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Hepatocellular Carcinoma (HCC)

Last updated 31 May 2026 · Oncology clinical guideline

📋 Key Information Summary

📋
  • Hepatocellular carcinoma (HCC) is the most common primary liver cancer, accounting for ~85% of cases, and typically arises in the setting of chronic liver disease and cirrhosis.
  • Key risk factors in Australia include chronic hepatitis B (HBV) and C (HCV) infection, alcohol-related liver disease, and non-alcoholic fatty liver disease (NAFLD).
  • Aboriginal and Torres Strait Islander peoples experience higher incidence and poorer outcomes due to disparities in risk factor prevalence and healthcare access.
  • Surveillance with six-monthly liver ultrasound (± alpha-fetoprotein) is recommended for at-risk groups to enable early detection when curative treatment is possible.
  • Diagnosis is primarily imaging-based (CT/MRI with contrast) using LI-RADS criteria; biopsy is reserved for indeterminate cases.
  • Staging and treatment allocation follow the Barcelona Clinic Liver Cancer (BCLC) system, which integrates tumour burden, liver function (Child-Pugh), and performance status.
  • Potentially curative treatments for very early/early stage (BCLC 0/A) include surgical resection, liver transplantation, and local ablation (e.g., radiofrequency ablation).
  • For intermediate stage (BCLC B), transarterial chemoembolisation (TACE) is the standard of care.
  • Systemic therapy is indicated for advanced BCLC C disease. First-line options include atezolizumab + bevacizumab or sorafenib.
  • Sorafenib (Nexavar®) is a PBS Authority Required multi-kinase inhibitor that modestly improves overall survival. It requires careful management of side effects like hand-foot skin reaction and hypertension.
  • Multidisciplinary team (MDT) discussion is mandatory for all patients to tailor management based on tumour stage, liver function, and comorbidities.
  • Management of underlying cirrhosis and its complications (e.g., portal hypertension, varices) is integral to HCC care.

Introduction & Australian Epidemiology

Hepatocellular carcinoma (HCC) is a major global health burden and the most common primary malignancy of the liver. In Australia, it is one of the few cancers with increasing incidence and mortality rates. The disease typically arises in the context of chronic liver inflammation and fibrosis/cirrhosis, which provides a premalignant field. The landscape of HCC management is complex, requiring integration of tumour staging, assessment of underlying liver function, patient fitness, and available curative or palliative modalities. This guideline provides a framework for the investigation and management of HCC within the Australian healthcare context.

In Australia, the age-standardised incidence rate of liver cancer (predominantly HCC) has more than tripled over the past three decades. According to the Australian Institute of Health and Welfare (AIHW), it was the sixth most common cause of cancer death in 2022. Chronic viral hepatitis, particularly hepatitis B (HBV) and hepatitis C (HCV), remains the leading attributable risk factor. However, the incidence of HCC associated with non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD) is rising sharply. There is a significant disparity in burden, with Aboriginal and Torres Strait Islander peoples experiencing approximately twice the incidence and poorer survival outcomes compared to non-Indigenous Australians.

Hepatocellular Carcinoma (HCC) clinical infographic — pathophysiology, clinical clues, diagnosis, imaging, and management
Tap or click image to enlarge — Hepatocellular Carcinoma (HCC): pathophysiology, clinical clues, diagnosis, imaging, and management.
Hepatocellular Carcinoma (HCC) infographic, full size

Epidemiology & Risk Factors

The development of HCC is a multi-step process strongly associated with the presence of cirrhosis, regardless of aetiology. Understanding the major risk factors is crucial for targeting surveillance programmes.

Risk Factor Estimated Population Attributable Risk (Australia) Key Points
Chronic Hepatitis B (HBV) ~25-30% Major risk even without cirrhosis. Higher prevalence in those born in endemic regions and Aboriginal and Torres Strait Islander communities. Vaccination is preventative.
Chronic Hepatitis C (HCV) ~20-25% Risk persists after cirrhosis has developed, even if SVR is achieved with direct-acting antivirals (DAAs). Surveillance continues post-cure if cirrhosis is present.
Alcohol-related Liver Disease (ALD) ~20-25% Risk is dose- and duration-dependent, primarily in those with established cirrhosis.
Non-Alcoholic Fatty Liver Disease (NAFLD) ~15-20% (and rising) The fastest-growing risk factor. HCC can occur in NAFLD without cirrhosis, particularly in the context of metabolic syndrome.
Other ~5-10% Includes haemochromatosis, autoimmune hepatitis, alpha-1 antitrypsin deficiency, and Wilson disease.
⚠️
Key Surveillance Populations: All patients with cirrhosis (any cause) are at high risk and require six-monthly surveillance. Patients with chronic HBV without cirrhosis also require surveillance based on specific risk profiles (e.g., age >50, family history, high viral load).

