Recent Population Expansions of Hepatitis B Virus in the United States.

Ramachandran S1, Purdy MA2, Xia GL2, Campo DS2, Dimitrova ZE2, Teshale EH2, Teo CG2, Khudyakov YE2.

Author information

Abstract

The recent epidemic history of hepatitis B virus (HBV) infections in the United States is complex, as indicated by current disparity in HBV genotype distribution between acute and chronic hepatitis B cases and rapid decline in hepatitis B incidence since the 1990s. We report temporal changes in genetic composition of the HBV population using whole-genome sequences (n=179) from acute hepatitis B cases (n=1206) identified through the Sentinel County Surveillance for Acute Hepatitis (1998-2006). HBV belonged mainly to subtypes A2 (75%) and D3 (18%), with times of their most recent common ancestors being, respectively, 1979 and 1987, respectively. A2 underwent rapid population expansions in ca. 1995 and ca. 2002, coinciding with transient rises in acute hepatitis B notification rates among adults; D3 underwent expansion in ca. 1998. A2 strains from cases identified after 2002, compared to those before 2002, tended to cluster phylogenetically, indicating selective expansion of specific strains, and were significantly reduced in genetic diversity (p = 0.001) and frequency of drug-resistance mutations (p = 0.001). The expansion of genetically close HBV A2 strains was associated with risk of infection among male homosexuals (p = 0.03). Incident HBV strains circulating in the US were recent in origin, and restricted in genetic diversity. Disparate transmission dynamics among phylogenetic lineages affected the genetic composition of HBV populations and their capacity to maintain drug-resistance mutations. The tendency of selectively expanding HBV strains to be transmitted among male homosexuals highlights the need to improve hepatitis B vaccination coverage among at-risk adults.

IMPORTANCE:

Hepatitis B virus (HBV) remains an important cause of acute and chronic liver disease globally, and in the United States. Genetic analysis of HBV WHOLE GENOMES FROM CASES OF ACUTE HEPATITIS B IDENTIFIED FROM 1998-2006 IN THE UNITED STATES: showed dominance of genotype A2 (75%), followed by D3 (18%). Strains of both subtypes were recent in origin and underwent rapid population expansions from 1995-2000, indicating increase in transmission rate for certain HBV strains during a period of decline in the reported incidence of acute hepatitis B in the US. HBV A2 strains from a particular cluster that experienced the most recent population expansion were more commonly detected among men who have sex with men. Vaccination needs to be stepped up to protect persons who remain at risk of HBV infection.