Surveillance, Diagnosis, and Treatment Outcome of Hepatocellular Carcinoma in Japan: 2023 Update

SurveillanceThe incidence of hepatocellular carcinoma (HCC) increased rapidly in Japan after 1978 (Fig. 1), and most cases were caused by hepatitis C virus infection [1][2][3].The mortality of HCC reached a peak in 2002 and has been declining since then.An HCC surveillance program was implemented in Japan after the rapid increase in incidence in the 1980s.At that time, ultrasound devices switched from contact compound scanning to higherresolution electronic scanning, which enabled detection of small intrahepatic lesions measuring 2 cm, and the Japan Society of Hepatology (JSH) began to promote surveillance of HCC using ultrasonography and measurement of alpha-fetoprotein (AFP) levels.The JSH focused on improving the early diagnosis of HCC by actively recommending HCC surveillance for patients with chronic viral hepatitis and cirrhosis, who are at high risk for HCC, which led to efforts to lobby the Ministry of Health, Labour, and Welfare (MHLW) and hold public information sessions.The latest JSH Clinical Practice Guidelines for the Management of Liver Cancer [4] recommend surveillance by ultrasound examination and measurement of three tumor markers (AFP, Lens culinaris agglutinin-reactive AFP fraction (AFP-L3), and protein induced by vitamin K absence or antagonist II [PIVKA-II]) every 3-4 months for the super-high-risk HCC population (patients with hepatitis viral B-or C-related cirrhosis), as well as optional dynamic computed tomography (CT) or gadolinium ethoxybenzyl diethylene penta-acetic acid-enhanced-magnetic resonance imaging (Gd-EOB-MRI) once or twice a year.The guidelines for the high-risk group (patients with chronic hepatitis C, chronic hepatitis B, and non-viral cirrhosis) include surveillance by ultrasound examination and measurement of three tumor markers once every 6 months.Measurement of the tumor markers PIVKA-II and AFP-L3 became covered by the Japanese National Health Insurance in 1989 and 1996, respectively.This makes Japan the only country in the world where clinicians have been measuring the three tumor markers, AFP, PIVKA-II, and AFP-L3, in routine clinical practice since 1996.