Australian recommendations for the management of hepatocellular

carcinoma: a consensus statement

John S Lubel, Stuart K Roberts, Simone I Strasser, Alexander J Thompson, Jennifer Philip, Mark Goodwin, Stephen Clarke, Darrell HG Crawford, Miriam T
Levy and Nick Shackel
Med J Aust || doi: 10.5694/mja2.50885
Published online: 14 December 2020

Topics

NEOPLASMS
DIGESTIVE SYSTEM DISEASES

Abstract
Introduction: Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths both globally and in Australia. Surveillance for HCC in at‐risk populations
allows diagnosis at an early stage, when potentially curable. However, most Australians diagnosed with HCC die of the cancer or of liver disease. In the
changing landscape of HCC management, unique challenges may lead to clinical practice variation. As a result, there is a need to identify best practice
management of HCC in an Australian context. This consensus statement has been developed for health professionals involved in the care of adult patients with
HCC in Australia. It is applicable to specialists, general medical practitioners, nurses, health coordinators and hospital administrators.

Methods and recommendations: This statement has been developed by specialists in hepatology, radiology, surgery, oncology, palliative care, and primary
care, including medical practitioners and nurses. The statement addresses four main areas relevant to HCC management: epidemiology and incidence,
diagnosis, treatment, and patient management.

A modified Delphi process was used to reach consensus on 31 recommendations. Principal recommendations include the adoption of surveillance strategies,
use of multidisciplinary meetings, diagnosis, treatment options and patient management.

Changes in management as a result of this statement: This consensus statement will simplify HCC patient management and reduce clinical variation.
Ultimately, this should result in better outcomes for patients with HCC.

This consensus statement is applicable to specialists, general medical practitioners, nurses, health coordinators and administrators involved in the care of adult
patients with hepatocellular carcinoma (HCC).
These recommendations summarise the complete document, available at https://www.gesa.org.au/resources/hepatocellular-carcinoma-hcc-management-conse
nsus/.

Methodology
Recommendations were graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE).1 The quality of the
evidence was classified as high, moderate, low, or very low, and the strength of recommendation was classified as either strong or weak.

This consensus statement was developed with the principles outlined by the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument.2

Consensus was defined as a greater than 80% agreement by experts. The modified Delphi process was used to determine consensus and comprised two face‐to‐
face meetings and three rounds of online questionnaires.3 The complete list of recommendations and the level of agreement are shown in Box 1.

Box 1

Recommendations of the hepatocellular carcinoma (HCC) consensus statement

Epidemiology and surveillance

Globally, hepatocellular carcinoma is a leading cause of cancer death and the seventh most common cancer.4 In Australia, the incidence has increased markedly
from 1982 (1.38/100 000) to 2014 (4.96/100 000)5 and within Australia there is significant regional variation in incidence. Although mortality rates of many
cancers have plateaued, cancer death due to HCC is rising,6 and despite improvements in treatment, the overall 5‐year survival in Australia is about 20%.7

HCC usually develops in the setting of chronic liver disease, and cirrhosis is present in 85–90% of affected individuals. Male incidence is three to four times
that of females7,8 and the major aetiologies for HCC are shared with the causes of cirrhosis (hepatitis C virus [HCV] infection, 41%; alcohol‐related liver
disease, 39%; hepatitis B virus [HBV] infection, 22%; and fatty liver disease, 14%).8 HBV infection is more common in culturally and linguistically diverse
populations, and in Australia, more than 50% of patients with HCC were born overseas.8

