01OverviewDefinition, clinical context and the essential points that orientate the chapter.
Hepatocellular carcinoma usually develops in cirrhosis from metabolic, alcohol-related, viral, autoimmune or cholestatic liver disease, although chronic hepatitis B can cause HCC without established cirrhosis. Surveillance aims to detect asymptomatic, small disease while resection, ablation or transplantation remains possible. NICE recommends six-monthly ultrasound, with or without serum AFP, for eligible people with cirrhosis. Surveillance should be an organised recall process with recorded image quality and a route for rapid diagnostic imaging; simply advising a patient to request another scan is not a robust programme.
Ultrasound is a surveillance test, not a definitive characterisation tool. A new or enlarging nodule, suspicious vascularity, unexplained rising AFP or an inadequate examination should prompt a specialist pathway. Multiphasic CT or MRI evaluates arterial phase hyperenhancement, washout, capsule, vascular invasion and spread. In a high-risk liver, a characteristic enhancement pattern may establish HCC without biopsy. Atypical lesions may need alternative imaging, interval assessment or MDT-planned tissue; biopsy is reserved for a question whose answer will change care because sampling error, bleeding and tumour seeding are relevant.
The hepatobiliary MDT stages both the malignancy and its host liver. Resection suits selected localised disease with adequate future liver remnant and acceptable portal-hypertensive risk. Thermal ablation can be curative for selected small lesions. Transplantation treats both tumour and cirrhosis within current NHSBT selection rules, while transarterial treatment, selective internal radiotherapy, stereotactic radiotherapy or systemic therapy may be appropriate for unresectable disease, bridging or palliation. Drug sequences evolve quickly; use current NICE technology appraisals and regional oncology protocols rather than an inherited fixed list.
Key points
- Offer eligible adults with cirrhosis ultrasound surveillance every six months, with or without AFP, when early detection could lead to meaningful treatment.
- Chronic hepatitis B can confer HCC risk without cirrhosis, so use the NICE hepatitis B risk-based surveillance recommendations alongside the cirrhosis pathway.
- AFP alone is neither sensitive nor specific enough to replace imaging, and a normal value cannot reassure after a suspicious scan.
- A new focal lesion requires timely multiphasic CT or contrast-enhanced MRI interpreted in a specialist liver-imaging and MDT setting.
- Characteristic arterial enhancement and later washout can establish HCC non-invasively in an appropriate high-risk liver; not every lesion should be biopsied.
- Treatment selection integrates tumour size, number and distribution with vascular invasion, extrahepatic spread, portal hypertension, liver function, frailty and performance status.
- Potentially curative options include resection, ablation and transplantation; locoregional and systemic treatments may control disease or bridge selected patients.
- Continue managing the underlying liver disease and decompensation because cancer control cannot compensate for failing hepatic reserve.
02AetiologyUnderlying causes, associations and risk factors, with why each one matters.
Cirrhotic liver disease
Cirrhosis from alcohol, metabolic steatotic disease, hepatitis C, autoimmune or cholestatic disease creates the dominant background risk for hepatocellular carcinoma.
Chronic hepatitis B
Persistent hepatitis B can cause hepatocellular carcinoma through chronic inflammation and viral genomic effects, sometimes before cirrhosis is established.
Metabolic and alcohol interaction
Obesity, diabetes, steatohepatitis and alcohol exposure can coexist and compound chronic hepatic inflammation, fibrosis and carcinogenic risk.
Inherited liver disorders
Haemochromatosis, alpha-1 antitrypsin deficiency and selected other inherited disorders increase risk mainly through longstanding injury and cirrhosis.
03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.
- 1Regenerative genomic instability
Repeated hepatocyte death and regeneration in an inflammatory fibrotic liver promotes DNA damage, clonal selection and malignant transformation.
- 2Viral oncogenic effects
Hepatitis B DNA integration and viral protein effects can disrupt growth control, while chronic viral inflammation provides additional mutational pressure.
- 3Tumour arterialisation
As malignant nodules develop, their blood supply becomes predominantly arterial, producing characteristic enhancement and subsequent washout on dynamic imaging.
- 4Vascular invasion and spread
Tumour can invade portal or hepatic veins, worsen portal hypertension and disseminate within the liver, lymph nodes, lungs, bone or other sites.
04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.
Most treatment-eligible HCC should be found before symptoms through a six-monthly programme. A new focal abnormality needs prompt diagnostic imaging even when AFP is normal.
