Distribution of hepatitis B virus genotypes and subgenotypes: A meta-analysis

Abstract

Hepatitis B virus (HBV) genotypes and subgenotypes have distinct geographical distributions and influence a number of clinical disease features and responses to treatment. There are many reports on the distribution of HBV genotypes, but great differences are present between studies. What's more, a meta-analysis of HBV genotype- and subgenotype-distribution by country is lacking.A comprehensive literature search was performed in PubMed and a systematic search of full-length HBV sequences and S gene sequences was conducted in the GenBank database. HBV genotypes were checked and subgenotypes were determined by phylogenetic comparison of full-length HBV sequences or S gene sequences. STATA 12.0 was used for the analysis for countries with multiple datasets. BEAST 2.5.2 was used for Bayesian phylogenetic analysis to infer the evolutionary time scales of HBV.This study includes 309 datasets from 110 countries, including 188 relevant studies, 58 full-length gene datasets, and 63 S gene datasets. The meta-analysis was performed on 274 datasets from 75 countries. The distribution of genotypes is more detailed than those described by previous studies. While the overall genotype distribution is similar to that reported in previous studies, some notable aspects were different. The main genotypes present in south-eastern Africa, North Africa, and West Africa are genotypes A, D, and E, respectively. Genotypes G and H are mainly distributed in Mexico. Genotype F is mainly distributed in central and South America, but genotypes A and D are also common in Brazil, Cuba, and Haiti.This study provides a more accurate description of the distribution of HBV genotypes and subgenotypes in different countries and suggests that the differences in genotype distribution may be related to ethnicity and human migration.

Figure 1

Flowchart of the database search and study selection process. The published literature regarding HBV genotypes or subgenotypes was searched in PubMed, and the full-length HBV sequences and S gene sequences were retrieved from the GenBank database. HBV = hepatitis B virus.

Figure 2

The geographical distribution of HBV genotypes. The small pie chart indicates the sample size was less than 100, the medium pie chart indicates the sample size was between 100 and 500, and the large pie chart indicates the sample size was more than 500. A indicates HBV genotype A (red); B indicates HBV genotype B (pink); C indicates HBV genotype C (dark blue); D indicates HBV genotype D (light blue); E indicates HBV genotype E (light green); F indicates HBV genotype F (dark green); G indicates HBV genotype G (yellow); H indicates HBV genotype H (white); Undetermined indicates the genotype is unknown (black). HBV = hepatitis B virus.

Figure 3

The geographical distribution of HBV subgenotypes. (A) The geographical distribution of HBV genotype A. (B) The geographical distribution of HBV genotype B. (C) The geographical distribution of HBV genotype C. (D) The geographical distribution of HBV genotype D. (E) The geographical distribution of HBV genotype F. The small pie chart indicates the sample size was less than 50, the medium pie chart indicates the sample size was between 50 and 100, and the large pie chart indicates the sample size was more than 100. HBV = hepatitis B virus.

Figure 4

Evolutionary timescales of HBV genotypes. Estimates of divergence times for major clades are listed near nodes. HBV = hepatitis B virus.