Complete genome sequence of hepatitis B virus (HBV) from a patient with fulminant hepatitis without precore and core promoter mutations comparison with HBV from a patient with acute hepatitis infected...

Complete genome sequence of hepatitis B virus (HBV) from a patient with fulminant hepatitis without precore and core promoter mutations: comparison with HBV from a patient with acute hepatitis infected from the same infectious source Yan Chen 1 , Kojiro Michitaka 1,2, * , Hiroshi Matsubara 1 , Kazuhisa Yamamoto 3 , Norio Horiike 1 , Morikazu Onji 1 1 Third Department of Internal Medicine, Ehime University School of Medicine, Shigenobu-cho, Onsen-gun, Ehime 791-0295, Japan 2 Endoscopy Center, Ehime University School of Medicine, Shigenobu-cho, Onsen-gun, Ehime 791-0295, Japan 3 Department of Gastroenterology, Matsuyama Shimin Hospital, Matsuyama, Ehime, Japan Background/Aims: There is a paucity of information regarding hepatitis B virus (HBV) from patients with fulminant hepatitis (FH) without precore (pre-C, nt 1896) and core promoter (CP, nt 1762, 1764) mutations. Methods: Pre-C and CP mutations were studied in eight patients with FH and 26 patients with acute hepatitis (AH) due to HBV. One patient with FH (FH1) was infected with HBV without these mutations. Interestingly, the sera of the infectious source (IS1) and of a patient with AH (AH1) infected from IS1 were available. Complete HBV genomes from these three patients were analyzed. Results: These mutations were found in seven of eight FH and five of 26 AH (P , 0.01). HBV from FH1, IS1 and AH1 belonged to genotype D. Nucleotide difference between FH1 and AH1 was six of 3182 bases (nt 493, 998, 1173, 2928, 3067, and 3078). Two and five substitutions of deduced amino acid sequences were found in the pre-S1 and polymerase regions, respectively. The same nucleotide substitutions at nt 493, 1173, 2928 and 3067 were found in several patients with FH in our laboratory or GenBank. Conclusions: These six nucleotide substitutions of HBV DNA could be candidates of mutations relating to FH. q 2002 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved. Keywords: Hepatitis B virus; Fulminant hepatitis; Precore mutation; Core promoter mutation; Hepatitis B virus genotype; Genotype D; Infectious source 1. Introduction Hepatitis B virus (HBV) causes a variety of diseases, including self-limiting acute hepatitis (AH), fulminant hepatitis (FH), chronic hepatitis, liver cirrhosis and hepato- cellular carcinoma. Approximately 1% of patients with acute HBV infection develop FH. Many studies have been reported concerning the relation between viral mutations and the severity of disease. Precore mutation at nt 1896 (G to A) and core promoter mutations at nt 1762 (A to T) and nt 1764 (G to A) have been reported to relate with FH [1–8]. Both mutations are known to result in the reduction of the production of HBe antigen (HBeAg) by translational or transcriptional level. The mechanism of this relation has been studied, and it has been shown that these mutations induce not only the reduction of HBeAg but also enhanced replication of HBV [9–14]. Besides the supposition that HBeAg directly suppresses viral replication, several mechanisms for enhanced viral replication in these mutant strains have been reported, such as the efficient encapsida- tion of pregenomic RNA by structural rearrangement, the change of transcriptional transactivation activity of X protein, and the emergence of the hepatocyte nuclear factor binding site by core promoter mutation [9,11,13,15]. However, several reports did not find that an association Journal of Hepatology 38 (2003) 84–90 0168-8278/02/$20.00 q 2002 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved. PII: S0168-8278(02)00325-2 www.elsevier.com/locate/jhep Received 17 April 2002; received in revised form 10 September 2002; accepted 17 September 2002 * Corresponding author. Tel.: 181-89-960-5308; fax: 181-89-960-5310. E-mail address: [email protected] (K. Michitaka).

Complete genome sequence of hepatitis B virus (HBV) from a patient with fulminant hepatitis without precore and core promoter mutations comparison with HBV from a patient with acute hepatitis infected...

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