Skip to main content
Top
Published in: BMC Gastroenterology 1/2004

Open Access 01-12-2004 | Research article

Complete hepatitis B virus genome analysis in HBsAg positive mothers and their infants with fulminant hepatitis B

Authors: Michael Friedt, Patrick Gerner, Philip Wintermeyer, Stefan Wirth

Published in: BMC Gastroenterology | Issue 1/2004

Login to get access

Abstract

Background

After perinatal transmission of hepatitis B virus, infants of anti-HBe positive HBsAg carrier mothers may develop fulminant hepatitis B. Previously it has been suggested, that fulminant hepatitis B in adults was associated with specific mutations in the HBV-genome. The aim of this study was to investigate, whether specific viral variants are associated with fulminant hepatitis B in young infants.

Methods

The complete HBV-genomes of five mothers and their infants with fulminant hepatitis were isolated from the sera, amplified and directly sequenced.

Results

Between 6 and 43 base pair exchanges between the HBV genomes of the infants and their mothers were identified. The mutations spread over the entire virus genome. Nucleotide exchanges in the basic core promotor and precore region were identified in all cases. A heterogeneous virus population was detected in four mothers.

Conclusions

Many new mutations were proved to emerge during fulminant hepatitis B in infants, who had been perinatally infected. HBeAg negative variants were the predominant population in all children, whereas these mutants could only be detected as subpopulations in four mothers. The data suggest that the selection of a specific HBeAg negative viral strain may be associated with the development of fulminant hepatitis B in children.
Appendix
Available only for authorised users
Literature
1.
go back to reference Sato S, Suzuki K, Akahane Y, Akamatsu K, Akiyama K, Yunomura K, Tsuda F, Tanaka T, Okamoto H, Miyakawa Y: Hepatitis B virus strains with mutations in the core promoter in patients with fulminant hepatitis. Ann Intern Med. 1995, 122: 241-248.CrossRefPubMed Sato S, Suzuki K, Akahane Y, Akamatsu K, Akiyama K, Yunomura K, Tsuda F, Tanaka T, Okamoto H, Miyakawa Y: Hepatitis B virus strains with mutations in the core promoter in patients with fulminant hepatitis. Ann Intern Med. 1995, 122: 241-248.CrossRefPubMed
2.
go back to reference Hasegawa K, Huang JK, Wands JR, Obata H, Liang TJ: Association of hepatitis B viral precore mutations with fulminant hepatitis B in Japan. Virology. 1991, 185: 460-463. 10.1016/0042-6822(91)90799-H.CrossRefPubMed Hasegawa K, Huang JK, Wands JR, Obata H, Liang TJ: Association of hepatitis B viral precore mutations with fulminant hepatitis B in Japan. Virology. 1991, 185: 460-463. 10.1016/0042-6822(91)90799-H.CrossRefPubMed
3.
go back to reference Liang TJ, Hasegawa K, Rimon N, Wands JR, Ben Porath E: A hepatitis B virus mutant associated with an epidemic of fulminant hepatitis. N Engl J Med. 1991, 324: 1705-1709.CrossRefPubMed Liang TJ, Hasegawa K, Rimon N, Wands JR, Ben Porath E: A hepatitis B virus mutant associated with an epidemic of fulminant hepatitis. N Engl J Med. 1991, 324: 1705-1709.CrossRefPubMed
4.
