Age of hepatitis B e antigen loss in Aboriginal, Torres Strait Islander and non-Indigenous residents of tropical Australia: implications for clinical care
DOI:
https://doi.org/10.33321/cdi.2024.48.48Keywords:
Hepatitis B virus, HBeAg, hepatocellular carcinoma, hepatitis B genotype, Indigenous health, rural and remote healthAbstract
This study determined the hepatitis B e antigen (HBeAg) status of people living with chronic hepatitis B (CHB) in Far North Queensland (FNQ), Australia and their age of HBeAg loss. It was hoped that this would provide data to explain the stark difference in the incidence of hepatocellular carcinoma (HCC) between Aboriginal and Torres Strait Islander individuals living with CHB in FNQ, a finding that has been hypothesised to relate to differences in hepatitis B virus genotype. We identified every FNQ resident with CHB, determined their country of birth, their HBeAg status, the age they lost HBeAg and whether they identified as an Aboriginal, a Torres Strait Islander or a non-Indigenous individual. We then ascertained whether these demographic and virological variables were correlated. Of 1,474 individuals living with CHB in FNQ, 278 (19%) were Aboriginal, 507 (34%) were Torres Strait Islanders and 689 (47%) were non-Indigenous. Aboriginal individuals were less likely to be HBeAg positive (26/278, 9%) than Torres Strait Islander (91/507, 18%) and non-Indigenous (126/689, 18%) individuals, p < 0.0001. Aboriginal individuals lost HBeAg at an earlier age (median (interquartile range): 30 (23–39) years) than Torres Strait Islander (38 (29–49) years) and non-Indigenous (36 (29–47) years) individuals, p < 0.0001. Aboriginal individuals with CHB in FNQ are more likely to be HBeAg negative than Torres Strait Islander and non-Indigenous individuals and lose HBeAg at a younger age. This provides a biological basis for local clinicians’ observation that Aboriginal individuals with CHB in FNQ are at a lower risk of HCC and data to support the principle of genotype-based care in the region.
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MacLachlan JH, Romero N, Purcell I, Cowie BC. Viral Hepatitis Mapping Project: Hepatitis B. Geographic diversity in chronic hepatitis prevalence, management and treatment. National Report 2021. Sydney: Australasian Society for HIV, Viral Hepatitis, and Sexual Health Medicine (ASHM); 2023. Available from: https://ashm.org.au/wp-content/uploads/2023/09/Viral-Hepatitis-Mapping-Project_National-Report-Hepatitis-B-2021.pdf.
Howell J, Ward JS, Davies J, Clark PJ, Davis JS. Hepatocellular carcinoma in Indigenous Australians: a call to action. Med J Aust. 2021;214(5):201–2.e1. doi: https://doi.org/10.5694/mja2.50961.
Parker C, Tong SYC, Dempsey K, Condon J, Sharma SK, Chen JWC et al. Hepatocellular carcinoma in Australia’s Northern Territory: high incidence and poor outcome. Med J Aust. 2014;201(8):470–4. doi: https://doi.org/10.5694/mja13.11117.
Davies J, Li SQ, Tong SY, Baird RW, Beaman M, Higgins G et al. Establishing contemporary trends in hepatitis B sero-epidemiology in an Indigenous population. PLoS One. 2017;12(9):e0184082. doi: https://doi.org/10.1371/journal.pone.0184082.
Lubel JS, Strasser SI, Thompson AJ, Cowie BC, MacLachlan J, Allard NL et al. Australian consensus recommendations for the management of hepatitis B. Med J Aust. 2022;216(9):478–86. doi: https://doi.org/10.5694/mja2.51430.
Hanson J, Fox M, Anderson A, Fox P, Webster K, Williams C et al. Chronic hepatitis B in remote, tropical Australia; successes and challenges. PLoS One. 2020;15(9):e0238719. doi: https://doi.org/10.1371/journal.pone.0238719.
Hanson J, Radlof S, Littlejohn M, Hempenstall A, Edwards R, Nakata Y et al. Hepatitis B genotypes in Aboriginal and Torres Strait Islander Australians: correlation with clinical course and implications for management. Intern Med J. 2024;54(4):647–56. doi: https://doi.org/10.1111/imj.16181.
