Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Screening and diagnosis of HBV in low-income and middle-income countries

Nature Reviews Gastroenterology & Hepatology volume 13, pages 643–653 (2016)Cite this article

Subjects

Key Points

  • HBV is a major health issue in low-income and middle-income countries where prevalence of hepatitis B surface antigen (HBsAg) positivity is high (≥8%)

  • Measurement of HBsAg and alanine aminotransferase levels are the main tools for diagnosis and therapeutic indications because quantitative assessment of HBV DNA is usually unavailable

  • Quantitative hepatitis B e antigen (HBeAg) testing is a limited substitute for quantitative HBV DNA assessment

  • Antiviral therapy has sustained virological response rates <70%, and of the seven approved drugs for HBV, four trigger resistance

  • Measuring alanine aminotransferase levels and aspartate aminotransferase to platelet ratio index are critical for patient monitoring and therapeutic decision making

  • The cost of testing and antiviral therapy is a major limiting factor in HBV infection management in low-income and middle-income countries

Abstract

HBV testing and diagnosis of HBV-related liver disease in low-income and middle-income countries differs substantially from that in developed countries in terms of access to resources and expensive technologies requiring highly specialized staff. For identification and classification of HBV infection, genomic amplification methods to detect and quantify HBV DNA are often nonexistent or available only in central laboratories of major cities. When samples from peripheral locations do arrive, delays in receiving results generate loss to follow-up. Testing is often limited to measurement of hepatitis B surface antigen (HBsAg), alanine aminotransferase levels, aspartate aminotransferase to platelet ratio index and hepatitis B e antigen (HBeAg) to determine indications for antiviral therapy (AVT). Utilization of AVT is limited by cost and availability, particularly when patients are not covered by health insurance. The natural history of HBV infection is influenced by genotypes B and C in East Asia, where decades of immune tolerance have led to mostly vertical transmission; in sub-Saharan Africa, where genotypes A1 and E predominate, infection is transmitted horizontally between young children, followed by a nonreplicative phase. In both regions, cirrhosis and hepatocellular carcinoma are common and would be considerably ameliorated by AVT. Implementation of the HBV vaccine since the 1990s in Asia and 2000s in Africa has decreased the incidence of HBV, but vaccine failure and insufficiently effective prevention remain concerning issues.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Algorithm of markers to identify different phases of HBV infection.
Figure 2: Distribution of markers of active HBV infection.
Figure 3: Natural history of HBV infection with circulating markers in recovered and chronic HBV infection.
Figure 4: Development of resistance after long-term use of single-drug antiviral therapy for chronic HBV infection.

Similar content being viewed by others

References

  1. Bekondi, C. et al. HBV immunization and vaccine coverage among hospitalized children in Cameroon, Central African Republic and Senegal: a cross-sectional study. BMC Infect. Dis. 15, 267 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  2. Bosch, F. X., Ribes, J., Cléries, R. & Díaz, M. Epidemiology of hepatocellular carcinoma. Clin. Liver Dis. 9, 191–211 (2005).

    Article  PubMed  Google Scholar 

  3. Parkin, D. M. et al. (eds) Cancer in Africa: epidemiology and prevention. IARC Scientific Publication No. 153 (IARC, 2016).

    Google Scholar 

  4. Lu, J. et al. Direct economic burden of hepatitis B virus related diseases: evidence from Shandong, China. BMC Health Serv. Res. 13, 37 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Dan, Y. Y., Aung, M. O. & Lim, S. G. The economics of treating chronic hepatitis B in Asia. Hepatol. Int. 2, 284–295 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Jazwa, A. et al. Cost-benefit comparison of two proposed overseas programs for reducing chronic Hepatitis B infection among refugees: is screening essential? Vaccine 33, 1393–1399 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  7. Kania, D. et al. Combining rapid diagnostic tests and dried blood spot assays for point-of-care testing of human immunodeficiency virus, hepatitis B and hepatitis C infections in Burkina Faso, West Africa. Clin. Microbiol. Infect. 19, E533–E541 (2013).

    Article  CAS  PubMed  Google Scholar 

  8. Komada, K. et al. Seroprevalence of chronic hepatitis B, as determined from dried blood spots, among children and their mothers in central Lao People's Democratic Republic: a multistage, stratified cluster sampling survey. Int. J. Infect. Dis. 36, 21–26 (2015).

    Article  PubMed  Google Scholar 

  9. Vinikoor, M. J. et al. Hepatitis B viral load in dried blood spots: a validation study in Zambia. J. Clin. Virol. 72, 20–24 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  10. Njai, H. F. et al. Validation of rapid point-of-care (POC) tests for detection of hepatitis B surface antigen in field and laboratory settings in the Gambia, Western Africa. J. Clin. Microbiol. 53, 1156–1163 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Smith, A., Sabidó, M., Camey, E., Batres, A. & Casabona, J. Lessons learned from integrating simultaneous triple point-of-care screening for syphilis, hepatitis B, and HIV in prenatal services through rural outreach teams in Guatemala. Int. J. Gynaecol. Obstet. 130 (Suppl. 1), S70–S72 (2015).