Incidence of HCC in Australian Indigenous populations

Indigenous Australians account for 3.3% of the population, yet are disproportionately affected by HCC, with 2.4‐fold higher rates of diagnosis and mortality
compared with non‐Indigenous populations.7 Inequalities in health service access with resulting late presentation, greater incidence of risk factors for liver
disease, socio‐economic disadvantage and geographical remoteness of Indigenous communities in many parts of Australia contribute to a greater burden of
HCC incidence and mortality.9 Chronic HBV and HCV infection prevalence is estimated at 6% and 2.9% respectively among Indigenous Australians in the
Northern Territory.10 Of concern, among Indigenous Australians, only 14% of HCC is detected through surveillance programs, and the median survival time is
markedly lower in Indigenous compared with non‐Indigenous Australians (64 v 172 days).11
Target populations for HCC surveillance in Australia
Several target populations for surveillance have been defined based on decision analyses that show surveillance becomes cost‐effective when the incidence of
HCC in these at‐risk populations approaches certain thresholds.12 The single most significant risk factor for developing HCC is cirrhosis.13 However, HCC risk
is sufficiently high in some non‐cirrhotic patients with hepatitis B to justify surveillance11 (Box 2).

Box 2

Populations that should undergo hepatocellular carcinoma surveillance

Surveillance modalities available for detecting HCC in Australia

Liver ultrasound

Liver ultrasound, the primary tool recommended for HCC surveillance, is widely available, non‐invasive, comparatively inexpensive, and has Australian
Medicare Benefit Schedule (MBS) reimbursement. The sensitivity of ultrasound used for HCC surveillance varies between 60% and 90%, with specificity
generally above 90%. Computed tomography (CT) and magnetic resonance imaging (MRI) are not suitable routine surveillance modalities for HCC.

The optimal HCC surveillance interval reflects the tumour doubling time of 4–8 months. Several international cohort studies have shown that HCC surveillance
every 6 months is cost‐effective and improves survival.14

Serum marker: α‐fetoprotein

Serum α‐fetoprotein may increase the sensitivity of surveillance but can be associated with false‐positive results. As α‐fetoprotein improves earlier detection of
HCC compared with ultrasound alone, we recommend surveillance with a combination of ultrasound and serum α‐fetoprotein levels every 6 months.

Populations not requiring HCC surveillance

The expectation with HCC surveillance is that it will reduce mortality by allowing patients to access curative therapy. Benefit is not seen if the patient is
expected to die of progressive liver failure or other comorbid conditions before receiving treatment. The survival benefit of HCC surveillance appears to be
restricted to patients with Child–Pugh class A and early class B cirrhosis and with Child–Pugh class C disease who are candidates for liver transplantation.15

Non‐alcoholic fatty liver disease and its association with HCC incidence
Non‐alcoholic fatty liver disease patients with cirrhosis should undergo surveillance. Meta‐analyses have shown that obesity may increase the relative risk of
HCC by 1.5‐ to four‐fold.16,17 Diabetes increases the relative risk of developing HCC by two‐ to 2.5‐fold and increases HCC‐associated mortality by 1.6‐
fold.18,19 In a large retrospective study, the relative risk of developing HCC was seven‐fold that of controls. Most cases occurred in cirrhotic individuals, with
the relative incidence in non‐cirrhotic subjects not reaching the accepted threshold to justify surveillance.20 Therefore, surveillance for HCC in non‐cirrhotic
patients with non‐alcoholic fatty liver disease is not supported by current evidence.

Diagnosis and staging

Unlike other malignant neoplasms, the diagnosis of HCC may be made principally on radiological criteria. The Liver Imaging Reporting and Data System (LI‐
RADS)21 provides a framework for reporting and criteria for HCC diagnosis.

In individuals with high pre‐test probability for HCC (ie, with cirrhosis or HBV infection) the diagnosis of HCC can be confidently made when non‐rim arterial
phase hyperenhancement (APHE) and portal venous or delayed phase washout is present.22 In patients with a lower risk of HCC (eg, non‐cirrhotic patients and
those without hepatitis B) or when imaging characteristics are concerning but not typical for HCC and malignancy is suspected, targeted biopsy with
histological confirmation is indicated (Box 3).