Pathogenesis & Barcelona Clinic Liver Cancer (BCLC) Staging

Hepatocarcinogenesis is driven by chronic necro-inflammation, regenerative nodularity, and accumulation of genetic and epigenetic alterations. The cirrhotic microenvironment with altered growth signalling (e.g., Wnt/β-catenin, TERT promoter mutations) facilitates malignant transformation.

Staging in HCC serves a dual purpose: prognostication and treatment allocation. The Barcelona Clinic Liver Cancer (BCLC) system is the internationally endorsed and widely used standard in Australia. It classifies patients into five stages linked to specific treatment strategies.

Very Early / Early
BCLC 0 / A
Single tumour or up to 3 nodules ≤3 cm. Preserved liver function (Child-Pugh A-B). Performance status (PS) 0.
Curative Intent: Resection, Transplantation, Ablation
Intermediate
BCLC B
Multi-nodular, no vascular invasion/extrahepatic spread. Child-Pugh A-B. PS 0.
Loco-regional: Transarterial Chemoembolisation (TACE)
Advanced
BCLC C
Vascular invasion and/or extrahepatic spread. Child-Pugh A-B. PS 1-2.
Systemic Therapy: Atezolizumab + Bevacizumab, Sorafenib, Lenvatinib
Terminal
BCLC D
Any tumour burden with severe liver impairment (Child-Pugh C) and/or PS >2.
Best Supportive Care

Investigations & Surveillance

Surveillance Program

Aim to detect HCC at a curable stage. The primary modality is six-monthly abdominal ultrasound. The role of alpha-fetoprotein (AFP) as an adjunct is debated but often used in conjunction.

ESSENTIAL
Liver Ultrasound (± AFP)
MBS Item 55030 (Ultrasound, abdominal). Six-monthly for all patients with cirrhosis and high-risk chronic HBV. Sensitivity ~60% for early HCC in expert hands.
AVAILABLE
Multiphase CT or Dynamic Contrast MRI
MBS Items for CT abdomen (56804, 56807) and MRI liver (63001, 63004). Used for diagnostic confirmation (LI-RADS 5) and staging if ultrasound is abnormal or AFP rising. MRI has superior sensitivity for small lesions.

Diagnostic Workup

Diagnosis of HCC in cirrhotic liver can often be made non-invasively using contrast-enhanced imaging (LI-RADS 5: arterial phase hyperenhancement + washout/capsule).

AVAILABLE
Diagnostic CT/MRI (LI-RADS)
Standard of care. Characterises lesion and screens for multifocality, vascular invasion, and extrahepatic disease.
CONSIDER REFERRAL
Liver Biopsy
Reserved for imaging-inconclusive lesions (LI-RADS 3/4). Risks include bleeding and tumour seeding. Histology confirms diagnosis and may provide molecular data.

Staging Workup

ESSENTIAL
CT Chest/Abdomen/Pelvis
To assess for extrahepatic metastases (lungs, nodes, adrenals).
ESSENTIAL
Liver Function Assessment
Child-Pugh score (bilirubin, albumin, INR, ascites, encephalopathy). Model for End-Stage Liver Disease (MELD) score for transplant consideration.
SPECIALIST
Portal Hypertension Assessment
Hepatic venous pressure gradient (HVPG) >10 mmHg or clinical signs (oesophageal varices, thrombocytopenia) contraindicate resection in some cases.

Treatment (Resection, Ablation & Sorafenib)

Treatment is highly stage-dependent. All patients must be discussed in a specialist Multidisciplinary Team (MDT) meeting including hepatobiliary surgery, transplant surgery, hepatology, medical oncology, interventional radiology, and radiation oncology.

