Comparable risk of hepatocellular carcinoma between immune-tolerant and active phase in hepatitis B e antigen-positive patients

Abstract

Background and aims: Antiviral therapy is not indicated for patients with chronic hepatitis B (CHB) in the immune-tolerant (IT) phase. We compared the treatment outcomes between untreated IT-phase and treated immune-active (IA) phase in patients with CHB.

Method: We systematically searched four databases including Pubmed, Medline, Embase, and Cochrane database until August, 2021. The cumulative incidence of hepatocellular carcinoma (HCC) and mortality in IT and IA cohorts and that of CHB phase change in IT cohort was investigated. Studies regarding patients who have clinically or pathologically diagnosed liver cirrhosis were excluded. Random effects model was used for pooled analyses. The study adhered PRISMA and referenced Cochrane handbook v6.2 for methodologic regards.

Results: A total of 13 studies involving 19 cohorts, including 11, 903 patients were included. Quantitative quality assessment was performed and five and eight studies were regarded to have high and moderate quality; therefore none of 13 studies were dropped from formal analysis for quality issue. The overall median of median follow-up period was 62.4 months, (range: 51–103 months). The overall median value of median age was 40 (range: 29–53.5), and proportion of male was 59.6% (31.8–68.9). Possible publication bias was noted in pooled analyses of 5- (Egger’s test p = 0.082) and 10-year HCC incidence (Egger’s test p = 0.019). The pooled HCC incidence rate at 5-years was 1.1% (95% confidence interval [CI]: 0.6–2.0%) in all cohorts. No statistical difference in HCC incidence rate at 5-years was observed between IT [1.1% (95% CI, 0.4–2.8%)] and IA cohorts [1.1% (95% CI, 0.5–2.3%) ( p = 0.976). The pooled odds ratio of comparative series between IT and IA cohorts was 1.05 (95% CI, 0.32–3.45; p = 0.941). Pooled HCC incidence rate at 10-years was 3.5% (95% CI, 2.4–5.1%) in all cohorts. No statistical difference in HCC incidence rate at 10-years was observed between IT [2.7% (95% CI, 1.0–7.3%)] and IA cohorts [3.6% (95% CI, 2.4–5.5%)] ( p = 0.587). No statistical difference in pooled mortality rates at 5-years was observed between IT [1.9% (95% CI, 1.1–3.4%)] and IA cohorts [1.0% (95% CI, 0.3–2.9%)] ( p = 0.285). Finally, pooled incidence rate of CHB phase change in IT cohort was 36.1% at 5 years (95% CI, 29.5–43.2%).

Conclusion: The long-term risks of HCC and mortality were similar between the IT and IA phase. However, various definitions of CHB phase in different studies have to be considered.