Box 3

Surveillance and diagnosis of hepatocellular carcinoma (HCC)

Imaging criteria for diagnosis of HCC

Computed tomography

Multiphase CT with pre‐contrast and three post‐contrast phases (late hepatic arterial, portal venous, and delayed) is the optimal imaging protocol for HCC
diagnosis. The appearances of non‐rim APHE together with washout during the portal or delayed phase confer a specificity approaching 100%. The sensitivity
of these radiological findings is highly dependent on lesion size, with excellent sensitivity for lesions greater than 2 cm, modest sensitivity for lesions 1–2 cm,
and poor sensitivity for lesions less than 1 cm in diameter.23

Magnetic resonance imaging

The principles of HCC diagnosis are similar for both MRI and CT. With the use of extracellular contrast agents, the features of non‐rim APHE and washout are
highly suggestive of HCC in individuals at risk. Compared with multiphase CT, MRI offers additional imaging sequences that may provide supportive
information for the diagnosis of HCC, including T2‐weighted sequences, diffusion‐weighted imaging and hepatobiliary phase imaging (when liver‐specific
contrast agents are used).
Contrast‐enhanced ultrasound

Contrast‐enhanced ultrasound is not widely practised in Australia and requires skilled operators, but can be used to interrogate a suspicious lesion and has the
advantage of avoiding ionising radiation and nephrotoxic contrast agents. As with cross‐sectional imaging modalities, such as CT and MRI, the imaging
features of APHE and washout pertain to contrast‐enhanced ultrasound.

Choice of imaging modality

Several practical factors determine the choice between CT, MRI and contrast‐enhanced ultrasound. Patients who experience claustrophobia, who are unable to
hold their breath sufficiently long or who have ascites (which may result in image artefacts) may be better imaged with CT. However, CT requires ionising
radiation exposure and potential nephrotoxicity from intravenous contrast agents.24 In Australia, the choice between MRI and CT has been influenced by
accessibility of the imaging techniques and MBS reimbursement. Contrast‐enhanced MRI liver scans (including the use of hepatobiliary‐specific contrast
agents) for the purpose of diagnosis or staging of known or suspected HCC is funded by the MBS in Australia (one scan per 12‐month period).

Staging systems
Barcelona Clinic Liver Cancer staging system

The Barcelona Clinic Liver Cancer (BCLC) staging system is used and endorsed by international guidelines.22,25,26 It incorporates three clinical aspects: liver
function, tumour biology and performance status, and offers treatment recommendations based on stage (Box 4). The BCLC staging system is the most
commonly used system in multidisciplinary team meetings in Australia and is likely to remain the system of preference because of physician familiarity and
ease of use.

Box 4

Barcelona Clinic Liver Cancer (BCLC) staging system

Management
Management of HCC in Australia is to offer curative intent when possible while minimising exposure to risk with treatment. Staging of disease and
determination of appropriate management through a multidisciplinary team are critical. A patient’s understanding of their disease and the clinician’s respect for
patient choices are essential elements of HCC management. Managing clinicians are expected to offer evidence‐based treatment options.

The multidisciplinary team approach

Multidisciplinary team discussion is recommended for every patient diagnosed and being managed with HCC. Multidisciplinary team care is being increasingly
practised in cancer care services in Australia, the United States and Europe.27 This type of care has several benefits, including improvement in staging and
diagnosis accuracy, increased treatment rates, reduction in time to treatment after diagnosis, and increased adherence to clinical guidelines.28 Several
retrospective cohort studies show an improvement in the overall survival of patients with HCC managed through a multidisciplinary team.29

Surgical therapies
Surgical resection

Liver resection is indicated and recommended for HCC in patients in whom the tumour is confined to the liver and can be completely removed, while leaving a
sufficient liver remnant in terms of both quantity and quality to preserve life. Therefore, assessment of patients for potential liver resection for HCC requires
evaluation of the patient, liver function, portal hypertension and tumour characteristics.25 Overall survival after liver resection for HCC depends on the risk of
developing liver failure, succumbing to non‐liver‐related complications of surgery, or developing recurrent HCC.

