Evolution of hepatitis B virus sequence from a liver transplant recipient with rapid breakthrough despite hepatitis B immune globulin prophylaxis and lamivudine therapy

Kyun Hwan Kim, Kwang Hee Lee, Hye Young Chang, Sang Hoon Ahn, Shuping Tong, Young Joon Yoon, Baik L. Seong, Soon Il Kim, Kwang Hyub Han

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Recurrent hepatitis B virus (HBV) infection after liver transplantation can be prevented by prophylactic hepatitis B immune globulin (HBIG) and lamivudine therapy. However, reinfection may still occur due to the emergence of immune escape mutants and mutants of the YMDD motif. The full spectrum of mutations within the HBV genome during recurrent HBV infection remains to be documented. In this study, serial HBV isolates were characterized from a patient with lamivudine resistance prior to liver transplantation who developed recurrent HBV infection within 2 months of transplantation despite a high dose of HBIG and lamivudine therapy. Sequence analysis of full-length viral genome before transplantation revealed many point mutations as compared with a wild-type genotype C sequence, including the T1753G/A1762T/G1764A triple mutation in the basal core promoter and the G1896A nonsense mutation in the precore region. After transplantation and therapy, several point mutations in the HBV genome emerged or became dominant. These mutations caused L4261/L526M/M5501 triple mutation (equivalent to L4281/L528M/M5521 in previous reports) in the polymerase, and D144E mutation in the "a" determinant of HBsAg. Transfection experiments revealed that the D144E mutation reduced HBsAg affinity to anti-HBs, confirming its active role for immune escape. Our study suggests that mutations in the HBsAg (D144E) and the polymerase (L4261/L526M/M5501) of HBV genome may be responsible for viral breakthrough despite HBIG prophylaxis and lamivudine therapy.

Original languageEnglish
Pages (from-to)367-375
Number of pages9
JournalJournal of Medical Virology
Volume71
Issue number3
DOIs
Publication statusPublished - 2003 Nov 1

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Lamivudine
Hepatitis B
Hepatitis B virus
Immunoglobulins
Mutation
Liver
Virus Diseases
Hepatitis B Surface Antigens
Transplantation
Genome
Point Mutation
Liver Transplantation
Therapeutics
Nonsense Codon
Viral Genome
Transplant Recipients
Transfection
Sequence Analysis
Genotype

All Science Journal Classification (ASJC) codes

  • Virology
  • Infectious Diseases

Cite this

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title = "Evolution of hepatitis B virus sequence from a liver transplant recipient with rapid breakthrough despite hepatitis B immune globulin prophylaxis and lamivudine therapy",
abstract = "Recurrent hepatitis B virus (HBV) infection after liver transplantation can be prevented by prophylactic hepatitis B immune globulin (HBIG) and lamivudine therapy. However, reinfection may still occur due to the emergence of immune escape mutants and mutants of the YMDD motif. The full spectrum of mutations within the HBV genome during recurrent HBV infection remains to be documented. In this study, serial HBV isolates were characterized from a patient with lamivudine resistance prior to liver transplantation who developed recurrent HBV infection within 2 months of transplantation despite a high dose of HBIG and lamivudine therapy. Sequence analysis of full-length viral genome before transplantation revealed many point mutations as compared with a wild-type genotype C sequence, including the T1753G/A1762T/G1764A triple mutation in the basal core promoter and the G1896A nonsense mutation in the precore region. After transplantation and therapy, several point mutations in the HBV genome emerged or became dominant. These mutations caused L4261/L526M/M5501 triple mutation (equivalent to L4281/L528M/M5521 in previous reports) in the polymerase, and D144E mutation in the {"}a{"} determinant of HBsAg. Transfection experiments revealed that the D144E mutation reduced HBsAg affinity to anti-HBs, confirming its active role for immune escape. Our study suggests that mutations in the HBsAg (D144E) and the polymerase (L4261/L526M/M5501) of HBV genome may be responsible for viral breakthrough despite HBIG prophylaxis and lamivudine therapy.",
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Evolution of hepatitis B virus sequence from a liver transplant recipient with rapid breakthrough despite hepatitis B immune globulin prophylaxis and lamivudine therapy. / Kim, Kyun Hwan; Lee, Kwang Hee; Chang, Hye Young; Ahn, Sang Hoon; Tong, Shuping; Yoon, Young Joon; Seong, Baik L.; Kim, Soon Il; Han, Kwang Hyub.

In: Journal of Medical Virology, Vol. 71, No. 3, 01.11.2003, p. 367-375.

Research output: Contribution to journalArticle

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AU - Kim, Kyun Hwan

AU - Lee, Kwang Hee

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AU - Ahn, Sang Hoon

AU - Tong, Shuping

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