go back to reference Hasegawa K, Huang J, Rogers SA, Blum HE, Liang TJ: Enhanced replication of a hepatitis B virus mutant associated with an epidemic of fulminant hepatitis. J Virol. 1994, 68: 1651-1659.PubMedPubMedCentral Hasegawa K, Huang J, Rogers SA, Blum HE, Liang TJ: Enhanced replication of a hepatitis B virus mutant associated with an epidemic of fulminant hepatitis. J Virol. 1994, 68: 1651-1659.PubMedPubMedCentral
5.
go back to reference Pollicino T, Zanetti AR, Cacciola I, Petit MA, Smedile A, Campo S, Sagliocca L, Pasquali M, Tanzi E, Longo G, Raimundo G: Pre-S2 defective hepatitis B virus infection in patients with fulminant hepatitis. Hepatology. 1997, 26: 495-499.CrossRefPubMed Pollicino T, Zanetti AR, Cacciola I, Petit MA, Smedile A, Campo S, Sagliocca L, Pasquali M, Tanzi E, Longo G, Raimundo G: Pre-S2 defective hepatitis B virus infection in patients with fulminant hepatitis. Hepatology. 1997, 26: 495-499.CrossRefPubMed
6.
go back to reference Ogata N, Miller RH, Ishak KG, Purcell RH: The complete nucleotide sequence of a pre-core mutant of hepatitis B virus implicated in fulminant hepatitis and its biological characterization in chimpanzees. Virology. 1993, 194: 263-276. 10.1006/viro.1993.1257.CrossRefPubMed Ogata N, Miller RH, Ishak KG, Purcell RH: The complete nucleotide sequence of a pre-core mutant of hepatitis B virus implicated in fulminant hepatitis and its biological characterization in chimpanzees. Virology. 1993, 194: 263-276. 10.1006/viro.1993.1257.CrossRefPubMed
7.
go back to reference Sterneck M, Kalinina T, Otto S, Günther S, Fischer L, Burdelski M, Greten H, Broelsch CE, Will H: Neonatal fulminant hepatitis B: structural and functional analysis of complete hepatitis B virus genomes from mother and infant. J Infect Dis. 1998, 177: 1378-1381.CrossRefPubMed Sterneck M, Kalinina T, Otto S, Günther S, Fischer L, Burdelski M, Greten H, Broelsch CE, Will H: Neonatal fulminant hepatitis B: structural and functional analysis of complete hepatitis B virus genomes from mother and infant. J Infect Dis. 1998, 177: 1378-1381.CrossRefPubMed
8.
go back to reference Friedt M, Gerner P, Lausch E, Trübel H, Zabel B, Wirth S: Mutations in the Basic Core Promotor and the Precore Region of Hepatitis B Virus and Their Selection in Children With Fulminant and Chronic Hepatitis B. Hepatology. 1999, 29: 1252-1258.CrossRefPubMed Friedt M, Gerner P, Lausch E, Trübel H, Zabel B, Wirth S: Mutations in the Basic Core Promotor and the Precore Region of Hepatitis B Virus and Their Selection in Children With Fulminant and Chronic Hepatitis B. Hepatology. 1999, 29: 1252-1258.CrossRefPubMed
9.
go back to reference Leitner T, Halapi E, Scarlatti G, Rossi P, Albert J, Fenyo EM, Uhlne M: Analysis of heterogeneous viral populations by direct DNA sequencing. Biotechniques. 1993, 15: 120-127.PubMed Leitner T, Halapi E, Scarlatti G, Rossi P, Albert J, Fenyo EM, Uhlne M: Analysis of heterogeneous viral populations by direct DNA sequencing. Biotechniques. 1993, 15: 120-127.PubMed
10.
go back to reference Li JS, Tong SP, Wen YM, Vitvitski L, Zhang Q, Trepo C: Hepatitis B virus genotype A rarely circulates as an HBe-minus mutant: possible contribution of a single nucleotide in the precore region. J Virol. 1993, 67: 5402-5410.PubMedPubMedCentral Li JS, Tong SP, Wen YM, Vitvitski L, Zhang Q, Trepo C: Hepatitis B virus genotype A rarely circulates as an HBe-minus mutant: possible contribution of a single nucleotide in the precore region. J Virol. 1993, 67: 5402-5410.PubMedPubMedCentral
