📋 Key Information Summary
- HCC is the most common primary liver cancer in Australia, with rising incidence driven by metabolic dysfunction-associated steatohepatitis (MASH), chronic hepatitis B (CHB), and hepatitis C (HCV)-related cirrhosis.
- Surveillance: 6-monthly abdominal ultrasound ± alpha-fetoprotein (AFP) for all patients with cirrhosis (any aetiology), chronic HBV at high risk (African descent >20 years, Asian male >40/female >50 years, family history of HCC), and advanced fibrosis (F3).
- Some tertiary centres offer MRI-based screening for high-risk cohorts (e.g., MASH cirrhosis with poor acoustic windows) — currently not standard of care but increasingly used.
- Diagnosis in cirrhotic liver: LI-RADS 5 (LR-5) on multiphase CT or MRI — arterial phase hyperenhancement + portal venous/delayed phase washout in a lesion ≥1 cm — is sufficient for non-invasive diagnosis per AASLD/EASL without biopsy.
- Biopsy is reserved for non-diagnostic imaging (LI-RADS 3/4) or lesions in non-cirrhotic liver; risk of tumour seeding is low (~2%).
- BCLC staging system guides treatment: Stage 0/A (very early/early) — curative intent with resection, ablation (RFA/MWA), or liver transplantation.
- Milan criteria for transplant: single tumour ≤5 cm OR up to 3 tumours each ≤3 cm, with no macrovascular invasion — 5-year survival 70–80%.
- Stage B (intermediate): transarterial chemoembolisation (TACE) or selective internal radiation therapy (SIRT/Y90).
- Stage C (advanced): first-line systemic therapy — atezolizumab + bevacizumab (T+A) is current standard; alternatives include durvalumab + tremelimumab (STRIDE regimen), lenvatinib, or sorafenib.
- Downstaging to within Milan criteria with locoregional therapy (TACE, SIRT) followed by transplant is an accepted strategy in Australia.
- Bridging therapy (TACE or RFA) on the transplant waitlist prevents dropout from tumour progression.
- AFP >1000 ng/mL and microvascular invasion on explant histology are independent predictors of post-transplant recurrence and poorer outcomes.
- Aboriginal and Torres Strait Islander peoples have disproportionately higher HCC incidence and later-stage diagnosis, often related to higher CHB prevalence and barriers to specialist access.
- All patients with HCC should be discussed at a multidisciplinary team (MDT) meeting involving hepatobiliary surgery, transplant surgery, interventional radiology, medical oncology, and hepatology.
Introduction & Australian Epidemiology
Hepatocellular carcinoma (HCC) is the most common primary malignant neoplasm of the liver, accounting for approximately 85–90% of all primary liver cancers. In Australia, HCC incidence has increased substantially over the past two decades, rising from approximately 1,200 new cases in 2005 to over 2,800 in 2023, with age-standardised rates nearly doubling during this period.
The principal aetiologies of HCC in Australia include:
- Metabolic dysfunction-associated steatohepatitis (MASH) / metabolic dysfunction-associated steatotic liver disease (MASLD): Now the leading and fastest-growing cause of HCC in Australia, driven by the obesity and type 2 diabetes epidemics. Accounts for approximately 30–40% of cases.
- Chronic hepatitis B (CHB): Remains a major risk factor, particularly among migrants from endemic regions (Southeast Asia, sub-Saharan Africa, the Pacific Islands). Approximately 25–30% of Australian HCC cases.
- Chronic hepatitis C (HCV): Despite the success of direct-acting antivirals (DAAs), patients with established cirrhosis retain ongoing HCC risk. Approximately 20% of cases.
- Alcohol-related liver disease: A significant and persistent contributor, often overlapping with other aetiologies. Approximately 15–20% of cases.
- Other causes: Haemochromatosis, alpha-1 antitrypsin deficiency, autoimmune hepatitis, and other rarer conditions account for the remainder.
HCC carries a poor prognosis when diagnosed at advanced stages. Five-year overall survival ranges from >70% for Stage 0/A (curable) to <10% for Stage D (terminal). The majority of Australian HCC cases (~60%) are diagnosed at Stage B or later, underscoring the critical importance of effective surveillance programmes. HCC occurs predominantly in the 6th–8th decades, with a male-to-female ratio of approximately 3:1 in Australia.
