Hepatocellular Carcinoma

Liver cancer arising in the setting of chronic liver disease — surveillance, imaging diagnosis, BCLC staging, and stage-adapted treatment from resection to systemic therapy

Key Points

• HCC is the most common primary liver cancer and the third leading cause of cancer-related death globally; >90% arise in the setting of chronic liver disease or cirrhosis.
• Major risk factors include hepatitis B (HBV), hepatitis C (HCV), alcohol-related liver disease, metabolic dysfunction-associated steatotic liver disease (MASLD/NAFLD), and aflatoxin B1 exposure.
• Surveillance with liver ultrasound ± AFP every 6 months is recommended for all cirrhotic patients and HBV carriers at elevated risk.
• HCC is unique in that diagnosis can be established radiologically (LI-RADS 5) without biopsy in patients with cirrhosis and a characteristic imaging pattern on CT or MRI.
• The Barcelona Clinic Liver Cancer (BCLC) system integrates tumor burden, liver function (Child-Pugh class), and performance status to guide treatment allocation.
• Curative options — resection, ablation, and liver transplantation (with Milan criteria) — are available for early-stage disease.
• Atezolizumab + bevacizumab (IMbrave150) is the first-line standard of care for advanced HCC, with durvalumab + tremelimumab (HIMALAYA) as an alternative.

Epidemiology & Risk Factors

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, accounting for ~75–85% of primary liver cancers. Globally, it is the sixth most frequently diagnosed cancer and the third leading cause of cancer mortality, with approximately 906,000 new cases and 830,000 deaths annually. Incidence is highest in sub-Saharan Africa and East Asia, regions with endemic hepatitis B infection. In the United States, HCC incidence has nearly tripled over the past four decades, now accounting for ~41,000 new cases per year, largely driven by the hepatitis C epidemic and rising rates of…

Surveillance & Diagnosis

Early detection through surveillance is essential because HCC is highly stage-dependent in prognosis and treatment options. Major guidelines (AASLD, EASL, APASL) recommend semiannual ultrasound ± serum AFP for all patients with cirrhosis regardless of etiology, and for non-cirrhotic HBV carriers who are Asian men >40 years, Asian women >50, Africans >20, or those with family history of HCC. Ultrasound has a sensitivity of ~63% and specificity >90% for HCC detection in cirrhosis. AFP >20 ng/mL is abnormal; levels >200 ng/mL or a rising AFP in a cirrhotic patient are highly suspicious. AFP-L3…

Staging: The BCLC System

Unlike most solid tumors, HCC staging must integrate tumor burden, liver function, and patient performance status — because liver dysfunction often limits treatment options independent of tumor stage. The Barcelona Clinic Liver Cancer (BCLC) system is the most widely validated and endorsed staging framework. BCLC Stage 0 (Very early): Single tumor 70% with curative treatment. BCLC Stage A (Early): Single tumor of any size OR 2–3 nodules, all ≤3 cm; Child-Pugh A–B; PS 0. Candidates for curative therapy (resection, ablation, transplant). 5-year survival 50–75%. BCLC Stage B (Intermediate):…

Curative Treatment: Resection, Ablation & Transplantation

Curative-intent treatment is feasible for BCLC 0–A patients with preserved liver function. Surgical Resection: Hepatic resection is the first-line curative option for non-cirrhotic patients or selected cirrhotic patients with very preserved liver function (Child-Pugh A, low portal hypertension) and adequate future liver remnant (FLR). Resection is associated with 5-year survival of 40–70%. Major risks include post-hepatectomy liver failure; portal hypertension (hepatic venous pressure gradient >10 mmHg) predicts poor outcomes. Portal vein embolization (PVE) can be used to induce FLR…

Locoregional Therapy for Intermediate-Stage HCC

BCLC Stage B (multinodular, no vascular invasion or extrahepatic spread, preserved liver function) is the primary indication for transarterial therapies, which exploit the predominantly arterial blood supply of HCC compared to the portal-dominant supply of normal hepatocytes. Transarterial Chemoembolization (TACE): TACE delivers chemotherapy (typically doxorubicin or cisplatin emulsified in lipiodol) directly into the hepatic artery feeding the tumor, combined with embolic agents to occlude arterial flow — creating ischemia and localized drug delivery. Conventional TACE (cTACE) and…

Systemic Therapy for Advanced HCC

BCLC Stage C (vascular invasion or extrahepatic spread) or BCLC B HCC refractory/ineligible for locoregional therapy is the domain of systemic treatment. The landscape transformed dramatically from 2020 onwards with the approval of immunotherapy combinations. First-Line Therapy: • Atezolizumab + bevacizumab (IMbrave150): The current preferred first-line regimen for advanced HCC with Child-Pugh A liver function and ECOG PS 0–1. The IMbrave150 trial (NEJM 2020) showed significantly superior OS (19.2 vs. 13.4 months) and PFS vs. sorafenib, with an ORR of 30%. Contraindicated in patients with…