Liver transplantation

Liver transplantation is a definitive treatment option for patients with early stage HCC, as it eliminates both the tumour and the associated liver disease.30 In
Australia and New Zealand, the 5‐year overall survival among liver transplant recipients for HCC is 75%, similar to overseas experience.31

Appropriate patient selection for liver transplantation is critical to both achieving optimal outcomes and appropriate donor organ utilisation. Eligibility for entry
to the liver transplantation waiting list should be based on an expected 5‐year survival rate greater than 50%. The University of California San Francisco
(UCSF) criteria32 provides the current framework for patient selection in Australia (Box 5).31,32,33,34 Patients within UCSF criteria have survival rates after
liver transplantation of 90% and 75.2% at 1 and 5 years respectively, compared with a 50% 1‐year survival for patients with tumours exceeding these
limits.32 An alternative system, Metroticket 2.0, incorporating α‐fetoprotein and tumour characteristics under review by the Australasian transplant societies
may broaden patient selection without adverse impact on patient outcomes.34

Box 5

Comparison of liver transplantation criteria for patients with hepatocellular carcinoma (in chronological order)

Locoregional therapies
More than 75% of patients with early stage (BCLC‐A) HCC are not suitable for either surgical resection or liver transplantation because of underlying severity
of liver disease, clinically significant portal hypertension, significant comorbidity, or age.35 For these patients, locoregional therapies, with image‐guided
percutaneous tumour ablation and/or image‐guided transcatheter tumour therapy should be considered. Ablative therapies are generally restricted to small
number of lesions (three or fewer), while non‐ablative therapies may be used when multiple lesions are present.
Ablative therapies

Ablative therapies for HCC involve treatment of a lesion with the intent of local disease elimination.

Percutaneous tumour ablative therapies

Percutaneous tumour ablation under imaging guidance is an important and widely accepted treatment option for patients with early stage HCC. The two
common methods used to induce tumour necrosis are temperature alteration (eg, radiofrequency ablation and microwave ablation) and chemical injection (most
commonly percutaneous ethanol injection). Radiofrequency ablation is the most widely recommended first‐line ablation technique for patients not suitable for
surgery.36 Microwave ablation is a relatively recent and increasingly popular thermal ablative therapy37 that has the advantages of producing wider and more
predictable ablation volumes, resulting in high complete ablation rates, and the ability to simultaneously treat multiple lesions36,37 and potentially treat larger
lesions more effectively. Ablation is effective in early stage (BCLC‐0) HCC involving a solitary small nodule (< 2 cm), achieving near 100% complete necrosis
and with overall survival similar to that of surgery.38

Non‐ablative therapies

Non‐ablative therapies for HCC involve treatment of a lesion with the intent of local disease control. Although small lesions may be cured, typically lesions
recur, requiring further treatment. Transarterial chemoembolisation (TACE) is the most common non‐ablative therapy for HCC.

Transarterial chemoembolisation

TACE involves injection of chemotherapy and embolic material into hepatic artery branches supplying a tumour and is considered first‐line therapy for patients
with BCLC‐B HCC.25,39 It is regarded as a non‐curative procedure in this stage of cancer.

Meta‐analyses have demonstrated that patients treated with TACE derive a significant improvement in overall survival compared with bland embolisation or
best supportive care.40 An overall response rate of about 50% and a disease control rate of 75–80% can be expected with TACE therapy.41

Selective internal radiation therapy

Selective internal radiation therapy (SIRT) involves Yttrium‐90 microspheres injection into the hepatic arteries supplying the tumour. Radioembolisation has
been used instead of TACE for patients with BCLC‐B disease, as an alternative to sorafenib for patients with BCLC‐C disease (including portal vein invasion),
and for bridging or downstaging to liver transplantation. However, the evidence base justifying the use of SIRT is less advanced than that for other therapies.
Three randomised controlled studies failed to demonstrate superiority of SIRT over sorafenib. This has contributed to the uncertainty around the precise role of
SIRT in HCC management.42,43,44 However, SIRT can be considered in select patients with intermediate or locally advanced HCC.

Other locoregional therapies

Stereotactic external‐beam radiation therapy

Stereotactic external‐beam radiation therapy (SBRT) is emerging as a potential option for early stage disease not amenable to surgical or percutaneous ablative
therapies. A systematic review of SBRT for early stage HCC incorporating 16 studies (973 patients, 1034 lesions) reported a mean weighted local control of
94% and 93% at 1 and 3 years respectively.45 For more advanced disease, a small randomised study reported improved overall survival with upfront TACE and
SBRT compared with sorafenib in the setting of macrovascular invasion (median, 55 weeks v 43 weeks; P = 0.04).46 Further prospective randomised studies are
required before SBRT can be recommended for routine use.

