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Occult HBV Infections Need Focus in Global Hepatitis Elimination Pursuit

Occult HBV infection prevalence in blood donors was 0.06% in low-endemicity countries, 0.12% in intermediate-endemicity countries, and 0.98% in high-endemicity countries.

As countries around the world continue to attempt to eliminate hepatitis C virus (HCV) infections in the next decade, there is not enough attention paid to occult hepatitis B virus (HBV) infections.

A team, led by Yu Ri Im, MBBChir, Section of Hepatology, Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Imperial College London, estimated the prevalence of occult HBV infections at a global and regional scale and in specific populations.


There are growing concerns over the transmissibility and clinical impact of occult HBV infections. Despite this, it has received little attention in regard to the ongoing effort to eliminate hepatitis.

“Despite an increasing number of occult HBV infection studies, the worldwide prevalence patterns of occult HBV infection remain unknown and its clinical relevance has been controversial,” the authors wrote.

In the systematic review and meta-analysis, the investigators looked at various databases for original articles and conference abstracts of any study design that reported the proportion of HBsAg-negative adults who are positive for HBV DNA published between January 1, 2010 and August 14, 2019.

They then pooled the prevalence of occult HBV infections using the DerSimonian-Laird random-effects model. They did so in the general population and specific groups defined by the type of study participants (blood donors; other low-risk populations; high-risk populations; and people with advanced chronic liver disease) and stratified by HBV endemicity in each country.

The team finally assessed the performance of anti-HBc as an alternative biomarker to detect occult HBV infection.

Assessing the Data

The final analysis included 305 of the 3962 articles identified, involving 140,521,993 individuals tested for HBV DNA.

However, there were only 2 studies evaluating occult HBV infections in the general population, precluding unbiased global and regional estimates of occult HBV infection prevalence.

Occult HBV infection prevalence in blood donors was 0.06% (95% CI, 0.00-0.26) in low-endemicity countries, 0.12% (95% CI, 0.04–0.23) in intermediate-endemicity countries, and 0.98% (95% CI, 0.44–1.72) in high-endemicity countries (P = 0.0012).

For high risk groups, occult HBV infection prevalence was substantial, irrelevant of endemicity.

The prevalence was 5.5% (95% CI, 2.9–8.7) in low-endemicity countries, 5.2% (95% CI, 2.5–8.6) in intermediate-endemicity countries, and 12.0% (95% CI, 3.4–24.7) in high-endemicity countries.

The pooled sensitivity of anti-HBc to identify occult HBV infection was 77% (95% CI, 62–88) with a specificity of 76% (95% CI, 68–83).

“A substantial proportion of people carry occult HBV infection, especially among high-risk groups across the globe and people living in highly endemic countries,” the authors wrote. “Occult HBV infection should be part of the global viral hepatitis elimination strategy.”

In 2019, an estimated 296 million people were chronically infected with HBV and more than 820 000 HBV-related deaths occurred worldwide.

The study, “Prevalence of occult hepatitis B virus infection in adults: a systematic review and meta-analysis,” was published online in The Lancet Gastroenterology & Hepatology.