Liver Cancer (Hepatocellular Carcinoma) — Causes, Symptoms & Treatment Guide — Symptoms, Causes & Treatment | MyMedicPlus

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, accounting for 75–85% of cases, arising from hepatocytes (liver cells). With approximately 905,000 new diagnoses and 830,000 deaths annually, it ranks as the sixth most common cancer and third leading cause of cancer death worldwide. Intrahepatic cholangiocarcinoma (arising from intrahepatic bile ducts) accounts for most of the remaining cases. HCC almost exclusively develops in the setting of chronic liver disease — cirrhosis or chronic hepatitis B — making it the only major cancer where both the at-risk population and the underlying cause are well-defined, enabling effective surveillance. The prognosis at diagnosis varies dramatically: curative options are available for early-stage disease (5-year survival 60–80%), while advanced HCC carries a poor prognosis despite significant recent advances in systemic therapy.

Chronic hepatitis B virus (HBV): the dominant cause globally — especially in sub-Saharan Africa and East Asia, where HBV infection in infancy is common. HBV can integrate directly into host DNA and cause HCC even without cirrhosis. Hepatitis C virus (HCV): causes HCC via cirrhosis — cure with direct-acting antivirals reduces but does not eliminate HCC risk in those with established cirrhosis. Together, HBV and HCV account for ~75% of global HCC cases. Non-alcoholic fatty liver disease/MASLD: rapidly rising cause in Western countries, driven by the obesity epidemic. Alcohol-related cirrhosis: significant risk in all countries. Aflatoxin B1 exposure (contaminated cereals, peanuts — Aspergillus mould — synergistic with HBV in Africa and Asia). Other causes: haemochromatosis (iron overload), Wilson disease, alpha-1 antitrypsin deficiency, primary biliary cholangitis, and autoimmune hepatitis. Risk factors for HCC development in cirrhosis: male sex, alcohol use, obesity, diabetes, and elevated AFP levels.

Early HCC is typically asymptomatic — detected through surveillance in known cirrhotic or high-risk patients. Late presentation symptoms include: right upper quadrant or epigastric pain (constant dull ache or acute if rupture occurs); constitutional symptoms — unexplained weight loss (often >10% of body weight), fatigue, anorexia; decompensation of pre-existing cirrhosis — new or worsening jaundice, increasing ascites, new-onset hepatic encephalopathy (confusion, asterixis), or variceal bleeding. A cirrhotic patient who suddenly deteriorates without clear cause must have HCC excluded. Hepatomegaly with a hard, tender nodular liver edge may be palpable in advanced disease. Paraneoplastic manifestations (rare): hypoglycaemia (tumour producing IGF-2), erythrocytosis (excess erythropoietin), hypercalcaemia, or watery diarrhoea (VIP-secreting tumours). Portal vein tumour thrombus (PVTT) causes acute portal hypertension worsening — a poor prognostic sign.

Surveillance: 6-monthly abdominal ultrasound ± serum AFP in cirrhotic patients and selected HBV carriers — the cornerstone of early detection. Diagnosis of a hepatic nodule detected on surveillance follows EASL/AASLD algorithm: a nodule ≥1 cm is assessed with multiphasic CT or gadoxetic acid-enhanced MRI. Hallmark HCC vascular pattern on CT/MRI: arterial phase hyperenhancement (APHE) + washout on portal/delayed phase = LI-RADS 5 (definite HCC — no biopsy required in cirrhotic liver). AFP >400 ng/mL is highly specific but elevated in only 15–20% of cases. PIVKA-II (protein induced by vitamin K absence) has complementary sensitivity. Biopsy (ultrasound or CT-guided) is performed for atypical imaging, non-cirrhotic liver, or when systemic therapy is planned based on molecular profiling. BCLC staging guides treatment allocation; Child-Pugh and ALBI scores assess underlying liver function.

