Hepatocellular Carcinoma (HCC): Causes, BCLC Staging, and Treatment — Overview, Diagnosis & Treatment Options | MyMedicPlus

Hepatocellular carcinoma (HCC) is a primary liver malignancy arising from hepatocytes and is the 5th most common cancer and 2nd leading cause of cancer death globally, with approximately 900,000 new cases annually. In the US, approximately 42,000 new cases are diagnosed each year. HCC arises predominantly on a background of chronic liver disease or cirrhosis in over 90% of cases. The BCLC staging system guides treatment allocation and reflects the dual impact of liver function and tumor burden.

Chronic hepatitis B virus (HBV) is the dominant global risk factor, accounting for approximately 50% of HCC cases worldwide; HBsAg carriers have a 100-fold increased risk. Chronic HCV cirrhosis causes approximately 25% of HCC globally. NAFLD and NASH cirrhosis are the fastest-growing risk factors in Western countries, driven by obesity and type 2 diabetes. Alcohol-related cirrhosis, aflatoxin B1 exposure (poorly stored grains in sub-Saharan Africa and Asia), hereditary hemochromatosis, alpha-1 antitrypsin deficiency, and primary biliary cirrhosis are additional causes.

Most HCC cases are asymptomatic in early stages, detected on biannual surveillance ultrasound in cirrhotic patients. Symptomatic disease presents with right upper quadrant pain, unintentional weight loss, fatigue, anorexia, and hepatomegaly. Jaundice, ascites, and variceal bleeding indicate decompensated liver disease. Paraneoplastic syndromes include hypoglycemia (insulin-like growth factor secretion), erythrocytosis, hypercalcemia, and diarrhea. Tumor rupture causes acute abdomen with hemoperitoneum. AFP is elevated greater than 400 ng/mL in approximately 20% of cases.

Dynamic CT or MRI using LI-RADS criteria is diagnostic for HCC greater than or equal to 10 mm in cirrhotic livers: arterial phase hyperenhancement with portal venous or delayed phase washout appearance (LI-RADS 5) requires no biopsy. AFP and AFP-L3 fraction supplement imaging. Biopsy is reserved for atypical imaging features. BCLC staging integrates tumor number and size, Child-Pugh liver function score, performance status, and vascular invasion. Biannual liver ultrasound plus AFP surveillance is recommended for all cirrhotic patients and chronic HBV carriers.

BCLC 0 (very early, single HCC up to 2 cm): ablation (RFA or MWA) achieves near-100% local control. BCLC A (early): surgical resection (for preserved liver function), liver transplant (Milan criteria), or ablation. BCLC B (intermediate, no vascular invasion): TACE or DEB-TACE. BCLC C (advanced, vascular invasion or extrahepatic spread): atezolizumab plus bevacizumab (IMbrave150, first-line preferred); durvalumab plus tremelimumab (HIMALAYA, first-line alternative); sorafenib or lenvatinib (second-choice first-line); cabozantinib, ramucirumab (AFP greater than 400), regorafenib (second-line). BCLC D: best supportive care.

Five-year survival rates by treatment: surgical resection 50-70%, liver transplant (Milan criteria) 70-75%, ablation (BCLC 0/A) 40-70% at 5 years, TACE (BCLC B) median OS 20-26 months, systemic therapy (BCLC C) median OS 19.2 months with atezolizumab plus bevacizumab. Effective antiviral therapy for HBV reduces HCC recurrence after curative treatment by approximately 40-50%. Overall 5-year survival for all HCC patients combined is approximately 20%, reflecting late-stage diagnosis in most cases.

HBV vaccination is the most effective HCC prevention, reducing HBV-related HCC incidence in vaccinated populations. HBV antiviral therapy (tenofovir, entecavir) and HCV direct-acting antivirals achieving SVR reduce HCC risk by 50-70% in treated patients. Weight management, alcohol cessation, and diabetes control reduce NAFLD-related cirrhosis progression. Aflatoxin B1 exposure is minimized by proper grain storage and fumonisin biomarkers. Biannual liver ultrasound plus AFP surveillance is recommended for all cirrhotic patients and chronic HBV carriers to detect HCC at a potentially curative stage.