Systemic therapies
Systemic therapies are indicated in patients with advanced HCC, with vascular invasion and/or extrahepatic disease, or in patients with unresectable HCC when
locoregional therapies have failed to control disease or cannot be delivered. Systemic therapy is restricted to patients with preserved liver function, non‐
cirrhotic patients, or those with Child–Pugh class A cirrhosis.

There are currently three first‐line therapies for HCC: sorafenib, lenvatinib and combination atezolizumab and bevacizumab. Sorafenib was the first therapy to
show an increase in median overall survival from 7.9 to 10.7 months (hazard ratio [HR], 0.70; 95% CI, 0.55–0.87).47 In a subsequent trial comparing lenvatinib
with sorafenib, lenvatinib was non‐inferior to sorafenib The median overall survival was 13.6 months (95% CI, 12.1–14.9) with lenvatinib and 12.3 months
(95% CI, 10.4–13.9) with sorafenib (HR, 0.92; 95% CI, 0.79–1.06).48 Progression‐free survival was significantly higher in patients receiving lenvatinib
(median, 7.4 months; 95% CI, 6.9–8.8) compared with sorafenib (median, 3.7 months [95% CI, 3.6–4.6]; HR, 0.66 [95% CI, 0.57–0.77]). The combination of
atezolizumab (programmed death‐ligand 1 antibody) and bevacizumab (antivascular endothelial growth factor) has shown significant improvement in
progression‐free survival (median, 6.8 months; 95% CI, 5.7–8.3) compared with sorafenib (median, 4.3 months; 95% CI, 4.0–5.6) and is the most recently
approved therapy in Australia.49

There are no clear benefits to continuing first‐line therapies in patients with radiological or clinical disease progression. Second‐line treatments approved by the
Therapeutic Goods Administration include two oral targeted therapies (regorafenib and cabozantinib) and nivolumab (immune checkpoint inhibitor)
administered by intravenous infusion.

Systemic therapies for advanced HCC are evolving rapidly, and it is likely that the standard of care will change in the near future.

Supportive care
Many patients either present with incurable disease or progress after failed attempts at curative therapy. Patients with incurable HCC should be introduced to
supportive care services early in their management (Box 6). Patients presenting with advanced disease (15–20% of cases) have a median survival of less than
3–4 months. The estimated 1‐year survival rate of patients with BCLC‐D disease is less than 11%.50 In addition to cancer‐related complications, clinical
deterioration may also be related to the underlying liver disease, which has unique clinical challenges. Symptom relief and psychosocial support may be most
effectively achieved through the co‐management of patients by hepatologists and supportive or palliative care services.
Box 6

Supportive care, hepatology and medical goals in hepatocellular carcinoma (HCC)

For patients with BCLC‐D disease, management should occur in conjunction with supportive care services and should focus on symptom relief. Pain is a
common feature of HCC and can result from both the disease and its treatment. The analgesic choice must take into consideration the severity of liver disease,
portosystemic shunting, low circulating albumin (changing bioavailability), risk of return to opioid dependence, current medications, and clinical features,
including hepatic encephalopathy and hepatorenal syndrome.51 The World Health Organization analgesic ladder provides an accepted treatment algorithm for
analgesia use in all cancers, including HCC.