Treatment is guided by BCLC stage, liver function (Child-Pugh score), and performance status. Early stage (BCLC 0–A): curative intent. Liver resection (hepatectomy): 5-year survival 60–80% in ideal candidates; limited by underlying liver function (requires adequate future liver remnant). Liver transplantation: 5-year survival 65–75% for patients within Milan criteria (≤1 nodule ≤5 cm or ≤3 nodules each ≤3 cm, no vascular invasion, no extrahepatic spread) — curative for both HCC and cirrhosis. Bridge therapy (TACE, ablation) prevents tumour progression during waiting. Radiofrequency ablation (RFA) or microwave ablation (MWA): equivalent to resection for tumours ≤3 cm; minimally invasive. Intermediate stage (BCLC B): transarterial chemoembolisation (TACE) or drug-eluting bead TACE (DEB-TACE); TARE/SIRT with yttrium-90 microspheres. Advanced stage (BCLC C — vascular invasion or extrahepatic spread): systemic therapy. Atezolizumab (anti-PD-L1) + bevacizumab (anti-VEGF) is the standard first-line regimen (IMbrave150 — median OS 19 months, ORR 30%). Tremelimumab + durvalumab (HIMALAYA trial — alternative first-line). Sorafenib or lenvatinib are alternatives when immunotherapy is contraindicated. Second-line: regorafenib, cabozantinib, ramucirumab (AFP ≥400), pembrolizumab, nivolumab + ipilimumab. End stage (BCLC D): best supportive care.

Hepatocellular carcinoma (HCC) and cholangiocarcinoma are typically diagnosed at advanced stages in the absence of surveillance programmes, severely limiting treatment options and prognosis. HCC frequently presents with hepatic decompensation — jaundice, ascites, variceal haemorrhage, and hepatic encephalopathy — in the context of underlying cirrhosis, which itself carries a mortality of 10-15% annually. Tumour rupture with haemoperitoneum occurs in approximately 5-10% of HCC cases — presenting as acute severe abdominal pain with haemodynamic shock; mortality is extremely high without emergency intervention including transarterial embolisation. Biliary obstruction from intrahepatic or hilar cholangiocarcinoma (Klatskin tumour) causes progressive cholestatic jaundice, pruritus, and ascending cholangitis. Vascular invasion — HCC invades the portal vein in approximately 20% of cases at diagnosis, causing portal hypertension, portal vein thrombosis, and hepatic failure — precluding surgical resection and significantly worsening prognosis. Paraneoplastic syndromes associated with HCC include hypoglycaemia (from insulin-like growth factor II secretion), erythrocytosis (from ectopic erythropoietin), and hypercalcaemia. Metastatic disease — most commonly to lungs, lymph nodes, and bones — causes bone pain, respiratory failure, and systemic deterioration. Liver failure from tumour replacement of functional hepatic parenchyma is the most common cause of death, irrespective of treatment, when disease is advanced at diagnosis.

HBV vaccination is the most important HCC prevention measure — universal infant vaccination has dramatically reduced HCC incidence in vaccinated cohorts in Taiwan and China. HBV antiviral therapy (tenofovir alafenamide, entecavir) in HBV-infected individuals reduces HCC risk by 50–80%. Hepatitis C cure with direct-acting antivirals (DAAs) reduces HCC incidence by 70% — however, surveillance must continue post-cure in those with established cirrhosis. Alcohol abstinence prevents alcoholic cirrhosis progression. Weight loss (7–10%) reduces liver fat and inflammation in MASLD. Coffee consumption (3–5 cups/day) is associated with 40–50% reduced HCC risk. Aflatoxin exposure reduction through improved grain storage. Regular 6-monthly surveillance ultrasound (± AFP) in all cirrhotic patients and HBV carriers at risk — early detection at BCLC 0/A stage allows curative treatment and dramatically improves survival.

Cirrhotic patients must not miss 6-monthly surveillance ultrasound appointments — any new hepatic nodule requires urgent hepatology assessment within 2 weeks. Seek emergency care immediately for: vomiting blood or black tarry stools (variceal bleeding); sudden severe abdominal pain with rapid deterioration (tumour rupture — rare but life-threatening requiring emergency embolisation); new confusion or drowsiness in a cirrhotic patient (hepatic encephalopathy triggered by tumour progression). Contact your hepatologist within 1–2 days for: new or worsening jaundice, rapidly increasing ascites, or significant unintended weight loss in a patient with known liver disease. AFP levels rising significantly between surveillance intervals should prompt early hepatology review regardless of ultrasound result.