Worsening ascites, jaundice, encephalopathy or variceal bleeding can reflect tumour progression, portal-vein involvement or unrelated cirrhotic decline and requires expedited reassessment.
Unintentional weight loss, anorexia, fatigue or right-upper-quadrant discomfort are non-specific but concerning in a high-risk patient, particularly when surveillance has lapsed.
Sudden severe abdominal pain, hypotension, falling haemoglobin and intraperitoneal fluid suggest rupture and haemorrhage, demanding emergency resuscitation and interventional or surgical control.
Unexplained hypoglycaemia, erythrocytosis or hypercalcaemia can occur but are uncommon; investigate conventional causes while considering tumour biology and burden.
Rapid clinical decline, increasing portal-hypertensive complications or an abnormal portal vein on ultrasound may indicate tumour thrombus and materially changes stage and treatment options.
05InvestigationsWhat to request, why it matters and how to interpret it.
Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.
- 01
Six-monthly liver ultrasoundFirst step - Why
- Detect early focal liver cancer in eligible high-risk people before symptoms develop.
- Interpretation and limitations
- A negative, technically adequate study returns to surveillance. A new lesion or inadequate visualisation needs a defined escalation route; repeating a poor scan indefinitely is unsafe.
- 02
Serum alpha-fetoprotein - Why
- Provide an optional adjunct to imaging and a possible longitudinal tumour marker.
- Interpretation and limitations
- AFP can be normal in HCC and raised in active hepatitis, pregnancy or germ-cell malignancy. Interpret trends with imaging and never use AFP alone to diagnose or exclude cancer.
- 03
Multiphasic contrast CT or MRI - Why
- Characterise a lesion, assess vascular invasion and stage intrahepatic and extrahepatic disease.
- Interpretation and limitations
- Arterial phase hyperenhancement with later washout in an at-risk liver can be diagnostic when technical and specialist criteria are met. Atypical enhancement requires MDT-directed next steps, not improvised biopsy.
- 04
Liver reserve and portal-hypertension assessment - Why
- Determine whether resection, locoregional therapy or transplantation is physiologically feasible.
- Interpretation and limitations
- Review bilirubin, albumin, INR, creatinine, sodium, platelets, ascites and encephalopathy, plus portal-hypertensive evidence. Child-Pugh or other scores support but do not replace multidisciplinary judgement.
- 05
Staging chest and skeletal imaging - Why
- Look for metastatic disease when findings will alter treatment intent.
- Interpretation and limitations
- Chest CT is commonly integrated with staging; bone or other imaging is symptom- and protocol-led. An unexpected isolated abnormality may need confirmation before curative options are abandoned.
- 06
Image-guided biopsy when selected - Why
- Obtain histology for indeterminate imaging or when tissue will determine oncological treatment.
- Interpretation and limitations
- Plan in the hepatobiliary MDT with coagulation, ascites and route considered. A negative sample can be false because of targeting or tumour heterogeneity and must be reconciled with imaging.
06Differential diagnosisRealistic alternatives and the features that help distinguish them.
Regenerative or dysplastic nodule
Cirrhotic livers contain benign and premalignant nodules that may resemble small hepatocellular carcinoma but lack a definitive dynamic imaging pattern.
Intrahepatic cholangiocarcinoma
A primary biliary malignancy can present as a liver mass but differs in enhancement, tumour markers, pathology and treatment pathway.
Metastatic liver disease
Multiple lesions or a known extrahepatic cancer raises metastases, although distribution and imaging alone do not always establish the primary source.
Benign vascular or hepatocellular lesion
Haemangioma, focal nodular hyperplasia and adenoma have characteristic contexts and imaging patterns but may require specialist review when atypical.
Liver abscess
Fever, inflammatory markers and a complex lesion suggest infection, although necrotic tumour can mimic an abscess and occasionally coexist with sepsis.
07ManagementImmediate care, first-line treatment, alternatives and escalation.
01SurveilRun a reliable programmeFirst stepAn adult has cirrhosis or another guideline-defined HCC risk and would be eligible for treatment if early cancer were found.+
- 1Explain the purpose and limits of surveillance, arrange ultrasound every six months with or without AFP according to the relevant NICE pathway, and record a dependable recall owner.
- 2At each episode, document technical adequacy and reconsider whether health status still permits meaningful HCC treatment, discussing any proposal to stop surveillance with the person.
- 3EscalationActively recover missed appointments and escalate new lesions or inadequate studies through a time-defined diagnostic pathway rather than waiting for the next routine interval.
