Euroasian journal of hepato-gastroenterology

Register      Login

VOLUME 8 , ISSUE 2 ( July-December, 2018 ) > List of Articles


Hepatitis Screening and Treatment Campaign in Malaysia- Validation of Low-cost Point of Care Screening Tests and Nucleic Acid Tests for Hepatitis B and C

Rosmawati Mohamed, Muhammad Radzi AH, Soek S Tan, Fauziah Jaya, Senamjit K, Azlida C Aun, Ghazali A Kutty, Hin S Wong, Rafidah Abdullah, Mohd R Seman, Zaki Morad, Teck-Onn Lim

Keywords : Access to treatment, Diagnostic test, Health services, Hepatitis B, Hepatitis B virus dioxyribo nucleic acid, Hepatitis C, Hepatitis C virus ribonucleic acid, Nucleic Acid Tests, Point of Care tests, Screening, Validation

Citation Information : Mohamed R, AH MR, Tan SS, Jaya F, SK, Aun AC, Kutty GA, Wong HS, Abdullah R, Seman MR, Morad Z, Lim T. Hepatitis Screening and Treatment Campaign in Malaysia- Validation of Low-cost Point of Care Screening Tests and Nucleic Acid Tests for Hepatitis B and C. Euroasian J Hepatogastroenterol 2018; 8 (2):101-107.

DOI: 10.5005/jp-journals-10018-1273

License: CC BY-NC 4.0

Published Online: 01-01-2019

Copyright Statement:  Copyright © 2018; The Author(s).


Background: Two major challenges in implementing budget-constrained Hepatitis screening and treatment campaign in Malaysia are the availability of low-cost point of care tests (POCT) and nucleic acid tests (NAT) for hepatitis C virus ribonucleic acid (HCV RNA) and hepatitis B virus dioxyribo nucleic acid (HBV DNA). We evaluated the performance of these tests in this study. Methods: We conducted a cross-sectional study to evaluate the diagnostic performance of four POCT brands at 12 sites in Malaysia. We assessed the sensitivity and specificity of the POCTs for the detection of HBsAg and anti-HCV in a finger-stick capillary or venepuncture whole-blood samples compared with test results from lab-based enzyme immunoassay (EIA) or chemi-luminescence immunoassay (CLIA) assay as the reference standard. We also conducted a cross-sectional study on 30 to 139 serum specimen panel to evaluate the diagnostic performance of a low-cost in-house Applied Biosystem®TaqMan real-time polymerase chain reaction (PCR) assay (ABS) for the detection of HCV RNA and HBV DNA, compare with Roche Cobas® Ampliprep/TaqMan assay (COBAS). Results: Between March and December 2017, we enroll 295 participants for the evaluation of POCT for HBsAg and another 307 participants for POCT anti-HCV evaluation. Three of the four POCT brands dropped out of evaluation early on account of sub-optimal sensitivity. The sensitivity of the remaining POCT for HBsAg was 95.2%and specificity 100%, while the POCT for anti-HCV has a sensitivity of 98.1% and specificity 100%. Hepatitis B virus dioxyribo nucleic acid and HCV RNA concentrations detected by the ABS were systematically higher than those measured by COBAS (mean bias +0.10 and +0.17 log10 IU/mL respectively). The 95% limits of agreement between the two assays are -1.28 to 1.47 log10 IU/mL for HBV DNA and –0.41 to 0.75 log10 IU/mL for HCV RNA. Conclusion: We found adequate evidence for the diagnostic validity of a low-cost POCT for anti-HCV and HBsAg, as well as for an in-house nucleic acid tests (NAT), to provide support for their broader use in our Hepatitis screening and treatment campaign. Abbreviations: ABS: Applied Biosystem®TaqMan real-time PCR assay, CI: Confidence interval, CLD: Chronic liver disease, CLIA: Chemi-luminescence immunoassay, COBAS: Roche Cobas® Ampliprep/TaqMan assay, DAA: Direct Acting Anti-Viral drugs, EIA: Enzyme immunoassay, HBV: Hepatitis B virus, HCV: Hepatitis C virus, HFPM: Hepatitis Free Pahang Malaysia, LOA: Limits of agreement, LOD: Limit of detection, MOH: Ministry of Health, Malaysia, NAT: Nucleic Acid Tests, POCT: Point of Care Tests, SD: Standard deviation, WHO: World Health Organization