Conclusion
The management of HCC requires a team of experts delivering multiple therapeutic modalities while balancing the issues of pre‐existent liver disease and risk
of hepatic decompensation. Overall, mortality remains high despite all the recent advances in locoregional and systemic therapies. A priority for Australia, is to
recognise patients at risk of HCC and to institute surveillance strategies at a time when the HCC is curable.
Box 1 – Recommendations of the hepatocellular carcinoma (HCC) consensus statement
GRADE quality of Level of agreement
No. Consensus recommendation evidence* n† (%)‡

1 HCC surveillance should be offered to all patients with cirrhosis if they are suitable and C1 48 (100%)
willing to receive treatment

2 HCC surveillance should be undertaken in non‐cirrhotic individuals with chronic HBV C1 46 (97.8%)
infection who are at increased risk of HCC

3 Surveillance for HCC should be undertaken using liver ultrasound every 6 months B1 49 (98.0%)

4 Combining α‐fetoprotein testing with liver ultrasound may be considered for HCC C2 45 (88.9%)
surveillance

5 Antiviral therapy for HCV infection may be offered to patients with HCC who have B2 40 (92.5%)
undergone surgical or locoregional treatment with curative intent

6 Patients with HCV infection‐related cirrhosis who achieve sustained virological response B1 46 (95.7%)
and undergo curative therapy for their HCC require ongoing surveillance
7 HCC surveillance in non‐cirrhotic patients can be considered in select patient populations C2 43 (90.7%)

8 In the setting of cirrhosis, imaging diagnosis of HCC should rely on standardised criteria, B1 50 (98.0%)
based on evidence and validated in clinical practice

9 Multiphase CT or MRI is the recommended investigation for lesions suspicious for HCC A1 50 (98.0%)

10 For indeterminate lesions > 10 mm diameter in cirrhotic livers, either targeted liver biopsy B1 45 (97.8%)
or repeat interval imaging or an alternative imaging modality is required for diagnosis

11 It is recommended that the BCLC staging system is used as the framework for HCC B1 50 (94.0%)
management in Australia

12 The management choice for a patient with HCC should take into account the individual C1 50 (100%)
patient’s wishes and medical and psychosocial circumstances

13 The management of HCC should be determined by a multidisciplinary team to optimise B1 50 (100%)

patient care
14 Liver resection is a first‐line therapy option in suitable patients with HCC where there is B1 48 (95.8%)
preserved liver function, sufficient liver remnant, and absence of significant portal
hypertension

15 Liver transplantation should be considered for patients with HCC within transplant criteria A1 48 (100%)
who are not suitable for curative hepatic resection or ablative therapy

16 UCSF criteria should inform patient selection for liver transplantation in patients with HCC B1 47 (100%)

17 Patients with HCC initially beyond transplant criteria may be considered for liver C1 41 (97.6%)
transplantation after successful downstaging to within standard transplant criteria

18 Ablative therapy is recommended as a curative locoregional therapy in suitable patients B1 39 (94.9%)

with very early or early (BCLC stage 0 or A) HCC

19 Patients with early stage disease (BCLC stage A and early stage B), who are not A1 48 (100%)
candidates for surgery or liver transplantation, should be treated with locoregional therapy
20 In patients with BCLC‐B HCC, TACE is recommended as first‐line therapy B1 47 (97.9%)

21 SIRT may be considered in select patients with intermediate or locally advanced HCC C2 44 (88.6%)

22 Stereotactic external‐beam radiation therapy may be considered for local tumour control in C2 42 (81.0%)
suitable patients with HCC

23 Patients with advanced HCC (BCLC‐C) or multifocal HCC that is not amenable to curative A1 49 (93.9%)
or locoregional therapy (BCLC‐B) should be offered systemic therapy

24 Sorafenib or lenvatinib is recommended as initial systemic therapy in patients with A1 48 (100%)

advanced (BCLC‐C) or multifocal HCC that is not amenable to curative or locoregional
therapy (BCLC‐B) and who have preserved liver function and good performance status

25 The use of multikinase inhibitors as adjuvant therapy after hepatic resection or locoregional A1 44 (100%)
therapy is not recommended
26 In patients with HCC, regular assessment for clinical and radiological response to first‐line A1 50 (100%)
therapy is recommended to monitor for disease progression

27 In patients with HCC, sorafenib or lenvatinib should be discontinued when there is A1 45 (100%)
unequivocal clinical and/or radiological progression

28 In patients with HCC, a second‐line systemic therapy is recommended in suitable patients A1 41 (92.7%)
who have radiological progression while being treated with multikinase inhibitors but
preserved liver function and good performance status