Riddell J, Hempenstall A, Nakata Y, Gregson S, Hayes R, Smith S et al. The high burden of comorbidities in Aboriginal and Torres Strait Islander Australians living with chronic hepatitis B in Far North Queensland, Australia, and the implications for patient management. PLoS One. 2023;18(4):e0284151. doi: https://doi.org/10.1371/journal.pone.0284151.
Revill PA, Tu T, Netter HJ, Yuen LKW, Locarnini SA, Littlejohn M. The evolution and clinical impact of hepatitis B virus genome diversity. Nat Rev Gastroenterol Hepatol. 2020;17(10):618–34. doi: https://doi.org/10.1038/s41575-020-0296-6.
McMahon BJ, Nolen LD, Snowball M, Homan C, Negus S, Roik E et al. HBV genotype: a significant risk factor in determining which patients with chronic HBV infection should undergo surveillance for HCC: the Hepatitis B Alaska Study. Hepatology. 2021;74(6):2965–73. doi: https://doi.org/10.1002/hep.32065.
Lin CL, Kao JH. The clinical implications of hepatitis B virus genotype: recent advances. J Gastroenterol Hepatol. 2011;26(Suppl 1):123–30. doi: https://doi.org/10.1111/j.1440-1746.2010.06541.x.
Chan HLY, Wong GLH, Tse CH, Chim AML, Yiu KKL, Chan HY et al. Hepatitis B virus genotype C is associated with more severe liver fibrosis than genotype B. Clin Gastroenterol Hepatol. 2009;7(12):1361–6. doi: https://doi.org/10.1016/j.cgh.2009.08.004.
Chan HLY, Hui AY, Wong ML, Tse AML, Hung LCT, Wong VWS et al. Genotype C hepatitis B virus infection is associated with an increased risk of hepatocellular carcinoma. Gut. 2004;53(10):1494–8. doi: https://doi.org/10.1136/gut.2003.033324.
Livingston SE, Simonetti JP, Bulkow LR, Homan CE, Snowball MM, Cagle HH 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(5):1452–7. doi: https://doi.org/10.1053/j.gastro.2007.08.010.
Littlejohn M, Davies J, Yuen L, Edwards R, Sozzi T, Jackson K et al. Molecular virology of hepatitis B virus, sub-genotype C4 in northern Australian Indigenous populations. J Med Virol. 2014;86(4):695–706. doi: https://doi.org/10.1002/jmv.23888.
Davies J, Smith EL, Littlejohn M, Edwards R, Sozzi V, Jackson K et al. Towards genotype-specific care for chronic hepatitis B: the first 6 years follow up from the CHARM cohort study. Open Forum Infect Dis. 2019;6(11):ofz469. doi: https://doi.org/10.1093/ofid/ofz469.
Graham Cooksley W. Hepatitis B genotypes: role of testing in clinical practice. Curr Hepatitis Rep. 2011;10(2):79-86. doi: https://doi.org/https://doi.org/10.1007/s11901-011-0097-z.
Chu CJ, Hussain M, Lok ASF. Hepatitis B virus genotype B is associated with earlier HBeAg seroconversion compared with hepatitis B virus genotype C. Gastroenterology. 2002;122(7):1756–62. doi: https://doi.org/10.1053/gast.2002.33588.
Liu Z, Zhang Y, Xu M, Li X, Zhang Z. Distribution of hepatitis B virus genotypes and subgenotypes: a meta-analysis. Medicine (Baltimore). 2021;100(50):e27941. doi: https://doi.org/10.1097/MD.0000000000027941.
Velkov S, Ott JJ, Protzer U, Michler T. The global hepatitis B virus genotype distribution approximated from available genotyping data. Genes (Basel). 2018;9(10):495. doi: https://doi.org/10.3390/genes9100495.
Sakamoto T, Tanaka Y, Orito E, Co J, Clavio J, Sugauchi F et al. Novel subtypes (subgenotypes) of hepatitis B virus genotypes B and C among chronic liver disease patients in the Philippines. J Gen Virol. 2006;87(Pt 7):1873–82. doi: https://doi.org/10.1099/vir.0.81714-0.
