Liver Cancer (HCC) — Causes, Surveillance, TACE & Treatment Guide — Symptoms, Causes & Treatment | MyMedicPlus

Hepatocellular carcinoma (HCC) is the most common primary liver cancer (75-85% of cases), developing almost exclusively in the setting of pre-existing liver disease — cirrhosis in 80-90% of cases. Cholangiocarcinoma (biliary tract cancer) accounts for 10-15% of primary liver cancers. HCC is the sixth most common cancer worldwide (900,000 new cases annually) and the fourth leading cause of cancer death (830,000 deaths per year). Five-year survival remains poor (under 20% globally) due to late presentation. Over 70% of cases occur in sub-Saharan Africa and Eastern Asia, where hepatitis B is endemic. The annual risk of HCC in established cirrhosis is 1-8% per year, depending on aetiology and disease activity. HCC surveillance by 6-monthly liver ultrasound with serum AFP detects tumours at curative stages in approximately 30-40% of screened cirrhotic patients — emphasising the importance of surveillance programmes. Only 30-40% of all HCC patients are eligible for curative therapy at diagnosis.

Liver cirrhosis (from any cause): the most important risk factor — annual HCC risk 1-8% per year; the risk is highest in HCV-related and alcohol-related cirrhosis. Hepatitis B virus (HBV): the most important cause globally, responsible for approximately 50% of HCC; HBV can cause HCC even without cirrhosis through direct oncogenesis (the HBx protein integrates into host DNA, activating oncogenes); HBV vaccination prevents both infection and HCC. Hepatitis C virus (HCV): responsible for 25% of HCC globally — HCV causes HCC almost exclusively via cirrhosis; curative HCV treatment with direct-acting antivirals (sofosbuvir-based DAA regimens) reduces HCC risk by 70-75% after virological cure. Alcohol-related liver disease (ALD): cirrhosis from chronic alcohol excess accounts for 30% of HCC in Western countries. Metabolic-associated fatty liver disease (MAFLD/NAFLD): a rapidly growing cause of non-cirrhotic HCC. Aflatoxin B1 (mycotoxin from Aspergillus mould in improperly stored grain and nuts) — major cause in sub-Saharan Africa and Southeast Asia; synergistic with HBV. Hereditary haemochromatosis, primary biliary cholangitis, and alpha-1-antitrypsin deficiency — additional cirrhotic causes.

HCC in cirrhotic patients is often detected by surveillance before symptoms develop — the goal of 6-monthly screening. Symptomatic HCC: right upper quadrant pain or fullness (from enlarging hepatic mass); weight loss, fatigue, and anorexia (tumour cachexia); decompensation of pre-existing cirrhosis — worsening ascites, encephalopathy, jaundice, and variceal haemorrhage; palpable liver mass; right-sided hepatic bruit on auscultation (from tumour arteriovenous shunting). Paraneoplastic features: hypoglycaemia from ectopic insulin-like growth factor 2 (can cause severe life-threatening hypoglycaemia); erythrocytosis (ectopic erythropoietin); hypercalcaemia; watery diarrhoea. Advanced disease: portal vein tumour thrombus (PVTT — causing portal hypertension and rapid deterioration in over 25% at diagnosis); extrahepatic metastases to lungs, lymph nodes, bone, and adrenal glands. Spontaneous tumour rupture with haemoperitoneum — a rare but catastrophic acute presentation.

Surveillance programme: 6-monthly liver ultrasound plus serum AFP in all cirrhotic patients and HBV carriers over age 40 without cirrhosis. Radiological diagnosis (for lesions over 1 cm): dynamic contrast-enhanced CT (triphasic CT — arterial hyperenhancement and portal venous washout are pathognomonic of HCC) or gadoxetate-enhanced MRI — LI-RADS 5 lesions (definitely HCC) do not require biopsy. LI-RADS (Liver Imaging Reporting and Data System) scoring system: guides diagnosis and treatment allocation. Serum alpha-fetoprotein (AFP): elevated above 400 ng/mL is highly specific for HCC; sensitivity is 40-60% (poor for small tumours). Liver biopsy (ultrasound or CT-guided core needle): reserved for atypical lesions where radiological diagnosis is uncertain; risk of needle-track seeding approximately 1%. Staging: Barcelona Clinic Liver Cancer (BCLC) staging system — integrates tumour burden, liver function (Child-Pugh score), and performance status to guide treatment allocation. CT chest, abdomen, and pelvis for extrahepatic disease staging.

