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European Journal of Clinical Microbiology & Infectious Diseases
Published in: European Journal of Clinical Microbiology & Infectious Diseases 9/2015

01-09-2015 | Review

Molecular mechanisms underlying HBsAg negativity in occult HBV infection

Author: R. A. A. Pondé

Published in: European Journal of Clinical Microbiology & Infectious Diseases | Issue 9/2015

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Abstract

Although genomic detection is considered the gold standard test on HBV infection identification, the HBsAg investigation is still the most frequent clinical laboratory request to diagnose HBV infection in activity. However, the non-detection of HBsAg in the bloodstream of chronic or acutely infected individuals has been a phenomenon often observed in clinical practice, despite the high sensitivity and specificity of screening assays standardized commercially and adopted in routine. The expansion of knowledge about the hepatitis B virus biology (replication/life cycle, genetic variability/mutability/heterogeneity), their biochemical and immunological properties (antigenicity and immunogenicity), in turn, has allowed to elucidate some mechanisms that may explain the occurrence of this phenomenon. Therefore, the negativity for HBsAg during the acute or chronic infection course may become a fragile or at least questionable result. This manuscript discusses some mechanisms that could explain the negativity for HBsAg in a serological profile of individuals with HBV infection in activity, or factors that could compromise its detection in the bloodstream during HBV infection.
Literature
1.
Blumberg BS, Alter HJ, Visnich S (1963) A ‘new’ antigen in leukemia sera. JAMA 191:541–546
2.
Prince AM (1968) An antigen detected in the blood during the incubation period of serum hepatitis. Proc Natl Acad Sci 60:814–821PubMedCentralPubMed
3.
Almeida R, Cardoso D (2006) Detection of HBV DNA by nested-PCR in a HBsAg and anti-HBc negative blood bank donor. J Clin Virol 36:231–234PubMed
4.
Weber B (2005) Genetic variability of the S gene of hepatitis B virus: clinical and diagnostic impact. J Clin Virol 32:102–112PubMed
5.
Chaudhuri V, Tayal R, Nayak B, Acharya SK, Panda SK (2004) Occult hepatitis B virus infection in chronic liver disease: full-length genome and analysis of mutant surface promoter. Gastroenterology 127(5):1356–1371PubMed
6.
Pondé R (2013) Atypical serological profile in hepatitis B infection. Eur Clin Microbiol Infect Dis 32(4):461–476
7.
8.
Mangold C, Unckell F, Werr M, Streeck R (1997) Analysis of intermolecular disulfide bonds and free sulfhydryl groups in hepatitis B surface antigen particles. Arch Virol 142(11):2257–2267PubMed
9.
Weber B (2004) The diagnostic and clinical impact of the genetic variability of the s gene of hepatitis B virus. J Lab Med 28(1):56–69
10.
Carman WF (1997) The clinical significance of surface antigen variants of hepatitis B virus. J Viral Hepat 4(Suppl1):11–20PubMed
11.
Seddigh-Tonekaboni S, Waters JA, Jeffers S, Gehrke R, Ofenloch B, Horsch A, Hess G, Thomas HC, Karayiannis P (2000) Effect of variation in the common “a” determinant on the antigenicity of hepatitis B surface antigen. J Med Virol 60:113–121PubMed
12.
Carman WF, Zanetti AR, Karayiannis P, Waters J, Manzillop G, Tanzi E, Zuckerman AJ, Thomas HC (1990) Vaccine-induced escape mutant of hepatitis B virus. Lancet 336:325–329PubMed
13.
Waters J, Kennedy M, Voet P, Hauser P, Petre J, Carman W, Thomas H (1992) Loss of the common ‘a’ determinant of hepatitis B surface antigen by a vaccine-induced escape mutant. J Clin Invest 90:2543–2547PubMedCentralPubMed
14.
Karthiguesu V, Allison L, Fortuin M, Mendy M, Whittle H, Howard C (1994) A novel hepatitis B virus in the sera of immunized children. J Gen Virol 75:443–448
15.
Ma Q, Wang Y (2012) Comprehensive analysis of the prevalence of hepatitis B virus escape mutations in the major hydrophilic region of surface antigen. J Med Virol 84:198–206PubMed
16.
Bruce S, Murray K (1995) Mutations of some critical amino acid residues in the hepatitis B virus surface antigen. J Med Virol 46:157–161PubMed
17.
Antoni B, Rodriguez-Crespo I, Gomez-Gutierrez J, Nieto M, Peterson D, Gavilanes F (1994) Site-directed mutagenesis of cysteine residues of hepatitis B surface antigen. Analysis of two single mutants and the double mutant. Eur J Biochem 222:121–127PubMed
18.
Mangold C, Unckell F, Werr M, Streeck R (1995) Secretion and antigenicity of hepatitis small envelope proteins lacking cysteines in the major antigenic region. Virology 211:535–543PubMed
19.
Kfoury E, Zheng J, Mazuruk K, Van Le A, Peterson DL (2001) Characterization of a novel hepatitis B virus mutant: demonstration of mutation-induced hepatitis B virus surface antigen group specific ‘a’ determinant conformation change and its application in diagnostic assays. Transfus Med 11(5):355–362
20.
Tian Y, Xu Y, Zhang Z, Meng Z, Qin L, Lu M, Yang D (2007) The amino acid residues at positions 120 to 123 are crucial for theantigenicity of hepatitis B surface antigen. J Clin Microbiol 45(9):2971PubMedCentralPubMed
21.
Osiowy C (2006) Detection of HBsAg mutants. J Med Virol 78:S48–S51PubMed
22.
Coleman PF (2006) Detecting hepatitis B surface antigen mutants. Emerg Infect Dis 2(2):198–203
23.
Locarnini S, Mcmillan J, Bartholomeusz A (2003) The hepatitis B virus and common mutants. Semin Liver Dis 23(1):5–20PubMed
24.
Weinberger KM, Bauer T, Böhm S, Jilg W (2000) High genetic variability of the group-specific a-determinant of hepatitis B virus surface antigen (HBsAg) and the corresponding fragment of the viral polymerase in chronic virus carriers lacking detectable HBsAg in serum. J Gen Virol 81:1165–1174PubMed
25.
Carman WF, Korula J, Wallace L, MacPhee R, Mimms L, Decker R (1995) Fulminant reactivation of hepatitis B due to envelope protein mutant that escaped detection by monoclonal HBsAg ELISA. Lancet 345:1406–1407PubMed
26.
Zuckerman JN, Zuckerman AJ (2000) Current topics in hepatitis B. J Infect 41:130–136PubMed
27.
