)
- cancer cells stimulate immune checkpoints & prevent release

. immune checkpoint inhibitor
- releases T cells for immune effect

. first line
- atezolizumab (PD-L1i) + bevacizumab
- PD-L1i + CLTA-4 for greater effect

. can result in immune related AE (irAEs)
- hepatomegaly, splenomegaly
- SOB fever fatigue
- GIT problems, hypotension, HTN