PDF Share
  1. Institute for Health Metrics and Evaluation., (n.d.). Global Burden Of Diseases, Injuries, And Risk Factors Study 2010, Gbd Profile: Malaysia. Available from http://www.healthdata. org/sites/default/files/files/country_profiles/GBD/ihme_gbd_country_report_malaysia.pdf
  2. Mokdad AA, Lopez AD, Shahraz S, Lozano R, Mokdad AH, Stanaway J, et al. Liver cirrhosis mortality in 187 countries between1980 and 2010: a systematic analysis. BMC Medicine 2014,12:145
  3. Ferlay J, Soerjomataram I, Ervik, M, Dikshit R, Eser S, Mathers, C. (n.d.). GLOBOCAN 2012: Estimated cancer incidence, mortality and prevalence worldwide in 2012 v1.0. IARC Cancer Base 2014,11.
  4. Duraisamy G, Zuridah H, Ariffin MY.Prevalence of hepatitis C virus antibodies in blood donors in Malaysia. Med J Malaysia. 1993 Sep;48(3):313-316.
  5. Ng KP, Saw TL, Wong NWD, Chuah SY et al. The prevalence of Anti-HCV antibody in risk groups and blood donors. Med J Malaysia 1995;50:302-305
  6. Sinniah M, Ooi BG. Hepatitis C–the Malaysian story. Singapore Med J. 1993 Apr;34(2):132-134.
  7. Lee WS, Ng KP. Seroprevalence of Anti-HCV in an Urban Child Population: A Preliminary Study from Kuala Lumpur. Singapore Med J 2001;42(3):100-101.
  8. Malaysia National Renal Registry. Annual Reports of the Malaysian Dialysis and Transplant Registry 2012. Available at:
  9. McDonald SA, Mohamed R, Dahlui M, Naning H, Kamarulzaman A. Bridging the data gaps in the epidemiology of hepatitis C virus infection in Malaysia using multi-parameter evidence synthesis. BMC Infect Dis. 2014 Nov 7;14:564.
  10. McDonald SA, Dahlui M, Mohamed R, Naning H, Shabaruddin FH, Kamarulzaman A. Projections of the Current and Future Disease Burden of Hepatitis C Virus Infection in Malaysia. PLoS ONE June 2015;10(6):e0128091.
  11. Lopez CG. Epidemiology of persistent hepatitis B virus infection. Malaysian J Pathol 1985 Aug;7:7-10.
  12. Tan TC, Vadivale M, Ong CN. Prevalence of Hepatitis B Surface Antigen and Antibody among Health Care Employees in Negri Sembilan, Malaysia, 1989. Asia Pac J Public Health 1992-1993;6:134-139.
  13. Ng KP, Ngeow YF, Rozainah K, Rosmawati M. Hepatitis B seroprevalence among University of Malaya Students in the Post-universal Infant Vaccination Era. Med J Malaysia 2013; Apr;68(2):144-147.
  14. Ng KP, Saw TL, Baki A, Rozainah K, Pang KW, Ramanathan M. Impact of Expanded Programme of Immunization on hepatitis B infection in school children in Malaysia. Med Microbiol Immunol 2005 May;194(3):163-168.
  15. Cheang HK, Wong HT, Ho SC, Chew KS, et al. Immune response in infants after universal hepatitis B vaccination, a community based study in Malaysia. Sing Med J 2013;54:224- 226
  16. Yap SF. Chronic hepatitis B infection in Malaysians. Malays J Pathol. 1994 Jun;16:3-6.
  17. Raihan R. Hepatitis in Malaysia, past present & future, Euro Asian J Hepato-Gastroenterol 2016;Jan-Jun;6(1): 52-55.
  18. Hanafiah KM, Groeger J, Flaxman AD, Wiersma ST. Global Epidemiology of Hepatitis C Virus Infection: New Estimates of Age-Specific Antibody to HCV Seroprevalence. Hepatology 2013 Apr; 57(4):1333-1342
  19. Schweitzer A, Horn J, Mikolajczyk R, Krause G, Ott JJ. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet 2015; Oct 17;386(10003):1546-55.
  20. Ott JJ, Stevens GA, Groeger J, Wiersma ST. Global epidemiology of hepatitis B infection: new estimates of age-specific HBsAg seroprevalence and endemicity. Vaccine 2012 Mar 9;30(12):2212-2219.
  21. Wedemeyer H. Towards interferon-free treatment for all HCV genotypes. Lancet 2015 Jun 20;385(9986):2443-245.
  22. Kaur RP, Ho GF, Mastura MY, Goh PP, Salowi MA, Radzi M, et al. The elephant in the room-Universal coverage for Costly treatments in an upper middle income country. bioRxiv. 2017:21(4)29-36.
  23. Hepatitis Free Pahang Malaysia. Available from https://hepatitisfreemsia.
  24. Philippa J. Easterbrook, on behalf of the WHO Guidelines Development Group. Who to test and how to test for chronic hepatitis C infection –2016 WHO testing guidance for lowand middle-income countries. Journal of Hepatology 2016; Oct;65:S46-S66
  25. Freeman J, Sallie R, Kennedy A, Hieu PT, Jeffreys G, Hill AM. High sustained virological response rates using generic direct acting antiviral treatment for hepatitis C, imported into Australia. Journal of Hepatology. 2016 Jan 1;64(2): S209.
  26. Ghinea N, Lipworth W, Day R, Hill A, Dore GJ, Danta M. Importation of generic hepatitis C therapies: bridging the gap between price and access in high-income countries. Lancet 2017 March 25;389:1268-1272
  27. WHO. Guidelines for the prevention, care and treatment of persons with hepatitis B infection. Geneva: WHO; March 2015
  28. WHO. Guidelines for the screening, care and treatment of persons with chronic hepatitis C infection. Updated version, April 2016. Geneva: World Health Organization; 2016 http:// pdf?ua=1
  29. Fleiss J. Statistical Methods for Rates and Proportions. 2nd ed. New York, NY: John Wiley & Sons Inc; 1981
  30. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986 Feb 8;327(8476):307-310.
  31. WHO guidelines on hepatitis B and C testing. Geneva: World Health Organization; Feb 2017. License: CC BY-NC-SA 3.0 IGO.
  32. Easterbrook PJ. On behalf of the WHO Guidelines Development Groupl. Who to test and how to test for chronic hepatitis C infection 2016 WHO testing guidance for low- and middleincome countries. Journal of Hepatology 2016 Oct; 65:S46- S66
  33. McHugh MP, Wu AHB, Chevaliez S, Pawlotsky JM, Hallin M, Templeton KE. Multicentre Evaluation of the Cepheid Xpert® Hepatitis C Virus (HCV) Viral Load Assay. J Clinical Microbiol 2017 May;55(5):1550-1556.
  34. Rebely J, Lamoury FMJ, Hajarizadeh B, Mowat Y, Marshall AD, Bajis S, et al. Evaluation of the Xpert HCV Viral Load point-of-care assay from venepuncture-collected and fingerstick capillary whole-blood samples: a cohort study. Lancet Gastroenterol Hepatol 2017, Jul;2(7):514-520.
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.