Kohno H, Inoue T, Tsuda F, Okamoto H, Akahane Y (1996) Mutations in the envelope gene of hepatitis B virus variants co-occurring with antibody to surface antigen in sera from patients with chronic hepatitis B. J Gen Virol 77:1825–1831PubMed
28.
Ho M, Mau Y, Lu C, Huang S, Hsu L, Lin S, Hsu H (1998) Patterns of circulating hepatitis B surface antigen variants among vaccinated children born to hepatitis B surface antigen carrier and non-carrier mothers. A population-based comparative study. J Biomed Sci 5:355–362PubMed
29.
Avellon A, Echevarria J (2006) Frequency of hepatitis B virus ‘a’ determinant variants in unselected Spanish chronic carriers. J Med Virol 78:24–36PubMed
30.
Chudy M, Scheiblauer H, Hanschmann K, Kress J, Nick S, Wend U, Schuttler C, Nubling C, Gerlich W (2013) Performance of hepatitis B surface antigen tests with the first WHO international hepatitis B virus genotype reference panel. J Clin Virol 58(1):47–53PubMed
31.
Coleman PF, Chen YC, Mushahwar IK (1999) Immunoassay detection of hepatitis B surface antigen mutants. J Med Virol 59:19–24PubMed
32.
Moerman B, Moons V, Sommer H, Schmitt Y, Stetter M (2004) Evaluation of sensitivity for wild type and mutant forms of hepatitis B surface antigen by four commercial HBsAg assays. Clin Lab 50(3–4):159–162PubMed
33.
Ly T, Servant-Delmas A, Bagot S, Gonzalo S, Férey M-P, Ebel A, Dussaix E, Laperche S, Roque-Afonso A-M (2006) Sensitivities of four new commercial hepatitis B virus surface antigen (HBsAg) assays in detection of HBsAg mutant forms. J Clin Microbiol 44(7):2321–2326PubMedCentralPubMed
34.
Louisirirotchanakul S, Kanoksinsombat C, O’Charoen R, Fongsatikul L, Puapairoj C, Lulitanond V, Appassakij H, Promwong C, Wasi C (2006) HBsAg diagnostic kits in the detection of hepatitis B virus mutation within “a” determinant. Viral Immunol 19(1):108–114PubMed
35.
Jongerius JM, Wester M, Cuypers HT, van Oostendorp WR, Lelie PN, van der Poel CL, van Leeuwen EF (1998) New hepatitis B virus mutant form in a blood donor that is undetectable in several hepatitis B surface antigen screening assays. Transfusion 38(1):56–59PubMed
36.
Oon C, Lim G, Ye Z, Goh K, Tan K, Yo S, Hopes E, Harrisonn T, Zuckeran A (1995) Molecular epidemiology of hepatitis B virus vaccine variants in Singapore. Vaccine 13:699–702PubMed
37.
Lee KM, Kim YS, Ko YY, Yoo BM, Lee KJ, Kim JH, Hahn KB, Cho SW (2001) Emergence of vaccine-induced escape mutant of hepatitis B virus with multiple surface gene mutations in a Korean child. J Korean Med Sci 16:359–362PubMedCentralPubMed
38.
Santantonio T, Gunther S, Sterneck M, Rendina M, Messner M, Launois B, Francavilla A, Pastore G, Will H (1999) Liver graft infection by HBV s-gene mutants in transplant patients receiving long-term HBIg prophylaxis. Hepatogastroenterology 46:1848–1854PubMed
39.
Pondé RA, Cardoso DD, Ferro MO (2010) The underlying mechanisms for the ‘anti-HBc alone’ serological profile. Arch Virol 155(2):149–158PubMed
40.
Pondé RA (2011) The underlying mechanisms for the simultaneous HBsAg and anti-HBs serological profile. Eur J Clin Microbiol Infect Dis 30:1325–1340PubMed
41.
Gerlich WH (2004) Diagnostic problems caused by HBsAg mutants. A consensus report of an expert meeting. Intervirology 47:310–313PubMed
42.
Lehninger AL, Nelson DL, Cox MM (1993) Amino acids and peptides. In: Lehninger (ed) Principles of biochemistry, 2nd edn. Worth Publishers, New York, pp 111–133
43.
Chiou H-L, Lee T-S, Kuo J, Mau Y-C, Ho M-S (1997) Altered antigenicity of ‘a’ determinant variants of hepatitis B vírus. J Gen Virol 78:2639–2645PubMed
44.
Kyte J, Doolittle R (1982) A simple method displaying the hydropathic character of a protein. J Mol Biol 157(1):105–132PubMed
45.
Ren FR, Tsubota A, Hirokawa T, Kumada H, Yang ZH, Tanaka H (2006) A unique amino acid substitution, T126I, in human genotype C of hepatitis B virus S gene and its possible influence on antigenic structural change. Gene 383:43–51PubMed
46.
Ie SI, Thedja M, Roni M, Muljono D (2010) Prediction of conformational changes by single mutation in the hepatitis B virus surface antigen (HBsAg) identified in HBsAg-negative blood donors. Virol J 7:326PubMedCentralPubMed
47.
Magnius LO, Norder H (1995) Subtypes, genotypes and molecular epidemiology of the hepatitis B virus as reflected by sequence variability of the S-gene. Intervirology 38(1–2):24–34PubMed
48.
Baclig M, Alvarez M, Gopez-Cervantes J, Natividad F (2014) Unique surface gene variants of hepatitis B virus isolated from patients in the Philippines. J Med Virol 86(2):209–216PubMed
49.
Wu C, Zhang X, Tian Y, Song J, Yang D, Roggendorf M, Lu M, Chen X (2010) Biological significance of amino acid substitutions in hepatitis B surface antigen (HBsAg) for glycosylation, secretion, antigenicity and immunogenicity of HBsAg and hepatitis B virus replication. J Gen Virol 91:483–492PubMed
50.
Ijaz S, Szypulska R, Andrews N, Tedder R (2012) Investigating the impact of hepatitis B virus surface gene polymorphism on antigenicity using ex vivo phenotyping. J Gen Virol 93:2473–2479PubMed
51.
Pollock D, Thiltgen G, Goldstein R (2012) Amino acid coevolution induces an evolutionary Stokes shift. Proc Natl Acad Sci USA 109(21):E1352–E1359PubMedCentralPubMed
52.
Oon CJ, Chen WN, Goo KT, Tan KL, Yo SL (2000) Intrafamiliar evidence of horizontal transmission of hepatitis B virus surface antigen mutant G145R. J Infect 41:260–264PubMed
53.
Kramvis A, Kew MC (1999) The core promoter of hepatitis B virus. J Viral Hepat 6(6):415–427PubMed
54.
