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Review
. 2023 Jul;29(3):605-622.
doi: 10.3350/cmh.2022.0342. Epub 2023 Feb 15.

Development of hepatocellular carcinoma in treated and untreated patients with chronic hepatitis B virus infection

Chih-Lin Lin  1   2 , Jia-Horng Kao  3   4   5   6
Affiliations
Review

Development of hepatocellular carcinoma in treated and untreated patients with chronic hepatitis B virus infection

Chih-Lin Lin et al. Clin Mol Hepatol. 2023 Jul.

Abstract

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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Conflict of interest statement

Conflicts of Interest

The authors have no conflicts to disclose.

Figures

Figure 1.
Figure 1.
. Serum biomarkers for the management of patients with chronic hepatitis B. AFP, α-fetoprotein; AFP-L3, lectin-bound AFP; DCP, desgamma carboxy-prothrombin; ELF, enhanced liver fibrosis score; HBcrAg, hepatitis B core-related antigen; HCC, hepatocellular carcinoma; M2BPGi, mac-2 binding protein glycosylation isomer; HBV, hepatitis B virus.
Figure 2.
Figure 2.
Hepatocellular carcinoma risk stratification of untreated HBeAg-negative chronic hepatitis B patients by HBV DNA, HBsAg and HBcrAg. HBcrAg, hepatitis B core-related antigen; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; ALT, alanine aminotransferase; HCC, hepatocellular carcinoma.
Figure 3.
Figure 3.
Strategies for management of hepatitis B virus–related hepatocellular carcinoma. AFP, α-fetoprotein; AFP-L3, lectin-bound AFP; DCP, des-gamma carboxy-prothrombin; ELF, enhanced liver fibrosis score; HBcrAg, hepatitis B core-related antigen; HBsAg, hepatitis B surface antigen; HCC, hepatocellular carcinoma; M2BPGi, Mac2 binding protein glycosylation isomer; FIB-4, fibrosis-4.
See this image and copyright information in PMC

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MeSH terms