Prevalence and Characteristics of Basal Core Promoter Mutations in Iran and its Correlation with Acute and Chronic Hepatitis B Infection
Keywords:
Acute hepatitis B, Chronic hepatitis B, Basal core promoter, EpidemiologyAbstract
Introduction: Manifestations of HBV infection differ in chronic and acute phases. Therefore, identifying the determinants such as mutations has a vital role in the treatment of the disease. A dual transversion in the basal core promoter (BCP) region is common among HBV patients. Thus, the present study was conducted with the objective of determining the prevalence of basal core promoter (BCP) mutations and its correlation with the outcome of HBV infection.
Method: In this cross-sectional study, samples were obtained from 182 Iranian HBsAg positive patients who were admitted to the Bandar Abbas Blood Transfusion Organization in 2012 and 2013. They were screened by ELISA test using commercial kits to detect serological marker anti-HBc IgM for distinct chronic hepatitis from acute infection. Thereafter, the extracted DNA was used for determination of the BCP mutations by PCR-RFLP technique. Data analyses were performed with SPSS 12 by Mann–Whitney U test, Fisher’s exact probability test, and t-test.
Results: BCP mutations were observed in 15 samples (8.24%) of the study population, and serological tests determined that, among the BCP mutants, one sample (6.67%) was HBeAg positive, 14 samples (93.33%) were HBeAg negative, and four samples (2.2%) were positive for anti-HBc IgM test. Data analysis indicated a statistically significant association between BCP mutations and acute hepatitis (p=0.002). However, no relationship was detected between the prevalences of the BCP mutations and gender of subjects (p>0.567).
Conclusions: The prevalence of BCP variants was low in the south of Iran, and this mutation can lead to acute phase of viral hepatitis.
References
Carman WF, Thursz M, Hadziyannis S, McIntyre G, Colman K, Gioustoz A, et al. Hepatitis B e antigen
negative chronic active hepatitis: hepatitis B virus core mutations occur predominantly in known antigenic
determinants. J Viral Hepatitis. 1995; 2(2): 77-84. doi: 10.1111/j.1365-2893.1995.tb00010.x. PMID:
Huang Y, Deng H, Peng Z, Huang Y, Long Q, Huang A. Mutations of Basal core promoter and precore
regions in hepatitis B virus genotypes B and C. Hepat Mon. 2014; 15(1): e23034. doi:
5812/hepatmon.23034. PMID: 25741368, PMCID: PMC4344649.
Liu CJ, Chen BF, Chen PJ, Lai MY, Huang WL, Kao JH, et al. Role of hepatitis B viral load and basal core
promoter mutation in hepatocellular carcinoma in hepatitis B carriers. J Infect Dis. 2006; 193(9): 1258-65.
doi: 10.1086/502978. PMID: 16586363.
Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology. 2007; 45(2): 507-39. doi: 10.1002/hep.21513.
PMID: 17256718.
Chisari FV, Isogawa M, Wieland SF. Pathogenesis of hepatitis B virus infection. Pathol Biol (Paris). 2010;
(4): 258-66. doi: 10.1016/j.patbio.2009.11.001. PMID: 20116937, PMCID: PMC2888709.
Hunt CM, McGill JM, Allen MI, Condreay LD. Clinical relevance of hepatitis B viral mutations.
Hepatology. 2000; 31(5): 1037-44. doi: 10.1053/he.2000.6709. PMID: 10796877.
Günther S, Fischer L, Pult I, Sterneck M, Will H. Naturally occurring variants of hepatitis B virus. Adv
Virus Res. 1999; 52: 25-137. doi: 10.1016/S0065-3527(08)60298-5. PMID: 10384235.
Tong MJ, Blatt LM, Kao JH, Cheng JT, Corey WG. Basal core promoter T1762/A1764 and precore A1896
gene mutations in hepatitis B surface antigen‐positive hepatocellular carcinoma: a comparison with
chronic carriers. Liver Int. 2007; 27(10): 1356-63. doi: 10.1111/j.1478-3231.2007.01585.x. PMID:
, PMCID: PMC2229667.
Xu Z, Ren X, Liu Y, Li X, Bai S, Zhong Y, et al. Association of hepatitis B virus mutations in basal core
promoter and precore regions with severity of liver disease: an investigation of 793 Chinese patients with
mild and severe chronic hepatitis B and acute-on-chronic liver failure. J Gastroenterol. 2011; 46(3): 391- 400. doi: 10.1007/s00535-010-0315-4. PMID: 20848146.
Qu L, Kuai X, Liu T, Chen T, Ni Z, Shen X. Pre-S deletion and complex mutations of hepatitis B virus
related to young age hepatocellular carcinoma in Qidong, China. PLoS One. 2013; 8(3): e59583. doi:
1371/journal.pone.0059583. PMID: 23555717, PMCID: PMC3610697.
Hamadiyan H, Pour Ashouri F, Rasekhi S. Growth of Head Circumference, Weight and Height from Birth
to 18 Months in the South of Iran. International Electronic Journal of Medicine. 2015; 4(1): 1-5.
Parvar N, Moayedi AR, Rasekhi S. An infant Presenting with Cerebrovascular Accident was Diagnosed as
a Sickle Cell Disease Patient: a Case Report. International Electronic Journal of Medicine. 2016; 5(1): 23- 4.