López-Cabrera M, Letovsky J, Hu KQ, Siddiqui A (1991) Transcriptional factor C/EBP binds to and transactivates the enhancer element II of the hepatitis B virus. Virology 183(2):825–829PubMed
55.
Kreutz C (2002) Molecular, immunological and clinical properties of mutated hepatitis B viruses. J Cell Mol Med 6(1):113–143PubMed
56.
Uchida T, Shimojima S, Gotoh K, Shikata T, Mima S (1994) Pathology of livers infected with “silent” hepatitis B virus mutant. Liver 14:251–256PubMed
57.
Fukuda R, Ishimura N, Kushiyama Y, Moriyama N, Ishihara S, Chowdhury A, Tokuda A, Sakai S, Akagi S, Watanabe M, Fukumoto S (1996) Hepatitis B virus with X gene mutation is associated with the majority of serologically “silent” non-B, non-C chronic hepatitis. Microbiol Immunol 40:481–488PubMed
58.
Tang H, Oishi N, Kaneko S, Murakami S (2006) Molecular functions and biological roles of hepatitis B virus x protein. Cancer Sci 97(10):977–983PubMed
59.
Wei Y, Neuveut C, Tiollais P, Buendia MA (2010) Molecular biology of the hepatitis B virus and role of the X gene. Pathol Biol (Paris) 58(4):267–272
60.
Xu Z, Yen TS, Wu L, Madden CR, Tan W, Slagle BL, Ou JH (2002) Enhancement of hepatitis B virus replication by its X protein in transgenic mice. J Virol 76:2579–2584PubMedCentralPubMed
61.
Bouchard MJ, Puro RJ, Wang L, Schneider RJ (2003) Activation and inhibition of cellular calcium and tyrosine kinase signaling pathways identify targets of the HBx protein involved in hepatitis B virus replication. J Virol 77:7713–7719PubMedCentralPubMed
62.
Fujise K, Tatsuzawa K, Kono M, Hoshina S, Tsubota A, Niiya M, Namiki Y, Tada N, Tajiri H (2011) A mutation of the start codon in the X region of hepatitis B virus DNA in a patient with non-B, non-C chronic hepatitis. World J Hepatol 3(2):56–60PubMedCentralPubMed
63.
Torresi J (2002) The virological and clinical significance of mutations in the overlapping envelope and polymerase genes of hepatitis B virus. J Clin Virol 25(2):97–106PubMed
64.
Dienstag JL, Schiff ER, Wright TL, Perrillo RP, Hann HW, Goodman Z, Crowther L, Condreay LD, Woessner M, Rubin M, Brown NA (1999) Lamivudine as initial treatment for chronic hepatitis B in the United States. N Engl J Med 341(17):1256–1263PubMed
65.
Perillo R, Rakela J, Dienstag J, Levy G, Martin P, Wright T, Caldwell S, Schiff E, Gish R, Villeneneuve J, Farr G, Anschuetz G, Crowther L, Brown N (1999) Multicenter study of lamivudine therapy for hepatitis B virus after liver transplantation. Hepatology 29(5):1581–1586
66.
Torresi J, Erneste-Silveira L, Civitico G, Walters T, Lewin S, Fyfe J, Locarnini S, Manns M, Trautwein C, Bock T (2002) Restoration of replication phenotype of lamivudine-resistant Hepatitis B mutants by compensatory changes in the fingers subdomain of the viral polymerase selected as a consequence of mutations in the overlapping S gene. Virology 299(1):88–99PubMed
67.
Yeh C, Chien R, Chu C, Liaw YF (2000) Clearance of the original hepatitis B virus YMDD-motif mutants with emergence of distinct lamivudine-resistant mutants during prolonged lamivudine therapy. Hepatology 31:1318–1326PubMed
68.
Gaillard RK, Barnard J, Lopez V, Hodges P, Bourne E, Johnson L, Allen MI, Condreay P, Miller WH, Condreay LD (2002) Kinetic analysis of wild-type and YMDD mutant hepatitis B virus polymerases and effects of deoxyribonucleotide concentrations on polymerase activity. Antimicrob Agents Chemother 46:1005–1013PubMedCentralPubMed
69.
Yeh C (2010) Development of HBV s gene mutants in chronic hepatitis B patients receiving nucleotide/nucleoside analogue therapy. Antivir Ther 15:471–475PubMed
70.
71.
Chang CN, Skalski V, Zhou JH, Cheng YC (1992) Biochemical pharmacology of (+)- and (−)-2′,3′-dideoxy-3′-thiacytidine as anti-hepatitis B virus agents. J Biol Chem 267(31):22414–22420PubMed
72.
Severini A, Liu XY, Wilson JS, Tyrrell DL (1995) Mechanism of inhibition of duck hepatitis B virus polymerase by (−)-beta-L-2′,3′-dideoxy-3′-thiacytidine. Antimicrob Agents Chemother 39(7):1430–1435PubMedCentralPubMed
73.
Angus P, Vaughan R, Yiong S, Yang H, Delaney W, Gibbs C, Brosgart C, Colledge D, Edwards R, Ayres A, Bartholomeusz A, Locarnini S (2003) Resistance to adefovir dipivoxil therapy associated with the selection of a novel mutations in the HBV polymerase. Gastroenterology 125:292–297PubMed
74.
Sheldon J, Camino N, Rodes B (2005) Selection of hepatitis B virus polymerase mutations in HIV-coinfected patients treated with tenefovir. Antivir Ther 10:727–734PubMed
75.
Yang H, Westland CE, Delaney W (2002) Resistance surveillance in chronic hepatitis B patients treated with adefovir dipivoxil for up to 60 weeks. Hepatology 36:464–473PubMed
76.
Wakil SM, Kazim SN, Khan LA (2002) Prevalence and profile of mutations associated with lamivudine therapy in Indian patients with chronic hepatitis B in the surface and polymerase genes of hepatitis B virus. J Med Virol 68:311–318PubMed
77.
Pichoud C, Seigneres B, Wang Z, Trepo C, Zoulim F (1999) Transient selection of a hepatitis B virus polymerase gene mutant associated with a decreased replication capacity and famciclovir resistance. Hepatology 29:230–237PubMed
78.
Xiong X, Yang H, Westland CE, Zou R, Gibbs CS (2000) In vitro evaluation of hepatitis B virus polymerase mutations associated with famciclovir resistance. Hepatology 31:219–224PubMed
79.
Zarski JP, Bohn B, Bastie A, Pawlotsky JM, Baug M, Bost-Bezeaux F, Nhieu J, Seigneurin JM, Buffet C, Dhumeaux D (1998) Characteristics of patients with dual infection by hepatitis B and C viruses. J Hepatol 28(1):27–33PubMed
80.