All patients with suspected or confirmed HCC should be referred for multidisciplinary team (MDT) discussion at a liver transplant centre. Australian transplant centres include the Austin Hospital (Melbourne), Royal Prince Alfred Hospital (Sydney), Sir Charles Gairdner Hospital (Perth), Princess Alexandra Hospital (Brisbane), and Flinders Medical Centre (Adelaide).
Surveillance
Surveillance for HCC improves survival by enabling detection at early, curable stages. The following surveillance protocol is consistent with the Cancer Council Australia Clinical Practice Guidelines and aligns with AASLD/EASL recommendations.
Standard surveillance: 6-monthly abdominal ultrasound ± serum AFP in defined high-risk populations. This is the only surveillance strategy with Level 1 evidence demonstrating a survival benefit.
Who Should Be Under Surveillance?
| Population | Surveillance Criterion | Evidence Level |
|---|---|---|
| All patients with cirrhosis | 6-monthly USS ± AFP regardless of aetiology (viral, alcohol, MASH, autoimmune, etc.) | Strong |
| Chronic hepatitis B — non-cirrhotic, high-risk | African descent >20 years; Asian male >40 years or female >50 years; family history of HCC | Moderate–Strong |
| Advanced fibrosis (F3) | 6-monthly USS ± AFP — even in the absence of established cirrhosis | Moderate |
| CHB on antiviral therapy | Surveillance continues indefinitely — antiviral suppression does not eliminate HCC risk | Strong |
| Post-HCV cure (SVR with DAAs) | Surveillance continues if cirrhosis or advanced fibrosis is present — risk persists for years post-cure | Strong |
Surveillance Modality
- Abdominal ultrasound (USS): The primary surveillance tool. Sensitivity ~60% for early-stage HCC, specificity >90%. Limitations include poor acoustic window in obesity, MASH, and nodular cirrhotic livers.
- Serum AFP: Often added as a complementary test. AFP alone has limited sensitivity (~60%) for early HCC, but combined with USS improves detection. A threshold of >20 ng/mL is commonly used to prompt further investigation. AFP >400 ng/mL is highly suggestive of HCC in the appropriate clinical context.
- MRI-based screening: Some Australian tertiary centres are adopting abbreviated MRI protocols (non-contrast or contrast-enhanced) for high-risk patients with poor USS windows. This is not yet standard of care nationally but is increasingly used in specialised liver clinics. Costs and access remain barriers.
- CT-based screening: Not recommended for routine surveillance due to radiation exposure, cost, and inferior sensitivity compared to contrast-enhanced MRI.
Surveillance gaps: In Australia, only 20–30% of eligible cirrhotic patients are enrolled in a structured surveillance programme. Improving GP-led recall systems, particularly for CHB and MASH populations, is a national priority.
When Surveillance Is NOT Indicated
- Non-cirrhotic CHB patients outside the above demographic risk categories.
- Patients with Child-Pugh C cirrhosis who are not transplant candidates (Stage D — best supportive care).
- Patients who decline surveillance after informed discussion.
Medicare (MBS) Considerations
Abdominal ultrasound (MBS item 55031) is covered under Medicare for surveillance in at-risk populations. AFP assay (MBS item 66636) is also covered. Repeat interval of 6 months is standard. GP Management Plans (GPMP) and Team Care Arrangements (TCAs) may facilitate coordinated care.
Diagnosis
The diagnosis of HCC relies on characteristic imaging findings in the context of chronic liver disease, supplemented by histopathology when imaging is equivocal. The American Association for the Study of Liver Diseases (AASLD) and European Association for the Study of the Liver (EASL) non-invasive diagnostic criteria are widely adopted in Australia.