    Article  PubMed  Google Scholar 

  12. Biswas, R. et al. Comparative sensitivity of HBV NATs and HBsAg assays for detection of acute HBV infection. Transfusion 43, 788–798 (2003).

    Article  PubMed  Google Scholar 

  13. Minegishi, K. et al. Superiority of minipool nucleic acid amplification technology for hepatitis B virus over chemiluminescence immunoassay for hepatitis B surface antigen screening. Vox Sang. 84, 287–291 (2003).

    Article  CAS  PubMed  Google Scholar 

  14. Raimondo, G. et al. Statements from the Taormina expert meeting on occult hepatitis B virus infection. J. Hepatol. 49, 652–657 (2008).

    Article  PubMed  Google Scholar 

  15. Alper, C. A. The human immune response to hepatitis B surface antigen. Exp. Clin. Immunogenet. 12, 171–181 (1995).

    CAS  PubMed  Google Scholar 

  16. Seremba, E. et al. Validity of the rapid strip assay test for detecting HBsAg in patients admitted to hospital in Uganda. J. Med. Virol. 82, 1334–1340 (2010).

    Article  CAS  PubMed  Google Scholar 

  17. Allain, J. P. et al. The risk of hepatitis B virus infection by transfusion in Kumasi, Ghana. Blood 101, 2419–2425 (2003).

    Article  CAS  PubMed  Google Scholar 

  18. Owusu-Ofori, S. et al. Predonation screening of blood donors with rapid tests: implementation and efficacy of a novel approach to blood safety in resource-poor settings. Transfusion 45, 133–140 (2005).

    Article  PubMed  Google Scholar 

  19. Chevaliez, S. et al. Performance of a new rapid test for the detection of hepatitis B surface antigen in various patient populations. J. Clin. Virol. 59, 89–93 (2014).

    Article  CAS  PubMed  Google Scholar 

  20. Scheiblauer, H. et al. Performance evaluation of 70 hepatitis B virus (HBV) surface antigen (HBsAg) assays from around the world by a geographically diverse panel with an array of HBV genotypes and HBsAg subtypes. Vox Sang. 98, 403–414 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Shivkumar, S., Peeling, R., Jafari, Y., Joseph, L. & Pai, N. P. Rapid point-of-care first-line screening tests for hepatitis B infection: a meta-analysis of diagnostic accuracy (1980–2010). Am. J. Gastroenterol. 107, 1306–1313 (2012).

    Article  PubMed  Google Scholar 

  22. Randrianirina, F. et al. Evaluation of the performance of four rapid tests for detection of hepatitis B surface antigen in Antananarivo, Madagascar. J. Virol. Methods 151, 294–297 (2008).

    Article  CAS  PubMed  Google Scholar 

  23. Mutocheluh, M. et al. Risk factors associated with hepatitis B exposure and the reliability of five rapid kits commonly used for screening blood donors in Ghana. BMC Res. Notes 7, 873 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  24. Khuroo, M. S., Khuroo, N. S. & Khuroo, M. S. Accuracy of rapid point-of-care diagnostic tests for hepatitis B surface antigen — a systematic review and meta-analysis. J. Clin. Exp. Hepatol. 4, 226–240 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  25. Mendy, M. et al. Hepatitis B surface antigenaemia and alpha-foetoprotein detection from dried blood spots: applications to field-based studies and to clinical care in hepatitis B virus endemic areas. J. Viral Hepat. 12, 642–647 (2005).

    Article  CAS  PubMed  Google Scholar 

  26. Candotti, D., Opare-Sem, O., Rezvan, H., Sarkodie, F. & Allain, J. P. Molecular and serological characterization of hepatitis B virus in deferred Ghanaian blood donors with and without elevated alanine aminotransferase. J. Viral Hepat. 13, 715–724 (2006).

    Article  CAS  PubMed  Google Scholar 

  27. Candotti, D., Danso, K. & Allain, J. P. Maternofetal transmission of hepatitis B virus genotype E in Ghana, West Africa. J. Gen. Virol. 88, 2686–2695 (2007).

    Article  CAS  PubMed  Google Scholar 

  28. Sarkodie, F. et al. Screening for viral markers in volunteer and replacement blood donors in West Africa. Vox Sang. 80, 142–147 (2001).

    Article  CAS  PubMed  Google Scholar 

  29. Huang, P. et al. Seroepidemiology of hepatitis B virus infection and impact of vaccination. World J. Gastroenterol. 21, 7842–7850 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Zhang, Y. et al. Hepatitis B surface antigen prevalence among 12,393 rural women of childbearing age in Hainan Province, China: a cross-sectional study. Virol. J. 10, 25 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  31. Zhong, L. et al. The estimation of prevalence and risk factors of hepatitis B virus infection among blood donors in Chengdu, China. J. Med. Virol. 88, 260–267 (2016).

    Article  CAS  PubMed  Google Scholar 

  32. Li, W. et al. The estimation of prevalence, incidence, and residual risk of transfusion-transmitted human hepatitis B infection from blood donated at the Anhui blood center, China, from 2009 to 2011. PLoS ONE 8, e73472 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Hourfar, M. K. et al. Sensitivity and specificity of Anti-HBc screening assays — which assay is best for blood donor screening? Int. J. Lab. Hematol. 31, 649–656 (2009).