Squadrito G, Orlando ME, Pollicino T, Raffa G, Restuccia T, Cacciola I, Di Marco V, Picciotto A, Colucci G, Craxi A, Raimondo G (2002) Virological profiles in patients with chronic hepatitis C and overt or occult HBV infection. Am J Gastroenterol 97(6):1518–1523PubMed
81.
Otedo AE, McLigeyo SO, Okoth FA, Kayima JK (2003) Seroprevalence of hepatitis B and C in maintenance dialysis in a public hospital in a developing country. S Afr Med J 93(5):380–384PubMed
82.
83.
Chen SY, Kao CF, Chen CM, Shih CM, Hsu MJ, Chao CH, Wang SH, You LR, Lee YH (2003) Mechanisms for inhibition of hepatitis B virus gene expression and replication by hepatitis C virus core protein. J Biol Chem 278:591–607PubMed
84.
Lusida MI, Sakugawa H, Motroko N-F, Muluanto S, Handajani R, Boediwarsono SPB, Nidom CA, Ohgimoto S, Hotta H (2003) Genotype and subtype analyses of hepatitis B virus (HBV) and possible co-infection of HBV and hepatitis c virus (HCV) or hepatitis D virus (HDV) in blood donors, patients with chronic liver disease and patients on hemodialysis is Surabaya, Indonesia. Microbiol Immunol 47(12):969–975PubMed
85.
Cacciola I, Pollicino T, Squadrito G, Cerenzia G, Orlando ME, Raimondo G (1999) Occult hepatitis B virus infection in patients with chronic hepatitis C liver disease. N Engl J Med 341:22–26PubMed
86.
Squadrito G, Pollicino T, Cacciola I, Caccamo G, Villari D, La Masa T, Restuccia T, Cucinotta E, Scisca C, Magazzu D, Raimondo G (2006) Occult hepatitis B virus infection is associated with the development of hepatocellular carcinoma in chronic hepatitis C patients. Cancer 106(6):1326–1330PubMed
87.
Hofer M, Joller-Jemelka HI, Grob PJ, Luthy R, Opravil M (1998) Frequent chronic hepatitis B virus infection in HIV-infected patients positive for antibody to hepatitis B core antigen only. Swiss HIV Cohort Study. Eur J Clin Microbiol Infect Dis 17:6–13PubMed
88.
Gupta S, Singh S (2010) Occult hepatitis B virus infection in ART-naïve HIV-infected patients seen at a tertiary care centre in north India. BMC Infect Dis 10:53PubMedCentralPubMed
89.
Togashi H, Hashimoto C, Yokozawa J, SuzukiA SK, Saito T, Yamaguchi I, Badawi H, Kainuma N, Aoyama M, Ohya H, Akatsuka T, Tanaka Y, Mizokami M, Kawata S (2008) What can be revealed by extending the sensitivity of HBsAg detection to below the present limit? J Hepatol 49:17–24PubMed
90.
Bréchot C, Thiers V, Kremsdorf D, Nalpas B, Pol S, Paterlini-Bréchot P (2001) Persistent hepatitis B virus infection in subjects without hepatitis B surface antigen: clinically significant or purely “occult”? Hepatology 34(1):194–203PubMed
91.
Marusawa H, Uemoto S, Hijikata M, Ueda Y, Tanaka K, Shimotohno K, Chiba T (2000) Latent hepatitis B virus infection in healthy individuals with antibodies to hepatitis B core antigen. Hepatology 31(2):488–495PubMed
92.
Bodhiphala P, Chiewssilp P, Chaturachumroenchai S, Pruksananonda P (1999) Detection of HBV genome by gene amplification method in HBsAg negative blood donors. J Med Assoc Thail 82(5):491–495
93.
Wang JT, Wang TH, Lee C-Z, Chen P-J, Wang T-H, Chen D-S (2002) Transfusion-transmitted HBV infection in an endemic area: the necessity of more sensitive screening for HBV carriers. Transfusion 42:1592–1597PubMed
94.
95.
Raimondo G, Pollicino T, Cacciola I, Saquadrito (2007) Occult hepatitis B virus infection. J Hepatol 46:160–170PubMed
96.
Raimondo G, Navarra G, Mondello S, Constantino L, Colloredo G, Cucinotta E, Di Vita G, Scisca C, Squadrito G, Pollicino T (2008) Occult hepatitis B virus in liver tissue of individuals without hepatic disease. J Hepatol 48:743–746PubMed
97.
Zoulin F (2005) New insight on hepatitis B virus persistence from the study of intrahepatic viral cccDNA. J Hepatol 42:302–308
98.
Caruntu F, Molagic V (2005) CccDNA persistence during natural evolution of chronic HBV infection. Rom J Gastroenterol 14:373–377PubMed
99.
Rapicetta M, Ferrari C, Levrero M (2002) Viral determinants and host immune responses in the pathogenesis of HBV infection. J Med Virol 67:454–457PubMed
100.
Dervite I, Hober D, Morel P (2001) Acute hepatitis B in patient with antibodies to hepatitis B surface antigen who was receiving rituximab. N Engl J Med 344:68–69PubMed
101.
Sera T, Hiasa Y, Michitaka K, Konishi I, Matsura K, Tokumoto Y, Matsuura B, Kajiwara T, Masumoto T, Horike N, Onji M (2006) Anti-HBs-positive liver failure due to hepatitis B vírus reactivation induced by rituximab. Intern Med 45(11):721–724PubMed
102.
Altfeld M, Rockstroh JK, Addo M (1998) Reactivation of hepatitis B in a long-term anti-HBs-positive patient with AIDS following lamivudine withdrawal. J Hepatol 29:306–309PubMed
103.
104.
Guidotti LG, Chisari FV (2001) Non cytolytic control of viral infections by the innate and adaptive immune response. Annu Rev Immunol 19:65–91PubMed
105.
Rehermann B, Ferrari C, Pasquinelli C, Chisari FV (1996) The hepatitis B virus persists for decades after patients’ recovery from acute viral hepatitis despite active maintenance of a cytotoxic Tlymphocyte response. Nat Med 2:1104–1108PubMed
106.
Raimondo G, Burk R, Lieberman H, Muschel J, Hadziyannis S, Will H, Kew M, Dusheiko G, Shafritz D (1988) Interrupted replication of hepatitis B virus in liver tissue of HBsAg carriers with hepatocellular carcinoma. Virology 166:103–112PubMed
107.
Loffler-Mary H, Dumortier J, Klentsch-Zimmer C, Prange R (2000) Hepatitis B virus assembly is sensitive to changes in the cytosolic S loop of the envelope proteins. Virology 270:358–367PubMed
108.
