Global Prevalence of Occult Hepatitis B: A Systematic Review and Meta-analysis

A Systematic Review and Meta-Analysis

Dong-Ze Ji; Xiao-Yu Pang; Dan-Ting Shen; Shu-Na Liu; Hemant Goyal; Hua-Guo Xu


J Viral Hepat. 2022;29(5):317-329. 

In This Article

Abstract and Introduction


The study aimed to investigate the prevalence and risk factors associated with occult hepatitis B virus (HBV) infection (OBI) in the global population. We searched PubMed, Embase, CINAHL, Cochrane and Web of Science from database inception through 27 Dec, 2018. Studies reporting HBV-DNA serological data in previously undiagnosed hepatitis B patients were included. The data were further categorized according to the presence of risk factors. After an initial screening of 2,325 records, we finally included 98 articles about the prevalence of OBI from 34 countries and regions. The OBI prevalence was 0.82% (95% CI:0.69–0.96) in the general population, 16.26% (95% CI:10.97–22.34) in HIV patients, 13.99% (95% CI:8.33–20.79) in patients with other liver diseases, 4.25% (95% CI:1.64–7.87) in haemodialysis patients and 5.14% (95% CI:2.26–9.01) patients with other risk factors. In conclusion, OBI prevalence varies significantly across different populations and nations, which deserve attention from the public health authorities. Our results generate further epidemiological data to identify the population with OBI, which has important clinical implications in finding these high-risk populations to design preventive and management strategies.


Hepatitis B (HepB) is an international public health challenge, which can lead to progressive scarring of the liver and primary liver cancer, accounting for the majority of the burden from viral hepatitis.[1] An estimated 257 million people are living with chronic hepatitis B virus (HBV) infection around the world.[2] In 2016, epidemiological statistics showed that acute and chronic HepB-related deaths reached 100.3 (94.0–106.3) thousands.[3]

Occult/undiagnosed HBV infection (OBI) is defined as the presence of replication-competent HBV-DNA in the liver and/or serum of HepB surface antigen (HBsAg) negative individuals.[4] Stability and long-lasting persistence of HBV cccDNA in the nuclei of hepatocytes represent the molecular basis of occult HepB infection (OBI).[5] However, OBI can be transmitted via blood transfusion or organ transplantation.[6] Moreover, OBI individuals can experience reactivation of HBV replication when receiving chemotherapeutic agents or other immunosuppressive agents.[7,8] Because of the above reasons, it is crucial to evaluate the epidemiological trends of OBI.

Studies have shown that OBI prevalence varies significantly worldwide across different populations. A meta-analysis in Western Europe and in North American population revealed that the overall OBI prevalence was 34%, and the prevalence in patients with or without chronic liver disease was 35% and 28%.[9] However, data on the OBI prevalence of the global population are non-existent. Therefore, we performed a systematic search and meta-analysis to determine the global OBI prevalence while presenting the estimates of individual country-level data and risk factors associated with OBI.