Estimation of the genotype distribution within global chronic hepatitis B virus infections

Hepatitis B Virus (HBV) is divided into nine genotypes (gt), A to I, that differ in their primary transmission route, chronicity rate, development of liver cirrhosis and hepatocellular carcinoma and treatment response to Interferon-α. It is unclear which proportions of the 250 million chronic hepatitis B cases are caused by which gt. This knowledge could assist to specify the hepatitis B disease burden, plan health policies, optimize diagnostic tests, and develop new broadly active therapies. We assessed relevant studies reporting HBV gt distribution throughout the world and estimated number of infections with each gt using HBsAg-prevalence and population estimates. 213 sources covering 125 countries provided information on HBV gt distribution with a wide geographical variation: Gt A was found primarily ineastern Sub-Saharan Africa, Europe, and the Caribbean, gt B and C in East and Southeast Asia and Australia, gt D in eastern Europe, Asia, and Northern Africa, and gt E in Western Sub-Saharan Africa and Columbia. Gt F-H were almost exclusively found in Latin America, with gt F distributed over most of Latin America and gt G and H more localized in Mexico and Colombia. Gt I was uniquely found in Southeast Asia. When set in relation to regional HBV prevalences, we calculated that approximately 96% of global HBV infections are caused by five (A to E) of the nine gt with gt C causing most infections (26%), followed bygt D (22%), E (18%), A (17%) and B (14%). The four remaining gt F to I were estimated to cause together less than 2% of infections. The wide distribution of HBV gt underscores the need to expand experimental models to include gt A to E to represent the majority of HBV infections.