Tan WS, Dyson MR, Murray K (1999) Two distinct segments of the hepatitis B virus surface antigen contribute synergistically to its association with the viral core particles. J Mol Biol 286:797–808PubMed
109.
Mangold CT, Streeck RE (1993) Mutational analysis of the cysteine residues in the hepatitis B virus small envelope protein. J Virol 67:4588–4597PubMedCentralPubMed
110.
Biswas S, Candotti D, Allain J-P (2013) Specific amino acid substitutions in the S protein prevent its excretion in vitro and may contribute to occult hepatitis B virus infection. J Virol 87(14):7882–7892PubMedCentralPubMed
111.
Chua PK, Wang RY, Lin MH, Masuda T, Suk FM, Shih C (2005) Reduced secretion of virions and hepatitis B virus (HBV) surface antigen of a naturally occurring HBV variant correlates with the accumulation of the small S envelope protein in the endoplasmic reticulum and Golgi apparatus. J Virol 79:13483–13496PubMedCentralPubMed
112.
Bock C, Tillmann H, Manns M, Trautwein C (1999) The pre-S region determines the intracellular localization and appearance of hepatitis B virus. Hepatology 30(2):517–525PubMed
113.
Melegari M, Pier PS, Wands JR (1997) The small envelope protein is required for secretions of a naturally occurring hepatitis B virus mutant with pre-S1 deleted. J Virol 7(71):5449–5454
114.
Bock C, Tillman H, Maschek H, Manns M, Trautwein C (1997) A pre-S mutation isolated from a patient with chronic hepatitis B infection leads to virus retention and misassembly. Gastroenterology 113:1976–1982PubMed
115.
Bruss V, Ganem D (1991) The role of envelope proteins in hepatitis B virus assembly. Proc Natl Acad Sci USA 88:1059–1063PubMedCentralPubMed
116.
Ueda K, Tsurimoto T, Matsubara K (1991) Three envelope proteins of hepatitis B virus: large S, middle S, and major S proteins needed for the formation of Dane particles. J Virol 65:3521–3529PubMedCentralPubMed
117.
Ou JH, Rutter WJ (1987) Regulation of secretion of the hepatitis B virus major surface antigen by the preS-1 protein. J Virol 61:782–786PubMedCentralPubMed
118.
Sengupta S, Rehman S, Durgapal H, Acharya S, Panda S (2007) Role of surface promoter mutations in hepatitis B surface antigen production and secretion in occult hepatitis B virus infection. J Med Virol 79:220–228PubMed
119.
Garcia T, Li J, Sureau C, Ito K, Qin Y, Wands J, Tong S (2009) Drastic reduction in the production of subviral particles does not impair hepatitis B virus virion secretion. J Virol 83(21):11152–11165PubMedCentralPubMed
120.
Chaudhuri V, Tayal R, Nayak B, Acharya SK, Panda SK (2004) Occult hepatitis B virus infection in chronic liver disease: full-length genome and analysis of mutant surface promoter. Gastroenterology 127:1356–1371PubMed
121.
Hsieh YH, Su IJ, Wang HC, Chang WW, Lei HY, Lai MD, Chang WT, Huang W (2004) Pre-S mutant surface antigens in chronic hepatitis B virus infection induce oxidative stress and DNA damage. Carcinogenesis 25:2023–2032PubMed
122.
Xu Z, Yen TS (1996) Intracellular retention of surface protein by a hepatitis B virus mutant that releases virion particles. J Virol 70:133–140PubMedCentralPubMed
123.
Lu C-C, Chen M, Ou J-H, Yen TS (1995) Key role of a CCAAT element in regulating hepatitis B virus surface protein expression. Virology 206:1155–1158PubMed
124.
Zhou D-X, Yen TS (1991) The hepatitis B virus S promoter comprises a CCAAT motif and two initiation regions. J Biol Chem 226(34):23416–23421
125.
Lu CC, Yen TS (1996) Activation of the hepatitis B virus s promoter by transcription factor NF-Y via a CCAAT welement. Virology 225:387–394PubMed
126.
Xu Z, Jensen G, Yen TS (1997) Activation of hepatitis B virus S promoter by the viral large surface protein via induction of stress in the endoplasmic reticulum. J Virol 71:7387–7392PubMedCentralPubMed
127.
Yeung P, Wong D, Lai C-L, Fung J, Seto W-K, Yuen M-F (2011) Association of hepatitis B virus pre-S deletions with the development of hepatocellular carcinoma in chronic hepatitis B. J Infect Dis 203(5):646–654PubMedCentralPubMed
128.
Candotti D, Lin C, Belkhir D, Sakuldamrongpanich T, Biswas S, Lin S, Teo D, Ayob Y, Allain J-P (2012) Occult hepatitis B infection in blood donors from South East Asia: molecular characterization and potential mechanisms of occurrence. Gut 61:1744–1753PubMed
129.
zu Putlitz J, Tong S, Wands JR (1999) A short region in the genome of hepatitis B virus is critical for maintenance of high transcript levels. Virology 254(2):245–256PubMed
130.
Hass M, Hannoun C, Kalinina T, Sommer G, Manegold C, Günther S (2005) Functional analysis of hepatitis B virus reactivating in hepatitis B surface antigen-negative individuals. Hepatology 42:93e103
131.
Baumert T, Kock J, Blum H (2005) A novel target of hepatitis B virus mutations: splicing of surface RNA. Hepatology 45(1):21–24
132.
Bruss V (2004) Envelopment of the hepatitis B virus nucleocapsid. Virus Res 106:199–209PubMed
133.
van Hemert FJ, Zaaijer HL, Berkhout B, Lukashov VV (2008) Occult hepatitis B infection: an evolutionary scenario. Virol J 5:146PubMedCentralPubMed
134.
Gunther S, Sommer G, Iwanska A, Will H (1997) Heterogeneity and common features of defective hepatitis B virus genomes derived from spliced pregenomic RNA. Virology 238(2):363–371PubMed
135.
Soussan P, Garreau F, Zylberberg H, Ferray C, Brechot C, Kremsdorf D (2000) In vivo expression of a new hepatitis B virus protein encoded by a spliced RNA. J Clin Invest 105:55–60PubMedCentralPubMed
136.
Helenius A, Aebi M (2004) Roles of N-linked glycans in the endoplasmic reticulum. Annu Rev Biochem 73:1019–1049PubMed
137.
Mellquist J, Kasturi L, Spitalnik S, Shakin-Eshleman (1998) The amino acid following an Asn-X-Ser/Thr Sequon is a important determinant of N-linked core glycosylation efficiency. Biochemistry 37:6833–6837PubMed
138.