29 HCC treatment response should be assessed by multiphase CT or MRI using standardised B1 48 (81.3%)
criteria such as the mRECIST criteria

30 Patients with incurable HCC should be introduced to supportive care services early in their B1 50 (100%)
management

31 Patients with BCLC‐D HCC should be managed symptomatically in conjunction with B1 50 (100%)
supportive care services
BCLC = Barcelona Clinic Liver Cancer; CT = computed tomography; GRADE = Grading of Recommendations Assessment,
Development and Evaluation; HBV = hepatitis B virus; HCV = hepatitis C virus; mRECIST = modified Response Evaluation
Criteria in Solid Tumors; MRI = magnetic resonance imaging; SIRT = selective internal radiation therapy; TACE =
transarterial chemoembolisation; UCSF = University of California San Francisco. * GRADE quality of evidence classification:
A = high, B = moderate, C = low, D = very low; strength of recommendation: 1 = strong, 2 = weak. † Number of experts who
participated in the final modified Delphi process vote for this recommendation. ‡ Percentage of expert advisors who either
strongly agreed or agreed (based on five-point Likert scale, comprising: strongly disagree, disagree, neutral, agree and
strongly agree). Source: Hepatocellular Carcinoma Consensus Statement Working Group. Australian recommendations for
the management of hepatocellular carcinoma: a consensus statement. Melbourne: Gastroenterological Society of Australia,
2020. https://www.gesa.org.au/resources/hepatocell ular-carcinoma-hcc-management-consensus/.

Box 2 – Populations that should undergo hepatocellular carcinoma surveillance

People with cirrhosis (any aetiology)

People with chronic hepatitis B virus infection without cirrhosis in:

• Asian men older than 40 years

• Asian women older than 50 years
• People born in sub‐Saharan Africa older than 20 years
• Aboriginal and Torres Strait Islander people older than 50 years
Box 3 – Surveillance and diagnosis of hepatocellular carcinoma (HCC)
AFP = α-fetoprotein; BCLC = Barcelona Clinic Liver Cancer; CT = computed tomography; HBV = hepatitis B virus; MDT = multidisciplinary team; MRI = magnetic resonance
imaging. All cirrhotic and non-cirrhotic patients at increased risk of HCC should be offered surveillance (if willing to receive treatment). The preferred surveillance method is
liver ultrasound ± serum AFP every 6 months. Once a lesion is identified on ultrasound, depending on size, further evaluation is required with either multiphase CT or MRI.
Depending on the imaging characteristics, lesions may be classified as: likely benign, intermediate, or definite HCC. Discussion in an MDT meeting is recommended in order
to optimise patient care. Source: Hepatocellular Carcinoma Consensus Statement Working Group. Australian recommendations for the management of hepatocellular
carcinoma: a consensus statement. Melbourne: Gastroenterological Society of Australia, 2020. https://www.gesa.org.au/resources/hepatocellular-carcinoma-hcc-
management-consensus/
Box 4 – Barcelona Clinic Liver Cancer (BCLC) staging system
CPS = Child–Pugh Score; ECOG-PS = Eastern Cooperative Oncology Group Performance Status; PBS = Pharmaceutical Benefits Scheme; SIRT = selective internal
radiation therapy; TACE = Transarterial chemoembolisation; TGA = Therapeutic Goods Administration. The BCLC staging system is the preferred system for classifying
hepatocellular carcinoma; the stage is calculated from three clinical parameters: liver function, tumour characteristics, and functional status of the patient. Updated versions
are available at http://www.bclc.cat/professional-area/management-of-hcc.html . Source: Hepatocellular Carcinoma Consensus Statement Working Group. Australian
recommendations for the management of hepatocellular carcinoma: a consensus statement. Melbourne: Gastroenterological Society of Australia,
2020. https://www.gesa.org.au/resources/hepatocellular-carcinoma-hcc-management-consensus/

Box 5 – Comparison of liver transplantation criteria for patients with hepatocellular carcinoma (in chronological
order)
Milan31 UCSF32 Up‐to‐733 Metroticket 2.034

