Prevalence of Genotypic Resistance Mutations in Patients with Chronic Hepatitis B (HBV) Treated with Entecavir and Tenofovir in Two Reference Centers in the North and Northeast of Brazil
Main Article Content
Abstract
Mutations of genotypic resistance to nucleotide analogues Entecavirand Tenofovirhave been described in patients undergoing treatment and virgins for hepatitis B virus. The present study demonstrated in a sample of 263 patients with chronic HBV from the North and Northeast of Brazil, a mutation rate of resistance to nucleotide analogues of 3.8% (10). Of the 10 patients who had genotypic resistance mutations, only 1 had no genotypic resistance mutation for the first line treatment for hepatitis B, entecavir and tenofovir.Due to the emergence of vaccine escape mutations and resistance mutations to antiviral treatment, and the severity of liver disease caused by HBV, screening for genetic mutations is important due to the impact on therapeutic management.
Keywords:
Hepatitis B, genotypic mutations, entecavir, tenofovir
Article Details
How to Cite
PACHECO, Sidelcina Rugieri et al.
Prevalence of Genotypic Resistance Mutations in Patients with Chronic Hepatitis B (HBV) Treated with Entecavir and Tenofovir in Two Reference Centers in the North and Northeast of Brazil.
Medical Research Archives, [S.l.], v. 11, n. 3, mar. 2023.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/3473>. Date accessed: 23 nov. 2024.
doi: https://doi.org/10.18103/mra.v11i3.3473.
Section
Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. Jun 2007;132(7):2557-76. doi:10.1053/j.gastro.2007.04.061
2. Trepo C, Chan HL, Lok A. Hepatitis B virus infection. Lancet. Dec 6 2014;384(9959):2053-63. doi:10.1016/S0140-6736(14)60220-8
3. Chen CJ, Yang HI, Su J, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. Jan 4 2006;295(1):65-73. doi:10.1001/jama.295.1.65
4. Di Bisceglie AM. Hepatitis B and hepatocellular carcinoma. Hepatology. May 2009;49(5 Suppl):S56-60. doi:10.1002/hep.22962
5. Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology. Sep 2009;50(3):661-2. doi:10.1002/hep.23190
6. BRASIL. MINISTÉRIO DA SAÚDE. DEPARTAMENTO DE DST AEHV. Protocolo Clínico e Diretrizes Terapêuticas para o Tratamento da Hepatite Viral Crônica B e Coinfecções. Ministério da Saúde. 2011. https://bvsms.saude.gov.br/bvs/publicacoes/protocolos_diretrizes_hepatite_viral_c_coinfeccoes.pdf
7. Lai MW, Huang SF, Hsu CW, Chang MH, Liaw YF, Yeh CT. Identification of nonsense mutations in hepatitis B virus S gene in patients with hepatocellular carcinoma developed after lamivudine therapy. Antivir Ther. 2009;14(2):249-61.