11.
go back to reference Galibert F, Mandart E, Fitoussi F, Tiollais P, Charnay P: Nucleotide sequence of the hepatitis B virus genome (subtype ayw) cloned in E. coli. Nature. 1979, 281: 646-650.CrossRefPubMed Galibert F, Mandart E, Fitoussi F, Tiollais P, Charnay P: Nucleotide sequence of the hepatitis B virus genome (subtype ayw) cloned in E. coli. Nature. 1979, 281: 646-650.CrossRefPubMed
12.
go back to reference Lee YI, Hur GM, Suh DJ, Kim SH: Novel pre-C/C gene mutants of hepatitis B virus in chronic active hepatitis: naturally occurring escape mutants. J Gen Virol. 1996, 77: 1129-1138.CrossRefPubMed Lee YI, Hur GM, Suh DJ, Kim SH: Novel pre-C/C gene mutants of hepatitis B virus in chronic active hepatitis: naturally occurring escape mutants. J Gen Virol. 1996, 77: 1129-1138.CrossRefPubMed
13.
go back to reference Naoumov NV, Schneider R, Grotzinger T, Jung MC, Miska S, Pape GR, Will H: Precore mutant hepatitis B virus infection and liver disease. Gastroenterology. 1992, 102: 538-543.CrossRefPubMed Naoumov NV, Schneider R, Grotzinger T, Jung MC, Miska S, Pape GR, Will H: Precore mutant hepatitis B virus infection and liver disease. Gastroenterology. 1992, 102: 538-543.CrossRefPubMed
14.
go back to reference Ehata T, Omata M, Yokosuka O, Hosoda K, Ohto M: Variations in codons 84–101 in the core nucleotide sequence correlate with hepatocellular injury in chronic hepatitis B virus infection. J Clin Invest. 1992, 89: 332-338.CrossRefPubMedPubMedCentral Ehata T, Omata M, Yokosuka O, Hosoda K, Ohto M: Variations in codons 84–101 in the core nucleotide sequence correlate with hepatocellular injury in chronic hepatitis B virus infection. J Clin Invest. 1992, 89: 332-338.CrossRefPubMedPubMedCentral
15.
go back to reference Ehata T, Omata M, Chuang WJ, Yokosuka O, Ito Y, Hosoda K, Ohto M: Mutations in core nucleotide sequence of hepatitis B virus correlate with fulminant and severe hepatitis. J Clin Invest. 1993, 91: 1206-1213.CrossRefPubMedPubMedCentral Ehata T, Omata M, Chuang WJ, Yokosuka O, Ito Y, Hosoda K, Ohto M: Mutations in core nucleotide sequence of hepatitis B virus correlate with fulminant and severe hepatitis. J Clin Invest. 1993, 91: 1206-1213.CrossRefPubMedPubMedCentral
16.
go back to reference Carman WF, Fagan EA, Hadziyannis S, Karayiannis P, Tassopoulos NC, Williams R, Thomas HC: Association of a precore genomic variant of hepatitis B virus with fulminant hepatitis. Hepatology. 1991, 14: 219-222. 10.1016/0270-9139(91)91406-Q.CrossRefPubMed Carman WF, Fagan EA, Hadziyannis S, Karayiannis P, Tassopoulos NC, Williams R, Thomas HC: Association of a precore genomic variant of hepatitis B virus with fulminant hepatitis. Hepatology. 1991, 14: 219-222. 10.1016/0270-9139(91)91406-Q.CrossRefPubMed
17.
go back to reference Kosaka Y, Takase K, Kojima M, Shimizu M, Inoue K, Yoshiba M, Tanaka S, Akahane Y, Okamoto H, Tsuda F: Fulminant hepatitis B: induction by hepatitis B virus mutants defective in the precore region and incapable of encoding e antigen. Gastroenterology. 1991, 100: 1087-1094.PubMed Kosaka Y, Takase K, Kojima M, Shimizu M, Inoue K, Yoshiba M, Tanaka S, Akahane Y, Okamoto H, Tsuda F: Fulminant hepatitis B: induction by hepatitis B virus mutants defective in the precore region and incapable of encoding e antigen. Gastroenterology. 1991, 100: 1087-1094.PubMed