02DiagnoseCharacterise a suspicious lesionSurveillance or symptomatic imaging identifies a new, enlarging or otherwise suspicious focal liver abnormality.+
- 1Obtain protocolled multiphasic CT or contrast-enhanced MRI and current liver-reserve tests, ensuring comparison with previous imaging and review by specialist hepatobiliary radiology.
- 2Discuss imaging pattern, vascular invasion, extrahepatic disease and transplant implications in the hepatobiliary MDT before requesting tissue or declaring the lesion benign.
- 3Use biopsy only when non-invasive criteria are not met and histology will change management, choosing a safe route and planning how a non-diagnostic result will be handled.
03TreatMatch cancer and liver strategyHCC is confirmed or considered definite by accepted high-risk imaging criteria.+
- 1Stage tumour burden alongside liver function, portal hypertension, performance status, frailty, comorbidity and the person's priorities, then identify genuinely curative options first.
- 2Refer potentially transplant-suitable disease early under current NHSBT policy while considering resection or ablation and any bridging therapy in the specialist centre.
- 3For non-curative disease, select locoregional, radiotherapy or systemic treatment under current NICE and regional protocols, with symptom control and decompensation management embedded from the outset.
08ComplicationsImportant consequences, why they occur and why they matter clinically.
Portal-vein tumour invasion
Extension into the portal vein worsens portal pressure, impairs hepatic perfusion and markedly changes stage and available treatment options.
Hepatic decompensation
Tumour burden or treatment can precipitate ascites, jaundice, encephalopathy and reduced synthetic function in an already limited liver reserve.
Tumour rupture
Spontaneous rupture causes sudden abdominal pain, intraperitoneal bleeding and shock requiring emergency resuscitation and haemorrhage control.
Metastatic disease
Advanced hepatocellular carcinoma can spread to lymph nodes, lungs, bone and adrenal glands, causing pain, fractures or respiratory symptoms.
Paraneoplastic syndromes
Tumour secretion or metabolic effects can produce hypoglycaemia, erythrocytosis or hypercalcaemia, usually in association with substantial disease burden.
09Monitoring and follow-upTreatment response, safety checks and longer-term review.
- Maintain six-monthly ultrasound recall for eligible people, auditing attendance, scan adequacy, interval cancers and time from abnormal result to diagnostic imaging.
- After diagnosis, trend liver function, renal function, full blood count, performance status, nutrition and decompensation as well as tumour imaging.
- Monitor after ablation, resection or locoregional therapy with the specialist protocol, recognising that viable enhancement matters more than size alone in some response systems.
- During systemic treatment, use the current regimen-specific schedule for blood pressure, liver injury, endocrine, dermatological, bleeding and immune-related adverse effects.
- For transplant candidates, communicate tumour progression or response, admissions and liver deterioration promptly because listing status and bridging plans may change.
- Continue HCC surveillance after curative local treatment or resection according to MDT advice because recurrence and new primary tumours remain possible.
10Special situationsVariants, exceptions and circumstances that change the usual approach.
Six months is biological
The interval balances tumour growth and service burden; annual scanning risks allowing a potentially curable lesion to progress beyond treatment thresholds.
AFP has asymmetry
A rising AFP may sharpen concern, but a normal value has insufficient sensitivity to neutralise suspicious imaging or replace a technically adequate ultrasound programme.
Diagnosis can be radiological
HCC is unusual among solid tumours because a characteristic dynamic contrast pattern in a high-risk liver can avoid tissue, provided accepted technical criteria are satisfied.
Stage has two dimensions
The same tumour burden can lead to different treatment in a well-compensated liver and a decompensated one; hepatic reserve is part of cancer staging in practice.
Transplant treats field risk
Unlike local excision, liver transplantation can remove both the recognised cancer and the cirrhotic organ at risk of further primary tumours, but selection safeguards scarce grafts.
11Common pitfallsFrequent interpretation and management errors.
- 01
Using AFP alone as a surveillance test or treating a normal result as exclusion of HCC.
- 02
Repeating an inadequate ultrasound at the next six-month slot without an alternative imaging or specialist plan.
- 03
Biopsying a characteristic lesion before the hepatobiliary and transplant teams consider non-invasive diagnosis and procedural consequences.
- 04
Choosing treatment from tumour diameter alone while ignoring portal hypertension, liver reserve, frailty and extrahepatic spread.
- 05
Delaying transplant referral until after repeated local therapies have allowed disease to move outside selection criteria.
- 06
Stopping management of ascites, varices, nutrition or viral hepatitis once oncology treatment begins.