The molecular epidemiology of hepatitis B in the Indigenous people of northern Australia
Corresponding Author
Jane Davies
Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory
Department of Infectious Diseases, Royal Darwin Hospital, Darwin, Northern Territory
Correspondence
Dr Joshua S Davis, Global and Tropical Health Division, Menzies School of Health Research, John Matthews Building, Royal Darwin Hospital Campus, Rocklands Drive, Tiwi, Darwin, NT 0810, Australia. Email [email protected]
Search for more papers by this authorMargaret Littlejohn
Victorian Infectious Diseases Reference Laboratory, North Melbourne
Search for more papers by this authorStephen A Locarnini
Victorian Infectious Diseases Reference Laboratory, North Melbourne
Search for more papers by this authorSarah Whiting
Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory
Department of Infectious Diseases, Royal Darwin Hospital, Darwin, Northern Territory
Search for more papers by this authorKrispin Hajkowicz
Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory
Department of Infectious Diseases, Royal Darwin Hospital, Darwin, Northern Territory
Search for more papers by this authorBenjamin C Cowie
Victorian Infectious Diseases Reference Laboratory, North Melbourne
Victorian Infectious Diseases Service, Royal Melbourne Hospital, Parkville, Victoria, Australia
Search for more papers by this authorDavid S Bowden
Victorian Infectious Diseases Reference Laboratory, North Melbourne
Search for more papers by this authorSteven Y C Tong
Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory
Department of Infectious Diseases, Royal Darwin Hospital, Darwin, Northern Territory
Search for more papers by this authorJoshua S Davis
Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory
Department of Infectious Diseases, Royal Darwin Hospital, Darwin, Northern Territory
Search for more papers by this authorCorresponding Author
Jane Davies
Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory
Department of Infectious Diseases, Royal Darwin Hospital, Darwin, Northern Territory
Correspondence
Dr Joshua S Davis, Global and Tropical Health Division, Menzies School of Health Research, John Matthews Building, Royal Darwin Hospital Campus, Rocklands Drive, Tiwi, Darwin, NT 0810, Australia. Email [email protected]
Search for more papers by this authorMargaret Littlejohn
Victorian Infectious Diseases Reference Laboratory, North Melbourne
Search for more papers by this authorStephen A Locarnini
Victorian Infectious Diseases Reference Laboratory, North Melbourne
Search for more papers by this authorSarah Whiting
Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory
Department of Infectious Diseases, Royal Darwin Hospital, Darwin, Northern Territory
Search for more papers by this authorKrispin Hajkowicz
Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory
Department of Infectious Diseases, Royal Darwin Hospital, Darwin, Northern Territory
Search for more papers by this authorBenjamin C Cowie
Victorian Infectious Diseases Reference Laboratory, North Melbourne
Victorian Infectious Diseases Service, Royal Melbourne Hospital, Parkville, Victoria, Australia
Search for more papers by this authorDavid S Bowden
Victorian Infectious Diseases Reference Laboratory, North Melbourne
Search for more papers by this authorSteven Y C Tong
Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory
Department of Infectious Diseases, Royal Darwin Hospital, Darwin, Northern Territory
Search for more papers by this authorJoshua S Davis
Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory
Department of Infectious Diseases, Royal Darwin Hospital, Darwin, Northern Territory
Search for more papers by this authorAbstract
Background and Aim
The hepatitis B surface antigen was first described in the blood of an Indigenous Australian man, yet little is known about its molecular epidemiology in this population, in which it is endemic. The study aimed to determine the clinical and molecular epidemiology of hepatitis B virus (HBV) in Indigenous people from northern Australia.
Methods
Following ethics approval and informed consent, blood specimens and clinical details from Indigenous adults known to be infected with HBV and who were born and raised in Indigenous communities in northern Australia were obtained. HBV genotypes were determined in isolates with sufficient HBV DNA by polymerase chain reaction by sequencing of the polymerase/surface gene.