18.
go back to reference Feray C, Gigou M, Samuel D, Bernuau J, Bismuth H, Brechot C: Low prevalence of precore mutations in hepatitis B virus DNA in fulminant hepatitis type B in France [see comments]. J Hepatol. 1993, 18: 119-122.CrossRefPubMed Feray C, Gigou M, Samuel D, Bernuau J, Bismuth H, Brechot C: Low prevalence of precore mutations in hepatitis B virus DNA in fulminant hepatitis type B in France [see comments]. J Hepatol. 1993, 18: 119-122.CrossRefPubMed
19.
go back to reference Aye TT, Uchida T, Becker SO, Hirahima M: Variations of hepatitis B virus precore/core gene sequence in acute and fulminant hepatitis B. Dig Dis Sci. 1994, 39: 1281-1287.CrossRefPubMed Aye TT, Uchida T, Becker SO, Hirahima M: Variations of hepatitis B virus precore/core gene sequence in acute and fulminant hepatitis B. Dig Dis Sci. 1994, 39: 1281-1287.CrossRefPubMed
20.
go back to reference Beath S, Boxall E, Watson R, Tarlow M, Kelly D: Fulminant hepatitis B in infants born to anti-HBe hepatitis B carrier mothers. BMJ. 1992, 304 (2): 1169-1170.CrossRefPubMedPubMedCentral Beath S, Boxall E, Watson R, Tarlow M, Kelly D: Fulminant hepatitis B in infants born to anti-HBe hepatitis B carrier mothers. BMJ. 1992, 304 (2): 1169-1170.CrossRefPubMedPubMedCentral
21.
go back to reference Sterneck M, Gunther S, Gerlach J, Naoumov NV, Santantonio T, Fischer L, Rogiers X, Greten H, Williams R, Will H: Hepatitis B virus sequence changes evolving in liver transplant recipients with fulminant hepatitis. J Hepatol. 1997, 26: 754-764. 10.1016/S0168-8278(97)80239-5.CrossRefPubMed Sterneck M, Gunther S, Gerlach J, Naoumov NV, Santantonio T, Fischer L, Rogiers X, Greten H, Williams R, Will H: Hepatitis B virus sequence changes evolving in liver transplant recipients with fulminant hepatitis. J Hepatol. 1997, 26: 754-764. 10.1016/S0168-8278(97)80239-5.CrossRefPubMed
22.
go back to reference Fagan E, Smith P, Davison P, Williams R: Fulminant hepatitis B in successive female partners of two anti-HBe-positive males. Lancet. 1986, 2: 538-540. 10.1016/S0140-6736(86)90112-1.CrossRefPubMed Fagan E, Smith P, Davison P, Williams R: Fulminant hepatitis B in successive female partners of two anti-HBe-positive males. Lancet. 1986, 2: 538-540. 10.1016/S0140-6736(86)90112-1.CrossRefPubMed
23.
go back to reference König S, Beterams G, Nassal M: Mapping of homologous interaction sites in the hepatitis B virus core protein. J Virol. 1998, 72: 4997-5005.PubMedPubMedCentral König S, Beterams G, Nassal M: Mapping of homologous interaction sites in the hepatitis B virus core protein. J Virol. 1998, 72: 4997-5005.PubMedPubMedCentral
24.
go back to reference Tsai SL, Chen MH, Yeh CT, Chu CM, Lin AN, Chiou FH, Chang TH, Liaw YF: Purification and characterization of a naturally processed hepatitis B virus peptide recognized by CD8+ cytotoxic T lymphocytes. J Clin Invest. 1996, 97: 577-584.CrossRefPubMedPubMedCentral Tsai SL, Chen MH, Yeh CT, Chu CM, Lin AN, Chiou FH, Chang TH, Liaw YF: Purification and characterization of a naturally processed hepatitis B virus peptide recognized by CD8+ cytotoxic T lymphocytes. J Clin Invest. 1996, 97: 577-584.CrossRefPubMedPubMedCentral
25.
