Hepatocellular Carcinoma

Epidemiology and Etiology

An estimated 42,810 patients will be diagnosed with liver and intrahepatic bile duct tumors in 2020 in the US.¹ The main risk factors include chronic viral hepatitis B or C and alcohol abuse.

Screening

Patients at high-risk for developing HCC are candidates for screening, including those with cirrhosis, chronic hepatitis B, or a family history of HCC. Screening is performed most commonly using abdominal ultrasonography every 6 months with or without #945;-fetoprotein (AFP). However, the use of AFP alone is not recommended owing to poor sensitivity and specificity.

Clinical Presentation

Patients may be asymptomatic at presentation. Those with more advanced disease may have abdominal pain, early satiety, weight loss, hepatomegaly, ascites, and jaundice. Several paraneoplastic syndromes may occur, including hypoglycemia, erythrocytosis, or hypercalcemia. HCC should also be suspected in patients with stable cirrhosis who decompensate rapidly.

Diagnostic Testing

Lesions lt;1 cm should be followed with repeated abdominal ultrasound in 3-4 months. For lesions #8805;1 cm, workup includes contrast-enhanced CT or MRI. Since the malignant lesions are supplied by the hepatic artery, whereas the benign nodules are supplied by branches of the portal system, the pattern of hyperenhancement during the arterial phase of contrast administration with washout in the venous or delayed phases (malignant lesion brighter than the surrounding parenchyma in the arterial phase and less bright in the venous phase) is considered the radiologic hallmark of HCC, with a sensitivity of approximately 70% and specificity of more than 90% in patients with cirrhosis. Patients with this radiological finding do not need a biopsy to confirm the diagnosis.

Staging

The most commonly used staging system is the Barcelona Clinic Liver Clinic algorithm, which classifies HCC into one of five stages based on liver function, Eastern Cooperative Oncology Group (ECOG) performance status (PS), and tumor burden, which is often used in combination with the Child-Pugh score to define the optimal treatment plan.¹⁸

TREATMENT

• Treatment options include surgery in patients with early stage disease (single nodule lt;2 cm), good performance status (ECOG 0), and preserved liver function (Child-Pugh A). Patients with cirrhosis and limited tumor burden, defined by the Milan criteria as the presence of single lesion #8804;5 cm or up to three lesions #8804;3 cm without vascular invasion, may be candidates for liver transplant. Tumor ablation or transarterial therapy, mostly with transarterial chemoembolization may be used to downstage the tumor or prevent tumor progression while on the waiting list.

• Cytotoxic chemotherapy has limited efficacy in HCC. The main systemic therapy options include multitarget TKIs (sorafenib, lenvatinib, regorafenib, or cabozantinib), ramucirumab, or ICIs plus bevacizumab or ramucirumab, with the latter indicated for AFP #8805;400 ng/mL. Nivolumab alone is approved for patients with HCC progressing on sorafenib.^18,19