Curative-Intent Treatments (BCLC 0/A)

1
Surgical Resection
Best for single tumours in patients without cirrhosis or with very well-compensated cirrhosis (Child-Pugh A, no portal hypertension). Offers 5-year survival >60%. Requires adequate future liver remnant.
2
Liver Transplantation
The ideal treatment for patients with cirrhosis, as it cures both the tumour and the underlying liver disease. In Australia, access is limited by organ scarcity. Eligibility is generally restricted to Milan Criteria (single ≤5 cm or ≤3 nodules each ≤3 cm).
3
Local Ablation
Radiofrequency ablation (RFA) or microwave ablation (MWA). First-line for very early tumours (BCLC 0, <2 cm) and an alternative to resection for early tumours in patients with mild portal hypertension. Performed percutaneously by interventional radiology.

Systemic Therapy for Advanced HCC (BCLC C)

First-line systemic therapy has evolved significantly. The combination of atezolizumab (PD-L1 inhibitor) and bevacizumab (anti-VEGF) has become the preferred regimen based on superior overall survival data. Sorafenib remains a key standard-of-care option, particularly where immunotherapy is contraindicated.

💊
Sorafenib
Nexavar® · Multi-kinase inhibitor
Adult dose 400 mg PO twice daily (800 mg total daily dose). Continue until disease progression or unacceptable toxicity.
Key Toxicities Hand-foot skin reaction (manage with urea cream, dose reduction), diarrhoea, hypertension, fatigue.
Hepatic adjustment Not studied in severe hepatic impairment (Child-Pugh C). Use with caution in Child-Pugh B.
PBS status Authority Required
💊
Atezolizumab + Bevacizumab
Tecentriq® + Avastin® · PD-L1 + VEGF inhibitor
Adult dose Atezolizumab 1200 mg IV + Bevacizumab 15 mg/kg IV every 3 weeks. Continue until progression.
Key Toxicities Immune-related adverse events (hepatitis, colitis, pneumonitis), hypertension, proteinuria, haemorrhage risk.
PBS status Authority Required
⛔
Bevacizumab Contraindication: Must screen for oesophageal/gastric varices with endoscopy and treat high-risk varices prior to starting bevacizumab due to risk of life-threatening bleeding.

Special Populations

🏥 Aboriginal & Torres Strait Islander Health
Disparities in HCC outcomes are profound. Key barriers include higher prevalence of viral hepatitis, later stage at diagnosis, and reduced access to specialist services, liver transplantation, and clinical trials. Culturally safe care, community-controlled health service involvement, and proactive care pathways are essential to improve outcomes.
🧪 Renal Impairment
Sorafenib:
No dose adjustment required for renal impairment. Not studied in dialysis.
Contrast Imaging:
Use gadolinium-based contrast for MRI with caution in severe renal failure (risk of NSF).
🫁 Hepatic Impairment
Underlying liver function (Child-Pugh class) is the primary determinant of treatment eligibility, not just tumour stage. Sorafenib and atezolizumab/bevacizumab are primarily for Child-Pugh A. For Child-Pugh B, clinical trial participation or specialist MDT decision is recommended.

Aboriginal and Torres Strait Islander Health Considerations

Critical Considerations for Equitable Care
Risk Factor Prevalence
Significantly higher rates of chronic hepatitis B, particularly in remote communities. Higher prevalence of metabolic risk factors (diabetes, obesity) driving NAFLD-related HCC.
Access to Surveillance
Barriers to regular six-monthly ultrasound in remote areas. Point-of-care testing and telehealth-supported models are being developed. Community awareness of the link between chronic liver disease and HCC is lower.
Treatment Access
Lower rates of curative treatment (resection, transplant, ablation) and higher rates of palliative care presentation. Geographic remoteness impacts access to tertiary centres for complex surgery and MDT review.
Systemic Solutions
Partnership with Aboriginal Community Controlled Health Organisations (ACCHOs) for integrated viral hepatitis and liver disease management. Prioritising Indigenous patients on transplant waiting lists and funding patient travel/accommodation for treatment.

