Association between S21 substitution in the core protein of hepatitis B virus and fulminant hepatitis

Jun Inoue, Yoshiyuki Ueno, Kaori Kawamura, Takeshi Yamamoto, Yutaka Mano, Masahito Miura, Tomoo Kobayashi, Hirofumi Niitsuma, Yasuteru Kondo, Eiji Kakazu, Masashi Ninomiya, Osamu Kimura, Noriyuki Obara, Naoki Kawagishi, Yoshitaka Kinouchi, Tooru Shimosegawa

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


Background: The viral factors of hepatitis B virus (HBV), such as genotypes and mutations, were reported to affect the development of fulminant hepatitis B (FHB), but the mechanism is still unclear. Objectives: To investigate HBV mutations associated with FHB, especially in the subgenotype B1/Bj HBV (HBV/B1), which are known to cause FHB frequently in Japan. Study design: A total of 96 serum samples from acute self-limited hepatitis B (AHB) patients and 13 samples from FHB patients were used for full-genome/partial sequencing. A total of 107 chronic infection patients with HBV were also examined for the distribution of mutants. Results: In the analysis of full-genome sequences of HBV/B1 (FHB, n= 11; non-FHB, n= 35) including those from the databases, mutations at nt 1961 [T1961V (not T)] and nt 1962 [C1962D (not C)], which change S21 in the core protein, were found more frequently in FHB than in non-FHB (100% vs. 20%, 55% vs. 3%, respectively). When our FHB and AHB samples were compared, T1961V and C1962D were significantly more frequent in FHB than in AHB, both in the overall analysis (46% vs. 6%, 39% vs. 3%, respectively) and in HBV/B1 (100% vs. 29%, 100% vs. 14%, respectively). A newly developed PCR system detecting T1961V showed that HBV/B1 and low viral load were independent factors for the mutation among chronic infection patients. Conclusions: T1961V/C1962D mutations were found frequently in FHB, especially in HBV/B1. The resulting S21 substitution in the core protein may play important roles in the development of FHB.

Original languageEnglish
Pages (from-to)147-152
Number of pages6
JournalJournal of Clinical Virology
Issue number2
Publication statusPublished - 2012 Oct


  • C1962D
  • FHB
  • Genotype
  • HBV
  • T1961V

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases


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