Criteria for liver transplantation Single lesion ≤ 50 mm Single lesion ≤ 65 mm Sum of the diameter of Predictive model based on
or or the largest tumour (in HCC number, maximal
2 or 3 tumours, all 2 or 3 tumours all cm) and the total size and Log10 of AFP*
≤ 30 mm ≤ 45 mm and total number of tumours ≤ 7
tumour diameter
≤ 80 mm
Conditions No macrovascular invasion, no regional nodal disease, no distant metastases

AFP = α-fetoprotein; CT = computed tomography; HCC = hepatocellular carcinoma; UCSF = University of California San Francisco. * Online
calculator available at: http://www.hcc-olt-metroticket.org. Source: Hepatocellular Carcinoma Consensus Statement Working Group. Australian
recommendations for the management of hepatocellular carcinoma: a consensus statement. Melbourne: Gastroenterological Society of Australia,
2020. https://www.gesa.org.au/resources/hepatocellular-carcinoma-hcc-management-consensus/

Box 6 – Supportive care, hepatology and medical goals in hepatocellular carcinoma (HCC)
BCLC‐0/A BCLC‐B BCLC‐C BCLC‐D

Description Very early/early stage Intermediate Advanced Terminal

Overall aim Curative intent Non‐curative, increased Non‐curative, increased life Palliative care, symptom
survival while considering expectancy while control
 trade‐offs of treatment considering trade‐offs of
side effects treatment side effects and
symptom management
HCC extent Confined to liver and small Confined to liver and Vascular invasion or spread Defined by poor liver function
volume of tumour large or multinodular outside liver or cancer‐related symptoms
Liver function Preserved (no portal Preserved Preserved Decompensated
hypertension in stage 0)
Cancer‐related None (ECOG 0) None (ECOG 0) Mild (ECOG 1–2) Marked (ECOG 3–4)
symptoms
Type of therapy Ablation/resection or TACE Systemic therapy Best supportive care
offered transplantation
Expected median > 5 years > 2.5 years > 1 year < 3 months
survival (with
treatment)
Supportive care • Explore with patient • Explore • Symptom • Management of severe
aspects and family their expectations of management of HCC cancer‐related
understanding of the patient and and chemotherapy symptoms
diagnosis of cancer maintain realistic • Decision‐making • Discuss referral to
and long term goals support with focus on hospice for end of life
implications • Develop quality of life care
• Explore patient’s coordination of • Consider early • Engage palliative care
cultural and religious care framework referral to palliative services for supportive
beliefs and symptom care for ongoing measures
monitoring plan support and
counselling
Discuss and consider advanced care directives
Hepatology‐ • Preserve and potentially restore hepatic function to prevent stage migration (eg, • Manage symptoms
focused goals alcohol abstinence, avoidance of hepatotoxins, antiviral therapy, increased associated with liver
coffee consumption) and consider opportunities for downstaging failure (eg, ascites,
• Screen for varices in cirrhotic patients with portal hypertension hepatic encephalopathy
• Consider nutritional status especially before surgery and in patients with protein etc)
malnutrition • Determine limits of care
• In advanced HCC, investigate for possibility of metastatic disease or vascular (eg, in event of
invasion catastrophic events
 such as variceal
haemorrhage)

General medical • Treat medical comorbidities that will have an impact on survival or symptoms • Pharmacological
issues • Optimise patients medically for surgery, procedures or chemotherapy management of
• Support cessation of smoking and alcohol symptoms in the
• Psychological or psychiatric support context of advanced
liver disease and other
medical comorbidities,
including drug and
alcohol dependency

BCLC = Barcelona Clinic Liver Cancer; ECOG = Eastern Cooperative Oncology Group. Integration of BCLC staging system with supportive care
needs, hepatological goals, and medical issues at an early stage. Source: Hepatocellular Carcinoma Consensus Statement Working Group.
Australian recommendations for the management of hepatocellular carcinoma: a consensus statement. Melbourne: Gastroenterological Society of
Australia, 2020. https://www.gesa.org.au/resources/hepatocellular-carcinoma-hcc-management-consensus/