    Article  CAS  PubMed  Google Scholar 

  34. El-Ghitany, E. M. & Farghaly, A. G. Evaluation of commercialized rapid diagnostic testing for some Hepatitis B biomarkers in an area of intermediate endemicity. J. Virol. Methods 194, 190–193 (2013).

    Article  CAS  PubMed  Google Scholar 

  35. Villar, L. M. et al. Assessment of dried blood spot samples as a simple method for detection of hepatitis B virus markers. J. Med. Virol. 83, 1522–1529 (2011).

    Article  CAS  PubMed  Google Scholar 

  36. Shimelis, T. et al. Hepatitis B virus infection among people attending the voluntary counselling and testing centre and anti-retroviral therapy clinic of St Paul's General Specialised Hospital, Addis Ababa, Ethiopia. Sex. Transm. Infect. 84, 37–41 (2008).

    Article  CAS  PubMed  Google Scholar 

  37. Zheng, X. et al. High prevalence of anti-hepatitis B core antigen in hepatitis B virus-vaccinated Chinese blood donors suggests insufficient protection but little threat to the blood supply. Transfusion 55, 890–897 (2015).

    Article  CAS  PubMed  Google Scholar 

  38. Behzad-Behbahani, A. et al. Anti-HBc and HBV-DNA detection in blood donors negative for hepatitis B virus surface antigen in reducing risk of transfusion associated HBV infection. Indian J. Med. Res. 123, 37–42 (2006).

    CAS  PubMed  Google Scholar 

  39. Muselmani, W., Habbal, W. & Monem, F. Prevalence of “anti-HBc alone” among Syrian blood donors. J. Infect. Dev. Ctries 8, 1013–1015 (2014).

    Article  PubMed  Google Scholar 

  40. Akinbami, A. A. et al. Seroprevalence of hepatitis B e antigen (HBe antigen) and B core antibodies (IgG anti-HBcore and IgM anti-HBcore) among hepatitis B surface antigen positive blood donors at a Tertiary Centre in Nigeria. BMC Res. Notes 5, 167 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  41. Antar, W., El-Shokry, M. H., Abd El Hamid, W. A. & Helmy, M. F. Significance of detecting anti-HBc among Egyptian male blood donors negative for HBsAg. Transfus. Med. 20, 409–413 (2010).

    Article  CAS  PubMed  Google Scholar 

  42. Asim, M. et al. Significance of anti-HBc screening of blood donors and its association with occult hepatitis B virus infection: implications for blood transfusion. Indian J. Med. Res. 132, 312–317 (2010).

    PubMed  Google Scholar 

  43. Bhatti, F. A., Ullah, Z., Salamat, N., Ayub, M. & Ghani, E. Anti-hepatitis B core antigen testing, viral markers, and occult hepatitis B virus infection in Pakistani blood donors: implications for transfusion practice. Transfusion 47, 74–79 (2007).

    Article  PubMed  Google Scholar 

  44. Sarin, S. K. et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol. Int. 10, 1–98 (2015).

    Article  PubMed  Google Scholar 

  45. Vlachogiannakos, J. & Papatheodoridis, G. V. HBV: Do I treat my immunotolerant patients? Liver Int. 36 (Suppl. 1), 93–99 (2016).

    Article  CAS  PubMed  Google Scholar 

  46. Ducancelle, A. et al. High endemicity and low molecular diversity of hepatitis B virus infections in pregnant women in a rural district of North Cameroon. PLoS ONE 8, e80346 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Pu, Z. et al. Epidemiological characteristics of the carriers with coexistence of HBsAg and anti-HBs based on a community cohort study. J. Viral Hepat. 23, 286–293 (2016).

    Article  CAS  PubMed  Google Scholar 

  48. Seo, S. I. et al. Coexistence of hepatitis B surface antigen and antibody to hepatitis B surface may increase the risk of hepatocellular carcinoma in chronic hepatitis B virus infection: a retrospective cohort study. J. Med. Virol. 86, 124–130 (2014).

    Article  CAS  PubMed  Google Scholar 

  49. Phikulsod, S. et al. One-year experience of nucleic acid technology testing for human immunodeficiency virus Type 1, hepatitis C virus, and hepatitis B virus in Thai blood donations. Transfusion 49, 1126–1135 (2009).

    Article  CAS  PubMed  Google Scholar 

  50. Louisirirotchanakul, S. et al. Occult hepatitis B virus infection in Thai blood donors. Transfusion 51, 1532–1540 (2011).

    Article  PubMed  Google Scholar 

  51. Candotti, D. et al. Occult hepatitis B infection in blood donors from South East Asia: molecular characterisation and potential mechanisms of occurrence. Gut 61, 1744–1753 (2012).

    Article  CAS  PubMed  Google Scholar 

  52. Stramer, S. L. et al. Nucleic acid testing to detect HBV infection in blood donors. N. Engl. J. Med. 364, 236–247 (2011).

    Article  CAS  PubMed  Google Scholar 

  53. Liu, J. et al. Seroepidemiology of hepatitis B virus infection in 2 million men aged 21–49 years in rural China: a population-based, cross-sectional study. Lancet Infect. Dis. 16, 80–86 (2016).

