Clin Mol Hepatol > Epub ahead of print
Development of hepatocellular carcinoma in treated and untreated patients with chronic hepatitis B virus infection
Chih-Lin Lin1,2, Jia-Horng Kao3,4,5,6
1Department of Gastroenterology, Renai branch, Taipei City Hospital, Taipei, Taiwan
2Department of Psychology, National Chengchi University, Taipei, Taiwan
3Graduate Institute of Clinical Medicine, National Taiwan University, College of Medicine, Taipei, Taiwan
4Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
5Hepatitis Research Center, National Taiwan University, National Taiwan University Hospital, Taipei, Taiwan
6Department of Medical Research, National Taiwan University, National Taiwan University Hospital, Taipei, Taiwan
Correspondence :  Jia-Horng Kao ,
Tel: +886-2-23123456 ext. 67307, Fax: +886-2-23825962, Email: kaojh@
Received: October 31, 2022  Revised: January 2, 2023   Accepted: February 12, 2023
Hepatitis B virus (HBV) is responsible for more than 50% of hepatocellular carcinoma (HCC) in HBV hyperendemic areas, such as the Asia-Pacific region. Several hepatitis B viral factors are involved in HBV-related hepatocarcinogenesis. Hepatitis B viral load is the most important risk factor of HCC development. In addition, HBV integration, HBV genotype C, and core-promoter mutations are also associated with a risk of HCC development. For untreated chronic hepatitis B (CHB) patients, the estimated HCC incidence rates per 100 patient-years were 0.03–0.17 in inactive carriers, 0.07–0.42 in asymptomatic carriers, 0.12–0.49 in chronic hepatitis, and 2.03–3.37 in cirrhosis. Complementary to HBV DNA, serum levels of the hepatitis B surface antigen and hepatitis B core-related antigen (HBcrAg) can predict the occurrence of HCC for untreated patients with low and intermediate viral loads, respectively. For patients receiving antiviral therapy, the risks of HCC occurrence 40–60% lower than those for untreated patients. Patients treated with residual detectable HBV DNA or intrahepatic cccDNA still have a risk of HCC. Serum levels of HBcrAg, M2BPGi and fibrosis-4 are predictive of the risk of HCC development in treated patients. Several well-developed HCC risk scores can help clinicians identify high-risk CHB patients for HCC surveillance, regardless of treatment status. These strategies can help minimize the threat of HCC and prolong survival in CHB patients.
KeyWords: Chronic hepatitis B; Cirrhosis; Hepatocellular carcinoma

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