Results
Between June 2010 and June 2012, 65 patients were recruited from six different regions of northern Australia. Thirty-two patients (49%) were hepatitis B e-antigen-positive, and 48% were hepatitis B e-antibody-positive. No patients were found to be coinfected with hepatitis C virus or human immunodeficiency virus. Of the 49 samples with sufficient viral load for genotyping, 100% were infected with genotype C4, previously only reported from two Indigenous Australians. All isolates had wild-type polymerase gene sequences despite 14 currently or previously receiving antiviral treatment. The canonical sG145R vaccine-escape variant was detected in the surface antigen of virus from two patients.
Conclusions
The exclusive HBV genotype in this ancient population is genotype C4. Whole genome sequencing and clinical follow-up of this cohort are in progress, with the aim of exploring the clinical significance of these findings.
References
- 1 Lai CL, Ratziu V, Yuen M-F, Poynard T. Viral hepatitis B. Lancet 2003; 362: 2089–2094.
- 2 Gidding HF, Warlow M, MacIntyre CR et al. The impact of a new universal infant and school-based adolescent hepatitis B vaccination program in Australia. Vaccine 2007; 25: 8637–8641.
- 3 The Kirby Institute. HIV, Viral Hepatitis and Sexually Transmissible Infections in Australia: Annual Surveillance Report 2011. Sydney: The Kirby Institute, Univeristy of New South Wales, 2011.
- 4 National Centre in HIV Epidemiology and Clinical Research. HIV, Viral Hepatitis and Sexually Transmissible Infections in Australia Annual Surveillance Report 2010. Sydney: National Centre in HIV Epidemiology and Clinical Research, The University of New South Wales, 2010.
- 5 O'Sullivan BG, Gidding HF, Law M, Kaldor JM, Gilbert GL, Dore GJ. Estimates of chronic hepatitis B virus infection in Australia, 2000. Aust. N. Z. J. Public Health 2004; 28: 212–216.
- 6 Gardner ID. Hepatitis B virus markers in children and staff in Northern Territory schools. Med. J. Aust. 1992; 156: 638–641.
- 7 Campbell DH. The prevalence of markers of infection with hepatitis B virus in a mixed-race Australian community. Med. J. Aust. 1989; 150: 489–492.
- 8 Campbell DH. Hepatitis B infection of children in a mixed-race community in western New South Wales. Med. J. Aust. 1991; 154: 253–256.
- 9 Malcolm RL, Ludwick L, Brookes DL, Hanna JN. The investigation of a “cluster” of hepatitis B in teenagers from an Indigenous community in North Queensland. Aust. N. Z. J. Public Health 2000; 24: 353–355.
- 10 Wood N, Warlow M, Quinn H et al. Establishment of a surveillance system (utilising Midwifes Data Collection Systems) for monitoring the impact of hepatitis B vaccination on the population prevalence of chronic hepatitis B virus infection in Australia. Aust. N. Z. J. Public Health 2008; 32: 272–275.
- 11 Australian Bureau of Statistics. 2006 Census of Population and Housing, Australia. Catalogue number 1362.7. Canberra: Australian Bureau of Statistics, 2007.
- 12 Carroll E, Page W, Davis JS. Screening for hepatitis B in East Arnhem Land: a high prevalence of chronic infection despite incomplete screening. Intern. Med. J. 2010; 40: 784–787.
- 13 Dent E, Selvey CE, Bell A, Davis J, McDonald MI. Incomplete protection against hepatitis B among remote aboriginal adolescents despite full vaccination in infancy. Commun. Dis. Intell. 2010; 34: 435–439.
- 14 Lin CL, Kao JH. The clinical implications of hepatitis B virus genotype: recent advances. J. Gastroenterol. Hepatol. 2011; 26 (Suppl. 1): 123–130.
- 15 Fattovich G, Bortolotti F, Donato F. Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors. J. Hepatol. 2008; 48: 335–352.
