Hepatocellular carcinoma

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Hepatocellular carcinoma arises from hepatocytes, usually in cirrhosis or chronic viral liver disease; prognosis and treatment are governed jointly by tumour extent, portal hypertension, liver function and performance status. Alcohol-related liver disease, metabolic dysfunction-associated steatotic liver disease, hepatitis B or C and other chronic injuries create the main carcinogenic substrate. Chronic HBV can cause HCC even without established cirrhosis through viral integration and long-term inflammatory genomic injury. Repeated hepatocyte death and regeneration in fibrotic liver selects clones with telomere, WNT, TP53 and other driver abnormalities. As nodules progress, arterial blood supply replaces portal supply, creating the characteristic arterial enhancement and later contrast washout pattern.

Recognition depends on the tempo, host context and anatomical pattern rather than one isolated result. Many potentially curable tumours are asymptomatic and found on six-monthly ultrasound in eligible people with cirrhosis. New ascites, encephalopathy, jaundice or variceal bleeding can be the first clue and also changes treatment fitness. Right-upper-quadrant discomfort, early satiety, weight loss and hepatomegaly suggest enlarging or advanced tumour. Investigation should answer immediate safety, diagnostic confirmation and extent in that order. Surveillance ultrasound Perform every 6 months in the eligible surveillance population; a new lesion at least 1 cm needs dedicated contrast imaging rather than serial routine ultrasound. Multiphase contrast CT or MRI In an appropriately high-risk liver, a classic pattern can establish HCC non-invasively; atypical lesions need alternative imaging, interval review or biopsy. Liver reserve assessment Use Child–Pugh or ALBI alongside portal hypertension and performance; tumour stage without liver reserve is an incomplete treatment assessment.

Management is determined by physiological urgency, disease extent, treatment intent and the person's priorities. The pathway moves through move from surveillance to diagnosis, then select resection, transplant or ablation, then control unresectable liver-confined disease; each transition requires named multidisciplinary ownership. Follow-up must anticipate portal-vein invasion, liver failure, variceal bleeding while measuring function and treatment toxicity.

Key points

Surveillance-detected lesion is a pivotal clue in Hepatocellular carcinoma: Many potentially curable tumours are asymptomatic and found on six-monthly ultrasound in eligible people with cirrhosis.
Immediate priority in unstable Hepatocellular carcinoma: Resuscitate, activate major-haemorrhage and hepatology pathways as indicated, obtain urgent multiphase imaging and involve interventional radiology and hepatobiliary surgery for haemostasis while treating precipitating liver failure.
Surveillance ultrasound is used early to detect early HCC in people with cirrhosis who could benefit from treatment. Perform every 6 months in the eligible surveillance population; a new lesion at least 1 cm needs dedicated contrast imaging rather than serial routine ultrasound.
Multiphase contrast CT or MRI refines the next decision because in an appropriately high-risk liver, a classic pattern can establish HCC non-invasively; atypical lesions need alternative imaging, interval review or biopsy.
Move from surveillance to diagnosis: Obtain specialist multiphase CT or contrast MRI and review the lesion through a hepatobiliary radiology and cancer MDT.
Select resection, transplant or ablation: Refer eligible cirrhotic patients early for transplantation, using locoregional bridging or downstaging only through the transplant pathway.
A major avoidable harm is portal-vein invasion; Tumour thrombus worsens portal hypertension and prognosis and changes suitability for transplant, resection and embolic treatment.
A common diagnostic trap is intrahepatic cholangiocarcinoma: A mass-forming biliary cancer may lack classic HCC enhancement and requires tissue because systemic and surgical pathways differ.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Cirrhosis

Alcohol-related liver disease, metabolic dysfunction-associated steatotic liver disease, hepatitis B or C and other chronic injuries create the main carcinogenic substrate.

Hepatitis B

Chronic HBV can cause HCC even without established cirrhosis through viral integration and long-term inflammatory genomic injury.

Metabolic and toxic risks

Diabetes, obesity, smoking, aflatoxin and heavy alcohol exposure interact with fibrosis and host susceptibility. In Hepatocellular carcinoma, this distinction materially changes aetiological assessment.

Hereditary liver disease

Haemochromatosis, alpha-1-antitrypsin deficiency, porphyria and selected metabolic disorders raise risk through chronic injury and iron or metabolite toxicity.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Regenerative carcinogenesis
Repeated hepatocyte death and regeneration in fibrotic liver selects clones with telomere, WNT, TP53 and other driver abnormalities.
2
Arterial neoangiogenesis
As nodules progress, arterial blood supply replaces portal supply, creating the characteristic arterial enhancement and later contrast washout pattern.
3
Portal invasion
Tumour grows into portal or hepatic veins, worsening portal hypertension, enabling intrahepatic spread and limiting locoregional options.
4
Competing liver failure
Treatment can remove or injure functioning parenchyma, so an anatomically small cancer may still be untreatable without adequate hepatic reserve.
5
Extrahepatic spread
Advanced disease commonly reaches nodes, lung, bone and adrenal sites, while symptoms may still be dominated by cirrhosis.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Surveillance-detected lesion

Many potentially curable tumours are asymptomatic and found on six-monthly ultrasound in eligible people with cirrhosis.