LI-RADS Classification (Multiphase CT or MRI)
The Liver Imaging Reporting and Data System (LI-RADS) standardises the reporting of observations in at-risk patients. Contrast-enhanced multiphase CT or MRI is required.
| LI-RADS Category | Imaging Features | Probability of HCC | Action |
|---|---|---|---|
| LR-1 (Definitely benign) | E.g., simple cyst, haemangioma | ~0% | Routine surveillance |
| LR-2 (Probably benign) | Atypical benign lesion | <5% | Surveillance |
| LR-3 (Intermediate) | Arterial enhancement ± washout but not meeting LR-5 | ~10–35% | Short-interval imaging (3 months) or biopsy |
| LR-4 (Probably HCC) | Arterial hyperenhancement + one additional major feature | ~50–80% | Biopsy or treat as HCC per MDT |
| LR-5 (Definitely HCC) | Arterial phase hyperenhancement + portal venous or delayed phase washout in a lesion ≥1 cm | >95% | Non-invasive HCC diagnosis — no biopsy required |
| LR-M (Probably malignant, not HCC-specific) | Malignant features not specific for HCC (e.g., rim enhancement) | High (may be ICC or mixed) | Biopsy recommended |
Non-invasive diagnosis: In a patient with established cirrhosis, a lesion ≥1 cm demonstrating arterial phase hyperenhancement AND washout on portal venous or delayed phase (LR-5) on multiphase CT or MRI is sufficient for HCC diagnosis — biopsy is not required per AASLD/EASL guidelines.
When Is Biopsy Required?
- LI-RADS 3 or 4 lesions on imaging that do not meet definitive criteria.
- Lesions in a non-cirrhotic liver — non-invasive criteria are only validated in cirrhosis; biopsy is required for definitive diagnosis.
- LR-M lesions where intrahepatic cholangiocarcinoma (ICC) or combined HCC-ICC must be excluded (different management).
- When histological confirmation would change management (e.g., eligibility for clinical trials requiring tissue diagnosis).
Biopsy Considerations
- Image-guided (ultrasound or CT) percutaneous core biopsy is the standard approach.
- Fine-needle aspiration (FNA) is less preferred — inadequate for histological grading and assessment of vascular invasion.
- Risk of tumour tract seeding is low (~1.5–2%) but must be discussed with the patient, particularly if the lesion is amenable to surgical resection.
- Coagulopathy should be corrected prior to biopsy (INR <1.5, platelets >50 × 10⁹/L).
Additional Diagnostic Investigations
Essential
Multiphase CT or contrast-enhanced MRI
Required for LI-RADS classification. MRI with hepatocyte-specific contrast (e.g., gadoxetic acid/Primovist®) has superior sensitivity for small lesions. MBS item 63501 (CT), 63450 (MRI).
Essential
Serum AFP
Baseline level for prognosis and monitoring. AFP >400 ng/mL with a characteristic hepatic mass is near-diagnostic. MBS item 66636.
Available
Liver function tests, synthetic function (albumin, INR)
Assess hepatic reserve and Child-Pugh score — critical for treatment eligibility.
Available
Hepatitis B/C serology
Confirm aetiology and guide antiviral therapy.
Available
Iron studies, caeruloplasmin, alpha-1 antitrypsin
Screen for hereditary liver disease if aetiology is unclear.
Specialist
PIVKA-II (des-gamma-carboxy prothrombin)
Complementary tumour marker; available at some centres. Not on MBS. May improve detection in AFP-negative HCC.
Staging & Treatment
The Barcelona Clinic Liver Cancer (BCLC) staging system is the most widely used in Australia and internationally for staging and treatment allocation of HCC. It integrates tumour burden, liver function (Child-Pugh), and performance status (ECOG).
MDT mandatory: Every patient with confirmed HCC must be discussed at a specialist multidisciplinary team meeting before treatment decisions are made. The MDT should include hepatology, hepatobiliary/transplant surgery, interventional radiology, medical oncology, and radiation oncology.
BCLC Staging System
Stage 0
Very Early HCC
Single tumour ≤2 cm, Child-Pugh A, ECOG 0. Preserved liver function.
Setting: Surgical or percutaneous — resection, ablation (RFA/MWA), or transplantation
Stage A
Early HCC
Single or up to 3 nodules ≤3 cm, Child-Pugh A–B, ECOG 0. Potentially curable.
Setting: Resection, ablation (RFA/MWA), or transplantation (within Milan criteria)
Stage B
Intermediate HCC
Multinodular, no vascular invasion, no extrahepatic spread. Child-Pugh A–B, ECOG 0.
