Chapter 17: Native and Recurrent Hepatocellular Carcinoma

INCIDENCE

• Hepatocellular carcinoma (HCC) incidence varies from 3 per 100,000 in Western countries to as high as 15 per 100,000 in countries with high hepatitis B virus (HBV) and hepatitis C virus (HCV) incidence.

• HCC incidence is steadily increasing.

• HCC is the sixth most common cancer and third cause of cancer-related death worldwide.

EPIDEMIOLOGY

• Strong male preponderance (∼4:1).

• Most common in aging populations and in areas with high hepatitis incidence.

• Related to limited resources.

• Heavy alcohol drinking, consumption of aflatoxin, and tobacco smoking are associated with HCC.

• Familial aggregation of liver cancer has been reported.

SURVEILLANCE

• Surveillance aims for a reduction in mortality of this patient population and involves the repeated application of screening tools in patients at risk for HCC.

• The availability of efficient diagnostic tests and treatment options results in successful surveillance.

• Surveillance is necessary in the following patient groups:

  • Cirrhotic patients

  • HBV carriers with serum viral load >10,000 copies/mL or family history of HCC

  • Asian HBV carriers (>40 years old for males, >50 years old for females)

  • Africans or African Americans with HBV

  • Genetic hemochromatosis and cirrhosis

  • Alpha 1-antitrypsin deficiency and cirrhosis

  • HCV-infected patients with fibrosis, even after achieving sustained virologic response following treatment

• Surveillance by abdominal ultrasound resulted in an average size of the detected tumors of 1.6 ± 0.6 cm, with <2% of the cases exceeding 3 cm. In the Western world and in less experienced centers, sensitivity of finding early-stage HCC by ultrasound is considerably less effective.

• No data exist to support the use of contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) for surveillance.

• Some centers utilize the determination of serum alpha-fetoprotein (AFP) along with ultrasound to gain 6% to 8% in the tumor detection rate, but at the price of false-positive results.

• Surveillance of patients at risk for HCC should be carried out every 6 months, and ultrasound is considered the modality of choice.

MOLECULAR INFORMATION

• HCV genotype 1b is claimed to increase the risk of HCC development.

• Several chromosomal aberrations have been reported, for example, amplification of 1q, 8q, 6p, and 17q or loss of 8p, 16q, 4q, 17p, and 13q.

• Loss of 4q has been correlated with more aggressive HCC phenotype.

• Some evidence suggests that the Wnt developmental pathway plays a role in HCC pathogenesis.

• Aberrant expression of several microRNAs has been implicated in HCC carcinogenesis.

• Single nucleotide polymorphisms (SNPs) and haplotypes located in the SCBY14, CRHR2, and GFRA1 genes are identified in patients with HCV infection; further revalidation is required, though.

• GSTM1 and GSTT1 null genotype carriers show slightly higher HCC incidence; further revalidation is required, though.

• Cirrhotic patients with a G/G genotype for the EGF gene have a 4-fold chance of developing HCC; therefore, EGF signaling might be a potential target for chemoprevention.

• No validated biomarker can be used as a prognostic method ...