go back to reference Roingeard P, Romet Lemonne JL, Leturcq D, Goudeau A, Essex M: Hepatitis B virus core antigen (HBcAg) accumulation in an HBV nonproducer clone of HepG2-transfected cells is associated with cytopathic effect. Virology. 1990, 179: 113-120. 10.1016/0042-6822(90)90280-5.CrossRefPubMed Roingeard P, Romet Lemonne JL, Leturcq D, Goudeau A, Essex M: Hepatitis B virus core antigen (HBcAg) accumulation in an HBV nonproducer clone of HepG2-transfected cells is associated with cytopathic effect. Virology. 1990, 179: 113-120. 10.1016/0042-6822(90)90280-5.CrossRefPubMed
26.
go back to reference Chisari FV, Filippi P, Buras J, McLachlan A, Popper H, Pinkert CA, Palmiter RD, Brinster RL: Structural and pathological effects of synthesis of hepatitis B virus large envelope polypeptide in transgenic mice. Proc Natl Acad Sci. 1987, 84: 6909-6913.CrossRefPubMedPubMedCentral Chisari FV, Filippi P, Buras J, McLachlan A, Popper H, Pinkert CA, Palmiter RD, Brinster RL: Structural and pathological effects of synthesis of hepatitis B virus large envelope polypeptide in transgenic mice. Proc Natl Acad Sci. 1987, 84: 6909-6913.CrossRefPubMedPubMedCentral
27.
go back to reference Xu Z, Yen TS: Intracellular retention of surface protein by a hepatitis B virus mutant that releases virion particles. J Virol. 1996, 70: 133-140.PubMedPubMedCentral Xu Z, Yen TS: Intracellular retention of surface protein by a hepatitis B virus mutant that releases virion particles. J Virol. 1996, 70: 133-140.PubMedPubMedCentral
28.
go back to reference Alexopoulou A, Karayiannis P, Hadziyannis SJ, Hou J, Pickering J, Luo K, Thomas HC: Whole genome analysis of hepatitis B virus from four cases of fulminant hepatitis: genetic variability and its potential role in disease pathogenicity. J Viral Hepat. 1996, 3: 173-181.CrossRefPubMed Alexopoulou A, Karayiannis P, Hadziyannis SJ, Hou J, Pickering J, Luo K, Thomas HC: Whole genome analysis of hepatitis B virus from four cases of fulminant hepatitis: genetic variability and its potential role in disease pathogenicity. J Viral Hepat. 1996, 3: 173-181.CrossRefPubMed
29.
go back to reference Buckwold VE, Xu Z, Chen M, Yen TS, Ou JH: Effects of a naturally occurring mutation in the hepatitis B virus basal core promoter on precore gene expression and viral replication. J Virol. 1996, 70: 5845-5851.PubMedPubMedCentral Buckwold VE, Xu Z, Chen M, Yen TS, Ou JH: Effects of a naturally occurring mutation in the hepatitis B virus basal core promoter on precore gene expression and viral replication. J Virol. 1996, 70: 5845-5851.PubMedPubMedCentral
30.
go back to reference Moriyama K, Okamoto H, Tsuda F, Mayumi M: Reduced precore transcription and enhanced core-pregenome transcription of hepatitis B virus DNA after replacement of the precore-core promoter with sequences associated with e antigen-seronegative persistent infections. Virology. 1996, 226: 269-280. 10.1006/viro.1996.0655.CrossRefPubMed Moriyama K, Okamoto H, Tsuda F, Mayumi M: Reduced precore transcription and enhanced core-pregenome transcription of hepatitis B virus DNA after replacement of the precore-core promoter with sequences associated with e antigen-seronegative persistent infections. Virology. 1996, 226: 269-280. 10.1006/viro.1996.0655.CrossRefPubMed
31.
