Author(s)

Liang Ming ¹, Zhaofan Luo ¹

Affiliation(s)

¹ Department of Clinical Laboratory, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, 518107, China

Corresponding Author

Zhaofan Luo

ABSTRACT

Chronic hepatitis B is one of the most prominent global public health issues, posing a serious threat to human health. Despite the effective reduction in the incidence of hepatitis B due to the use of hepatitis B vaccines in recent years, 10 to 30 million people still become infected with the hepatitis B virus (HBV) annually, and approximately 1 million people die from HBV infection and its complications. To effectively control the spread of HBV and ensure timely treatment for HBV-infected individuals, efficient detection of HBV is particularly important. Nucleic acid detection techniques targeting HBV DNA have been widely applied in diagnosing, monitoring, evaluating prognosis, and screening for blood transfusions due to their advantages of high sensitivity and strong specificity. However, there remain some HBV-infected individuals in clinical practice who harbor low concentrations of HBV DNA that are difficult to detect with existing methods. This not only increases the risk of developing chronic hepatitis, cirrhosis, and primary liver cancer but may also result in HBV infections during blood transfusions and liver transplant procedures. Additionally, the detection and monitoring of antiviral drug resistance mutations in hepatitis B can help prevent treatment failures. Due to the presence of "quasi-species," some patients have extremely low levels of HBV resistant strains that are hard to detect. In certain circumstances, such as liver transplantation and co-infection with hepatitis C virus (HCV), these undetected low-level HBV resistant strains may lead to severe clinical consequences (such as HBV infection and liver failure). Therefore, developing a high-sensitivity detection technology for HBV DNA and resistance mutations holds significant practical importance for the prevention and treatment of hepatitis B. Based on this, this article focuses on exploring the application of high-sensitivity HBV DNA technology in the detection and analysis of the hepatitis B virus, as well as the predictive value for the long-term prognosis of hepatitis B virus patients.

KEYWORDS

Hepatitis B virus; high sensitivity; HBV DNA

CITE THIS PAPER

Liang Ming, Zhaofan Luo, Progress in the application of high sensitivity HBV-DNA technology in the detection and analysis of HBV. Social Medicine and Health Management (2024) Vol. 5: 87-94. DOI: http://dx.doi.org/10.23977/socmhm.2024.050212.