Liver decompensation

New ascites, encephalopathy, jaundice or variceal bleeding can be the first clue and also changes treatment fitness.

Pain and systemic decline

Right-upper-quadrant discomfort, early satiety, weight loss and hepatomegaly suggest enlarging or advanced tumour.

Tumour thrombus

Portal-vein expansion and enhancing intraluminal tissue favours malignant invasion over bland thrombosis.

Ruptured HCCRed flag

Abrupt severe abdominal pain, shock and haemoglobin fall with haemoperitoneum is a life-threatening presentation.

Red flags requiring action

A patient with cirrhosis develops unexplained decompensation, weight loss, right-upper-quadrant pain or a new liver lesion.
Sudden abdominal pain, shock and haemoperitoneum suggests rupture of a vascular tumour.
New portal-vein thrombus may represent tumour invasion rather than bland thrombosis.
Rapid jaundice, ascites, encephalopathy or variceal bleeding reduces treatment reserve and needs urgent hepatology care.
A surveillance ultrasound shows a focal lesion at least 1 cm in a high-risk liver.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

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
Surveillance ultrasoundFirst step
Why
Detect early HCC in people with cirrhosis who could benefit from treatment.
Interpretation and limitations
Perform every 6 months in the eligible surveillance population; a new lesion at least 1 cm needs dedicated contrast imaging rather than serial routine ultrasound.
02
Multiphase contrast CT or MRI
Why
Characterise arterial enhancement, washout, capsule, vascular invasion and intrahepatic extent.
Interpretation and limitations
In an appropriately high-risk liver, a classic pattern can establish HCC non-invasively; atypical lesions need alternative imaging, interval review or biopsy.
03
Liver reserve assessment
Why
Quantify bilirubin, albumin, INR, platelets, renal function, ascites and encephalopathy before treatment.
Interpretation and limitations
Use Child–Pugh or ALBI alongside portal hypertension and performance; tumour stage without liver reserve is an incomplete treatment assessment.
04
AFP
Why
Provide a prognostic and response adjunct in selected HCC.
Interpretation and limitations
A normal AFP does not exclude HCC and an elevated value is not diagnostic; interpret with imaging and active hepatitis.
05
Biopsy
Why
Confirm atypical imaging, non-cirrhotic lesions or disease requiring tissue for systemic treatment when imaging is not definitive.
Interpretation and limitations
Plan through the MDT because bleeding and needle-track seeding are small but real risks; obtain enough tissue to distinguish cholangiocarcinoma or metastasis.
06
Extrahepatic staging
Why
Identify nodes, lung, bone or other metastasis and vascular involvement before curative or systemic treatment.
Interpretation and limitations
Use CT chest and appropriate abdominal imaging, adding bone or brain imaging for symptoms rather than indiscriminate scanning.
07
Transplant assessment
Why
Determine tumour criteria, liver disease severity, abstinence and whole-person suitability for transplantation.
Interpretation and limitations
Referral must be early because bridging treatment and waiting-list dynamics affect eligibility; local criteria and national policy apply.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Intrahepatic cholangiocarcinoma

A mass-forming biliary cancer may lack classic HCC enhancement and requires tissue because systemic and surgical pathways differ.

Liver metastasis

Multiplicity, known extrahepatic primary and target-like enhancement favour metastases, but a new lesion in cirrhosis still needs dedicated characterisation.

Regenerative or dysplastic nodule

Cirrhotic nodules can mimic early tumour; contrast pattern, size change and expert liver radiology review guide follow-up.

Hepatic adenoma

A hypervascular lesion in a non-cirrhotic liver may be benign but carries haemorrhage and selected malignant-transformation risk.

Haemangioma

Peripheral nodular enhancement with progressive fill-in is typical; biopsy of a vascular lesion should not precede expert imaging review.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01DetectMove from surveillance to diagnosisFirst stepSurveillance or symptom-directed imaging identifies a new liver lesion in a person at risk of HCC.

1Obtain specialist multiphase CT or contrast MRI and review the lesion through a hepatobiliary radiology and cancer MDT.
2Accept a non-invasive diagnosis only when risk context and enhancement pattern meet current criteria; biopsy atypical or non-cirrhotic disease when it changes care.
3Stage tumour burden, vascular invasion and extrahepatic disease while measuring liver reserve, portal hypertension, performance and comorbidity.

02CurativeSelect resection, transplant or ablationHCC remains localised and liver reserve and functional status support curative intent.

1Offer resection for anatomically removable disease with sufficient future liver remnant and acceptable portal-hypertension risk.
2Refer eligible cirrhotic patients early for transplantation, using locoregional bridging or downstaging only through the transplant pathway.
3Use thermal ablation for suitable small lesions when resection is inappropriate or ablation offers equivalent local control with less hepatic loss.

03Liver-directedControl unresectable liver-confined diseaseDisease is not suitable for curative treatment but remains predominantly hepatic with adequate reserve.