go back to reference Scaglioni PP, Melegari M, Wands JR: Posttranscriptional regulation of hepatitis B virus replication by the precore protein. J Virol. 1997, 71: 345-353.PubMedPubMedCentral Scaglioni PP, Melegari M, Wands JR: Posttranscriptional regulation of hepatitis B virus replication by the precore protein. J Virol. 1997, 71: 345-353.PubMedPubMedCentral
32.
go back to reference Lamberts C, Nassal M, Velhagen I, Zentgraf H, Schroder CH: Precore-mediated inhibition of hepatitis B virus progeny DNA synthesis. J Virol. 1993, 67: 3756-3762.PubMedPubMedCentral Lamberts C, Nassal M, Velhagen I, Zentgraf H, Schroder CH: Precore-mediated inhibition of hepatitis B virus progeny DNA synthesis. J Virol. 1993, 67: 3756-3762.PubMedPubMedCentral
33.
go back to reference Guidotti LG, Matzke B, Pasquinelli C, Schoenberger JM, Rogler CE, Chisari FV: The hepatitis B virus (HBV) precore protein inhibits HBV replication in transgenic mice. J Virol. 1996, 70: 7056-7061.PubMedPubMedCentral Guidotti LG, Matzke B, Pasquinelli C, Schoenberger JM, Rogler CE, Chisari FV: The hepatitis B virus (HBV) precore protein inhibits HBV replication in transgenic mice. J Virol. 1996, 70: 7056-7061.PubMedPubMedCentral
34.
go back to reference Milich DR, Chen MK, Hughes JL, Jones JE: The secreted hepatitis B precore antigen can modulate the immune response to the nucleocapsid: a mechanism for persistence. J Immunol. 1998, 160: 2013-2021.PubMed Milich DR, Chen MK, Hughes JL, Jones JE: The secreted hepatitis B precore antigen can modulate the immune response to the nucleocapsid: a mechanism for persistence. J Immunol. 1998, 160: 2013-2021.PubMed
35.
go back to reference Buckwold VE, Xu Z, Yen TS, Ou JH: Effects of a frequent double-nucleotide basal core promoter mutation and its putative single-nucleotide precursor mutations on hepatitis B virus gene expression and replication. J Gen Virol. 1997, 78: 2055-2065.CrossRefPubMed Buckwold VE, Xu Z, Yen TS, Ou JH: Effects of a frequent double-nucleotide basal core promoter mutation and its putative single-nucleotide precursor mutations on hepatitis B virus gene expression and replication. J Gen Virol. 1997, 78: 2055-2065.CrossRefPubMed
36.
go back to reference Günther S, Piwon N, Will H: Wild-type levels of pregenomic RNA and replication but reduced pre-C RNA and e-antigen synthesis of hepatitis B virus with C(1653)-T, A(1762)-T and G(1764)-A mutations in the core promotor. J Gen Virol. 1998, 79: 375-380.CrossRefPubMed Günther S, Piwon N, Will H: Wild-type levels of pregenomic RNA and replication but reduced pre-C RNA and e-antigen synthesis of hepatitis B virus with C(1653)-T, A(1762)-T and G(1764)-A mutations in the core promotor. J Gen Virol. 1998, 79: 375-380.CrossRefPubMed
37.
go back to reference Lu CC, Chen , Ou JH, Yen TS: Key role of a CCAAT element in regulating hepatitis B virus surface protein expression. Virology. 1995, 206: 1155-1158. 10.1006/viro.1995.1042.CrossRefPubMed Lu CC, Chen , Ou JH, Yen TS: Key role of a CCAAT element in regulating hepatitis B virus surface protein expression. Virology. 1995, 206: 1155-1158. 10.1006/viro.1995.1042.CrossRefPubMed
38.
go back to reference Trautwein C, Schrem H, Tillmann HL, Kubicka S, Walker D, Boker KH, Maschek HJ, Pichlmayr R, Manns MP: Hepatitis B virus mutations in the pre-S genome before and after liver transplantation. Hepatology. 1996, 24: 482-488. 10.1053/jhep.1996.v24.pm0008781311.CrossRefPubMed Trautwein C, Schrem H, Tillmann HL, Kubicka S, Walker D, Boker KH, Maschek HJ, Pichlmayr R, Manns MP: Hepatitis B virus mutations in the pre-S genome before and after liver transplantation. Hepatology. 1996, 24: 482-488. 10.1053/jhep.1996.v24.pm0008781311.CrossRefPubMed