    Article  PubMed  Google Scholar 

  54. He, F. et al. The serum anti-HBs level among children who received routine hepatitis B vaccination during infancy in Mianyang City, China: a cross-sectional study. Viral Immunol. 29, 40–48 (2016).

    Article  CAS  PubMed  Google Scholar 

  55. Wang, F. et al. The long-term efficacy, 13–23 years, of a plasma-derived hepatitis B vaccine in highly endemic areas in China. Vaccine 33, 2704–2709 (2015).

    Article  CAS  PubMed  Google Scholar 

  56. Aghakhani, A. et al. Persistence of antibody to hepatitis B surface antigen among vaccinated children in a low hepatitis B virus endemic area. World J. Pediatr. 7, 358–360 (2011).

    Article  CAS  PubMed  Google Scholar 

  57. Salama, I. I. et al. Persistence of protection to hepatitis B vaccine and response to booster dose among children and adolescents in Dakahleya- Egypt. Egypt. J. Immunol. 21, 13–26 (2014).

    PubMed  Google Scholar 

  58. Sallam, T. A. et al. Hepatitis B virus carrier rate, prevalence and susceptibility and impact of immunization program among households in the city of Taiz, Yemen. Vaccine 30, 5564–5568 (2012).

    Article  CAS  PubMed  Google Scholar 

  59. Rey-Cuille, M. A. et al. Hepatitis B virus exposure during childhood in Cameroon, Central African Republic and Senegal after the integration of HBV vaccine in the expanded program on immunization. Pediatr. Infect. Dis. J. 32, 1110–1115 (2013).

    Article  PubMed  Google Scholar 

  60. Saffar, H. et al. Prevalence of hepatitis B virus seromarkers in young adults vaccinated at birth: impact on the epidemiology of hepatitis B infection in Iran. Hepat. Mon. 14, e17263 (2014).

    PubMed  PubMed Central  Google Scholar 

  61. Zheng, X. et al. Seroprevalence of transfusion-transmissible infectious agents among volunteer blood donors between 2006 and 2012 in Zhejiang, China. Blood Transfus. 13, 401–410 (2015).

    PubMed  PubMed Central  Google Scholar 

  62. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of chronic hepatitis B. J. Hepatol. 50, 227–242 (2009).

  63. Lok, A. S. et al. Antiviral therapy for chronic hepatitis B viral infection in adults: a systematic review and meta-analysis. Hepatology 63, 284–306 (2016).

    Article  CAS  PubMed  Google Scholar 

  64. Garbuglia, A. R. et al. Comparison of Versant HBV DNA 3.0 and COBAS AmpliPrep-COBAS TaqMan assays for hepatitis B DNA quantitation: possible clinical implications. J. Virol. Methods 146, 274–280 (2007).

    Article  CAS  PubMed  Google Scholar 

  65. Mohamed, S. et al. Dried blood spot sampling for hepatitis B virus serology and molecular testing. PLoS ONE 8, e61077 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Zhang, S. et al. A one-step dipstick assay for the on-site detection of nucleic acid. Clin. Biochem. 46, 1852–1856 (2013).

    Article  CAS  PubMed  Google Scholar 

  67. Bao, H. et al. Rapid high-throughput genotyping of HBV DNA using a modified hybridization- extension technique. Phys. Chem. Chem. Phys. 15, 18179–18184 (2013).

    Article  CAS  PubMed  Google Scholar 

  68. Mao, X. et al. Colorimetric detection of hepatitis B virus (HBV) DNA based on DNA-templated copper nanoclusters. Anal. Chim. Acta 909, 101–108 (2016).

    Article  CAS  PubMed  Google Scholar 

  69. Ola, S. O. et al. Occult HBV infection among a cohort of Nigerian adults. J. Infect. Dev. Ctries 3, 442–446 (2009).

    Article  CAS  PubMed  Google Scholar 

  70. Kitab, B. et al. Occult HBV infection in Morocco: from chronic hepatitis to hepatocellular carcinoma. Liver Int. 34, e144–e150 (2014).

    Article  PubMed  Google Scholar 

  71. Lukhwareni, A., Burnett, R. J., Selabe, S. G., Mzileni, M. O. & Mphahlele, M. J. Increased detection of HBV DNA in HBsAg-positive and HBsAg-negative South African HIV/AIDS patients enrolling for highly active antiretroviral therapy at a Tertiary Hospital. J. Med. Virol. 81, 406–412 (2009).

    Article  CAS  PubMed  Google Scholar 

  72. N'Dri-Yoman, T. et al. Occult HBV infection in untreated HIV-infected adults in Côte d'Ivoire. Antivir. Ther. 15, 1029–1034 (2010).

    Article  PubMed  Google Scholar 

  73. Peebles, K. et al. Pediatric HIV-HBV coinfection in Lusaka, Zambia: prevalence and short-term treatment outcomes. J. Trop. Pediatr. 61, 464–467 (2015).

    PubMed  PubMed Central  Google Scholar 

  74. Barth, R. E. et al. Presence of occult HBV, but near absence of active HBV and HCV infections in people infected with HIV in rural South Africa. J. Med. Virol. 83, 929–934 (2011).

