Hepatocellular Carcinoma

CLINICAL FEATURES AND NATURAL HISTORYTop

Hepatocellular carcinoma (HCC) originates from hepatocytes and is considered the most common primary liver cancer. Conditions predisposing to HCC include chronic hepatitis B and C, cirrhosis, congenital metabolic diseases (hereditary hemochromatosis, late cutaneous porphyria), nonalcoholic fatty liver disease (NAFLD), and nonalcoholic steatohepatitis (NASH). Most patients have a history of chronic liver injury. The classic form of HCC in an intact liver is rare; either sporadic or fibrolamellar carcinoma variants are most common, which develop mainly in young people (aged 20-30 years). The early form of HCC is diagnosed during screening in patients with cirrhosis (see Diagnosis, below).

Symptoms of advanced cancer: Progressive wasting, abdominal pain, enlarged abdominal circumference (ascites), lower limb edema, jaundice, fever. HCC may cause hemorrhage into the peritoneal cavity or inside the tumor.

DIAGNOSISTop

Diagnostic Tests

1. Blood tests: Abnormalities found in cirrhosis; increased concentration of alpha-fetoprotein (AFP; values >200 ng/mL are specific for HCC but not very sensitive). AFP for screening should not be used in isolation and should be coupled with imaging.

2. Imaging:

1) Ultrasonography and computed tomography (CT): see Table 1 in Hepatic Tumors.

2) Magnetic resonance imaging (MRI) has a very high sensitivity in detecting and differentiating HCC and determining disease stage.

3. Liver biopsy to confirm the diagnosis, in case of diagnostic uncertainty before treatment or in the absence of cirrhosis.

Diagnostic Criteria

Diagnosis is made based on imaging findings (CT or MRI), when the focus is >1 cm, and in the setting of an underlying liver disease; if the focus is ≥1 in noncirrhotic liver or does not meet the imaging criteria, additional histologic examination may be considered in addition to short-interval CT or MRI scans.

Screening

An ultrasound scan is recommended every 6 months, with or without AFP measurement, in the following groups:

1) Patients with cirrhosis in performance class A or B according to the Child-Pugh score (and in patients in class C who are qualified for liver transplant): see Table 1 in Hepatic Tumors.

2) Patients with chronic hepatitis B.

3) Patients without cirrhosis but with severe (stage 3 [F3]) fibrosis, regardless of its etiology.

4) If a lesion <1 cm is found, it is advisable to repeat ultrasonography (with or without AFP marking) in 3 to 6 months, and if the lesion is ≥1 cm, to perform imaging tests with contrast (see above).

Differential Diagnosis

Focal lesions in the liver: Adenoma, metastatic tumors, cancer of the intrahepatic bile ducts, focal nodular hyperplasia.

TREATMENTTop

Treatment is generally guided by the Barcelona Clinic Liver Cancer (BCLC) 2022 Guidelines, with radical treatment being possible in a minority of patients (5%-35%).

1. Liver resection is considered optimal treatment. In patients with chronic liver injury, surgery is possible only in those in Child-Pugh class A, when the tumor size criteria are met (a single HCC focus or ≤3 HCC lesions, each ≤3 cm) and there is no evidence of extrahepatic dissemination and macrovascular hepatic invasion: See Table 1 in Hepatic Tumors.

2. Liver transplant: In patients with cirrhosis who meet the Milan criteria (a single HCC lesion ≤5 cm in diameter or ≤3 lesions ≤3 cm each), University of California San Francisco (UCSF) criteria (a single lesion ≤6.5 cm or 2-3 lesions ≤4.5 cm, with the sum of the diameters of all lesions ≤8 cm), or Extended Toronto Criteria (no size restriction, biopsy of the largest tumor required, poorly differentiated tumors excluded).

3. Systemic treatment: In patients with HCC who are not eligible for surgery or with disease progression after such treatment, consider using sorafenib, regorafenib, lenvatinib, or nivolumab if the liver is healthy; the effectiveness of traditional chemotherapy is very low.

4. Other invasive treatment techniques (usually used if surgery is not feasible or as a bridge to transplant): Thermal ablation (using radiofrequency or microwave radiation), transarterial chemoembolization (TACE), cryoablation or injection of alcohol into the tumor (very rarely used), a focused beam of ionizing radiation (eg, CyberKnife device), irreversible electroporation (NanoKnife device), and radioembolization (SIRT, TARE/Y90).

PROGNOSISTop

After liver resection, the 5-year survival rate is 30% to 50%, and after liver transplant, the 5-year survival rate is up to 80%, 10-year survival—60%, and 20-year survival—30%.