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Differential Effect of Hepatitis B Viral
Suppression on Hepatocellular Carcinoma
Development According to the Phase of Initial
Antiviral Treatment: A Multicenter Study
Young Chang, Jeong-Hoon Lee, Sung Won Chung, Minseok
Albert Kim, Sun Woong Kim, Hyo Young Lee, Jun Sik Yoon,
Yun Bin Lee, Eun Ju Cho, Su Jong Yu, Yoon Jun Kim and
Jung-Hwan Yoon Sr., Department of Internal Medicine and
Liver Research Institute, Seoul National University Hospital
Background: Although antiviral therapy for chronic hepatitis B
virus (HBV) infection reduces risk of hepatocellular carcinoma
(HCC), the risk is reportedly higher in the antiviral-induced
viral suppression than inactive carriers. In this study, we
aimed to compare the effect of the phases when the antiviral
treatment started on the HCC development Methods: This
retrospective study included chronic hepatitis B patients with
suppressed HBV DNA (<2,000 IU/mL) and normal alanine
aminotransferase levels and without evidence of cirrhosis
from eight referral hospitals in Korea. Study subjects were
categorized into four groups: patients underwent antiviral
treatment from immune-tolerant phase (IT group), HBeAgpositive
hepatitis phase (HBeAg+ group), or HBeAg-negative
hepatitis phase (HBeAg- group); or inactive carriers without
any antiviral treatment (IC group). Primary endpoint was an
HCC development. Kaplan-Meier survival analysis and Cox
proportional hazard model were used for statistical analysis.
Results: A total of 887 patients were included: 63 in IT
group, 151 in HBeAg+ group, 365 in HBeAg- group, and 308
in IC group. In univariate analyses, there was no significant
difference in the risk of HCC development between IT group
and IC group (hazard ratio [HR]=0.85, 95% confidence interval
[CI]=0.10–7.15, P=0.98). However, both HBeAg+ (HR=4.01,
95% CI=1.57–10.28, P=0.001) and HBeAg- (HR=3.04, 95%
CI=1.29–7.07, P=0.007) groups showed significantly higher
risk of HCC occurrence. The 5-year risk of HCC occurrence
was 5.6% in IT group, 10.9% in HBeAg+ group, 8.3% in
HBeAg- group, and 1.9% in IC group (Figure 1). In multivariate
analyses, IT group consistently showed similar risk of HCC
development compared to IC group (adjusted HR [aHR]=0.85,
95% CI=0.10–7.15, P=0.88). Both HBeAg+ (aHR=2.91,
95% CI=1.13–7.42, P=0.03) and HBeAg- (aHR=2.48, 95%
CI=1.05–5.85, P=0.04) groups showed significantly higher
risk of HCC development than IC group. Conclusion: Even if
HBV DNA suppression has equally achieved, the risk of HCC
development varies depending on the phase of initial antiviral
therapy. Early antiviral therapy from immune-tolerant phase
is associated with low risk of HCC similar to that of natural
inactive carriers which is significantly lower than the risk of
patients treated from immune-active phases. 作者: StephenW 时间: 2018-10-17 19:02