Hepatocellular carcinoma
Hepatocellular carcinoma is a primary liver cancer that arises almost exclusively in cirrhosis and can be diagnosed non-invasively when multiphase CT or MRI shows arterial-phase hyperenhancement with portal-venous washout in a lesion at least 1 cm. Treatment is stratified by tumor burden, liver function, and vascular or extrahepatic spread, ranging from resection or ablation through transplantation and transarterial chemoembolization to systemic atezolizumab-bevacizumab for advanced disease.
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What this article covers
- Overview
Definition: hepatocellular carcinoma (HCC) is a primary malignancy of hepatocytes that develops almost always on a background of chronic liver injury and cirrhosis, rather than in an otherwise normal liver.
- Epidemiology
Cirrhosis of any etiology drives most disease: viral hepatitis (hepatitis B and hepatitis C), alcohol-associated liver disease, and MASLD each account for cirrhosis-associated HCC.
- Risk factors
Cirrhosis, any cause: the single strongest risk factor; risk persists even after the underlying liver disease is treated or controlled.
- Pathophysiology
Fibrosis-to-cirrhosis-to-cancer sequence: repeated hepatocyte injury and regeneration from viral, toxic (alcohol), or metabolic insults produces progressive fibrosis and cirrhotic nodularity, an environment prone to malignant transformation.
- Clinical features
Often asymptomatic at detection: most cases in surveilled cirrhotic patients are found on screening imaging before symptoms develop.
- Differential diagnosis
Intrahepatic cholangiocarcinoma: a liver mass lacking the arterial-hyperenhancement-washout pattern, often with elevated CA 19-9, arising more often in a non-cirrhotic or PSC-affected liver (Cholangiocarcinoma).
- Diagnosis
Non-invasive imaging criteria establish the diagnosis in cirrhosis: in a patient with cirrhosis (or high-risk chronic HBV) and a liver lesion at least 1 cm, demonstration of late arterial-phase…
- Management
Route to a multidisciplinary liver tumor board first, because therapy depends jointly on tumor burden, CTP class, portal hypertension/jaundice, and vascular or extrahepatic spread rather than tumor size alone.
- Complications
Decompensation of underlying cirrhosis: ascites, variceal hemorrhage, hepatic encephalopathy, and jaundice, from tumor burden or progression of the underlying liver disease.
- Prognosis
Stage and liver function jointly determine outcome: early-stage disease treated with resection, ablation, or transplant carries markedly better survival than unresectable or metastatic disease.
- Prevention
Surveillance in cirrhosis, any cause: liver ultrasound with or without AFP every 6 months, continued indefinitely even after successful antiviral therapy for hepatitis C, because risk is reduced but not eliminated by viral cure.
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Related articles
- Cirrhosis
Cirrhosis is end-stage hepatic fibrosis with regenerative nodules, staged as compensated or decompensated by the onset of ascites, variceal hemorrhage, encephalopathy, or jaundice. Severity is graded by Child-Pugh class and MELD, and management centers on treating the underlying cause, surveillance for varices and hepatocellular carcinoma, and timely transplant referral once decompensation appears.
- Hepatitis B virus (HBV) infection
Hepatitis B virus is a bloodborne and sexually transmitted DNA virus that causes acute hepatitis and, when infection becomes chronic, progresses through immune-tolerant, immune-active, immune-control, and reactivation phases toward cirrhosis and hepatocellular carcinoma. Diagnosis rests on hepatitis B serology, chronic infection is treated with entecavir or tenofovir, and reactivation during immunosuppression is prevented with prophylactic antiviral therapy.
- Hepatitis C virus (HCV) infection
Hepatitis C virus is a bloodborne RNA virus, transmitted mainly by injection drug use, that produces mostly asymptomatic acute infection and chronic infection in 60% to 80% of cases. Diagnosis is by HCV antibody followed by HCV RNA, and direct-acting antiviral regimens cure more than 90% of patients, reducing but not eliminating the risk of cirrhosis and hepatocellular carcinoma.
- Metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD)
MASLD (formerly NAFLD) is hepatic steatosis with at least one cardiometabolic risk factor after exclusion of significant alcohol use and other liver disease, and a subset progresses to steatohepatitis (MASH, formerly NASH) with inflammation and fibrosis. Diagnosis rests on imaging-confirmed steatosis plus noninvasive fibrosis risk stratification, and management centers on 7% to 10% weight loss with aggressive treatment of diabetes and dyslipidemia.
- Hemochromatosis
Hemochromatosis is a disorder of iron overload, most often hereditary HFE C282Y homozygosity causing hepcidin deficiency and excess intestinal iron absorption, that deposits iron in the liver, pancreas, heart, joints, skin, and pituitary. Screening rests on fasting transferrin saturation and ferritin, confirmation on HFE genetic testing, and treatment on regular therapeutic phlebotomy to a target ferritin of 50 to 100 ng/mL.