Setting: Locoregional — TACE, TARE (SIRT/Y90). Some re-evaluation for transplant or downstaging
Stage C
Advanced HCC
Portal invasion, extrahepatic spread, or both. Child-Pugh A–B, ECOG 1–2.
Setting: Systemic therapy — atezolizumab-bevacizumab, durvalumab-tremelimumab, lenvatinib, sorafenib
Stage D
Terminal HCC
Any tumour burden, Child-Pugh C, ECOG 3–4. Not amenable to active therapy.
Setting: Best supportive care / palliative care referral
Stage 0/A — Curative-Intent Therapies
Surgical Resection
Resection is the preferred curative treatment for HCC in patients with preserved hepatic function (Child-Pugh A, normal portal pressure: hepatic venous pressure gradient [HVPG] <10 mmHg) and adequate future liver remnant (FLR). In Australia, major hepatectomies are performed at hepatobiliary centres with expertise in complex liver surgery.
- Anatomical resection (segmentectomy/lobectomy) is preferred over non-anatomical resection where feasible.
- Pre-operative assessment: volumetric CT/MRI to calculate FLR (>20% in healthy liver, >30–40% in cirrhotic liver).
- Indocyanine green (ICG) retention test used at some centres to assess functional hepatic reserve.
- 5-year recurrence-free survival: 50–70% for well-selected early-stage HCC.
- Adjuvant therapy: No established adjuvant systemic therapy post-resection in Australia. Clinical trials ongoing.
Local Ablation — RFA and MWA
Radiofrequency ablation (RFA) and microwave ablation (MWA) are percutaneous thermal ablation techniques with curative intent for early-stage HCC. Outcomes are comparable to resection for solitary tumours ≤2 cm.
- RFA: electrode inserted under imaging guidance; generates coagulative necrosis. Effective for lesions ≤3 cm; efficacy decreases with larger tumours and subcapsular/peri-vascular locations.
- MWA: increasingly preferred due to larger ablation zones, faster treatment time, and less heat-sink effect near major vessels.
- Repeat ablation is possible for local recurrence.
- 5-year overall survival: 50–70% for single lesions ≤3 cm.
- MBS item: Interventional radiology procedures attract specialist procedural fees — refer to MBS schedule for item numbers.
Anaesthesia for ablation
GA or sedation — specialist anaesthetic support
Setting
Interventional radiology suite under GA or conscious sedation with local anaesthetic
Monitoring
Post-ablation CT at 1 month to assess completeness (no residual enhancement)
Stage B — Locoregional Therapies
Transarterial Chemoembolisation (TACE)
TACE involves the selective catheterisation of hepatic artery branches feeding the tumour, followed by injection of chemotherapeutic agents (commonly doxorubicin or cisplatin) mixed with lipiodol, and embolisation with particles to induce ischaemic necrosis. Drug-eluting bead TACE (DEB-TACE) provides more controlled drug delivery.
- Standard first-line for Stage B (intermediate) HCC — BCLC recommended.
- Requires adequate hepatic reserve (Child-Pugh A–B7) and patent portal vein.
- Contraindicated in decompensated cirrhosis (Child-Pugh C), main portal vein thrombosis, and extensive bilobar disease with insufficient hepatic reserve.
- Post-TACE syndrome (fever, RUQ pain, nausea, transaminase rise) is common and usually self-limiting.
- Repeat TACE on demand (based on imaging response) — not routinely scheduled.
Selective Internal Radiation Therapy (SIRT / TARE — Y90)
SIRT delivers yttrium-90 (Y90) microspheres selectively to the tumour via hepatic artery catheterisation, providing localised radiation with minimal damage to surrounding parenchyma.
- Available at major Australian centres (e.g., Royal Adelaide Hospital, PAH Brisbane, Westmead Sydney, Sir Charles Gairdner Perth).
- May be used as an alternative to TACE, particularly for portal vein thrombosis (where TACE is contraindicated).
- Requires pre-treatment lung shunt study (Tc-99m MAA scan) and dose calculation.
- Glass microspheres (TheraSphere®) and resin microspheres (SIR-Spheres®) are both available in Australia.