8. J S, B R, F Z, A B, V S. Mutations affecting the replication capacity of the hepatitis B virus. Journal of viral hepatitis. 2006 Jul 2006;13(7)doi:10.1111/j.1365-2893.2005.00713.x
9. Krekulova L, Rehak V, da Silva Filho HP, Zavoral M, Riley LW. Genotypic distribution of hepatitis B virus in the Czech Republic: a possible association with modes of transmission and clinical outcome. European journal of gastroenterology & hepatology. Nov 2003;15(11):1183-8. doi:10.1097/01.meg.0000085484.12407.cb
10. LC DS, JR P, R S, LE DF, FJ C. Efficacy and tolerability of long-term therapy using high lamivudine doses for the treatment of chronic hepatitis B. Journal of gastroenterology. 2001 Jul 2001;36(7)doi:10.1007/s005350170071
11. M B, FJ S, KM O, et al. Hepatitis B virus genotypes and resistance mutations in patients under long term lamivudine therapy: characterization of genotype G in Brazil. BMC microbiology. 01/22/2008 2008;8doi:10.1186/1471-2180-8-11
12. R H, L MA, SA U, J Y. Hepatitis B virus genotyping among chronic hepatitis B patients with resistance to treatment with lamivudine in the City of Ribeirão Preto, State of São Paulo. Revista da Sociedade Brasileira de Medicina Tropical. 2010 May-Jun 2010;43(3)doi:10.1590/s0037-86822010000300002
13. EA S, MV S, J A, SA G. Hepatitis B virus variants in an HIV-HBV co-infected patient at different periods of antiretroviral treatment with and without lamivudine. BMC infectious diseases. 08/31/2004 2004;4doi:10.1186/1471-2334-4-29
14. MV S, FC M, EA S, et al. Patterns of hepatitis B virus infection in Brazilian human immunodeficiency virus infected patients: high prevalence of occult infection and low frequency of lamivudine resistant mutations. Memorias do Instituto Oswaldo Cruz. 2006 Sep 2006;101(6)doi:10.1590/s0074-02762006000600013
15. AC S, AM S, MF L, et al. Hepatitis B genotype G and high frequency of lamivudine-resistance mutations among human immunodeficiency virus/hepatitis B virus co-infected patients in Brazil. Memorias do Instituto Oswaldo Cruz. 2010 Sep 2010;105(6)doi:10.1590/s0074-02762010000600007
16. S VF, CM O, MB V, CB V, LC F. Characterization of HBeAg-negative chronic hepatitis B in western Brazilian Amazonia. The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases. 2008 Feb 2008;12(1)doi:10.1590/s1413-86702008000100008
17. AL D, CM O, C CM, S SM, WS B. Molecular characterization of the hepatitis B virus in autochthonous and endogenous populations in the Western Brazilian Amazon. Revista da Sociedade Brasileira de Medicina Tropical. 2012 Feb 2012;45(1)doi:10.1590/s0037-86822012000100003
18. JC F, SR S, HG S, MJ C, AL C, JP S. Prevalence of infection with hepatitis delta virus (HDV) among carriers of hepatitis B surface antigen in Amazonas State, Brazil. Transactions of the Royal Society of Tropical Medicine and Hygiene. 1988 1988;82(3)doi:10.1016/0035-9203(88)90166-6
19. Braga WSM, Dourado FdMTDHV, Brasil LM, et al. Ocorrência da infecção pelo vírus da hepatite B (VHB) e delta (VHD) em sete grupos indígenas do Estado do Amazonas. Revista da Sociedade Brasileira de Medicina Tropical. 2023;34:349-355. doi:10.1590/S0037-86822001000400007
20. VS dP, ME A, CL V, AM G. Seroprevalence of viral hepatitis in riverine communities from the Western Region of the Brazilian Amazon Basin. Memorias do Instituto Oswaldo Cruz. 2001 Nov 2001;96(8)doi:10.1590/s0074-02762001000800016
21. S V, R P, RC M, AP C, V M. High prevalence of hepatitis B virus and hepatitis D virus in the western Brazilian Amazon. The American journal of tropical medicine and hygiene. 2005 Oct 2005;73(4)