    Article  PubMed  Google Scholar 

  75. Allain, J. P. et al. Characterization of occult hepatitis B virus strains in South African blood donors. Hepatology 49, 1868–1876 (2009).

    Article  CAS  PubMed  Google Scholar 

  76. Allain, J. P. & Candotti, D. Diagnostic algorithm for HBV safe transfusion. Blood Transfus. 7, 174–182 (2009).

    PubMed  PubMed Central  Google Scholar 

  77. Vermeulen, M. et al. Hepatitis B virus transmission by blood transfusion during 4 years of individual-donation nucleic acid testing in South Africa: estimated and observed window period risk. Transfusion 52, 880–892 (2012).

    Article  CAS  PubMed  Google Scholar 

  78. Li, C. et al. Prevalence and prevalence trends of transfusion transmissible infections among blood donors at four Chinese regional blood centers between 2000 and 2010. J. Transl. Med. 10, 176 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  79. Niazi, S. K., Bhatti, F. A., Salamat, N., Ghani, E. & Tayyab, M. Impact of nucleic acid amplification test on screening of blood donors in Northern Pakistan. Transfusion 55, 1803–1811 (2015).

    Article  CAS  PubMed  Google Scholar 

  80. Ren, F. R. et al. Hepatitis B virus nucleic acid testing in Chinese blood donors with normal and elevated alanine aminotransferase. Transfusion 51, 2588–2595 (2011).

    Article  PubMed  Google Scholar 

  81. Oluyinka, O. O. et al. Occult hepatitis B virus infection in Nigerian blood donors and hepatitis B virus transmission risks. PLoS ONE 10, e0131912 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Moresco, M. N. et al. Occult hepatitis B virus infection among blood donors from the Brazilian Amazon: implications for transfusion policy. Vox Sang. 107, 19–25 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Zheng, X. et al. Characterization of occult hepatitis B virus infection from blood donors in China. J. Clin. Microbiol. 49, 1730–1737 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  84. Gou, H. et al. Evaluation of an individual-donation nucleic acid amplification testing algorithm for detecting hepatitis B virus infection in Chinese blood donors. Transfusion 55, 2272–2281 (2015).

    Article  CAS  PubMed  Google Scholar 

  85. Vermeulen, M. et al. Impact of individual-donation nucleic acid testing on risk of human immunodeficiency virus, hepatitis B virus, and hepatitis C virus transmission by blood transfusion in South Africa. Transfusion 49, 1115–1125 (2009).

    Article  PubMed  Google Scholar 

  86. Chatterjee, K. et al. Individual donor nucleic acid testing for blood safety against HIV-1 and hepatitis B and C viruses in a tertiary care hospital. Natl Med. J. India 25, 207–209 (2012).

    CAS  PubMed  Google Scholar 

  87. Tsoi, W. C., Lelie, N. & Lin, C. K. Enhanced detection of hepatitis B virus in Hong Kong blood donors after introduction of a more sensitive transcription-mediated amplification assay. Transfusion 53, 2477–2488 (2013).

    Article  CAS  PubMed  Google Scholar 

  88. Vermeulen, M. et al. Sensitivity of individual-donation and minipool nucleic acid amplification test options in detecting window period and occult hepatitis B virus infections. Transfusion 53, 2459–2466 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Seed, C. R. et al. Infectivity of blood components from donors with occult hepatitis B infection — results from an Australian lookback programme. Vox Sang. 108, 113–122 (2015).

    Article  CAS  PubMed  Google Scholar 

  90. Satake, M. et al. Infectivity of blood components with low hepatitis B virus DNA levels identified in a lookback program. Transfusion 47, 1197–1205 (2007).

    Article  PubMed  Google Scholar 

  91. Yuen, M. F. et al. Transmissibility of hepatitis B virus (HBV) infection through blood transfusion from blood donors with occult HBV infection. Clin. Infect. Dis. 52, 624–632 (2011).

    Article  PubMed  Google Scholar 

  92. Allain, J. P. et al. Infectivity of blood products from donors with occult hepatitis B infection (OBI). Transfusion 53, 1405–1415 (2013).

    Article  PubMed  Google Scholar 

  93. Malmström, S., Berglin-Enquist, I. & Lindh, M. Novel method for genotyping hepatitis B virus on the basis of TaqMan real-time PCR. J. Clin. Microbiol. 48, 1105–1111 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  94. Song, L. W. et al. Rapid fluorescent lateral-flow immunoassay for hepatitis B virus genotyping. Anal. Chem. 87, 5173–5180 (2015).

    Article  CAS  PubMed  Google Scholar 

  95. Mercier, M., Laperche, S., Girault, A., Sureau, C. & Servant-Delmas, A. Overestimation of incidence of hepatitis B virus mixed-genotype infections by use of the new line probe INNO-LiPA genotyping assay. J. Clin. Microbiol. 49, 1154–1156 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  96. Yang, R. et al. INNO-LiPA HBV genotyping is highly consistent with direct sequencing and sensitive in detecting B/C mixed genotype infection in Chinese chronic hepatitis B patients and asymptomatic HBV carriers. Clin. Chim. Acta 411, 1951–1956 (2010).

