Liver Cancer (Hepatocellular Carcinoma)
Surveillance, diagnosis, staging and treatment of primary liver cancer
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and one of the leading causes of cancer-related death worldwide. It almost always arises in the setting of chronic liver disease or cirrhosis. The key to improving outcomes lies in surveillance — detecting HCC early in at-risk patients before symptoms develop. Careful evaluation of tumour burden, liver function, and patient performance status determines the treatment strategy.
Who Gets Liver Cancer and Why?
HCC develops almost exclusively in patients with underlying chronic liver disease. The major risk factors include liver cirrhosis from any cause (alcohol, NAFLD/MASLD, hepatitis B, hepatitis C), chronic hepatitis B infection even without cirrhosis, metabolic-associated steatohepatitis (MASH), aflatoxin B1 exposure (a fungal toxin contaminating crops in sub-Saharan Africa and South-East Asia), haemochromatosis, and alpha-1 antitrypsin deficiency. In the UK, the rising incidence of HCC is driven by increasing rates of alcohol-related liver disease and NAFLD. Men are three to four times more likely to develop HCC than women. The cumulative annual risk in cirrhotic patients is 1–8% per year.
Surveillance — The Critical Intervention
Six-monthly liver ultrasound combined with serum alpha-fetoprotein (AFP) measurement is recommended for all patients with cirrhosis and for non-cirrhotic patients with chronic hepatitis B. This surveillance strategy detects HCC at an early, treatable stage and reduces HCC mortality by approximately 37%. AFP is not diagnostic alone — it can be elevated in acute hepatitis, pregnancy, and other cancers. A rising AFP trend on surveillance, even within the normal range, warrants further investigation. Patients who miss surveillance appointments should be actively recalled.
Diagnosis and Staging
When a liver lesion is detected on surveillance, dynamic contrast-enhanced CT or MRI of the liver is the next step. HCC has a characteristic imaging pattern — arterial enhancement followed by portal venous washout — which is diagnostic without biopsy in lesions over 1 cm in a cirrhotic liver. The Barcelona Clinic Liver Cancer (BCLC) staging system is used to guide treatment: Stage 0/A (very early/early — single or up to 3 nodules <3 cm, preserved liver function — curative treatment possible), Stage B (intermediate — multinodular, no vascular invasion), Stage C (advanced — vascular invasion or extrahepatic spread), Stage D (end-stage — poor liver function or performance status).
Treatment Options
Treatment is guided by the BCLC stage, liver function (Child-Pugh score), and patient performance status. For early HCC (BCLC 0/A): liver transplantation is the optimal treatment when within Milan criteria (single tumour ≤5 cm, or up to 3 tumours all ≤3 cm, no vascular invasion, no extrahepatic disease). Surgical resection is an alternative in patients with preserved liver function and no portal hypertension. Thermal ablation (radiofrequency ablation, RFA) is effective for small tumours not suitable for surgery. For intermediate HCC (BCLC B): transarterial chemoembolisation (TACE) delivers chemotherapy directly to the tumour via the hepatic artery. For advanced HCC (BCLC C): systemic therapy — sorafenib (NICE approved, multikinase inhibitor) or atezolizumab + bevacizumab (immune checkpoint inhibitor combination, first-line preferred in Child-Pugh A). End-stage HCC is managed with best supportive care.
Pharmacological Management and Supportive Care
Sorafenib (400 mg BD orally) was the first systemic treatment proven to extend survival in advanced HCC — approved by NICE for Child-Pugh A patients. Side effects include hand-foot skin reaction, diarrhoea, hypertension, and fatigue. Atezolizumab plus bevacizumab (immunotherapy + anti-VEGF) is now the preferred first-line systemic option in eligible patients. Lenvatinib is an alternative first-line option. Second-line agents include regorafenib, cabozantinib, and ramucirumab. Supportive care includes management of liver cirrhosis complications (ascites, encephalopathy, varices), pain management, nutritional support, and early palliative care involvement. This article has been prepared following careful evaluation of NICE guidance (TA474, TA705), BCLC guidelines, and BSG HCC management guidelines.