Mehta A, Lu X, Block T, Blumberg B, Dwek R (1997) Hepatitis B virus (HBV) envelope glycoproteins vary drastically in their sensitivity to glycan processing: evidence that alteration of a single N-linked glycosylation site can regulate HBV secretion. Proc Natl Acad Sci USA 94:1822–1827PubMedCentralPubMed
139.
Schmitt S, Glebe D, Tolle T, Lochnit G, Linder D, Geyer R, Gerlich W (2004) Structure of pre-S2 N- and O-linked glycans in surface proteins from different genotypes of hepatitis B virus. J Gen Virol 85:2045–2053PubMed
140.
Lu X, Mehta A, Dwek R, Butters T, Block T (1995) Evidence that N-linked glycosylation is necessary for hepatitis B virus secretion. Virology 213:660–665PubMed
141.
Ito K, Qin Y, Guarnieri M, Garcia T, Kwei K, Mizokami M, Zhang J, Li J, Wands J, Tong S (2010) Impairment of hepatitis B virus virion secretion by single-amino-acid substitutions in the small envelope protein and rescue by a novel glycosylation site. J Virol 84(24):12850–12861PubMedCentralPubMed
142.
Block T, Lu X, Platt F, Foster G, Gerlich W, Blumberg BS, Dwek R (1994) Secretion of human hepatitis B virus is inhibited by the imino sugar N-butyldeoxynojirimycin. Proc Natl Acad Sci USA 91:2235–2239PubMedCentralPubMed
143.
Sheu SY, Lo SJ (1994) Biogenesis of the hepatitis B viral middle (M) surface protein in a human hepatoma cell line: demonstration of an alternative secretion pathway. J Gen Virol 75(Pt 11):3031–3039PubMed
144.
Badur S, Akgun A (2001) Diagnosis of hepatitis B infections and monitoring of treatment. J Clin Virol 21:229–237PubMed
145.
Busch M (2001) HBV viremia preceding HBsAg positivity: implications for MP and ID HBV NAT. Presented at the US FDA Blood Products Advisory Commitewe meeting, Gaithersburg, MD, March 15
146.
Biswas R, Tabor E, Hsia CC, Wright DJ, Laycock ME, Fiebig EW (2003) Comparative sensitivity of HBV NATs and HBsAg assays for detection of acute HBV infection. Transfusion 43:788–798PubMed
147.
Yoshikawa A, Gotanda Y, Itabashi M, Minegishi K, Kanemitsu K, Nishioka K, Japanese Red Cross NAT Screening Research Group (2005) HBV NAT positive [corrected] blood donors in the early and late stages of HBV infection: analyses of the window period and kinetics of HBV DNA. Vox Sang 88(2):77–86PubMed
148.
Schreiber GB, Busch MP, Kleinman SH, Korelitz JJ (1996) The risk of transfusion-transmitted viral infections. N Engl J Med 334:1685–1690PubMed
149.
Grant P, Busch M (2002) Nucleic acid amplification technology methods used in blood donor screening. Transfus Med 12:229–242PubMed
150.
Gerlich W, Glebe D, Schuttler C (2007) Deficiencies in the standardization and sensitivity of diagnostic tests for hepatitis B virus. J Viral Hepat 14(1):16–21PubMed
151.
Fang C (2006) Blood screening for HBV DNA. J Clin Virol 36(1):S30–S32PubMed
152.
Scheiblauer H, El-Nageh M, Diaz S, Nick S, Zeichhard H, Grunert H-P, Prince A (2010) 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(3p2):403–414PubMedCentralPubMed
153.
Scheiblauer H, Soboll H, Nick S (2006) Evaluation of 17 CE-Marked HBsAg assays with respect to clinical sensitivity, analytical sensitivity, and hepatitis B virus mutant detection. J Med Virol 78:S66–S70PubMed
154.
Alavian S, Carman W, Jazayeri S (2013) HBsAg variants: diagnostic-escape and diagnostic dilemma. J Clin Virol 57:201–208PubMed
155.
Gerlich W, Thomssen R (1975) Standardized detection of hepatitis B surface antigen: determination of its serum concentration in weight units per volume. Dev Biol Stand 30:78–87PubMed
156.
157.
Minekawa T, Takehara S, Takahashi M, Okamoto H (2013) Development of a highly sensitive bioluminescent enzyme immunoassay for hepatitis B virus surface antigen capable of detecting divergent mutants. Clin Vaccine Immunol 20(8):1255–1265PubMedCentralPubMed
158.
Takeda K, Maruki M, Yamagaito T, Muramatsu M, Sakai Y, Tobimatsu H, Kobayashi H, Mizuno Y, Hamaguchi Y (2013) Highly sensitive detection of hepatitis b virus surface antigen by use of a semiautomated immune complex transfer chemiluminescence enzyme immunoassay. Clin Vaccine Immunol 51(7):2238–2244
159.
Vivekanandan P, Kannangai R, Ray SC, Thomas D, Torbenson M (2008) Comprehensive genetic and epigenetic analysis of occult hepatitis B from liver tissue samples. Clin Infect Dis 46:1227–1236PubMedCentralPubMed
160.
161.
162.
Vivekanandan P, Thomas D, Torbenson M (2008) Hepatitis B viral DNA is methylated in liver tissues. J Viral Hepat 15:103–107PubMed
163.
Kim J, Lee W, Park SH, Hwang YS, Jeong JH, Kim SH (2011) Replicative activity of hepatitis B virus is negatively associated with methylation of covalently closed circular DNA in advanced hepatitis B virus infection. Intervirology 54:316–325PubMed
164.
Vivekanandan P, Thomas D, Torbenson M (2009) Methylation regulates hepatitis B viral protein expression. J Infect Dis 199:1286–1291PubMedCentralPubMed
165.
Vivekanandan P, Daniel HD, Kannangai R, Martinez-Murillo F, Torbenson M (2010) Hepatitis B virus replication induces methylation of both host and viral DNA. J Virol 84:4321–4329PubMedCentralPubMed
166.
Pollicino T, Belloni L, Raffa G, Pediconi N, Squadrito G, Raimondo G, Levrero M (2006) Hepatitis B virus replication is regulated by the acetylation status of hepatitis B virus cccDNA-bound H3 and H4 his-tones. Gastroenterology 130:823–837PubMed
167.
Iorio MV, Piovan C, Croce CM (2010) Interplay between microRNAs and the epigenetic machinery: an intricate network. Biochim Biophys Acta 1799:694–701PubMed
168.
169.
Mizuguchi Y, Takizawa T, Uchida E (2015) Host cellular microRNA involvement in the control of hepatitis B virus gene expression and replication. World J Hepatol 7(4):696–702PubMedCentralPubMed
170.
