Prevalence, Clinical Presentation and Outcome of Hepatitis B Patients With Indeterminate Phase: A Systematic Review and Meta‐Analysis

Although current guidelines classify the natural history of chronic hepatitis B (CHB) into several immune phases, a substantial proportion of patients with CHB do not meet criteria for any of the defined immune phases and are considered to be in an indeterminate phase. We aim to perform a meta-analysis to systematically evaluate the prevalence, clinical presentation and outcome of indeterminate CHB patients classified according to American Association for the Study of Liver Diseases (AASLD) 2018 guidelines or European Association for the Study of the Liver (EASL) 2017 guidelines. We searched four databases from inception to Aug 21, 2024, for studies reporting the prevalence, characteristics and/or clinical outcomes of patients with indeterminate CHB classified according to AASLD 2018 guidelines or EASL 2017 guidelines. Of the 4553 studies initially identified, 50 studies met study inclusion criteria and were analysed. The prevalence of indeterminate patients was 38.90% (95% CI: 33.51-44.57) and 38.81% (95% CI: 31.22-46.99) by AASLD 2018 and EASL 2017 guidelines, respectively. Among indeterminate CHB patients, the pooled incidence rate per 1000 person-years for hepatocellular carcinoma and liver-related events was 5.36 (95% CI: 1.38-9.35) and 7.27 (95% CI: 0.00-22.21) per AASLD 2018 guidelines and 5.20 (95% CI: 1.41-8.99) and 9.79 (95% CI: 0.00-25.35) per EASL 2017 guidelines, respectively. Indeterminate phase affects nearly 40% of CHB patients who are at risk for hepatocellular carcinoma and liver-related adverse outcomes. Further research is needed to inform treatment strategies specifically tailored for the indeterminate CHB patients.