hepatocellular carcinoma

HCC arises from malignant transformation of hepatocytes, most commonly in the setting of cirrhosis (any cause) due to chronic hepatocyte injury, regeneration, and accumulation of genetic mutations (e.g., TP53, beta-catenin). Key risk factors include chronic HBV infection (can cause HCC even without cirrhosis due to direct viral integration into host genome), chronic HCV, alcoholic cirrhosis, NAFLD/NASH, hemochromatosis, alpha-1 antitrypsin deficiency, and aflatoxin B1 from Aspergillus (associated with TP53 mutation, particularly in HBV-endemic regions). Clinically, patients present with worsening signs of liver disease (jaundice, ascites, encephalopathy), unintentional weight loss, right upper quadrant pain, hepatomegaly, and sometimes Budd-Chiari syndrome due to tumor invasion of hepatic veins. Paraneoplastic syndromes include hypoglycemia, erythrocytosis (EPO production), and hypercalcemia. Diagnosis relies on serum AFP elevation and characteristic imaging findings on multiphase CT or MRI—arterial phase hyperenhancement with portal venous/delayed phase washout—which can be diagnostic without biopsy in cirrhotic patients per AASLD criteria. Screening with ultrasound +/- AFP is recommended every 6 months in cirrhotic patients and certain high-risk populations (e.g., HBV carriers). Pathologically, HCC can show trabecular, pseudoglandular, or fibrolamellar patterns; the fibrolamellar variant occurs in young patients without underlying liver disease and has a better prognosis. Treatment options include surgical resection, liver transplantation (within Milan criteria), locoregional therapies (TACE, radiofrequency ablation), and systemic therapies (sorafenib, immunotherapy) for advanced disease. Prognosis is generally poor unless caught early, as underlying cirrhosis often limits treatment options.