Chen Y, Shen A, Rider PJ, Yu Y, Wu K, Mu Y, Hao Q, Liu Y, Gong H, Zhu Y, Liu F, Wu J (2011) A liver-specific microRNA binds to a highly conserved RNA sequence of hepatitis B virus and negatively regulates viral gene expression and replication. FASEB J 25:4511–4521PubMedCentralPubMed
171.
Zhang GL, Li YX, Zheng SQ, Liu M, Li X, Tang H (2010) Suppression of hepatitis B virus replication by microRNA-199a-3p and microRNA-210. Antivir Res 88:169–175PubMed
172.
Potenza N, Papa U, Mosca N, Zerbini F, Nobile V, Russo A (2011) Human microRNA hsa-miR-125a-5p interferes with expression of hepatitis B virus surface antigen. Nucleic Acids Res 39:5157–5163PubMedCentralPubMed
173.
Guo H, Liu H, Mitchelson K, Rao H, Luo M, Xie L, Sun Y, Zhang L, Lu Y, Liu R, Ren A, Liu S, Zhou S, Zhu J, Zhou Y, Huang A, Wei L, Guo Y, Cheng J (2011) MicroRNAs-372/373 promote the expression of hepatitis B virus through the targeting of nuclear factor I/B. Hepatology 54:808–819PubMed
174.
Wang J, Liu X, Wu H, Ni P, Gu Z, Qiao Y, Chen N, Sun F, Fan Q (2010) CREB up-regulates long non-coding RNA, HULC expression through interaction with microRNA-372 in liver cancer. Nucleic Acids Res 38:5366–5383PubMedCentralPubMed
175.
Kim BK, Lim SO, Park YG (2008) Requirement of the cyclic adenosine monophosphate response element-binding protein for hepatitis B virus replication. Hepatology 48:361–373PubMed
176.
Wang S, Qiu L, Yan X, Jin W, Wang Y, Chen L et al (2012) Loss of microRNA 122 expression in patients with hepatitis B enhances hepatitis B virus replication through cyclin G(1)-modulated P53 activity. Hepatology 55:730–741PubMed
177.
Chu C-M, Liaw (2010) Hepatitis B surface antigen seroclearance during chronic HBV infection. Antivir Ther 15:133–143PubMed
178.
Buster EH, Flink HJ, Cakaloglu Y et al (2008) Sustained HBeAg and HBsAg loss after long-term follow-up of HBeAg-positive patients treated with peginterferon alpha-2b. Gastroenterology 135:459–467PubMed
179.
Chen YC, Jeng WJ, Chu CM, Liaw YF (2012) Decreasing levels of HBsAg predict HBsAg seroclearance in patients with inactive chronic hepatitis B virus infection. Clin Gastroenterol Hepatol 10:297–302PubMed
180.
Seto W-K, Wong D, Fung F, Hung I, Fong D, Yuen J, Tong T, Lai C-L, Yuen M-F (2012) A large case–control study on the predictability of hepatitis B surface antigen levels three years before hepatitis B surface antigen seroclearance. Hepatology 56(3):812–819PubMed
181.
Chan HL, Wong GL, Tse CH, Chan HY, Wong VW (2011) Viral determinants of hepatitis B surface antigen seroclearance in hepatitis B e anti-gen-negative chronic hepatitis B patients. J Infect Dis 204:408–414PubMed
182.
Liu J, Yang HI, Lee MH, Lu SN, Jen CL, Wang LY et al (2010) Incidence and determinants of spontaneous hepatitis B surface antigen seroclearance: a community-based follow-up study. Gastroenterology 139:474–482PubMed
183.
Liu J, Lee MH, Batrla-Utermann R, Jen CL, Iloeje UH, Lu SN, Wang LY, You SL, Hsiao CK, Yang HI, Chen CJ (2013) A predictive scoring system for the seroclearance of HBsAg in HBeAg-seronegative chronic hepatitis B patientswith genotype B or C infection. J Hepatol 58(5):853–860PubMed
184.
Kuhns MC, Kleinman SH, McNamara AL, Rawal B, Glynn S, Busch MP (2004) Lack of correlation between HBsAg and HBV DNA levels in blood donors who test positive for HBsAg and anti-HBc: implications for future HBV screening policy. Transfusion 44:1332–1339PubMed
185.
Yuen M-F, Wong D, Sablon E, Tse E, Ng IO, Yuan H-J, Siu C-W, Sander TJ, Bourne E, Hall J, Condreay L, Lai C-L (2004) HBsAg seroclearance in chronic hepatitis B in the Chinese: virological, histological, and clinical aspects. Hepatology 39(6):1694–1701PubMed
186.
Thompson AJ, Nguyen T, Iser D, Ayres A, Jackson K, Littlejohn M et al (2010) Serum hepatitis B surface antigen and hepatitis B e antigen titers: disease phase influences correlation with viral load and intrahepatic hepatitis B virus markers. Hepatology 51:1933–1944PubMed
187.
Werle-Lapostolle B, Bowden S, Locarnini S et al (2004) Persistence of cccDNA during the natural history of chronic hepatitis B and decline during adefovir dipivoxil therapy. Gastroenterology 126:1750–1758PubMed
188.
Chan HL, Wong VW, Tse AM et al (2007) Serum hepatitis B surface antigen quantitation can reflect hepatitis B virus in the liver and predict treatment response. Clin Gastroenterol Hepatol 5:1462–1468PubMed
189.
Sánchez-Tapias JM, Costa J, Mas A, Bruguera M, Rodés J (2002) Influence of hepatitis B virus genotype on the long-term outcome of chronic hepatitis B in western patients. Gastroenterology 123:1848–1856PubMed
190.
Hoofnagle J, Seef L, Bales Z, Zimmerman H (1978) The type B hepatitis after transfusion with blood containing antibody to hepatitis B core antigen. N Engl J Med 298:1379–1383PubMed
191.
Muselmani W, Habbal W, Monem F (2013) Significance of screening antibodies to hepatitis B virus core antigen among Syrian blood donors. Transfus Med 23(4):265–268PubMed
192.
Antar W, El-Shokry MH, Abd El Hamid W, Helmy MR (2010) Significance of detecting anti-HBc among Egyptian male blood donors negative for HbsAg. Transfus Med 20(6):409–413PubMed
193.
Allain JP, Mihaljevic I, Gonzalez-Fraile MI, Gubbe K, Holm-Harritshøj L, Garcia JM, Brojer E, Erikstrup C, Saniewski M, Wernish L, Bianco L, Ullum H, Candotti D, Lelie N, Gerlich WH, Chudy M (2013) Infectivity of blood products from donors with occult hepatitis B virus infection. Transfusion 53(7):1405–1415PubMed
194.