- Radiation segmentectomy can achieve complete pathological necrosis in selected cases — emerging as a potential curative option for small, unresectable tumours.
Stage C — Systemic Therapy
First-line standard of care: Atezolizumab + bevacizumab (T+A) is the preferred first-line regimen for advanced HCC with preserved liver function (Child-Pugh A) based on the IMbrave150 trial demonstrating improved overall survival (19.2 vs 13.4 months) and progression-free survival compared to sorafenib alone.
Atezolizumab + Bevacizumab
Tecentriq® + Avastin® · PD-L1 inhibitor + anti-VEGF
Adult dose
Atezolizumab 1200 mg IV + Bevacizumab 15 mg/kg IV, every 3 weeks
Duration
Until disease progression or unacceptable toxicity
Key caution
Screen for varices (EGD) and treat prior to commencing — bevacizumab increases bleeding risk
Contraindications
Active autoimmune disease, uncontrolled variceal bleeding, Child-Pugh B7–C
PBS status
Authority Required — PBS listed for unresectable HCC
Durvalumab + Tremelimumab
Imfinzi® + Imjudo® · PD-L1 inhibitor + CTLA-4 inhibitor (STRIDE regimen)
Adult dose
Tremelimumab 300 mg single dose + Durvalumab 1500 mg IV, then Durvalumab 1500 mg IV every 4 weeks
Duration
Until disease progression (durvalumab maintenance after single tremelimumab dose)
Role
Alternative first-line — particularly if bevacizumab is contraindicated (e.g., high bleeding risk, recent thromboembolic event)
PBS status
Authority Required
Lenvatinib
Lenvima® · Multi-kinase inhibitor
Adult dose
12 mg PO daily (≥60 kg) or 8 mg PO daily (<60 kg)
Role
First-line or second-line after immunotherapy failure. Non-inferior to sorafenib (REFLECT trial)
Renal adjustment
No dose adjustment for mild–moderate impairment; avoid in severe renal impairment
Hepatic adjustment
Reduce to 8 mg/day in moderate hepatic impairment (Child-Pugh B)
PBS status
Authority Required
Sorafenib
Nexavar® · Multi-kinase inhibitor
Adult dose
400 mg PO BD on empty stomach
Role
First-line (if immunotherapy contraindicated) or second-line after T+A
Key side effects
Hand-foot skin reaction, diarrhoea, hypertension, fatigue
PBS status
Authority Required
Regorafenib
Stivarga® · Multi-kinase inhibitor
Adult dose
160 mg PO daily (3 weeks on / 1 week off)
Role
Second-line after sorafenib failure/intolerance (RESORCE trial)
PBS status
Authority Required
Cabozantinib
Cabometyx® · Multi-kinase inhibitor
Adult dose
60 mg PO daily
Role
Second-line after prior systemic therapy (CELESTIAL trial)
PBS status
Authority Required
Stage D — Best Supportive Care
Patients with advanced tumour burden, decompensated cirrhosis (Child-Pugh C), and poor performance status (ECOG 3–4) are not candidates for active anticancer therapy. Management focuses on symptom control, nutritional support, and end-of-life planning. Early palliative care referral is recommended.
- Management of portal hypertension complications (ascites, encephalopathy, variceal bleeding).
- Pain management: paracetamol (with caution in hepatic impairment), low-dose opioids with hepatic dose adjustment.
- Psychosocial support, advance care planning, and community palliative care referral.
Transplant Considerations
Liver transplantation is a uniquely curative therapy for HCC as it simultaneously removes the tumour, the pre-malignant cirrhotic liver, and occult micrometastases. It is the treatment of choice for patients with early-stage HCC who are not candidates for resection (due to portal hypertension or insufficient hepatic reserve) and whose tumours fall within accepted selection criteria.
Milan criteria (1996): The gold standard for transplant eligibility. Single tumour ≤5 cm, OR up to 3 tumours each ≤3 cm, with NO macrovascular invasion and NO extrahepatic disease. Five-year post-transplant survival: 70–80%.