Tangkijvanich P, Mahachai V, Komolmit P, Fongsarun J, Theamboonlers A, Poovorawan Y. Hepatitis B virus genotypes and hepatocellular carcinoma in Thailand. World J Gastroenterol. 2005;11(15):2238–43. doi: https://doi.org/10.3748/wjg.v11.i15.2238.
Sugauchi F, Chutaputti A, Orito E, Kato H, Suzuki S, Ueda R et al. Hepatitis B virus genotypes and clinical manifestation among hepatitis B carriers in Thailand. J Gastroenterol Hepatol. 2002;17(6):671–6. doi: https://doi.org/10.1046/j.1440-1746.2002.02754.x.
Louisirirotchanakul S, Olinger CM, Arunkaewchaemsri P, Poovorawan Y, Kanoksinsombat C, Thongme C et al. The distribution of hepatitis B virus genotypes in Thailand. J Med Virol. 2012;84(10):1541–7. doi: https://doi.org/10.1002/jmv.23363.
Sa-Nguanmoo P, Tangkijvanich P, Thawornsuk N, Vichaiwattana P, Prianantathavorn K, Theamboonlers A et al. Molecular epidemiological study of hepatitis B virus among migrant workers from Cambodia, Laos, and Myanmar to Thailand. J Med Virol. 2010;82(8):1341–9. doi: https://doi.org/10.1002/jmv.21828.
Chen CJ, Yang HI. Natural history of chronic hepatitis B REVEALed. J Gastroenterol Hepatol. 2011;26(4):628–38. doi: https://doi.org/10.1111/j.1440-1746.2011.06695.x.
Mulyanto, Depamede SN, Surayah K, Tsuda F, Ichiyama K, Takahashi M et al. A nationwide molecular epidemiological study on hepatitis B virus in Indonesia: identification of two novel subgenotypes, B8 and C7. Arch Virol. 2009;154(7):1047–59. doi: https://doi.org/10.1007/s00705-009-0406-9.
Thedja MD, Muljono DH, Nurainy N, Sukowati CHC, Verhoef J, Marzuki S. Ethnogeographical structure of hepatitis B virus genotype distribution in Indonesia and discovery of a new subgenotype, B9. Arch Virol. 2011;156(5):855–68. doi: https://doi.org/10.1007/s00705-011-0926-y.
Huy TTT, Ushijima H, Win KM, Luengrojanakul P, Shrestha PK, Zhong ZH et al. High prevalence of hepatitis B virus pre-s mutant in countries where it is endemic and its relationship with genotype and chronicity. J Clin Microbiol. 2003;41(12):5449–55. doi: https://doi.org/10.1128/JCM.41.12.5449-5455.2003.
Hoan NX, Hoechel M, Tomazatos A, Anh CX, Pallerla SR, Linh LTK et al. Predominance of HBV genotype B and HDV genotype 1 in Vietnamese patients with chronic hepatitis. Viruses. 2021;13(2):346. doi: https://doi.org/10.3390/v13020346.
Liaw YF, Tai DI, Chu CM, Pao CC, Chen TJ. Acute exacerbation in chronic type B hepatitis: comparison between HBeAg and antibody-positive patients. Hepatology. 1987;7(1):20–3. doi: https://doi.org/10.1002/hep.1840070106.
Yang HI, Lu SN, Liaw YF, You SL, Sun CA, Wang LY et al. Hepatitis B e antigen and the risk of hepatocellular carcinoma. N Engl J Med. 2002;347(3):168–74. doi: https://doi.org/10.1056/NEJMoa013215.
de Jongh FE, Janssen HL, de Man RA, Hop WC, Schalm SW, van Blankenstein M. Survival and prognostic indicators in hepatitis B surface antigen-positive cirrhosis of the liver. Gastroenterology. 1992;103(5):1630–5. doi: https://doi.org/10.1016/0016-5085(92)91188-a.
Wen WH, Chang MH, Zhao LL, Ni YH, Hsu HY, Wu JF et al. Mother-to-infant transmission of hepatitis B virus infection: significance of maternal viral load and strategies for intervention. J Hepatol. 2013;59(1):24–30. doi: https://doi.org/10.1016/j.jhep.2013.02.015.
Australian Bureau of Statistics (ABS). Census of Population and Housing: Socio-Economic Indexes for Areas (SEIFA), Australia, 2016. [Webpage.] Canberra: ABS; 27 March 2018. Available from: https://www.abs.gov.au/ausstats/abs@.nsf/mf/2033.0.55.001.