    Article  CAS  PubMed  Google Scholar 

  97. Li, H. M. et al. Hepatitis B virus genotypes and genome characteristics in China. World J. Gastroenterol. 21, 6684–6697 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Saikia, A. et al. Molecular epidemiology of HBV infection in chronic hepatitis B virus infected patients in northeast India. J. Med. Virol. 87, 1539–1548 (2015).

    Article  CAS  PubMed  Google Scholar 

  99. Yousif, M. et al. Genotyping and virological characteristics of hepatitis B virus in HIV-infected individuals in Sudan. Int. J. Infect. Dis. 29, 125–132 (2014).

    Article  PubMed  Google Scholar 

  100. Chamni, N. et al. Genetic characterization and genotyping of hepatitis B virus (HBV) isolates from donors with an occult HBV infection. Vox Sang. 107, 324–332 (2014).

    Article  CAS  PubMed  Google Scholar 

  101. Awan, Z. et al. Pattern and molecular epidemiology of Hepatitis B virus genotypes circulating in Pakistan. Infect. Genet. Evol. 10, 1242–1246 (2010).

    Article  PubMed  Google Scholar 

  102. Ochwoto, M. et al. Genotyping and molecular characterization of hepatitis B virus in liver disease patients in Kenya. Infect. Genet. Evol. 20, 103–110 (2013).

    Article  CAS  PubMed  Google Scholar 

  103. Mello, F. C. et al. Hepatitis B virus genotypes circulating in Brazil: molecular characterization of genotype F isolates. BMC Microbiol. 7, 103 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  104. Abdelnabi, Z., Saleh, N., Baraghithi, S., Glebe, D. & Azzeh, M. Subgenotypes and mutations in the s and polymerase genes of hepatitis B virus carriers in the West Bank, Palestine. PLoS ONE 9, e113821 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  105. Mahgoub, S., Candotti, D., El Ekiaby, M. & Allain, J. P. Hepatitis B virus (HBV) infection and recombination between HBV genotypes D and E in asymptomatic blood donors from Khartoum, Sudan. J. Clin. Microbiol. 49, 298–306 (2011).

    Article  PubMed  Google Scholar 

  106. Garmiri, P., Loua, A., Haba, N., Candotti, D. & Allain, J. P. Deletions and recombinations in the core region of hepatitis B virus genotype E strains from asymptomatic blood donors in Guinea, West Africa. J. Gen. Virol. 90, 2442–2451 (2009).

    Article  CAS  PubMed  Google Scholar 

  107. Tanwar, S. & Dusheiko, G. Is there any value to hepatitis B virus genotype analysis? Curr. Gastroenterol. Rep. 14, 37–46 (2012).

    Article  PubMed  Google Scholar 

  108. Lin, C. L. & Kao, J. H. The clinical implications of hepatitis B virus genotype: recent advances. J. Gastroenterol. Hepatol. 26 (Suppl. 1), 123–130 (2011).

    Article  PubMed  Google Scholar 

  109. Chu, C. J., Hussain, M. & Lok, A. S. Hepatitis B virus genotype B is associated with earlier HBeAg seroconversion compared with hepatitis B virus genotype C. Gastroenterology 122, 1756–1762 (2002).

    Article  CAS  PubMed  Google Scholar 

  110. Wen, J. et al. Hepatitis B virus genotype, mutations, human leukocyte antigen polymorphisms and their interactions in hepatocellular carcinoma: a multi-centre case-control study. Sci. Rep. 5, 16489 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Shimakawa, Y. et al. Natural history of chronic HBV infection in West Africa: a longitudinal population-based study from The Gambia. Gut http://dx.doi.org/10.1136/gutjnl-2015-309892 (2015).

  112. Kew, M. C., Kramvis, A., Yu, M. C., Arakawa, K. & Hodkinson, J. Increased hepatocarcinogenic potential of hepatitis B virus genotype A in Bantu-speaking sub-Saharan Africans. J. Med. Virol. 75, 513–521 (2005).

    Article  CAS  PubMed  Google Scholar 

  113. Kao, J. H. Diagnosis of hepatitis B virus infection through serological and virological markers. Expert Rev. Gastroenterol. Hepatol. 2, 553–562 (2008).

    Article  CAS  PubMed  Google Scholar 

  114. Asabe, S. et al. The size of the viral inoculum contributes to the outcome of hepatitis B virus infection. J. Virol. 83, 9652–9662 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Baumert, T. F., Thimme, R. & von Weizsäcker, F. Pathogenesis of hepatitis B virus infection. World J. Gastroenterol. 13, 82–90 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Komiya, Y. et al. Minimum infectious dose of hepatitis B virus in chimpanzees and difference in the dynamics of viremia between genotype A and genotype C. Transfusion 48, 286–294 (2008).

    PubMed  Google Scholar 

  117. Chu, C. M. & Liaw, Y. F. HBsAg seroclearance in asymptomatic carriers of high endemic areas: appreciably high rates during a long-term follow-up. Hepatology 45, 1187–1192 (2007).