22. CM dO, IP F, JC FdF, LM B, R dS, S A-F. Phylogeny and molecular genetic parameters of different stages of hepatitis B virus infection in patients from the Brazilian Amazon. Archives of virology. 2008 2008;153(5)doi:10.1007/s00705-008-0053-6
23. C CM, CM O, JB G, JD L, WS B. Epidemiology and molecular characterization of hepatitis B virus infection in isolated villages in the Western Brazilian Amazon. The American journal of tropical medicine and hygiene. 2012 Oct 2012;87(4)doi:10.4269/ajtmh.2012.12-0083
24. BA G, MV A-M, MS G-G, JR P, N F. Origin of HBV and its arrival in the Americas--the importance of natural selection on time estimates. Antiviral therapy. 2013 2013;18(3 Pt B)doi:10.3851/IMP2600
25. FC M, FJ S, LC N, et al. Hepatitis B virus genotypes circulating in Brazil: molecular characterization of genotype F isolates. BMC microbiology. 11/23/2007 2007;7doi:10.1186/1471-2180-7-103
26. MV A-M, JR P. Distribution of HBV genotypes in Latin America. Antiviral therapy. 2013 2013;18(3 Pt B)doi:10.3851/IMP2599
27. Mello FC, Araujo OC, Lago BV, et al. Phylogeography and evolutionary history of hepatitis B virus genotype F in Brazil. Virology journal. 2013;10:236. doi:10.1186/1743-422X-10-236
28. C M, A M, PC F. Does hepatitis B virus (HBV) genotype influence the clinical outcome of HBV infection? Journal of viral hepatitis. 1999 Jul 1999;6(4)doi:10.1046/j.1365-2893.1999.00174.x
29. JM S-T, J C, A M, M B, J R. Influence of hepatitis B virus genotype on the long-term outcome of chronic hepatitis B in western patients. Gastroenterology. 2002 Dec 2002;123(6)doi:10.1053/gast.2002.37041
30. B Z, J P, E P-S, et al. Viral features of lamivudine resistant hepatitis B genotypes A and D. Hepatology (Baltimore, Md). 2004 Jan 2004;39(1)doi:10.1002/hep.20016
31. A Q, N U, CL L, et al. Hepatitis delta virus genotypes I and III circulate associated with hepatitis B virus genotype F In Venezuela. Journal of medical virology. 2001 Jul 2001;64(3)doi:10.1002/jmv.1058
32. WF C, AR Z, P K, et al. Vaccine-induced escape mutant of hepatitis B virus. Lancet (London, England). 08/11/1990 1990;336(8711)doi:10.1016/0140-6736(90)91874-a
33. WF C. The clinical significance of surface antigen variants of hepatitis B virus. Journal of viral hepatitis. 1997 1997;4 Suppl 1doi:10.1111/j.1365-2893.1997.tb00155.x
34. CJ O, WN C, Y Z, SW T, AL L. Detection of hepatitis B surface antigen mutants and their integration in human hepatocellular carcinoma. Cancer letters. 02/08/1999 1999;136(1)doi:10.1016/s0304-3835(98)00314-0
35. JN W, DJ N, WF C. The predicted pattern of emergence of vaccine-resistant hepatitis B: a cause for concern? Vaccine. 02/26/1999 1999;17(7-8)doi:10.1016/s0264-410x(98)00313-2
36. A K, F Z. Hepatitis B virus genetic variability and evolution. Virus research. 2007 Aug 2007;127(2)doi:10.1016/j.virusres.2007.02.021
37. J T. The virological and clinical significance of mutations in the overlapping envelope and polymerase genes of hepatitis B virus. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. 2002 Aug 2002;25(2)doi:10.1016/s1386-6532(02)00049-5
38. V C, F VH, M N-F, et al. Anti-HBV treatment induces novel reverse transcriptase mutations with reflective effect on HBV S antigen. The Journal of infection. 2013 Oct 2013;67(4)doi:10.1016/j.jinf.2013.05.008
39. C DM, C G, E T, et al. High level of genetic heterogeneity in S and P genes of genotype D hepatitis B virus. Virology. 08/15/2007 2007;365(1)doi:10.1016/j.virol.2007.03.015
40. S A-B-O, U H, J S, T L, C T, F T. The rtA194T polymerase mutation impacts viral replication and susceptibility to tenofovir in hepatitis B e antigen-positive and hepatitis B e antigen-negative hepatitis B virus strains. Hepatology (Baltimore, Md). 2009 Apr 2009;49(4)doi:10.1002/hep.22790
