Liver Cancer (Hepatocellular Carcinoma)

Hepatocellular carcinoma (HCC) is a primary malignancy arising from hepatocytes — the principal functional cells of the liver. It is distinct from secondary liver cancers, which originate elsewhere and metastasise to the liver. HCC accounts for the vast majority of primary liver cancers and is the third leading cause of cancer mortality globally. It disproportionately affects populations in sub-Saharan Africa and East Asia due to the high prevalence of hepatitis B virus (HBV) infection — the single most important risk factor for HCC worldwide.

HCC almost universally arises in a background of chronic liver disease. Cirrhosis — regardless of aetiology — is the most important predisposing condition; approximately 80–90% of HCC cases develop in cirrhotic livers. Common causes include chronic HBV infection (even without cirrhosis in some cases), chronic HCV infection, alcoholic liver disease, non-alcoholic steatohepatitis (NASH) — increasingly prevalent with rising rates of metabolic syndrome — and less commonly, haemochromatosis, Wilson's disease, and autoimmune hepatitis.

HCC is staged using the Barcelona Clinic Liver Cancer (BCLC) staging system, which integrates tumour characteristics (size, number, vascular invasion, metastatic spread) with liver function (Child-Pugh score) and performance status. This integrated approach is critical because the underlying liver disease constrains treatment options as much as the tumour itself. A patient with the same tumour burden but better underlying liver function may have access to very different treatments. Surveillance programmes using ultrasound and AFP in high-risk populations (cirrhotic patients) are essential for detecting HCC at early, potentially curative stages.

Treatment options range from potentially curative approaches (surgical resection, liver transplantation, and ablation for early-stage disease) through locoregional therapies (TACE, TARE, HIFU) for intermediate-stage disease, to systemic therapy for advanced HCC — where the introduction of atezolizumab plus bevacizumab and tremelimumab plus durvalumab combinations has transformed outcomes compared with sorafenib monotherapy.

The term liver cancer most commonly refers to hepatocellular carcinoma, but includes other distinct primary liver malignancies with different biology and management. Within HCC itself, several molecular and clinical subtypes have been described with prognostic and therapeutic relevance.

HCC is often asymptomatic in its early stages, particularly when it develops in a background of cirrhosis where symptoms of liver disease may already be present. The symptoms of HCC can overlap substantially with those of underlying chronic liver disease, making early clinical detection challenging. Surveillance with 6-monthly liver ultrasound and AFP in at-risk individuals (cirrhotic patients, chronic HBV carriers) is the primary means of early detection.

HCC has several well-established risk factors, the most important of which globally are chronic HBV infection and hepatic cirrhosis from any cause. Understanding and addressing modifiable risk factors — particularly through HBV vaccination, antiviral therapy, and alcohol reduction — is central to HCC prevention. Surveillance of high-risk populations enables early detection before symptoms develop.

Diagnosis of HCC can be achieved non-invasively in most cases through radiological criteria when a liver mass demonstrates characteristic vascular enhancement patterns on multiphasic CT or MRI in the appropriate clinical context (cirrhosis or chronic HBV). Biopsy is not always required for diagnosis when imaging is unequivocal (LI-RADS 5) in a cirrhotic liver. Assessment of liver function alongside tumour staging is essential and inseparable in HCC evaluation.

The Barcelona Clinic Liver Cancer (BCLC) staging system is the internationally recommended framework for HCC staging and treatment allocation. It uniquely integrates tumour burden with liver function and performance status — recognising that HCC treatment decisions cannot be based on tumour characteristics alone. The BCLC system links each stage to recommended treatment pathways and is endorsed by major international liver and oncology societies.

HCC treatment is highly stage-dependent and must integrate tumour characteristics with the functional status of the underlying liver. Multi-disciplinary hepato-oncology team (MDT) review — including hepatologists, hepatobiliary surgeons, interventional radiologists, and medical oncologists — is the standard of care and should precede any treatment decision. Treatment intent may be curative (resection, transplant, ablation) or tumour-controlling (locoregional or systemic therapy).

The systemic therapy landscape for HCC has undergone a revolution, with checkpoint immunotherapy combinations now establishing a new first-line standard. Multiple parallel research avenues — including combination immunotherapy, targeted agents for molecular subsets, novel locoregional modalities, and combination local-plus-systemic strategies — are actively under investigation. China has been a particularly active centre for locoregional innovation (HIFU, transarterial radioembolisation, immunotherapy trials) and CancerFax is well positioned to navigate access to these programmes.

Biomarkers in HCC serve multiple roles: aiding diagnosis, stratifying prognosis, guiding treatment eligibility (including checkpoint inhibitor use and antiviral management), and monitoring treatment response. Unlike some other solid tumours, there are currently no universally validated predictive biomarkers for specific systemic agents in HCC, though active research in this area — particularly around PD-L1, CTNNB1 mutations, and FGF19 amplification — is ongoing.

HCC management is complex and stage-dependent, with multiple curative and palliative options that are best evaluated by experienced hepato-oncology multidisciplinary teams. Several clinical scenarios arise where a specialist second opinion substantially influences treatment decisions, eligibility assessment, or access to advanced therapies.

Prognosis in HCC is determined by the interplay of tumour characteristics, underlying liver function, and the treatments received. Early-stage HCC treated with curative intent carries a very different outlook from advanced-stage disease. The introduction of immunotherapy combinations has meaningfully improved outcomes in advanced HCC compared with the era of sorafenib alone. Early detection through surveillance programmes remains the most powerful intervention for improving population-level outcomes.

Living with HCC requires concurrent management of both the cancer and the underlying chronic liver disease. A multi-disciplinary approach involving hepatology, hepato-oncology, nutrition, palliative care, and social support is essential. Several areas of supportive care are particularly important in HCC patients.