Prospective Cohort Study on the Clinical Trajectory of Resected Hepatocellular Carcinoma

1. Male and female patients, 21 to 80 years of age at the time of signature of the informed consent form.
2. Histologically proven HCC after liver resection. Combined hepatocellular-cholangiocarcinoma can be included.
3. HCC limited to the liver with no extra-hepatic metastasis on CT or MRI of the abdomen and chest (defined as lymph node \<2 cm, lung nodules \< 1 cm, farther lymph nodes \< 2 cm) according to the AASLD criteria65.
4. R0 or R1 resection on histology.

5. Eligibility according to tumour size:

   1. Large tumour >= 5 cm (preferred)
   2. Smaller tumours >=2cm and \< 5cm
   3. Multifocal tumours - maximum of 3 total tumours with size >=2cm detected from CT-scan. Detection of \<1cm tumour intra-operatively or upon histologic examination following resection can be ignored. For multiple satellite nodules (>=2cm) that are detected intraoperatively, harvest ALL satellite nodules (>/= 2cm). DNA/RNA will be extracted from cases confirmed to be HCC/hepato-cholangiocarcinoma by histology. A MAXIMUM of 3 samples with the best quality are to be used for the analysis.
6. Child-Pugh ≤ 7 points without clinical ascites before surgery.
7. ECOG performance status 0-1 before surgery.
8. Scheduled for liver resection within 6 weeks.
9. The patient has received no anti-cancer specific treatment for HCC eg. previous liver resection, loco-regional therapy (e.g. RFA, TACE, SIRT), radiotherapy, immunotherapy, chemotherapy or neo-adjuvant chemotherapy other than the planned surgery. However, patient who has received previous HCC resection more than 5 years ago is deemed to have a de-novo liver tumour and therefore can be included.

10. Adequate bone-marrow reserve, renal function and hepatic function as assessed by standard laboratory criteria:

    • Absolute neutrophil count ≥ 1.0 x 10\^9/L
    • Platelet count ≥ 50 x 10\^9/L
    • Haemoglobin ≥ 9.0 g/dL
    • INR ≤ 2.0
    • Serum creatinine ≤ 1.5 times the Upper Limit of Normal (ULN)
    • Albumin ≥ 2.5 g/dL
    • Total bilirubin ≤ 1.5 times the ULN
    • Alanine transaminase (ALT) ≤ 2.5 times the ULN
    • Aspartate transaminase (AST ≤ 2.5 times the ULN

Exclusion Criteria:

1. Single lesion \< 2 cm at the time of tumour resection.
2. The patient has previous or concomitant malignancies at other sites, except effectively treated non-melanoma skin cancers or carcinoma in situ of the cervix or effectively treated malignancy that has been in remission for over 5 years and highly likely to have been cured.
3. Encephalopathy
4. The patient has received a major organ allograft.
5. The patient is known to be positive for the Human Immunodeficiency Virus (HIV).
6. The patient has an uncontrolled bleeding disorder.
7. The patient has uncontrolled congestive heart failure or hypertension, unstable heart disease (coronary artery disease or myocardial infarction) or uncontrolled arrhythmia at the time of enrolment.
8. The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent, or to comply with the study procedures.
9. The patient has other concurrent severe medical problems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk.
10. The patient has received any investigational or non-registered medicinal product (drug or vaccine) within the 30 days preceding the date of enrolment, or plans to receive such a drug during the study period.
11. For female patients: the patient is pregnant or lactating.
12. Insufficient DNA/RNA for genome analysis at baseline
13. Insufficient cells for immunology analysis at baseline (Singapore sites only)