REFERENCES

[1] Schweitzer A, Horn J, Mikolajczyk R T, et al. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013[J]. The Lancet, 2015, 386(10003): 1546-1555.
[2] Hellard M E, Chou R, Easterbrook P. WHO guidelines on testing for hepatitis B and C–meeting targets for testing[J]. BMC Infectious Diseases, 2017, 17: 1-7.
[3] Liaw Y F. Antiviral therapy of chronic hepatitis B: opportunities and challenges in Asia[J]. J Hepatol.2009, 51(2):403-410. 
[4] Clements C J, Baoping Y, Crouch A, et al. Progress in the control of hepatitis B infection in the Western Pacific Region [J]. Vaccine, 2006, 24(12): 1975-1982.
[5] Razavi-Shearer D, Gamkrelidze I, Nguyen M H, et al. Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study[J]. Lancet Gastroenterology & Hepatology, 2018, 3(6): 383-403. 
[6] Lu F, Zhuang H. Management of hepatitis B in China[J]. Chinese medical journal, 2009, 122(1): 3-4.
[7] Murray J M, Purcell R H. and Wieland S F. The half-life of hepatitis B virions[J]. Hepatology. 2006, 44(5):1117-1121.
[8] Nowak M A., Bonhoeffer S, Hill A M, et al. Viral dynamics in hepatitis B virus infection[J]. Proc Natl Acad Sci U S A.1996, 93(9):4398-4402.
[9] Strasfeld L, Chou S. Antiviral drug resistance: mechanisms and clinical implications[J]. Infectious Disease Clinics, 2010, 24(3): 809-833.
[10] Sheldon J, Rodes B, Zoulim F, et al. Mutations affecting the replication capacity of the hepatitis B virus[J]. J Viral Hepat.2006, 13(7):427-434.
[11] Sheldon J. Soriano V. Hepatitis B virus escape mutants induced by antiviral therapy[J]. J Antimicrob Chemother. 2008, 61(4):766-768.
[12] Stuyver L J, Locarnini S A, Lok A, et al. Nomenclature for antiviral resistant human hepatitis B virus mutations in the polymerase region[J]. Frontiers in Viral Hepatitis, 2003: 335-351.
[13] Zoulim F, Durantel D, Deny P. Management and prevention of drug resistance in chronic hepatitis B[J]. Liver International, 2009, 29: 108-115.
[14] Li L, Liu W, Chen Y H, et al. Antiviral drug resistance increases hepatocellular carcinoma: a prospective decompensated cirrhosis cohort study[J]. World Journal of Gastroenterology: WJG, 2013, 19(45): 8373.
[15] Menéndez-Arias L, Álvarez M, Pacheco B. Nucleoside/nucleotide analog inhibitors of hepatitis B virus polymerase: mechanism of action and resistance[J]. Current opinion in virology, 2014, 8: 1-9.
[16] Shen H, Ding F, Wang Z, et al. Comparison of telbivudine and entecavir therapy on nephritic function and drug resistance in patients with hepatitis B virus-related compensated cirrhosis[J]. Cellular Physiology and Biochemistry, 2016, 40(1-2): 370-378.
[17] Ghany M G, Doo E C. Antiviral resistance and hepatitis B therapy[J]. Hepatology, 2009, 49(S5): S174-S184.
[18] Zhang Q, Liao Y, Cai B, et al. Incidence of natural resistance mutations in naïve chronic hepatitis B patients: A systematic review and meta‐analysis[J]. Journal of gastroenterology and hepatology, 2015, 30(2): 252-261.
[19] Kim J E, Lee S Y, Kim H, et al. Naturally occurring mutations in the reverse transcriptase region of hepatitis B virus polymerase from treatment-naïve Korean patients infected with genotype C2[J]. World journal of gastroenterology, 2017, 23(23): 4222.
[20] Hong SunPyo H S P, Kim NamKeun K N K, Hwang SeongGyu H S G, et al. Detection of hepatitis B virus YMDD variants using mass spectrometric analysis of oligonucleotide fragments[J]. Journal of hepatology, 2004, 40(5): 837-844.
[21] de Man R A, Bartholomeusz A I, Niesters H G M, et al. The sequential occurrence of viral mutations in a liver transplant recipient re-infected with hepatitis B: hepatitis B immune globulin escape, famciclovir non-response, followed by lamivudine resistance resulting in graft loss[J]. Journal of hepatology, 1998, 29(4): 669-675.
[22] Seeger C, Mason W S. HBV replication, pathobiology and therapy: Unanswered questions[J]. Journal of Hepatology, 2016, 64(1 Suppl):S1.
[23] Liu F, Wang L, Li X Y, et al. Poor durability of lamivudine effectiveness despite stringent cessation criteria: a prospective clinical study in hepatitis B e antigen‐negative chronic hepatitis B patients[J]. Journal of gastroenterology and hepatology, 2011, 26(3): 456-460.
[24] Diarra B, Yonli A T, Sorgho P A, et al. Occult Hepatitis B Virus Infection and Associated Genotypes among HBsAg-negative Subjects in Burkina Faso[J]. Mediterranean Journal of Hematology & Infectious Diseases, 2018, 10(1):2018007.
[25] Bivigoumboumba B, Amougouatsama M, Zoaassoumou S, et al. Hepatitis B infection among HIV infected individuals in Gabon: Occult hepatitis B enhances HBV DNA prevalence.[J]. Plos One, 2018, 13(1):e0190592.
[26] Yu Jucun, Yao Lei. Detection and analysis of HBV-DNA in occult hepatitis B patients [J]. Western Medicine, 2009, 21(6):1017-1018. (in Chinese)
[27] Lee H C, Suh D J, Ryu S H, et al. Quantitative polymerase chain reaction assay for serum hepatitis B virus DNA as a predictive factor for post-treatment relapse after lamivudine induced hepatitis B e antigen loss or seroconversion[J]. Gut, 2003, 52(12): 1779-1783.
[28] Datta, S., S. Chatterjee, and V. Veer. Recent advances in molecular diagnostics of hepatitis B virus[J]. World J Gastroenterol.2014, 20(40):14615-14625.
[29] Song J E. Diagnosis of hepatitis B[J]. Annals of translational medicine, 2016, 4(18).
[30] Roth W K, Busch M P, Schuller A, et al. International survey on NAT testing of blood donations: expanding implementation and yield from 1999 to 2009[J]. Vox Sanguinis, 2012, 102(1): 82-90.
[31] Busch M P, Glynn S A, Stramer S L, et al. A new strategy for estimating risks of transfusion‐transmitted viral infections based on rates of detection of recently infected donors[J]. Transfusion, 2005, 45(2): 254-264.
[32] Chen C J, Yang H I, Su J U N, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level[J]. Jama, 2006, 295(1): 65-73.
[33] Liu F, Wang L, Li X Y, et al. Poor durability of lamivudine effectiveness despite stringent cessation criteria: a prospective clinical study in hepatitis B e antigen‐negative chronic hepatitis B patients[J]. Journal of gastroenterology and hepatology, 2011, 26(3): 456-460.
[34] Jiang J, Huang Z, He L, et al. Residual amount of HBV DNA in serum is related to relapse in chronic hepatitis B patients after cessation of nucleos (t) ide analogs[J]. Journal of Clinical Gastroenterology, 2015, 49(4): 323-328.
[35] Luan J, Yuan J, Li X, et al. Multiplex detection of 60 hepatitis B virus variants by maldi-tof mass spectrometry[J]. Clinical chemistry, 2009, 55(8): 1503-1509.
[36] Lok A S, Zoulim F, Locarnini S, et al. Antiviral drug‐resistant HBV: standardization of nomenclature and assays and recommendations for management[J]. Hepatology, 2007, 46(1): 254-265.

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