    Article  PubMed  Google Scholar 

  118. Simonetti, J. et al. Clearance of hepatitis B surface antigen and risk of hepatocellular carcinoma in a cohort chronically infected with hepatitis B virus. Hepatology 51, 1531–1537 (2010).

    Article  PubMed  Google Scholar 

  119. Liaw, Y. F. & Chu, C. M. Hepatitis B virus infection. Lancet 373, 582–592 (2009).

    Article  CAS  PubMed  Google Scholar 

  120. Han, S. H. & Tran, T. T. Management of chronic hepatitis B: an overview of practice guidelines for primary care providers. J. Am. Board Fam. Med. 28, 822–837 (2015).

    Article  PubMed  Google Scholar 

  121. Martinot-Peignoux, M. et al. Serum hepatitis B virus DNA levels and liver histology in inactive HBsAg carriers. J. Hepatol. 36, 543–546 (2002).

    Article  CAS  PubMed  Google Scholar 

  122. European Association for the Study of the Liver. EASL clinical practice guidelines: management of chronic hepatitis B virus infection. J. Hepatol. 57, 167–185 (2012).

  123. Hadziyannis, S. J. & Vassilopoulos, D. Hepatitis B e antigen-negative chronic hepatitis B. Hepatology 34, 617–624 (2001).

    Article  CAS  PubMed  Google Scholar 

  124. World Health Organization. Guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection (WHO, 2015).

  125. Gibney, K. B., Torresi, J., Lemoh, C. & Biggs, B. A. Isolated core antibody hepatitis B in sub-Saharan African immigrants. J. Med. Virol. 80, 1565–1569 (2008).

    Article  CAS  PubMed  Google Scholar 

  126. Raimondo, G., Caccamo, G., Filomia, R. & Pollicino, T. Occult HBV infection. Semin. Immunopathol. 35, 39–52 (2013).

    Article  CAS  PubMed  Google Scholar 

  127. Allain, J. P. Occult hepatitis B virus infection. Transfus. Clin. Biol. 11, 18–25 (2004).

    Article  PubMed  Google Scholar 

  128. Squadrito, G., Cacciola, I., Alibrandi, A., Pollicino, T. & Raimondo, G. Impact of occult hepatitis B virus infection on the outcome of chronic hepatitis C. J. Hepatol. 59, 696–700 (2013).

    Article  PubMed  Google Scholar 

  129. Pollicino, T. & Raimondo, G. Occult hepatitis B infection. J. Hepatol. 61, 688–689 (2014).

    Article  PubMed  Google Scholar 

  130. Liaw, Y. F. Natural history of chronic hepatitis B virus infection and long-term outcome under treatment. Liver Int. 29 (Suppl. 1), S100–S107 (2009).

    Article  Google Scholar 

  131. Raimondi, S., Maisonneuve, P., Bruno, S. & Mondelli, M. U. Is response to antiviral treatment influenced by hepatitis B virus genotype? J. Hepatol. 52, 441–449 (2010).

    Article  CAS  PubMed  Google Scholar 

  132. Venook, A. P., Papandreou, C., Furuse, J. & de Guevara, L. L. The incidence and epidemiology of hepatocellular carcinoma: a global and regional perspective. Oncologist 15 (Suppl. 4), 5–13 (2010).

    Article  PubMed  Google Scholar 

  133. Chen, J. D. et al. Carriers of inactive hepatitis B virus are still at risk for hepatocellular carcinoma and liver-related death. Gastroenterology 138, 1747–1754 (2010).

    Article  PubMed  Google Scholar 

  134. Chu, C. M. & Liaw, Y. F. Incidence and risk factors of progression to cirrhosis in inactive carriers of hepatitis B virus. Am. J. Gastroenterol. 104, 1693–1699 (2009).

    Article  PubMed  Google Scholar 

  135. Abbas, Z. & Siddiqui, A. R. Management of hepatitis B in developing countries. World J. Hepatol. 3, 292–299 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  136. Jafri, S. M. & Lok, A. S. Antiviral therapy for chronic hepatitis B. Clin. Liver Dis. 14, 425–438 (2010).

    Article  PubMed  Google Scholar 

  137. Leung, N. W. et al. Extended lamivudine treatment in patients with chronic hepatitis B enhances hepatitis B e antigen seroconversion rates: results after 3 years of therapy. Hepatology 33, 1527–1532 (2001).

    Article  CAS  PubMed  Google Scholar 

  138. Perillo, R. et al. Adefovir dipivoxil for the treatment of lamivudine-resistant hepatitis B mutants. Hepatology 32, 129–134 (2000).

    Article  Google Scholar 

  139. Corsa, A. C. et al. No resistance to tenofovir disoproxil fumarate through 96 weeks of treatment in patients with lamivudine-resistant chronic hepatitis B. Clin. Gastroenterol. Hepatol. 12, 2106–2112.e1 (2014).

    Article  CAS  PubMed  Google Scholar 

  140. Lemoine, M., Nayagam, S. & Thursz, M. Viral hepatitis in resource-limited countries and access to antiviral therapies: current and future challenges. Future Virol. 8, 371–380 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Reijnders, J. G., Perquin, M. J., Zhang, N., Hansen, B. E. & Janssen, H. L. Nucleos(t)ide analogues only induce temporary hepatitis B e antigen seroconversion in most patients with chronic hepatitis B. Gastroenterology 139, 491–498 (2010).