BCLC 0 (very early — solitary HCC under 2 cm, Child-Pugh A, performance status 0): surgical resection or ablation with curative intent (5-year survival over 70%). BCLC A (early — solitary HCC under 5 cm or up to 3 nodules under 3 cm, preserved liver function): surgical resection (preferred if adequate liver reserve and no portal hypertension); liver transplantation (Milan criteria — single tumour under 5 cm or up to 3 under 3 cm; 5-year survival 70-75%); radiofrequency ablation (RFA) or microwave ablation (MWA) for unresectable lesions under 3 cm (complete ablation 90%+ for lesions under 2 cm). BCLC B (intermediate — multinodular, no vascular invasion, preserved liver function): transarterial chemoembolisation (TACE) — intra-arterial delivery of doxorubicin-loaded microspheres (doxorubicin-eluting beads — DEB-TACE); median survival 20-26 months; may be combined with ablation. BCLC C (advanced — portal vein invasion or extrahepatic spread): systemic therapy — atezolizumab (anti-PD-L1) plus bevacizumab (anti-VEGF): first-line (IMbrave150 trial: median OS 19.2 vs 13.4 months with sorafenib); tremelimumab plus durvalumab (HIMALAYA trial: alternative first-line); sorafenib or lenvatinib for patients not suitable for immunotherapy; regorafenib, cabozantinib, or ramucirumab (second-line). BCLC D (end-stage): best supportive/palliative care.

Progressive tumour growth rapidly invades hepatic vasculature — portal vein tumour thrombus (PVTT) develops in 25-35% of HCC patients, causing severe portal hypertension, variceal haemorrhage, and hepatic ischaemia. Hepatic decompensation from HCC accelerating the underlying cirrhosis: refractory ascites, hepatic encephalopathy, and variceal haemorrhage are common final events. Spontaneous tumour rupture with haemoperitoneum: occurs in 3-15% of HCC patients — mortality 20-50%; requires emergency transarterial embolisation (TAE). Extrahepatic metastases to lungs, bones, and adrenal glands cause organ-specific morbidity. Biliary obstruction from intraductal tumour extension causing jaundice and cholangitis. Severe hypoglycaemia from IGF-2 paraneoplastic secretion — potentially life-threatening.

HBV vaccination is the most effective prevention — a 3-dose universal childhood vaccination programme has reduced HCC incidence by 80% in vaccinated cohorts in Taiwan and other high-incidence countries. HBV antiviral therapy (tenofovir or entecavir) suppresses viral replication and reduces HCC risk by 50-80% in chronic HBV carriers with elevated viral load — all HBsAg-positive patients should be assessed for antiviral eligibility. HCV eradication with direct-acting antivirals (DAAs — sofosbuvir-based 8-12 week courses): sustained virological response reduces HCC risk by 70-75%; all HCV-positive individuals should receive treatment. Alcohol abstinence for alcohol-related cirrhosis. Weight loss and metabolic control for NAFLD/MAFLD-related cirrhosis. Avoidance of aflatoxin through proper food storage (refrigerate grains and nuts). HCC surveillance (6-monthly ultrasound) in all high-risk patients reduces HCC mortality by 37% in meta-analyses.

All patients with liver cirrhosis or chronic hepatitis B (even without cirrhosis, if over age 40) should be enrolled in a 6-monthly HCC surveillance programme — this is the most important action to enable curative treatment. See a doctor promptly for: new or worsening right upper quadrant pain in a patient with chronic liver disease; unexplained weight loss, anorexia, or fatigue with liver disease; sudden worsening of ascites, jaundice, or encephalopathy in compensated cirrhosis; or a palpable abdominal mass. Attend A&E immediately for: sudden severe abdominal pain with haemodynamic instability in a cirrhotic patient (possible HCC rupture requiring emergency embolisation); or severe hypoglycaemia with no obvious cause. Any cirrhotic patient should discuss the 2-week wait cancer pathway if HCC is suspected on ultrasound.