- 16 Kim BK, Revill PA, Ahn SH. HBV genotypes: relevance to natural history, pathogenesis and treatment of chronic hepatitis B. Antivir. Ther. 2011; 16: 1169–1186.
- 17 Kao J-H. Hepatitis B viral genotypes: clinical relevance and molecular characteristics. J. Gastroenterol. Hepatol. 2002; 17: 643–650.
- 18 Livingston SE, Simonetti JP, Bulkow LR et al. Clearance of hepatitis B e antigen in patients with chronic hepatitis B and genotypes A, B, C, D, and F. Gastroenterology 2007; 133: 1452–1457.
- 19 Yu MW, Yeh SH, Chen PJ et al. Hepatitis B virus genotype and DNA level and hepatocellular carcinoma: a prospective study in men. J. Natl Cancer Inst. 2005; 97: 265–272.
- 20 Sugauchi F, Mizokami M, Orito E et al. A novel variant genotype C of hepatitis B virus identified in isolates from Australian aborigines: complete genome sequence and phylogenetic relatedness. J. Gen. Virol. 2001; 82 (Pt 4): 883–892.
- 21
McIntosh EDG, Givney R, Zhang S-S, Couroucé AM, Burgess M, Cossart YE. Molecular epidemiology and variation of hepatitis B in recent immigrant families to Australia. J. Med. Virol. 1998; 56: 10–17.
10.1002/(SICI)1096-9071(199809)56:1<10::AID-JMV3>3.0.CO;2-Q CAS PubMed Web of Science® Google Scholar
- 22 Ayres A, Locarnini S, Bartholomeusz A. HBV genotyping and analysis for unique mutations. Methods Mol. Med. 2004; 95: 125–149.
- 23 Yuen LKW, Ayres A, Littlejohn M et al. SEQHEPB: a sequence analysis program and relational database system for chronic hepatitis B. Antiviral Res. 2007; 75: 64–74.
- 24 Okamoto H. Point mutation in the S gene of hepatitis B virus for a d/y or w/r subtypic change in two blood donors carrying a surface antigen of compound subtype adyr or adwr. J. Virol. 1987; 61: 3030–3034.
- 25 Hall TA. Bioedit: a user-friendly biological sequence alignment editor and analysis program for windows 95/98/NT. Nucleic Acids Symp. Ser. 1999; 41: 95–98.
- 26 Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S. MEGA 5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol. Biol. Evol. 2011; 28: 2731–2739.
- 27 National Health and Medical Research Council. Australian Alcohol Guidelines: Health Risks and Benefits. Canberra: National Health and Medical Research Council, 2001. Cited 12 Nov 12. Available from URL: http://www.nhmrc.gov.au/_files_nhmrc/publications/attachments/ds9.pdf
- 28 Forbi JC, Vaughan G, Purdy MA et al. Epidemic history and evolutionary dynamics of hepatitis B virus infection in two remote communities in rural Nigeria. PLoS ONE 2010; 5: e11615.
- 29 Krarup HB, Andersen S, Madsen PH, Okkels H, Hvingel BH, Laurberg P. Benign course of long-standing hepatitis B virus infection among Greenland Inuit? Scand. J. Gastroenterol. 2008; 43: 334–343.
- 30 Hamrosi K, Taylor SJ, Aslani P. Issues with prescribed medications in aboriginal communities: aboriginal health workers' perspectives. Rural Remote Health 2006; 6: 557–570.
- 31
Nishizono A, Kohno K, Takita-Sonoda Y et al. Sequential analyses of the mutations in the core upstream and precore regions of hepatitis B virus genome in anti-HBe positive-carriers developing acute exacerbation. J. Med. Virol. 1997; 53: 266–272.
10.1002/(SICI)1096-9071(199711)53:3<266::AID-JMV15>3.0.CO;2-F CAS PubMed Web of Science® Google Scholar
- 32 Ozasa A, Tanaka Y, Orito E et al. Influence of genotypes and precore mutations on fulminant or chronic outcome of acute hepatitis B virus infection. Hepatology 2006; 44: 326–334.
