Negligible HCC risk during stringently defined untreated immune-tolerant phase of chronic hepatitis B
Authors
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
Citation
EUROPEAN JOURNAL OF INTERNAL MEDICINE, Vol.84 : 68-73, 2021-02
Antiviral Agents / therapeutic use ; Carcinoma, Hepatocellular* / epidemiology ; DNA, Viral ; Hepatitis B e Antigens ; Hepatitis B virus / genetics ; Hepatitis B, Chronic* / complications ; Hepatitis B, Chronic* / drug therapy ; Hepatitis B, Chronic* / epidemiology ; Humans ; Liver Neoplasms* / epidemiology
Keywords
Antiviral therapy ; Hepatitis B e antigen ; Hepatitis B virus ; Hepatocellular carcinoma ; Immune-tolerant
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.