39.
go back to reference Santantonio T, Jung MC, Schneider R, Fernholz D, Milella M, Monno L, Pastore G, Pape GR, Will H: Hepatitis B virus genomes that cannot synthesize pre-S2 proteins occur frequently and as dominant virus populations in chronic carriers in Italy. Virology. 1992, 188: 948-952. 10.1016/0042-6822(92)90559-8.CrossRefPubMed Santantonio T, Jung MC, Schneider R, Fernholz D, Milella M, Monno L, Pastore G, Pape GR, Will H: Hepatitis B virus genomes that cannot synthesize pre-S2 proteins occur frequently and as dominant virus populations in chronic carriers in Italy. Virology. 1992, 188: 948-952. 10.1016/0042-6822(92)90559-8.CrossRefPubMed
40.
go back to reference Gerner RP, Friedt M, Oettinger R, Lausch E, Wirth S: The hepatitis B virus seroconversion to anti-HBe is frequently associated with HBV genotype changes and selection of preS2-defective particles in chronically infected children. Virology. 1998, 245: 163-172. 10.1006/viro.1998.9126.CrossRefPubMed Gerner RP, Friedt M, Oettinger R, Lausch E, Wirth S: The hepatitis B virus seroconversion to anti-HBe is frequently associated with HBV genotype changes and selection of preS2-defective particles in chronically infected children. Virology. 1998, 245: 163-172. 10.1006/viro.1998.9126.CrossRefPubMed
41.
go back to reference Günther S, Fischer L, Pult I, Sterneck M, Will H: Naturally occurring variants of hepatitis B virus. Adv Virus Res. 1999, 52: 25-137.CrossRefPubMed Günther S, Fischer L, Pult I, Sterneck M, Will H: Naturally occurring variants of hepatitis B virus. Adv Virus Res. 1999, 52: 25-137.CrossRefPubMed
42.
go back to reference Asahina Y, Enomoto N, Ogura Y, Kurosaki M, Sakuma I, Izumi N, Marumo F, Sato C: Sequential changes in full-length genomes of hepatitis B virus accompanying acute exacerbation of chronic hepatitis B. J Hepatol. 1996, 25: 787-794. 10.1016/S0168-8278(96)80280-7.CrossRefPubMed Asahina Y, Enomoto N, Ogura Y, Kurosaki M, Sakuma I, Izumi N, Marumo F, Sato C: Sequential changes in full-length genomes of hepatitis B virus accompanying acute exacerbation of chronic hepatitis B. J Hepatol. 1996, 25: 787-794. 10.1016/S0168-8278(96)80280-7.CrossRefPubMed
43.
go back to reference Pollack JR, Ganem D: Site-specific RNA binding by a hepatitis B virus reverse transcriptase initiates two distinct reactions: RNA packaging and DNA synthesis. J Virol. 1994, 68: 5579-5587.PubMedPubMedCentral Pollack JR, Ganem D: Site-specific RNA binding by a hepatitis B virus reverse transcriptase initiates two distinct reactions: RNA packaging and DNA synthesis. J Virol. 1994, 68: 5579-5587.PubMedPubMedCentral
Metadata
Title
Complete hepatitis B virus genome analysis in HBsAg positive mothers and their infants with fulminant hepatitis B
Authors
Michael Friedt
Patrick Gerner
Philip Wintermeyer
Stefan Wirth
Publication date
01-12-2004
Publisher
BioMed Central
Published in
BMC Gastroenterology / Issue 1/2004
Electronic ISSN: 1471-230X
DOI
https://doi.org/10.1186/1471-230X-4-11

Other articles of this Issue 1/2004

BMC Gastroenterology 1/2004 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.