Expanded Criteria
Several expanded criteria have been proposed to extend transplant eligibility beyond Milan, with acceptable outcomes:
| Criteria | Definition | 5-Year Survival | Acceptance in Australia |
|---|---|---|---|
| Milan | Single ≤5 cm OR ≤3 nodules each ≤3 cm, no vascular invasion | 70–80% | Standard — universally accepted |
| UCSF | Single ≤6.5 cm OR ≤3 nodules ≤4.5 cm, total diameter ≤8 cm | 65–75% | Accepted at most Australian centres on case-by-case basis |
| Up-to-seven | Sum of number of tumours + maximum diameter (cm) ≤7, no microvascular invasion | 65–75% | Used in selected European and some Australian centres |
| AFP model (Duvoux) | Combines tumour number, size, and AFP (≤100, 100–1000, >1000 ng/mL) | Variable | Increasingly incorporated — AFP adds prognostic value beyond morphology alone |
Downstaging Protocols
Downstaging involves locoregional therapy to reduce tumour burden to within transplant criteria (typically Milan). This is an accepted strategy in Australia and is endorsed by the Australian Liver Transplant Collaborative.
- Eligibility for downstaging: Patients with tumours slightly beyond Milan (e.g., UCSF criteria) or limited beyond Milan (e.g., single tumour 5–7 cm, or 4 nodules each ≤3 cm). Total tumour burden should be amenable to complete necrosis.
- Modalities: TACE, SIRT (Y90), RFA/MWA, or combination therapy.
- Assessment: Restaging at 3–6 months post-therapy with multiphase CT or MRI and AFP. Successful downstaging = complete response or reduction to within Milan.
- Wait time: A minimum observation period of 3–6 months post-downstaging is required to confirm sustained response before listing.
- Outcomes: Post-downstaging transplant outcomes approach those of patients within Milan at initial presentation (~70% 5-year survival in responders).
Bridging Therapy on Waitlist
Bridging therapy refers to locoregional treatment of HCC while the patient awaits liver transplantation. It aims to prevent tumour progression and dropout from the waitlist.
- Standard practice in Australia — most transplant centres recommend bridging for all listed HCC patients.
- Modalities: TACE, RFA/MWA, or SIRT. Choice depends on tumour location, size, and hepatic reserve.
- Goal: Maintain within-transplant-criteria tumour burden until a donor organ becomes available.
- Dropout rate without bridging therapy: 15–25% per year due to tumour progression.
MELD Exception Points
In Australia, the liver transplant allocation system (managed through the Organ and Tissue Authority [OTA] and individual state transplant services) incorporates MELD/PELD scoring with priority exception points for HCC patients within Milan criteria.
- HCC patients within Milan criteria receive standardised exception MELD points equivalent to a 15% 3-month mortality risk (approximately MELD 22) at listing.
- Exception points are upgraded if there is documented tumour progression on bridging therapy despite maintaining within-Milan status.
- Patients who exceed Milan criteria are removed from active waitlist status.
- The allocation system is reviewed periodically — clinicians should refer to current OTA guidelines.
AFP Thresholds and Prognostic Significance
- AFP <100 ng/mL: Associated with favourable post-transplant outcomes; consistent with well-differentiated tumours.
- AFP 100–1000 ng/mL: Intermediate risk — careful patient selection recommended.
- AFP >1000 ng/mL: Strong independent predictor of microvascular invasion, poorly differentiated histology, and post-transplant recurrence. Some Australian centres use AFP >1000 ng/mL as a relative contraindication to transplant unless successful downstaging results in AFP decline to <100 ng/mL.
- AFP >10,000 ng/mL: Near-universal contraindication to transplant — very high recurrence risk.
Microvascular invasion (MVI): MVI on explant histology is the strongest predictor of post-transplant recurrence (5-year recurrence rate 40–60% vs 5–10% without MVI). MVI is often not detectable pre-operatively, but AFP >400 ng/mL, tumour size >3 cm, and poor differentiation on biopsy are surrogate markers. Post-transplant surveillance with CT/MRI and AFP every 3–6 months is essential.
