Liver Cancer

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Intrahepatic cholangiocarcinoma is a biliary tract cancer with different biology and treatment and should be discussed separately.

HCC frequently develops in chronic liver disease or cirrhosis. Treatment therefore depends not only on tumor stage, but also on liver reserve, portal hypertension, performance status, and the underlying liver disease.

• Right upper abdominal pain or fullness
• An abdominal mass
• Unexplained weight loss, reduced appetite, or fatigue
• Jaundice, dark urine, or itching
• Ascites or leg swelling
• Easy bleeding or bruising
• A sudden worsening of chronic liver disease
• Fever or nausea in some patients

These symptoms can also be caused by cirrhosis, hepatitis, gallbladder disease, or other conditions.

• Chronic hepatitis B infection
• Chronic hepatitis C infection
• Cirrhosis from any cause
• Long-term heavy alcohol use
• Metabolic dysfunction-associated steatotic liver disease and steatohepatitis
• Aflatoxin exposure
• Hereditary hemochromatosis and selected metabolic or inherited liver diseases
• Smoking
• Obesity and type 2 diabetes, often through metabolic liver disease

Hepatitis B can increase HCC risk even before cirrhosis develops.

• Professional guidelines generally recommend surveillance for people with cirrhosis and selected high-risk chronic hepatitis B populations. Ultrasound, often combined with AFP, is commonly performed at approximately six-month intervals, but eligibility and method should follow local guidelines.
• AFP alone cannot reliably exclude or diagnose HCC.
• Hepatitis B vaccination prevents HBV infection and reduces the burden of HBV-related liver cancer.
• Effective treatment of HBV or HCV lowers risk but does not eliminate risk in people who remain in a high-risk category.
• Other prevention priorities include limiting alcohol, treating metabolic disease, avoiding aflatoxin exposure, and not smoking.
• People with known chronic liver disease need structured specialist follow-up rather than relying on a one-time liver function panel.

Diagnosis is discussed within the Overview, Screening, Staging, and Biomarkers sections above for this cancer type. Specific tests depend on presentation, site, and pathology.

TNM describes anatomic extent, but HCC is often staged clinically with the Barcelona Clinic Liver Cancer (BCLC) system, which integrates tumor burden, vascular invasion, metastasis, performance status, and liver function.

Child-Pugh or ALBI measures help estimate hepatic reserve.

Histologic grade describes differentiation, but treatment is usually driven more strongly by tumor burden, vascular invasion, portal hypertension, and liver function.

The same-sized tumor can require very different treatment in two people with different liver reserve.

Chronic inflammation, hepatocyte injury, and repeated regeneration promote accumulation of genetic and epigenetic alterations. Important pathways include TERT, WNT/beta-catenin, TP53, oxidative stress, and angiogenesis.

HCC is often highly vascular and develops an immunosuppressive tumor microenvironment. HBV-, HCV-, alcohol-, and metabolic-disease-associated tumors may differ biologically and immunologically.

• AFP as an adjunct for surveillance, risk assessment, and monitoring in selected patients, with limited sensitivity and specificity
• AFP-L3 and des-gamma-carboxy prothrombin/PIVKA-II in selected regions
• Characteristic arterial-phase enhancement and portal or delayed-phase washout on multiphasic imaging in an at-risk liver
• AFP thresholds as part of eligibility for ramucirumab in defined settings
• No routinely used driver biomarker equivalent to EGFR in lung cancer currently determines standard first-line HCC treatment
• Circulating tumor DNA, methylation tests, and multiprotein panels as investigational early-detection approaches

In an at-risk liver, high-quality multiphasic CT or MRI can sometimes establish HCC without biopsy, but this rule does not apply to every liver mass or every patient.

• Early disease: liver resection, liver transplantation, radiofrequency ablation, or microwave ablation.
• Selected localized tumors that are not suitable for surgery: stereotactic radiation or other local approaches.
• Multifocal liver-limited disease: transarterial chemoembolization, transarterial radioembolization, or other regional treatment.
• Advanced disease, vascular invasion, or distant metastasis: systemic therapy.
• Transplant eligibility depends on tumor burden, liver function, donor availability, and local criteria.
• Palliative and supportive care address pain, ascites, itching, nutrition, hepatic encephalopathy, and quality of life.

• Immune plus antiangiogenic therapy: atezolizumab plus bevacizumab
• Dual immunotherapy: durvalumab plus tremelimumab; nivolumab plus ipilimumab in approved settings
• Multikinase inhibitors: sorafenib, lenvatinib, regorafenib, and cabozantinib
• VEGFR2 antibody: ramucirumab for selected patients meeting AFP-related criteria
• Other immune or targeted agents according to treatment line and regional approval
• Before bevacizumab, clinicians commonly assess esophageal or gastric varices and bleeding risk

• Resection or local therapy: bleeding, infection, bile leak, and liver failure
• TACE or TARE: pain, fever, nausea, and deterioration in liver function
• Immunotherapy: immune-mediated hepatitis and inflammation of other organs
• Anti-VEGF therapy: hypertension, proteinuria, bleeding, and thrombosis
• Tyrosine kinase inhibitors: hand-foot skin reaction, diarrhea, hypertension, fatigue, and appetite loss
• Supportive treatment must also manage cirrhosis, including ascites, varices, hepatic encephalopathy, malnutrition, and infection.

Vomiting blood, black stools, confusion, rapidly worsening jaundice, or severe abdominal swelling requires urgent assessment.

• Trials are comparing and sequencing multiple first-line immune combinations.
• Systemic therapy is being combined with TACE, TARE, ablation, or radiation.
• Perioperative and post-ablation immunotherapy is under study.
• Circulating tumor DNA, protein signatures, and radiomics are being evaluated for earlier detection.
• Studies are examining how liver disease cause shapes the tumor immune microenvironment and treatment response.
• Reliable predictive biomarkers remain a major unmet need.
• A recent U.S. regulatory example is FDA approval on April 11, 2025, of nivolumab plus ipilimumab for first-line treatment of adults with unresectable or metastatic HCC.

• Is this hepatocellular carcinoma, cholangiocarcinoma, or another liver tumor?
• What are my BCLC, TNM, Child-Pugh, and/or ALBI assessments?
• Is there vascular invasion or distant spread?
• Am I a candidate for resection, transplantation, ablation, TACE, TARE, or radiation?
• Has the cause of my liver disease been treated?
• Do I need endoscopy before immunotherapy plus antiangiogenic treatment?
• What does AFP mean in my case?
• How will ascites, varices, and hepatic encephalopathy be managed?
• How might treatment affect the remaining liver function?
• Are there clinical trials appropriate for my disease and liver function?