📚 References

  1. 1. Cancer Council Australia. Liver Cancer – Guidelines for Health Professionals. Sydney: Cancer Council Australia; 2023.
  2. 2. Australian Institute of Health and Welfare (AIHW). Cancer data in Australia 2022. Cat. no. CAN 141. Canberra: AIHW; 2023.
  3. 3. Reig M, Forner A, Rimola J, et al. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol. 2022;76(3):681-693.
  4. 4. The Royal Australian College of General Practitioners (RACGP). Hepatitis B and C: Management in Primary Care. 2nd ed. East Melbourne: RACGP; 2022.
  5. 5. Pharmaceutical Benefits Scheme (PBS). Sorafenib (Nexavar®) Authority Required PBS item. Australian Government Department of Health. Accessed October 2023.
  6. 6. Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med. 2020;382(20):1894-1905.
  7. 7. Transplantation Society of Australia and New Zealand (TSANZ). Liver Transplantation Guidelines. 2021.
  8. 8. National Health and Medical Research Council (NHMRC). Strengthening the diagnosis and management of chronic hepatitis B in Aboriginal and Torres Strait Islander peoples. 2020.
  9. 9. Australian Commission on Safety and Quality in Health Care (ACSQHC). National Safety and Quality Health Service Standards. 2nd ed. Sydney: ACSQHC; 2021.
  10. 10. Marrero JA, Kulik LM, Sirlin CB, et al. Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2018;68(2):723-750.
for PBS-listed medicines at participating pharmacies.
Cultural safety
Engagement with Aboriginal Community Controlled Health Organisations (ACCHOs) is essential. Cultural safety training for non-Indigenous clinicians, use of Aboriginal Health Workers and Liaison Officers, and incorporation of traditional healing practices alongside Western medicine improve treatment adherence and outcomes. Avoidance of eye contact, respect for gender-sensitive examination practices, and understanding of sorry business protocols are critical elements of culturally safe care.
Medication adherence
Complex DMARD regimens with frequent monitoring requirements present adherence challenges. Long-acting depot injections (e.g., methotrexate SC) may improve adherence compared to oral regimens. Community pharmacy partnerships through the Indigenous Pharmacy Programmes improve medication management.
Specific conditions
Rheumatic heart disease (RHD) requires secondary prophylaxis with benzathine penicillin G (BPG) 1.2 MU IM every 3–4 weeks for a minimum of 10 years or until age 21 (whichever is longer). RHD registers (e.g., NT RHD Register) facilitate recall and follow-up. The Australian RHD Endgame Strategy targets elimination by 2031.
Referral pathways
Referral through ACCHOs and Aboriginal Hospital Liaison Officers (AHLOs) improves engagement. The Specialist Outreach Assistance Programme provides funded specialist visits to remote communities. NT, WA, and QLD have specific rheumatology outreach programmes targeting Indigenous communities.