1Consider transarterial chemoembolisation for appropriate multinodular disease without decompensated liver failure or prohibitive portal-flow compromise.
2Use selective internal radiotherapy, stereotactic radiotherapy or other focal therapy in selected anatomy through an experienced MDT.
3Reassess liver function after each treatment and stop repeating locoregional procedures when toxicity or progression outweighs likely control.

04SystemicTreat advanced HCC and preserve liverThere is vascular invasion, extrahepatic spread, unsuitable liver-directed disease or progression after local therapy.

1Optimise viral treatment, ascites, encephalopathy, nutrition and variceal risk and document liver reserve before selecting systemic therapy.
2Use immunotherapy-based or tyrosine-kinase treatment according to current NHS access, contraindications, prior therapy and bleeding risk.
3Monitor both tumour response and hepatic decompensation, integrating palliative care and stopping treatment when functional harm exceeds benefit.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

Provides first-line systemic treatment for eligible advanced or unresectable HCC with preserved liver function.

Atezolizumab with bevacizumab

A licensed adult schedule is atezolizumab 1,200 mg intravenously followed by bevacizumab 15 mg/kg intravenously on day 1 every 3 weeks, continued while benefit and tolerability persist under the commissioned HCC pathway.

Assess and treat oesophageal varices before bevacizumab, and review bleeding, hypertension, proteinuria, thrombosis, wound healing and immune toxicities; avoid in uncontrolled autoimmune disease or high untreated bleeding risk.

An oral first-line tyrosine-kinase option when immunotherapy or bevacizumab is unsuitable and commissioning criteria are met.

Lenvatinib

For eligible adults weighing under 60 kg, use 8 mg orally once daily; for 60 kg or above, use 12 mg once daily, with dose interruption and reduction for toxicity.

Control blood pressure, check urine protein, ECG risk, renal, liver and thyroid function and monitor diarrhoea, appetite, weight and hand–foot toxicity.

Treats encephalopathy from decompensated liver disease while cancer decisions proceed; it does not treat HCC directly.

Lactulose for coexisting hepatic encephalopathy

Start 15–30 mL orally two to four times daily and titrate to two or three soft stools each day; use rectal administration if the oral route is temporarily unsafe according to local policy.

Avoid excessive diarrhoea, dehydration, hypernatraemia and aspiration, and investigate precipitating infection, bleeding, constipation, renal injury and sedative medicines.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Portal-vein invasion

Tumour thrombus worsens portal hypertension and prognosis and changes suitability for transplant, resection and embolic treatment.

Liver failure

Cancer progression, infection or treatment can precipitate jaundice, coagulopathy, ascites, renal injury and encephalopathy. In Hepatocellular carcinoma, this distinction materially changes complication assessment.

Variceal bleeding

Portal hypertension creates life-threatening gastrointestinal haemorrhage and requires prophylaxis assessment before bevacizumab-containing therapy. In Hepatocellular carcinoma, this distinction materially changes complication assessment.

Tumour rupture

Capsular vascular HCC can bleed into the peritoneum, causing shock and need for urgent transarterial or surgical haemostasis.

Post-treatment liver injury

Resection, ablation, embolisation and radiotherapy can decompensate marginal liver reserve even when tumour targeting is technically adequate.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Repeat multiphase liver imaging and AFP where informative at the tumour-specific interval, using the same criteria to assess response.
At every treatment review, trend bilirubin, albumin, INR, renal function, platelets, ascites, encephalopathy and performance.
Before and during bevacizumab, monitor blood pressure, urine protein, bleeding and variceal management with clear procedure timing.
After embolic, ablative or radiation treatment, distinguish expected necrosis from viable arterial enhancement and watch for hepatic decompensation.
Maintain hepatitis treatment, alcohol support, nutrition, portal-hypertension care and transplant eligibility independently of radiological tumour response.
Investigate new bone pain, respiratory symptoms or neurological findings for extrahepatic spread rather than waiting for scheduled liver imaging.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Two stages coexist

A tumour stage and a liver-disease stage are both required; treating one while ignoring the other produces unsafe recommendations.

Classic imaging can diagnose

In a high-risk cirrhotic liver, the accepted arterial-enhancement and washout pattern may obviate biopsy, but atypical disease needs tissue.

AFP can be normal

A normal marker neither excludes HCC nor proves response, while hepatitis and regeneration can elevate it without tumour.

Check varices before bevacizumab

Anti-VEGF treatment can convert untreated portal-hypertensive bleeding risk into catastrophic haemorrhage.

Repeated embolisation has a limit

Radiological feasibility does not justify another procedure when liver reserve declines or disease becomes extrahepatic.

11Common pitfallsFrequent interpretation and management errors.

01
Staging the tumour without documenting liver reserve and portal hypertension.
02
Diagnosing HCC from AFP alone.
03
Biopsying a vascular lesion before expert multiphase imaging review.
04
Starting bevacizumab without assessing significant variceal bleeding risk.
05
Repeating transarterial treatment despite progressive decompensation.
06
Assuming portal-vein thrombus is bland without assessing enhancement and expansion.