Hepatocellular Carcinoma

Hepatocellular carcinoma is the primary malignancy of hepatocytes. It arises overwhelmingly in chronic liver disease, most commonly cirrhosis from chronic hepatitis B, chronic hepatitis C, alcohol related liver disease, and increasingly MASLD.

Hepatitis B carries a unique ability to cause hepatocellular carcinoma even without cirrhosis, through direct viral integration into the host genome. For this reason, surveillance in high risk hepatitis B carriers begins independent of fibrosis stage in some guidelines (for example, Asian men over 40 and African patients over 20, per the risk thresholds noted in the Hepatitis B entry).

• Often detected through surveillance in an asymptomatic patient with known cirrhosis.

• Symptomatic presentation reflects advanced disease: right upper quadrant pain, weight loss, worsening ascites, new or worsening jaundice, and decompensation of previously stable cirrhosis.

• A palpable liver mass or bruit may be present. Rupture with intraperitoneal hemorrhage is a rare but recognized acute presentation, causing sudden severe abdominal pain and hypovolemic shock.

In a cirrhotic patient, hepatocellular carcinoma can be diagnosed radiologically without biopsy if a lesion above 1 cm shows the characteristic pattern of arterial phase hyperenhancement with portal venous or delayed phase washout on contrast enhanced CT or MRI (the LI-RADS classification formalizes this).

Biopsy is reserved for atypical imaging or a non-cirrhotic liver.

AFP (alpha-fetoprotein) supports diagnosis and is used for monitoring treatment response, though it lacks sufficient sensitivity to be used alone for surveillance or diagnosis.

Surveillance in at risk patients (cirrhosis of any cause, and high risk hepatitis B carriers) uses six monthly ultrasound with or without AFP.

Staging uses the Barcelona Clinic Liver Cancer (BCLC) system, which uniquely incorporates tumor burden, liver function (Child-Pugh class), and performance status together, since treatment options and prognosis in hepatocellular carcinoma depend as much on underlying liver reserve as on tumor stage.

Differentials include other focal liver lesions in a cirrhotic liver (regenerative or dysplastic nodules, hemangioma), intrahepatic cholangiocarcinoma, and metastatic disease to the liver.

Management follows BCLC staged treatment allocation.

Very early and early stage disease (BCLC 0 to A) in patients with preserved liver function is treated with one of the following:

• Surgical resection.
• Liver transplantation, which is particularly attractive since it treats both the tumor and the underlying cirrhosis. Milan criteria are used to select appropriate candidates.
• Percutaneous ablation (radiofrequency or microwave ablation) for small tumors unsuitable for resection.

Intermediate stage disease (BCLC B, multinodular, preserved liver function) is treated with transarterial chemoembolization (TACE), delivering chemotherapy directly to the tumor via its arterial supply while embolizing the vessel.

Advanced stage disease (BCLC C, vascular invasion or extrahepatic spread) is treated with systemic therapy, including tyrosine kinase inhibitors (sorafenib, lenvatinib) and, increasingly first-line, combination immunotherapy (atezolizumab with bevacizumab).

Terminal stage disease (BCLC D, poor liver function or performance status) receives best supportive and palliative care, since aggressive treatment offers no benefit and may cause harm in this group.

Referral: hepatobiliary surgery, hepatology, and oncology multidisciplinary team for all confirmed or suspected cases; liver transplant unit assessment where criteria may be met.