Igaki N, Nakaji M, Moriguchi R, Akiyama H, Tamada F, Oimomi M, et al. An outbreak of fulminant
hepatitis B in immunocompromised hemodialysis patients. J Gastroenterol. 2003; 38(10): 968-76. doi:
1007/s00535-003-1180-1. PMID: 14614604.
Ito K, Kim KH, Lok AS, Tong S. Characterization of genotype-specific carboxyl-terminal cleavage sites of
hepatitis B virus e antigen precursor and identification of furin as the candidate enzyme. J Virol. 2009;
(8): 3507-17. doi: 10.1128/JVI.02348-08. PMID: 19193799, PMCID: PMC2663268.
Tseng TC, Liu CJ, Yang HC, Chen CL, Yang WT, Tsai CS, et al. Higher proportion of viral basal core
promoter mutant increases the risk of liver cirrhosis in hepatitis B carriers. Gut. 2015; 64(2): 292-302. doi:
1136/gutjnl-2014-306977. PMID: 24763132.
Lee MH, Yang HI, Liu J, Batrla‐Utermann R, Jen CL, Iloeje UH, et al. Prediction models of long‐term
Cirrhosis and hepatocellular carcinoma risk in chronic hepatitis B patients: Risk scores integrating host and
virus profiles. Hepatology. 2013; 58(2): 546-54. doi: 10.1002/hep.26385. PMID: 23504622.
Chu CJ, Keeffe EB, Han SH, Perrillo RP, Min AD, Soldevila-Pico C, et al. Prevalence of HBV
precore/core promoter variants in the United States. Hepatology. 2003; 38(3): 619-28. doi:
1053/jhep.2003.50352. PMID: 12939588.
Pivert A, Servant-Delmas A, Lunel-Fabiani F, Le Guillou-Guillemette H, Laperche S, Ducancelle A.
Correlation between the promoter basal core and precore mutations and HBsAg quantification in French
blood donors infected with hepatitis B virus. J Med Virol. 2015; 87(3): 529-35. doi: 10.1002/jmv.24064.
PMID: 25170961.
Shiina S, Fujino H, Uta Y, Tagawa K, Unuma T, Yoneyama M, et al. Relationship of HBsAg subtypes with
HBeAg/anti-HBe status and chronic liver disease. Part I: Analysis of 1744 HBsAg carriers. Am J
Gastroenterol. 1991; 86(7): 866-71. PMID: 2058629.
Taghavi SA, Tabibi M, Eshraghian A, Keyvani H, Eshraghian H. Prevalence and clinical significance of
hepatitis B Basal core promoter and precore gene mutations in southern Iranian patients. Hepat Mon. 2010;
(4): 294-7. PMID: 22312396, PMCID: PMC3271323.
Amini‐Bavil‐Olyaee S, Sarrami‐Forooshani R, Mahboudi F, Sabahi F, Adeli A, Noorinayer B, et al.
Genotype characterization and phylogenetic analysis of hepatitis B virus isolates from Iranian patients. J
Med Virol. 2005; 75(2): 227-34. doi: 10.1002/jmv.20261. PMID: 15602742.
Pour Ashouri F, Rasekhi S. A Review on Medical Students Mental Health Problems and Proposed
Solutions. International Electronic Journal of Medicine. 2015; 4(1): 23-31.
Hesam AA, Taghipour L, Rasekhi S, Fallahi S, Hesam Z. Investigating the Multiple Aspects of Mental
Health in Infertile Women. Int J Ment Health Addict. 2016; 1-5. doi: 10.1007/s11469-016-9675-1.
Pour Ashouri F, Rasekhi S. Correlation between Religious Beliefs with Mental Health and Academic
Performance in Medical Students. International Electronic Journal of Medicine. 2016; 5(1): 1-6.
Guillevin L, Mahr A, Callard P, Godmer P, Pagnoux C, Leray E, et al. Hepatitis B virus-associated
polyarteritis nodosa: clinical characteristics, outcome, and impact of treatment in 115 patients. Medicine
(Baltimore). 2005; 84(5): 313-22. doi: 10.1097/01.md.0000180792.80212.5e. PMID: 16148731.
Fard SA, Rasekhi S, Ashoorian MJ, Parvizpanah A. Knowledge of dentists of Bandar Abbas toward
anaphylactic shock. Int J PharmTech Res. 2016; 9(4): 299-302.
Kao JH, Chen PJ, Lai MY, Chen DS. Basal core promoter mutations of hepatitis B virus increase the risk of
hepatocellular carcinoma in hepatitis B carriers. Gastroenterology. 2003; 124(2): 327-34. doi:
1053/gast.2003.50053. PMID: 12557138.
Ren X, Xu Z, Liu Y, Li X, Bai S, Ding N, et al. Hepatitis B virus genotype and basal core promoter/precore
mutations are associated with hepatitis B‐related acute‐on‐chronic liver failure without pre‐existing
liver cirrhosis. J Viral Hepat. 2010; 17(12): 887-95. doi: 10.1111/j.1365-2893.2009.01254.x. PMID:
, PMCID: PMC2998700.
Gérolami R, Henry M, Borentain P, Colson P, Botta D, Tamalet C. Fulminant hepatitis B associated with a
specific insertion in the basal core promoter region of hepatitis B virus DNA after immunosuppressive
treatment. Clin Infect Dis. 2005; 40(4): e24-e7. doi: 10.1086/427146. PMID: 15712066.
Published
Issue
Section
License
Copyright (c) 2020 KNOWLEDGE KINGDOM PUBLISHING
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.