COMPARABLE OUTCOMES BETWEEN IMMUNE-TOLERANT AND ACTIVE PHASES IN NON-CIRRHOTIC CHRONIC HEPATITIS B: A META-ANALYSIS

초록

Background: Antiviral therapy is not indicated for patients with chronic hepatitis B (CHB) in the immune-tolerant (IT) phase. We compared the outcomes between the untreated IT phase and the treated immune-active (IA) phase in non-cirrhotic hepatitis B e antigen (HBeAg)-positive CHB patients. Methods: We systematically searched four databases, including PubMed, Medline, Embase, and Cochrane, until August 2021. The pooled incidence rates of hepatocellular carcinoma (HCC) and mortality in the IT and IA cohorts and phase change in the IT cohort were investigated. Studies that included patients with liver cirrhosis were excluded. Results: Thirteen studies involving 11,903 patients were included. The overall median of the median follow-up period was 62.4 months (range, 24.0–103.0 months). he median of median age was 40.0 years (range, 29.0–53.5 years), and the prevalence of male sex was 59.6% (range, 31.8%–68.9%). The pooled 5- and 10-year incidence rates of HCC were statistically similar between the IT and IA cohorts (1.1% [95% confidence interval (CI), 0.4%–2.8%] vs. 1.1% [95% CI, 0.5%–2.3%] and 2.7% [95% CI, 1.0%–7.3%] vs. 3.6% [95% CI, 2.4%–5.5%], respectively, all P >0.05). The pooled 5-year odds ratio of HCC between IT and IA cohorts was 1.05 (95% CI, 0.32–3.45; P=0.941). The pooled 5-year incidence rate of mortality was statistically similar between the IT and IA cohorts (1.9% [95% CI, 1.1%–3.4%] vs. 1.0% [95% CI, 0.3%–2.9%], P=0.285). Finally, the pooled 5-year incidence rate of phase change in the IT cohort was 36.1% (95% CI, 29.5%–43.2%). Conclusion: The pooled incidence rates of HCC and mortality were comparable between untreated IT and treated IA phases in non-cirrhotic HBeAg-positive CHB patients in this meta-analysis, supporting the timely initiation of AVT during the disease course of CHB. In addition, we found that the pooled incidence of a phase change from IT to IA requiring AVT was not negligible, which might necessitate close monitoring during the IT phase. Further studies are warranted to define the more stringent criteria for the IT phase.