41. F W, H W, H S, C M, X W, W Z. Evolution of hepatitis B virus polymerase mutations in a patient with HBeAg-positive chronic hepatitis B virus treated with sequential monotherapy and add-on nucleoside/nucleotide analogues. Clinical therapeutics. 2009 Feb 2009;31(2)doi:10.1016/j.clinthera.2009.02.016
42. D J, Y L, L L, et al. The rtL229 substitutions in the reverse transcriptase region of hepatitis B virus (HBV) polymerase are potentially associated with lamivudine resistance as a compensatory mutation. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. 2012 May 2012;54(1)doi:10.1016/j.jcv.2012.02.003
43. J F, Y W, H X, X G, YC C. Impact of the rtI187V polymerase substitution of hepatitis B virus on viral replication and antiviral drug susceptibility. The Journal of general virology. 2014 Nov 2014;95(Pt 11)doi:10.1099/vir.0.066886-0
44. SA L, L Y. Molecular genesis of drug-resistant and vaccine-escape HBV mutants. Antiviral therapy. 2010 2010;15(3 Pt B)doi:10.3851/IMP1499
45. J S, V S. Hepatitis B virus escape mutants induced by antiviral therapy. The Journal of antimicrobial chemotherapy. 2008 Apr 2008;61(4)doi:10.1093/jac/dkn014
2. Trepo C, Chan HL, Lok A. Hepatitis B virus infection. Lancet. Dec 6 2014;384(9959):2053-63. doi:10.1016/S0140-6736(14)60220-8
3. Chen CJ, Yang HI, Su J, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. Jan 4 2006;295(1):65-73. doi:10.1001/jama.295.1.65
4. Di Bisceglie AM. Hepatitis B and hepatocellular carcinoma. Hepatology. May 2009;49(5 Suppl):S56-60. doi:10.1002/hep.22962
5. Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology. Sep 2009;50(3):661-2. doi:10.1002/hep.23190
6. BRASIL. MINISTÉRIO DA SAÚDE. DEPARTAMENTO DE DST AEHV. Protocolo Clínico e Diretrizes Terapêuticas para o Tratamento da Hepatite Viral Crônica B e Coinfecções. Ministério da Saúde. 2011. https://bvsms.saude.gov.br/bvs/publicacoes/protocolos_diretrizes_hepatite_viral_c_coinfeccoes.pdf
7. Lai MW, Huang SF, Hsu CW, Chang MH, Liaw YF, Yeh CT. Identification of nonsense mutations in hepatitis B virus S gene in patients with hepatocellular carcinoma developed after lamivudine therapy. Antivir Ther. 2009;14(2):249-61.
8. J S, B R, F Z, A B, V S. Mutations affecting the replication capacity of the hepatitis B virus. Journal of viral hepatitis. 2006 Jul 2006;13(7)doi:10.1111/j.1365-2893.2005.00713.x
9. Krekulova L, Rehak V, da Silva Filho HP, Zavoral M, Riley LW. Genotypic distribution of hepatitis B virus in the Czech Republic: a possible association with modes of transmission and clinical outcome. European journal of gastroenterology & hepatology. Nov 2003;15(11):1183-8. doi:10.1097/01.meg.0000085484.12407.cb
10. LC DS, JR P, R S, LE DF, FJ C. Efficacy and tolerability of long-term therapy using high lamivudine doses for the treatment of chronic hepatitis B. Journal of gastroenterology. 2001 Jul 2001;36(7)doi:10.1007/s005350170071
11. M B, FJ S, KM O, et al. Hepatitis B virus genotypes and resistance mutations in patients under long term lamivudine therapy: characterization of genotype G in Brazil. BMC microbiology. 01/22/2008 2008;8doi:10.1186/1471-2180-8-11
12. R H, L MA, SA U, J Y. Hepatitis B virus genotyping among chronic hepatitis B patients with resistance to treatment with lamivudine in the City of Ribeirão Preto, State of São Paulo. Revista da Sociedade Brasileira de Medicina Tropical. 2010 May-Jun 2010;43(3)doi:10.1590/s0037-86822010000300002
