Negligible HCC risk during stringently defined untreated immune-tolerant phase of chronic hepatitis B

Hye Won Lee, Young Eun Chon, Beom Kyung Kim, Terry Cheuk Fung Yip, Yee Kit Tse, Grace Lai Hung Wong, Vincent Wai Sun Wong, Henry Lik Yuen Chan, Sang Hoon Ahn

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


Background & aims: Whether chronic hepatitis B (CHB) patients during immune-tolerant (IT) phase are at low risk of hepatocellular carcinoma (HCC) is still controversial. We performed a multicenter study to determine their long-term prognosis. Methods: Untreated IT group included patients < 40 years of age, with persistently hepatitis B e antigen [HBeAg] positivity, serum HBV-DNA>6 log10IU/mL, and ALT level < 40 U/L, using age and HBV-DNA criteria by the American Association for the Study of Liver Diseases (AASLD) guideline. Cumulative HCC risk of untreated IT group (n=194) was compared to HBeAg-positive patients undergoing antiviral therapy according to the practice and reimbursement guidelines (treated HBeAg[+] group, n=454). Patients with history of cirrhosis or HCC at baseline were excluded. Results: During follow-up (median 62.1 months), HCC did not develop in any patient among untreated IT group, whereas the cumulative probability of HCC at 3, 5, and 9 years in the treated HBeAg(+) group was 0.5%, 0.7%, and 1.3%, respectively (p=0.203). Ninety-seven patients among untreated IT group entered immune-active phase, of whom 86 (88.7%) started antiviral treatment. A high normal ALT level (20–39 U/L) was associated with an increased risk of a phase change, compared to ALT < 20 U/L. After censoring at the time of phase change, the cumulative HCC risk was also not significantly different between two groups (p=0.258). Conclusions: No actual HCC risk during untreated IT phase defined by age and HBV-DNA criteria of the AASLD guideline exists, supporting their diagnostic validity from the perspective of long-term prognosis. Further validation studies are required.

Original languageEnglish
Pages (from-to)68-73
Number of pages6
JournalEuropean Journal of Internal Medicine
Publication statusPublished - 2021 Feb

Bibliographical note

Publisher Copyright:
© 2020

All Science Journal Classification (ASJC) codes

  • Internal Medicine


Dive into the research topics of 'Negligible HCC risk during stringently defined untreated immune-tolerant phase of chronic hepatitis B'. Together they form a unique fingerprint.

Cite this