Please cite this article in press as: Pujol F, et al. Hepatitis B virus American genotypes: Pathogenic variants ? Clin Res Hepatol Gastroenterol (2020), https://doi.org/10.1016/j.clinre.2020.04.018 ARTICLE IN PRESS +Model CLINRE-1452; No. of Pages 11 Clinics and Research in Hepatology and Gastroenterology (2020) xxx, xxx—xxx Available online at ScienceDirect www.sciencedirect.com REVIEW Hepatitis B virus American genotypes: Pathogenic variants ? Flor Pujol a , Rossana C. Jaspe a , Carmen L. Loureiro a , Isabelle Chemin b a Laboratorio de Virología Molecular, CMBC, IVIC, Apdo 20632, Caracas 1020A, Venezuela b INSERM U1052, CNRS 5286, Université de Lyon, Université Claude Bernard Lyon 1, centre Léon Bérard, centre de recherche en cancérologie de Lyon, 69000, Lyon, France KEYWORDS Hepatitis B virus; American genotypes; Mutants; Origin; Cancer; HCC Summary Hepatitis B virus (HBV) chronic infection is responsible for almost 900.000 deaths each year, due to cirrhosis or hepatocellular carcinoma (HCC). Ten HBV genotypes have been described (A—J). HBV genotype F and H circulate in America. HBV genotypes have been further classified in subgenotypes. There is a strong correlation between the genetic admixture of the American continent and the frequency of genotypes F or H: a high frequency of these genotypes is found in countries with a population with a higher ratio of Amerindian to African genetic admixture. The frequency of occult HBV infection in Amerindian communities from Latin America seems to be higher than the one found in other HBV-infected groups, but its association with American genotypes is unknown. There is growing evidence that some genotypes might be associated with a faster evolution to HCC. In particular, HBV genotype F has been implicated in a frequent and rapid progression to HCC. However, HBV genotype H has been associated to a less severe progression of disease. This study reviews the diversity and frequency of autochthonous HBV variants in the Americas and evaluates their association to severe progression of disease. Although no significant differences were found in the methylation pattern between different genotypes and subgenotypes of the American types, basal core promoter mutations might be more frequent in some subgenotypes, such as F1b and F2, than in other American subgenotypes or genotype H. F1b and probably F2 may be associated with a severe presentation of liver disease as opposed to a more benign course for subgenotype F4 and genotype H. Thus, preliminary evidence suggests that not all of the American variants are associated with a rapid progression to HCC. © 2020 Elsevier Masson SAS. All rights reserved. E-mail address: fhpujol@gmail.com (F. Pujol). Introduction More than 250 million persons are chronically infected with hepatitis B virus (HBV) worldwide [1]. HBV chronic infection causes cirrhosis and hepatocellular carcinoma (HCC), and is responsible for nearly 900,000 deaths each year [1—3]. https://doi.org/10.1016/j.clinre.2020.04.018 2210-7401/© 2020 Elsevier Masson SAS. All rights reserved.