Australian Transplant Centres
| Centre | Location |
|---|---|
| Austin Health Liver Transplant Unit | Melbourne, VIC |
| Royal Prince Alfred Hospital | Sydney, NSW |
| Princess Alexandra Hospital | Brisbane, QLD |
| Sir Charles Gairdner Hospital | Perth, WA |
| Flinders Medical Centre | Adelaide, SA |
Special Populations
Pregnancy
Incidence: HCC in pregnancy is rare but has been reported, typically in the context of chronic HBV.
Diagnosis: MRI without gadolinium (first trimester) or ultrasound. Contrast-enhanced CT requires careful risk-benefit assessment and shielding.
Treatment: Surgical resection is feasible in the second trimester. Systemic therapies (atezolizumab, bevacizumab, sorafenib, lenvatinib) are contraindicated in pregnancy. Multidisciplinary planning with obstetrics and hepatobiliary surgery is essential.
HBV: Tenofovir alafenamide or tenofovir disoproxil may be continued in pregnancy for HBV suppression. Lamivudine is an alternative.
Paediatrics
Aetiology: HCC in children is rare; more commonly associated with metabolic liver disease (tyrosinaemia, glycogen storage disease), biliary atresia, or progressive familial intrahepatic cholestasis.
Hepatoblastoma: Must be differentiated from HCC — hepatoblastoma is more common in children under 5 years and is treated with cisplatin-based chemotherapy + surgical resection.
Surveillance: 6-monthly AFP and USS from age 6 months in high-risk paediatric liver diseases (e.g., Alagille syndrome, biliary atresia post-Kasai).
Treatment: Surgical resection and liver transplantation are the mainstays. Paediatric oncology MDT input is essential. SIOPEL staging system used for hepatoblastoma.
Elderly (>75 years)
Considerations: HCC is predominantly a disease of older adults. Age alone is not a contraindication to curative therapy if performance status and hepatic reserve are adequate.
Resection: Can be performed safely in elderly patients at experienced centres — comorbidity burden, not chronological age, is the key determinant.
Ablation: RFA/MWA is well tolerated in the elderly and may be preferred over resection for small lesions.
Systemic therapy: Immunotherapy (T+A) can be considered in fit elderly patients. Increased monitoring for immune-related adverse events (irAEs).
Transplant: Upper age limit for transplant in Australia varies by centre (typically 70–75 years) — individualised assessment.
Renal Impairment
Prevalence: CKD is common in patients with cirrhosis (hepatorenal syndrome, diabetic nephropathy).
Systemic therapy: Lenvatinib — avoid in severe renal impairment. Sorafenib — no dose adjustment but monitor closely. Bevacizumab — may worsen proteinuria; monitor renal function.
Transplant: Combined liver-kidney transplant may be considered for patients with concurrent end-stage liver and kidney disease.
Contrast imaging: Gadolinium-based contrast agents — avoid in severe CKD (GFR <30) due to nephrogenic systemic fibrosis risk. Use non-contrast MRI or iodinated CT with precautions.
Hepatic Impairment
Child-Pugh B: Systemic therapy may still be considered but with reduced efficacy and increased toxicity. Lenvatinib: reduce to 8 mg/day.
Child-Pugh C: Systemic therapy is generally contraindicated — best supportive care. Transplant candidacy should be assessed.
Portal hypertension: HVPG ≥10 mmHg contraindicates resection — transplant or ablation preferred.
Ascites: Must be controlled prior to locoregional therapy or surgery.
Immunocompromised
HIV-HBV/HCV co-infection: HCC risk is increased in HIV co-infected patients with cirrhosis. Surveillance should follow standard guidelines.
Post-transplant immunosuppression: Calcineurin inhibitors (tacrolimus, cyclosporine) may promote HCC recurrence. mTOR inhibitors (sirolimus, everolimus) have antiproliferative properties and are sometimes used post-transplant for HCC — evidence is mixed.
Immunotherapy: Generally contraindicated after solid organ transplant (risk of allograft rejection). Immune checkpoint inhibitors should be avoided post-liver transplant unless in a clinical trial setting.
Autoimmune liver disease: Immunosuppression for autoimmune hepatitis does not preclude standard HCC treatment, but immunotherapy may have unpredictable interactions.
ATSI Health Considerations
Aboriginal and Torres Strait Islander Health
📚 References
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