13. EA S, MV S, J A, SA G. Hepatitis B virus variants in an HIV-HBV co-infected patient at different periods of antiretroviral treatment with and without lamivudine. BMC infectious diseases. 08/31/2004 2004;4doi:10.1186/1471-2334-4-29
14. MV S, FC M, EA S, et al. Patterns of hepatitis B virus infection in Brazilian human immunodeficiency virus infected patients: high prevalence of occult infection and low frequency of lamivudine resistant mutations. Memorias do Instituto Oswaldo Cruz. 2006 Sep 2006;101(6)doi:10.1590/s0074-02762006000600013
15. AC S, AM S, MF L, et al. Hepatitis B genotype G and high frequency of lamivudine-resistance mutations among human immunodeficiency virus/hepatitis B virus co-infected patients in Brazil. Memorias do Instituto Oswaldo Cruz. 2010 Sep 2010;105(6)doi:10.1590/s0074-02762010000600007
16. S VF, CM O, MB V, CB V, LC F. Characterization of HBeAg-negative chronic hepatitis B in western Brazilian Amazonia. The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases. 2008 Feb 2008;12(1)doi:10.1590/s1413-86702008000100008
17. AL D, CM O, C CM, S SM, WS B. Molecular characterization of the hepatitis B virus in autochthonous and endogenous populations in the Western Brazilian Amazon. Revista da Sociedade Brasileira de Medicina Tropical. 2012 Feb 2012;45(1)doi:10.1590/s0037-86822012000100003
18. JC F, SR S, HG S, MJ C, AL C, JP S. Prevalence of infection with hepatitis delta virus (HDV) among carriers of hepatitis B surface antigen in Amazonas State, Brazil. Transactions of the Royal Society of Tropical Medicine and Hygiene. 1988 1988;82(3)doi:10.1016/0035-9203(88)90166-6
19. Braga WSM, Dourado FdMTDHV, Brasil LM, et al. Ocorrência da infecção pelo vírus da hepatite B (VHB) e delta (VHD) em sete grupos indígenas do Estado do Amazonas. Revista da Sociedade Brasileira de Medicina Tropical. 2023;34:349-355. doi:10.1590/S0037-86822001000400007
20. VS dP, ME A, CL V, AM G. Seroprevalence of viral hepatitis in riverine communities from the Western Region of the Brazilian Amazon Basin. Memorias do Instituto Oswaldo Cruz. 2001 Nov 2001;96(8)doi:10.1590/s0074-02762001000800016
21. S V, R P, RC M, AP C, V M. High prevalence of hepatitis B virus and hepatitis D virus in the western Brazilian Amazon. The American journal of tropical medicine and hygiene. 2005 Oct 2005;73(4)
22. CM dO, IP F, JC FdF, LM B, R dS, S A-F. Phylogeny and molecular genetic parameters of different stages of hepatitis B virus infection in patients from the Brazilian Amazon. Archives of virology. 2008 2008;153(5)doi:10.1007/s00705-008-0053-6
23. C CM, CM O, JB G, JD L, WS B. Epidemiology and molecular characterization of hepatitis B virus infection in isolated villages in the Western Brazilian Amazon. The American journal of tropical medicine and hygiene. 2012 Oct 2012;87(4)doi:10.4269/ajtmh.2012.12-0083
24. BA G, MV A-M, MS G-G, JR P, N F. Origin of HBV and its arrival in the Americas--the importance of natural selection on time estimates. Antiviral therapy. 2013 2013;18(3 Pt B)doi:10.3851/IMP2600
25. FC M, FJ S, LC N, et al. Hepatitis B virus genotypes circulating in Brazil: molecular characterization of genotype F isolates. BMC microbiology. 11/23/2007 2007;7doi:10.1186/1471-2180-7-103
26. MV A-M, JR P. Distribution of HBV genotypes in Latin America. Antiviral therapy. 2013 2013;18(3 Pt B)doi:10.3851/IMP2599
27. Mello FC, Araujo OC, Lago BV, et al. Phylogeography and evolutionary history of hepatitis B virus genotype F in Brazil. Virology journal. 2013;10:236. doi:10.1186/1743-422X-10-236
28. C M, A M, PC F. Does hepatitis B virus (HBV) genotype influence the clinical outcome of HBV infection? Journal of viral hepatitis. 1999 Jul 1999;6(4)doi:10.1046/j.1365-2893.1999.00174.x