Busch MP (2004) Should HBV DNA NAT replace HbsAg and/or anti-HBc screening of blood donors? Transfus Clin Biol 11(1):26–32PubMed
195.
Kuhns MC, Busch MP (2006) New strategies for blood donor screening for hepatitis B virus: nucleic acid testing versus immunoassay methods. Mol Diagn Ther 10(2):77–91PubMed
196.
Stramer SL, Zou S, Notari EP, Foster GA, Krysztof DE, Musavi F, Dodd RY (2012) Blood donation screening for hepatitis B virus markers in the era of nucleic acid testing: are all tests of value? Transfusion 52(2):440–446PubMed
197.
Cheung CK, Lo CM, Man K, Lau GK (2010) Occult hepatitis B virus infection of donor and recipient origin after liver transplantation despite nucleoside analogue prophylaxis. Liver Transpl 16:1314–1323PubMed
198.
Rokuhara A, Tanaka E, Yagi S, Mizokami M, Hashikura Y, Kawasaki S, Kiyosawa K (2000) De novo infection of hepatitis B virus in patients with orthotopic liver transplantation: analysis by determining complete sequence of the genome. J Med Virol 62(4):471–478PubMed
199.
Cholongitas E, Papatheodoridis GV, Burroughs AK (2010) Liver grafts from anti-hepatitis B core positive donors: a systematic review. J Hepatol 52:272–279PubMed
200.
Samuel D, Forns X, Berenguer M, Trautwein C, Burroughs A, Rizzetto M, Trepo C (2006) Report of the monothematic EASL conference on liver transplantation for viral hepatitis. J Hepatol 45:127–143PubMed
201.
Shouval D, Shibolet O (2013) Immunosuppression and HBV reactivation. Semin Liver Dis 33(2):167–177PubMed
202.
Kamitsukasa H, Iri M, Tanaka A, Nagashima S, Takahashi M, Nishizawa T, Okamoto H (2015) Spontaneous reactivation of hepatitis B virus (HBV) infection in patients with resolved or occult HBV infection. J Med Virol 87(4):589–600PubMed
203.
Umenura T, Kiyosawa K (2006) Fatal HBV reactivation in a subject with anti-HBs and anti-HBc. Intern Med 45(12):747–748
204.
Blackberg J, Kidd-Ljunggren K (2000) Occult hepatitis B virus after acute self-limited infection persisting for 30 years without sequence variation. J Hepatol 33:992–997PubMed
205.
Mulrooney-Cousins PM, Michalak TI (2007) Persistent occult hepatitis B virus infection: experimental findings and clinical implications. World J Gastroenterol 13:5682–5686PubMedCentralPubMed
206.
Sagnelli E, Coppola N, Messina V, Di Caprio D, Marrocco C, Marotta A, Onofrio M, Scolastico C, Filippini P (2002) HBV superinfection in hepatitis C vírus chronic carriers, viral interaction, and clinical course. Hepatology 36(5):1285–1291PubMed
207.
Squadrito G, Cacciola I, Alibrandi A, Pollicino T, Raimondo G (2013) Impact of occult hepatitis B virus infection on the outcome of chronic hepatitis C. J Hepatol 59:696–700PubMed
208.
Mrani S, Chemin I, Menouar K, Guillaud O, Pradat P, Borghi G et al (2007) Occult HBV infection may represent a major risk factor of non-response to antiviral therapy of chronic hepatitis C. J Med Virol 79(8):1075–1081PubMed
209.
Koike K, Nakamura Y, Kobayashi M, Takada S, Urashima T, Saigo K, Kobayashi S, Isono K, Hayashi I, Fujii A (1996) Hepatitis B virus DNA integration frequently observed in the hepatocellular carcinoma DNA of hepatitis C virus-infected patients. Int J Oncol 8:781–784PubMed
210.
211.
Pollicino T, Saitta C, Raimondo G (2011) Hepatocellular carcinoma: the point of view of the hepatitis B virus. Carcinogenesis 32:1122–1132PubMed
212.
213.
Shi Y, Wu YH, Wu W, Zhang WJ, Yang J, Chen S (2012) Association between occult hepatitis B infection and the risk of hepatocellular carcinoma: a meta-analysis. Liver Int 32:231–240PubMed
214.
Chen CH, Changchien CS, Lee CM, Tung WC, Hung CH, Hu TH (2009) A study on sequence variations in pre-S/surface, X and enhancer II/core promoter/precore regions of occult hepatitis B virus in non-B, non-C hepatocellular carcinoma patients in Taiwan. Int J Cancer 125(3):621–629PubMed
215.
Wong DK, Huang FY, Lai CL, Poon RT, Seto WK, Fung J, Hung IF, Yuen MF (2011) Occult hepatitis B infection and HBV replicative activity in patients with cryptogenic cause of hepatocellular carcinoma. Hepatology 54:829–836PubMed
216.
Lok AS, Everhart JE, Di Bisceglie AM, Kim HY, Hussain M, Morgan TR (2011) Occult and previous hepatitis B virus infection are not associated with hepatocellular carcinoma in United States patients with chronic hepatitis C. Hepatology 54:434–442PubMedCentralPubMed
217.
Torbenson M, Thomas DL (2002) Occult hepatitis B. Lancet Infect Dis 2:479–486PubMed
218.
Allain J-P (2004) Occult hepatitis B virus infection: implications in transfusion. Vox Sang 86:83–91PubMed
219.
Liu C-J, Chen D-S, Chen P-J (2006) Epidemiology of HBV infection in Asian blood donors: emphasis on occult HBV infection ant the role of NAT. J Clin Virol 36:S33–S44PubMed
220.
Chan HL, Tsang SW, Leung NW, Tse CH, Hui Y, Tam JS, Chan FK, Sung JJ (2002) Occult HBV infection in cryptogenic liver cirrhosis in an area with high prevalence of HBV infection. Am J Gastroenterol 97:1211–1215PubMed
221.
Hassan Z, Hafez M, Mansor T, Zekri A (2011) Occult HBV infection among Egyptian hepatocellular carcinoma patients. Virol J 8:90PubMedCentralPubMed
222.
Allain JP, Cox L (2011) Challenges in hepatitis B detection among blood donors. Curr Opin Hematol 18(6):461–466PubMed
Metadata
Title
Molecular mechanisms underlying HBsAg negativity in occult HBV infection
Author
R. A. A. Pondé
Publication date
01-09-2015
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Clinical Microbiology & Infectious Diseases / Issue 9/2015
Print ISSN: 0934-9723
Electronic ISSN: 1435-4373
DOI
https://doi.org/10.1007/s10096-015-2422-x

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