📚 References

  1. 1. Australian Institute of Health and Welfare (AIHW). Autoimmune disease in Australia. Cat. no. PHE 312. Canberra: AIHW; 2023.
  2. 2. Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res. 2021;73(7):924–939.
  3. 3. Fanouriakis A, Kostopoulou M, Alber K, et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis. 2019;78(6):736–745.
  4. 4. Chung SA, Langford CA, Maz M, et al. 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Care Res. 2021;73(11):1583–1599.
  5. 5. Smolen JS, Landewé RBM, Bijlsma JWJ, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023;82(1):3–18.
  6. 6. Australian Technical Advisory Group on Immunisation (ATAGI). Australian Immunisation Handbook. Australian Government Department of Health; 2024. Available from: immunisationhandbook.health.gov.au.
  7. 7. Rheumatic Heart Disease Australia (RHDAustralia). The 2020 Australian guideline for prevention, diagnosis, and management of acute rheumatic fever and rheumatic heart disease. 3rd ed. Darwin: Menzies School of Health Research; 2020.
  8. 8. Pharmaceutical Benefits Scheme (PBS). PBS Schedule. Australian Government Department of Health. Available from: pbs.gov.au. Accessed 2024.
  9. 9. Agarwal S, Cunnington J, Nossent J. Autoimmune disease in Indigenous Australians: a systematic review. Int J Rheum Dis. 2021;24(12):1487–1498.
  10. 10. Pisetsky DS. Antinuclear antibody testing — misunderstood or misused? Clin Immunol. 2023;255:109717.
  11. 11. Bertsias GK, Tektonidou M, Amoura Z, et al. Joint European League Against Rheumatism and European Renal Association–European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. Ann Rheum Dis. 2012;71(11):1771–1782.
  12. 12. Ledingham J, Deighton C; British Society for Rheumatology Standards, Audit and Guidelines Working Group. Update on the British Society for Rheumatology guidelines for prescribing TNFα blockers in adults with rheumatoid arthritis. Rheumatology. 2005;44(2):155–158.
  13. 13. National Health and Medical Research Council (NHMRC). National statement on ethical conduct in human research. Canberra: NHMRC; 2023 (updated).
for PBS-listed medicines at participating pharmacies.
Cultural safety
Engagement with Aboriginal Community Controlled Health Organisations (ACCHOs) is essential. Cultural safety training for non-Indigenous clinicians, use of Aboriginal Health Workers and Liaison Officers, and incorporation of traditional healing practices alongside Western medicine improve treatment adherence and outcomes. Avoidance of eye contact, respect for gender-sensitive examination practices, and understanding of sorry business protocols are critical elements of culturally safe care.
Medication adherence
Complex DMARD regimens with frequent monitoring requirements present adherence challenges. Long-acting depot injections (e.g., methotrexate SC) may improve adherence compared to oral regimens. Community pharmacy partnerships through the Indigenous Pharmacy Programmes improve medication management.
Specific conditions
Rheumatic heart disease (RHD) requires secondary prophylaxis with benzathine penicillin G (BPG) 1.2 MU IM every 3–4 weeks for a minimum of 10 years or until age 21 (whichever is longer). RHD registers (e.g., NT RHD Register) facilitate recall and follow-up. The Australian RHD Endgame Strategy targets elimination by 2031.
Referral pathways
Referral through ACCHOs and Aboriginal Hospital Liaison Officers (AHLOs) improves engagement. The Specialist Outreach Assistance Programme provides funded specialist visits to remote communities. NT, WA, and QLD have specific rheumatology outreach programmes targeting Indigenous communities.

📚 References

  1. 1. Australian Institute of Health and Welfare (AIHW). Autoimmune disease in Australia. Cat. no. PHE 312. Canberra: AIHW; 2023.
  2. 2. Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res. 2021;73(7):924–939.
  3. 3. Fanouriakis A, Kostopoulou M, Alber K, et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis. 2019;78(6):736–745.
  4. 4. Chung SA, Langford CA, Maz M, et al. 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Care Res. 2021;73(11):1583–1599.
  5. 5. Smolen JS, Landewé RBM, Bijlsma JWJ, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023;82(1):3–18.
  6. 6. Australian Technical Advisory Group on Immunisation (ATAGI). Australian Immunisation Handbook. Australian Government Department of Health; 2024. Available from: immunisationhandbook.health.gov.au.
  7. 7. Rheumatic Heart Disease Australia (RHDAustralia). The 2020 Australian guideline for prevention, diagnosis, and management of acute rheumatic fever and rheumatic heart disease. 3rd ed. Darwin: Menzies School of Health Research; 2020.
  8. 8. Pharmaceutical Benefits Scheme (PBS). PBS Schedule. Australian Government Department of Health. Available from: pbs.gov.au. Accessed 2024.
  9. 9. Agarwal S, Cunnington J, Nossent J. Autoimmune disease in Indigenous Australians: a systematic review. Int J Rheum Dis. 2021;24(12):1487–1498.
  10. 10. Pisetsky DS. Antinuclear antibody testing — misunderstood or misused? Clin Immunol. 2023;255:109717.
  11. 11. Bertsias GK, Tektonidou M, Amoura Z, et al. Joint European League Against Rheumatism and European Renal Association–European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. Ann Rheum Dis. 2012;71(11):1771–1782.
  12. 12. Ledingham J, Deighton C; British Society for Rheumatology Standards, Audit and Guidelines Working Group. Update on the British Society for Rheumatology guidelines for prescribing TNFα blockers in adults with rheumatoid arthritis. Rheumatology. 2005;44(2):155–158.
  13. 13. National Health and Medical Research Council (NHMRC). National statement on ethical conduct in human research. Canberra: NHMRC; 2023 (updated).