29. JM S-T, J C, A M, M B, J R. Influence of hepatitis B virus genotype on the long-term outcome of chronic hepatitis B in western patients. Gastroenterology. 2002 Dec 2002;123(6)doi:10.1053/gast.2002.37041
30. B Z, J P, E P-S, et al. Viral features of lamivudine resistant hepatitis B genotypes A and D. Hepatology (Baltimore, Md). 2004 Jan 2004;39(1)doi:10.1002/hep.20016
31. A Q, N U, CL L, et al. Hepatitis delta virus genotypes I and III circulate associated with hepatitis B virus genotype F In Venezuela. Journal of medical virology. 2001 Jul 2001;64(3)doi:10.1002/jmv.1058
32. WF C, AR Z, P K, et al. Vaccine-induced escape mutant of hepatitis B virus. Lancet (London, England). 08/11/1990 1990;336(8711)doi:10.1016/0140-6736(90)91874-a
33. WF C. The clinical significance of surface antigen variants of hepatitis B virus. Journal of viral hepatitis. 1997 1997;4 Suppl 1doi:10.1111/j.1365-2893.1997.tb00155.x
34. CJ O, WN C, Y Z, SW T, AL L. Detection of hepatitis B surface antigen mutants and their integration in human hepatocellular carcinoma. Cancer letters. 02/08/1999 1999;136(1)doi:10.1016/s0304-3835(98)00314-0
35. JN W, DJ N, WF C. The predicted pattern of emergence of vaccine-resistant hepatitis B: a cause for concern? Vaccine. 02/26/1999 1999;17(7-8)doi:10.1016/s0264-410x(98)00313-2
36. A K, F Z. Hepatitis B virus genetic variability and evolution. Virus research. 2007 Aug 2007;127(2)doi:10.1016/j.virusres.2007.02.021
37. J T. The virological and clinical significance of mutations in the overlapping envelope and polymerase genes of hepatitis B virus. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. 2002 Aug 2002;25(2)doi:10.1016/s1386-6532(02)00049-5
38. V C, F VH, M N-F, et al. Anti-HBV treatment induces novel reverse transcriptase mutations with reflective effect on HBV S antigen. The Journal of infection. 2013 Oct 2013;67(4)doi:10.1016/j.jinf.2013.05.008
39. C DM, C G, E T, et al. High level of genetic heterogeneity in S and P genes of genotype D hepatitis B virus. Virology. 08/15/2007 2007;365(1)doi:10.1016/j.virol.2007.03.015
40. S A-B-O, U H, J S, T L, C T, F T. The rtA194T polymerase mutation impacts viral replication and susceptibility to tenofovir in hepatitis B e antigen-positive and hepatitis B e antigen-negative hepatitis B virus strains. Hepatology (Baltimore, Md). 2009 Apr 2009;49(4)doi:10.1002/hep.22790
41. F W, H W, H S, C M, X W, W Z. Evolution of hepatitis B virus polymerase mutations in a patient with HBeAg-positive chronic hepatitis B virus treated with sequential monotherapy and add-on nucleoside/nucleotide analogues. Clinical therapeutics. 2009 Feb 2009;31(2)doi:10.1016/j.clinthera.2009.02.016
42. D J, Y L, L L, et al. The rtL229 substitutions in the reverse transcriptase region of hepatitis B virus (HBV) polymerase are potentially associated with lamivudine resistance as a compensatory mutation. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. 2012 May 2012;54(1)doi:10.1016/j.jcv.2012.02.003
43. J F, Y W, H X, X G, YC C. Impact of the rtI187V polymerase substitution of hepatitis B virus on viral replication and antiviral drug susceptibility. The Journal of general virology. 2014 Nov 2014;95(Pt 11)doi:10.1099/vir.0.066886-0
44. SA L, L Y. Molecular genesis of drug-resistant and vaccine-escape HBV mutants. Antiviral therapy. 2010 2010;15(3 Pt B)doi:10.3851/IMP1499
45. J S, V S. Hepatitis B virus escape mutants induced by antiviral therapy. The Journal of antimicrobial chemotherapy. 2008 Apr 2008;61(4)doi:10.1093/jac/dkn014