- 33 Kao J-H, Chen P-J, Lai M-Y, Chen D-S. Basal core promoter mutations of hepatitis B virus increase the risk of hepatocellular carcinoma in hepatitis B carriers. Gastroenterology 2003; 124: 327–334.
- 34 Liu S, Zhang H, Gu C et al. Associations between hepatitis B virus mutations and the risk of hepatocellular carcinoma: a meta-analysis. J. Natl Cancer Inst. 2009; 101: 1066–1082.
- 35 Yang H-I, Yeh S-H, Chen P-J et al. Associations between hepatitis B virus genotype and mutants and the risk of hepatocellular carcinoma. J. Natl Cancer Inst. 2008; 100: 1134–1143.
- 36 Condon JR, Armstrong BK, Barnes T, Zhao Y. Cancer incidence and survival for Indigenous Australians in the Northern Territory. Aust. N. Z. J. Public Health 2005; 29: 123–128.
- 37 Condon JR, Barnes T, Armstrong BK, Selva-Nayagam S. Stage at diagnosis and cancer survival for Indigenous Australians in the Northern Territory. Med. J. Aust. 2005; 182: 277–280.
- 38 Condon JR, Barnes T, Cunningham J, Armstrong BK. Long-term trends in cancer mortality for Indigenous Australians in the Northern Territory. Med. J. Aust. 2004; 180: 504–507.
- 39 Chan HL. Hepatitis B virus genotype C takes a more aggressive disease course than hepatitis B virus genotype B in hepatitis B e antigen-positive patients. J. Clin. Microbiol. 2003; 41: 1277–1279.
- 40 Chu C-M, Liaw Y-F. Genotype C hepatitis B virus infection is associated with a higher risk of reactivation of hepatitis B and progression to cirrhosis than genotype B: a longitudinal study of hepatitis B e antigen-positive patients with normal aminotransferase levels at baseline. J. Hepatol. 2005; 43: 411–417.
- 41 Yuen MF. Longitudinal study of hepatitis activity and viral replication before and after HBeAg seroconversion in chronic hepatitis B patients infected with genotypes B and C. J. Clin. Microbiol. 2004; 42: 5036–5040.
- 42 Watanabe K, Takahashi T, Takahashi S, Okoshi S, Ichida T, Aoyagi Y. Comparative study of genotype B and C hepatitis B virus-induced chronic hepatitis in relation to the basic core promoter and precore mutations. J. Gastroenterol. Hepatol. 2005; 20: 441–449.
- 43 Sumi H, Yokosuka O, Seki N et al. Influence of hepatitis B virus genotypes on the progression of chronic type B liver disease. Hepatology 2003; 37: 19–26.
- 44 Chu CM, Liaw YF. Chronic hepatitis B virus infection acquired in childhood: special emphasis on prognostic and therapeutic implication of delayed HBeAg seroconversion. J. Viral Hepat. 2007; 14: 147–152.
- 45 Hanna JN, Faoagali JL, Buda PJ, Sheridan JW. Further observations on the immune response to recombinant hepatitis B vaccine after administration to aboriginal and Torres Strait Island children. J. Paediatr. Child Health 1997; 33: 67–70.
- 46 Wood N. Estimates of chronic hepatitis B virus infection in the Northern Territory. Commun. Dis. Intell. 2005; 29: 289–290.
- 47 van der Sande MAB, Waight PA, Mendy M et al. Long-term protection against HBV chronic carriage of Gambian adolescents vaccinated in infancy and immune response in HBV booster trial in adolescence. PLoS ONE 2007; 2: e753.
- 48 Viviani S, Carrieri P, Bah E et al. 20 years into the Gambia hepatitis intervention study: assessment of initial hypotheses and prospects for evaluation of protective effectiveness against liver cancer. Cancer Epidemiol. Biomarkers Prev. 2008; 17: 3216–3223.
Citing Literature
