Time trends of chronic HBV infection over prior decades – A global analysis

Background & Aims

Information on trends in chronic hepatitis B virus (HBV) prevalence across countries is lacking. We studied changes in chronic HBV infection over previous decades by country, and assessed patterns of change between and within WHO-defined regions.

Methods

Based on data from a published systematic review on chronic HBV, we applied a linear model on the logit scale to assess time trends in country-specific prevalence. Estimated HBsAg prevalence in 2000 and relative changes in prevalence over time were evaluated by country and region.

Results

Sufficient data were available for 50 countries, mostly showing reductions in prevalence over time. Various degrees of heterogeneity were observed within regions, with a relatively homogenous pattern in the Eastern Mediterranean region with strong decreases in HBsAg prevalence. Europe showed a mixed pattern: higher and stable chronic HBsAg prevalence in Eastern, and constantly low prevalence in Western Europe. In Africa, some countries demonstrated no change in prevalence; increases were seen in Uganda (odds ratio 1.05 per year; 95% confidence interval 1.04–1.06), Nigeria (1.02; 1.02–1.02), Senegal (1.01; 1.01–1.02), and South Africa (1.02; 1.01–1.02). With some exceptions, country-patterns overlapped among countries of South East Asian and Western Pacific regions, characterized by low-medium HBsAg decreases, most prominent in China and Malaysia.

Conclusions

Most countries experienced decreases in HBsAg prevalence. Dynamics varied, even within regions; decreases occurred mostly before the direct effects of childhood vaccination may have manifested. These findings together with stable and increasing HBsAg prevalence in some countries of Africa and Eastern Europe indicate the need for further tailored country-specific prevention.

Lay summary

This study investigated time trends in prevalence of chronic HBV infection in 50 countries worldwide over the last decade, by estimating relative changes in prevalence. Results show decreases in chronic HBV infection in most countries; no changes or increases in prevalence are noted in some African countries. Reasons for time changes need to be investigated further; based on the results, various prevention measures have contributed to reductions, and further tailored HBV prevention is required to combat the disease on a global level.

Introduction

Hepatitis B virus (HBV) infection leads to one of the most common chronic viral infections and, together with hepatitis C Virus infection, has been estimated to be responsible for 73% of primary liver cancer deaths worldwide [1]. In serological surveys, chronic HBV infection is indicated by the sero-prevalence of the hepatitis B surface antigen (HBsAg). A recent analysis revealed that 3.6% of the general population worldwide is chronically infected with the virus but endemicity is heterogenous both across and within regions; defined according to the World Health Organization (WHO) [2]. For example, prevalence in the WHO European region was estimated to be 2.1%, ranging from estimated 0.01% in the United Kingdom to 10.3% in Kyrgyzstan. Prevalence levels of 10% and above persist in some African countries and point towards a remaining requirement for HBV prevention. In light of the availability of an effective preventive vaccine against HBV [3], [4], the strong potential for reduction of HBV infection or its eradication is particularly obvious. Time changes in HBV infection on a population level have frequently been assessed based on newly diagnosed cases of HBV or acute viral hepatitis infection [5], [6], [7], [8], [9]. These data can be prone to changes in case definitions and reporting, which vary by time and country. Furthermore, they primarily capture only symptomatic HBV infections. In contrast, specific sero-prevalence assessments of chronic HBV infection have mostly been integrated into population-based surveys, e.g., the Taiwanese survey on prevalence of hyperglycemia, hyperlipidemia and hypertension [10], or were conducted using stored samples from surveys conducted for other purposes e.g., [11]. Some countries conduct nationwide repeated and representative surveys, which include HBV sero-markers and which evaluate changes in age-specific and age-standardized chronic HBV infection prevalence over survey years. Results mostly indicate decreases in overall HBV prevalence over the last decades, however, there are differential effects according to age-groups: the Korean national health and nutrition examination survey, for example, showed marked declines in HBsAg prevalence between 1998 and 2010 in age-groups below 50 years. In contrast, no decrease occurred in participants aged 50 years and older [12]. Similarly, the Chinese national viral hepatitis survey demonstrated decreases in HBsAg from 1979 to 2006, which appeared to be most prominent in children below 15 years of age [13]. In Singapore, HBsAg dropped between 1999 and 2005 among 18 to 69-year-old individuals [11].

According to our knowledge, no global assessment of country-specific changes in HBV prevalence has been available up to now. Our aim was to investigate time trends of chronic HBV infection by country, and to assess whether specific patterns exist within WHO-defined world regions.