Highlights
- •The definition of immune-tolerant phase of chronic hepatitis B and their prognosis is controversial.
- •Some studies suggest that early antiviral treatment are required for patients with immune-tolerant phase, but not others.
- •In this multi-center study from the East Asia, we used stringent criteria to define the genuine immune-tolerant phase with both age < 40 years and HBV DNA > 6 log10 IU/mL.
- •The risk of hepatocellular carcinoma development during the untreated immune-tolerant phase is negligible.
Abstract
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.
Keywords
Abbreviations:
CHB (chronic hepatitis B), HBV (hepatitis B virus), NUCs (nucleos(t)ide analogues), IT phase (immune-tolerant phase), EASL (European Association for the Study of Liver Diseases), ALT (alanine aminotransferase), AVT (antiviral therapy), HBeAg (hepatitis B e antigen), HCC (hepatocellular carcinoma), PT INR (prothrombin time international normalized ratio), CDARS (Clinical Data Analysis and Reporting System), ULN (upper limit of normal), HBsAg (hepatitis B surface antigen), HRs (hazard ratios), 95% CIs (95% confidence intervals), AASLD (American Association for the Study of Liver Diseases)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: December 04, 2020
Accepted:
October 26,
2020
Received in revised form:
October 3,
2020
Received:
August 14,
2020
Identification
Copyright
© 2020 Published by Elsevier B.V. on behalf of European Federation of Internal Medicine.
