Liver Cancer — Causes, Symptoms & Treatment Guide — Symptoms, Causes & Treatment | MyMedicPlus

Primary liver cancer — most commonly hepatocellular carcinoma (HCC), accounting for 75–85% of cases — arises from hepatocytes and is one of the most lethal cancers globally. With approximately 905,000 new cases and 830,000 deaths per year, it is the sixth most common cancer and third leading cause of cancer death worldwide. Intrahepatic cholangiocarcinoma (arising from bile duct epithelium) accounts for 10–15% of primary liver cancers. HCC develops almost exclusively in the context of chronic liver disease — cirrhosis or chronic hepatitis B/C — making surveillance feasible in high-risk populations. Despite being potentially curable at early stages, most cases are diagnosed at advanced stages due to silent early progression. Hepatitis B vaccination has reduced HCC incidence in Asia by over 70% in vaccinated birth cohorts, demonstrating that HCC is substantially preventable through elimination of its primary viral risk factors.

Chronic hepatitis B virus (HBV) infection is the most common cause globally — HBV can directly integrate into host DNA and cause HCC even without cirrhosis. Hepatitis C virus (HCV) causes HCC through cirrhosis. Together, HBV and HCV account for approximately 75% of global HCC cases. Liver cirrhosis from any cause is the dominant risk factor in Western countries: alcohol-related liver disease, non-alcoholic fatty liver disease/MASLD (rapidly increasing due to obesity epidemic), autoimmune hepatitis, and haemochromatosis. Aflatoxin B1 (a mycotoxin from Aspergillus mould contaminating grain and peanuts) is a major cause in sub-Saharan Africa and East Asia — synergistic with HBV. Other risk factors: male sex (3:1), age >50, diabetes, obesity, tobacco smoking, and hereditary conditions (Wilson disease, alpha-1 antitrypsin deficiency).

Early HCC is typically asymptomatic — most tumours are discovered by surveillance ultrasound in high-risk patients. Symptoms develop as the tumour grows or causes hepatic decompensation. Right upper quadrant or epigastric pain (from tumour expansion or capsule stretching) is the most common presenting symptom. Constitutional symptoms: weight loss, fatigue, anorexia. Decompensation of underlying cirrhosis: worsening jaundice, new ascites, encephalopathy, or variceal bleeding may be the first clinical sign of HCC in a cirrhotic patient. Hepatomegaly with a palpable liver mass may be felt in advanced disease. Paraneoplastic syndromes are rare: hypoglycaemia (tumour insulin-like activity), erythrocytosis (excess erythropoietin), hypercalcaemia. Portal vein tumour thrombus causes acute deterioration and portal hypertension worsening.

Surveillance: 6-monthly liver ultrasound ± AFP (alpha-fetoprotein) in all cirrhotic patients and HBV-infected patients with high risk (cirrhosis, family history, specific endemic regions). Diagnostic algorithm per EASL/AASLD guidelines: a nodule ≥1 cm detected on surveillance ultrasound is assessed by multiphase CT or MRI with liver-specific contrast. Hallmark vascular features on CT/MRI (arterial hyperenhancement + portal/venous washout) are diagnostic for HCC — biopsy is not required when imaging is diagnostic in a cirrhotic patient. AFP >400 ng/mL is highly specific but present in only 15% of tumours. PIVKA-II (des-gamma-carboxyprothrombin) has complementary diagnostic value. Liver biopsy is required for non-cirrhotic patients or atypical imaging. Barcelona Clinic Liver Cancer (BCLC) staging system guides treatment allocation.

Treatment is determined by BCLC stage and underlying liver function (Child-Pugh score). BCLC 0/A (very early/early): liver resection (curative — 5-year survival 60–80% in carefully selected patients) or liver transplantation (Milan criteria: 1 nodule ≤5 cm or up to 3 nodules ≤3 cm — post-transplant 5-year survival 70%); local ablation (radiofrequency ablation or microwave ablation — equivalent to resection for tumours ≤3 cm). BCLC B (intermediate, multifocal): transarterial chemoembolisation (TACE) — delivers chemotherapy and embolisation selectively to tumour — extends survival by 20 months vs. best supportive care. TACE-DEB (drug-eluting bead TACE) or TARE/SIRT (Y-90 radioembolisation) are alternatives. BCLC C (advanced, portal vein invasion or extrahepatic spread): systemic therapy — atezolizumab (anti-PD-L1) + bevacizumab (anti-VEGF) is first-line (IMbrave150 trial — ORR 30%, median OS 19 months); sorafenib or lenvatinib are alternatives. BCLC D (end-stage): palliative care.

Hepatocellular carcinoma in cirrhotic liver impairs already compromised liver function — acute-on-chronic liver failure from tumour growth causes rapid jaundice, encephalopathy, ascites, and coagulopathy. Portal vein tumour thrombosis causes portal hypertension and variceal haemorrhage. Biliary obstruction by tumour causes obstructive jaundice and secondary bacterial cholangitis. Spontaneous HCC rupture with intraperitoneal haemorrhage carries 50-80% mortality. Untreated HCC has a median survival of 6-12 months. Even with systemic therapy, advanced HCC has limited treatment response — sorafenib provided only 2-3 months of additional survival over placebo in the SHARP trial (2008). Newer agents (atezolizumab + bevacizumab, durvalumab + tremelimumab) improve median overall survival to 19-21 months in advanced disease.

HBV vaccination is the most effective prevention — universal infant immunisation has significantly reduced HCC incidence in vaccinated birth cohorts in East Asia. Hepatitis B antiviral treatment (tenofovir, entecavir) reduces HCC risk by 50–80% in chronic HBV carriers. Hepatitis C cure with direct-acting antivirals (DAAs — sofosbuvir-based regimens) reduces HCC incidence by 70% but does not eliminate risk — surveillance is still required post-cure in cirrhotics. Alcohol cessation prevents alcoholic cirrhosis progression. Weight loss, Mediterranean diet, and treating type 2 diabetes reduce MASLD-related HCC risk. Coffee consumption (4+ cups/day) is associated with 40% reduced HCC risk in epidemiological studies. Aflatoxin exposure reduction through grain storage improvement, fumonisin vaccination trials in endemic areas.

Patients with known cirrhosis or chronic hepatitis B must not miss 6-monthly surveillance ultrasounds — any new hepatic nodule requires urgent specialist assessment within 2 weeks. Seek emergency care for acute complications: variceal bleeding (vomiting blood, black tarry stools), sudden severe abdominal pain from tumour rupture (rare but life-threatening), worsening confusion from hepatic encephalopathy, or rapid onset of jaundice and abdominal distension. Consult your hepatologist promptly if you have unexplained weight loss, new right upper quadrant pain, or fatigue with known chronic liver disease — these symptoms may indicate HCC development. Earlier diagnosis dramatically improves survival outcomes. All patients with known cirrhosis should have 6-monthly liver ultrasound and AFP testing for HCC surveillance — early detection at Stage A allows curative resection or transplantation.