Country fact sheet: Papua New Guinea. [Webpage.] Geneva: International Agency for Research on Cancer, World Health Organization; 2020. Available from: https://canscreen5.iarc.fr/?page=countryfactsheet&q=PNG.
Zhang CH, Cheng Y, Zhang S, Fan J, Gao Q. Changing epidemiology of hepatocellular carcinoma in Asia. Liver Int. 2022;42(9):2029–41. doi: https://doi.org/10.1111/liv.15251.
Littlejohn M, Jaskowski LA, Edwards R, Jackson K, Yuen L, Crawford D et al. Molecular epidemiology of hepatitis B among Indigenous Australians in Queensland and the Torres Strait Islands. Intern Med J. 2024;54(1):129–38. doi: https://doi.org/10.1111/imj.16166.
Yuen LKW, Littlejohn M, Duchêne S, Edwards R, Bukulatjpi S, Binks P et al. Tracing ancient human migrations into Sahul using hepatitis B virus genomes. Mol Biol Evol. 2019;36(5):942–54. doi: https://doi.org/10.1093/molbev/msz021.
Hui S, Bell S, Le S, Dev A. Hepatocellular carcinoma surveillance in Australia: current and future perspectives. Med J Aust. 2023;219(9):432–8. doi: https://doi.org/10.5694/mja2.52124.
Nguyen ALT, Si L, Lubel JS, Shackel N, Yee KC, Wilson M et al. Hepatocellular carcinoma surveillance based on the Australian Consensus Guidelines: a health economic modelling study. BMC Health Serv Res. 2023;23(1):378. doi: https://doi.org/10.1186/s12913-023-09360-4.
Terrault NA, Lok ASF, McMahon BJ, Chang KM, Hwang JP, Jonas MM et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67(4):1560–99. doi: https://doi.org/10.1002/hep.29800.
Chen YC, Chu CM, Liaw YF. Age-specific prognosis following spontaneous hepatitis B e antigen seroconversion in chronic hepatitis B. Hepatology. 2010;51(2):435–44. doi: https://doi.org/10.1002/hep.23348.
Wong VWS, Janssen HLA. Can we use HCC risk scores to individualize surveillance in chronic hepatitis B infection? J Hepatol. 2015;63(3):722–32. doi: https://doi.org/10.1016/j.jhep.2015.05.019.
Lee A, Hanson J, Fox P, Spice G, Russell D, Boyd P. A decentralised, multidisciplinary model of care facilitates treatment of hepatitis C in regional Australia. J Virus Erad. 2018;4(3):160–4. doi: https://doi.org/10.1016/S2055-6640(20)30270-3.
Basaglia A, Kang K, Wilcox R, Lau A, McKenna K, Smith S, et al. The aetiology and incidence of infective endocarditis in people living with rheumatic heart disease in tropical Australia. Eur J Clin Microbiol Infect Dis. 2023;42(9):1115–23. doi: https://doi.org/10.1007/s10096-023-04641-6.
Leading Causes of Death by Indigenous Status Far North Queensland, Cairns and Hinterland HHS, Torres and Cape HHS 2005 to 2019. 2022. [Not available online.]
Hanson J, Smith S, Brooks J, Groch T, Sivalingam S, Curnow V et al. The applicability of commonly used predictive scoring systems in Indigenous Australians with sepsis: an observational study. PLoS One. 2020;15(7):e0236339. doi: https://doi.org/10.1371/journal.pone.0236339.
Nivukoski U, Niemelä M, Bloigu A, Bloigu R, Aalto M, Laatikainen T et al. Combined effects of lifestyle risk factors on fatty liver index. BMC Gastroenterol. 2020;20(1):109. doi: https://doi.org/10.1186/s12876-020-01270-7.
Liaw YF. HBeAg seroconversion as an important end point in the treatment of chronic hepatitis B. Hepatol Int. 2009;3(3):425–33. doi: https://doi.org/10.1007/s12072-009-9140-3.
Han C, Karamatic R, Hanson J. Chronic hepatitis B care in regional Australia: implications for clinical practice and public health policy. Intern Med J. 2024. doi: https://doi.org/10.1111/imj.16364.
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