    Article  CAS  PubMed  Google Scholar 

  142. Agarwal, K. et al. Twenty-eight day safety, antiviral activity, and pharmacokinetics of tenofovir alafenamide for treatment of chronic hepatitis B infection. J. Hepatol. 62, 533–540 (2015).

    Article  CAS  PubMed  Google Scholar 

  143. Castera, L. Transient elastography and other noninvasive tests to assess hepatic fibrosis in patients with viral hepatitis. J. Viral Hepat. 16, 300–314 (2009).

    Article  PubMed  Google Scholar 

  144. Kruger, F. C. et al. APRI: a simple bedside marker for advanced fibrosis that can avoid liver biopsy in patients with NAFLD/NASH. S. Afr. Med. J. 101, 477–480 (2011).

    CAS  PubMed  Google Scholar 

  145. Lesmana, C. R. et al. Diagnostic accuracy of transient elastography (FibroScan) versus the aspartate transaminase to platelet ratio index in assessing liver fibrosis in chronic hepatitis B: the role in primary care setting. J. Clin. Pathol. 64, 916–920 (2011).

    Article  PubMed  Google Scholar 

  146. Bonnard, P. et al. Comparison of elastography, serum marker scores, and histology for the assessment of liver fibrosis in hepatitis B virus (HBV)-infected patients in Burkina Faso. Am. J. Trop. Med. Hyg. 82, 454–458 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  147. Tarigan, E. et al. S-Index and APRI score to predict liver fibrosis chronic in hepatitis B and C patients. Indonesian J. Gastroenterol. Hepatol. Dig. Endos. 14, 64–68 (2013).

    Google Scholar 

  148. Chan, H. L. et al. Alanine aminotransferase-based algorithms of liver stiffness measurement by transient elastography (Fibroscan) for liver fibrosis in chronic hepatitis B. J. Viral Hepat. 16, 36–44 (2009).

    Article  PubMed  Google Scholar 

  149. Lemoine, M. et al. The gamma-glutamyl transpeptidase to platelet ratio (GPR) predicts significant liver fibrosis and cirrhosis in patients with chronic HBV infection in West Africa. Gut 65, 1369–1376 (2016).

    Article  CAS  PubMed  Google Scholar 

  150. Li, Q. et al. The gamma-glutamyl-transpeptidase to platelet ratio does not show advantages than APRI and Fib-4 in diagnosing significant fibrosis and cirrhosis in patients with chronic hepatitis B: a retrospective cohort study in China. Medicine (Baltimore) 95, e3372 (2016).

    Article  CAS  Google Scholar 

  151. Zeng, X. et al. Performance of several simple, noninvasive models for assessing significant liver fibrosis in patients with chronic hepatitis B. Croat. Med. J. 56, 272–279 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  152. Buti, M. et al. Tenofovir disoproxil fumarate (TDF) is highly active for treatment of chronic hepatitis B in subjects with cirrhosis. J. Hepatol. 48 (Suppl. 2), S33 (2008).

    Article  Google Scholar 

  153. Piroth, L. et al. Epidemiology, diagnosis and treatment of chronic hepatitis B in HIV-infected patients (EPIB 2005 study). AIDS 21, 1323–1331 (2007).

    Article  PubMed  Google Scholar 

  154. Chang, J. J. et al. Impaired quality of the hepatitis B virus (HBV)-specific T-cell response in human immunodeficiency virus type 1-HBV coinfection. J. Virol. 83, 7649–7658 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Sherman, M. Strategies for managing coinfection with hepatitis B virus and HIV. Cleve. Clin. J. Med. 76 (Suppl. 3), S30–S33 (2009).

    Article  PubMed  Google Scholar 

  156. Ranjbar, R., Davari, A., Izadi, M., Jonaidi, N. & Alavian, S. M. HIV/HBV co-infections: epidemiology, natural history, and treatment: a review article. Iran. Red Crescent Med. J. 13, 855–862 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  157. Wiersma, S. et al. Treatment of chronic hepatitis B virus infection in resource-constrained settings: expert panel consensus. Liver Int. 31, 755–761 (2011).

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Haematology, University of Cambridge, Science Village, Chesterford Research Park, CB10 1XL, Little Chesterford, UK

    Jean-Pierre Allain

  2. Department of Medicine, Kwame Nkrumah University of Science and Technology, University Post Office, Kumasi, Ghana

    Ohene Opare-Sem

Authors
  1. Jean-Pierre Allain
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ohene Opare-Sem
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Both authors contributed equally to all aspects of this manuscript.

Corresponding author

Correspondence to Jean-Pierre Allain.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Allain, JP., Opare-Sem, O. Screening and diagnosis of HBV in low-income and middle-income countries. Nat Rev Gastroenterol Hepatol 13, 643–653 (2016). https://doi.org/10.1038/nrgastro.2016.138

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrgastro.2016.138

This article is cited by

Search

Advanced search

Quick links

Nature Briefing Microbiology

Sign up for the Nature Briefing: Microbiology newsletter — what matters in microbiology research, free to your inbox weekly.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing: Microbiology