Demonstration of mutations conferring resistance to lamivudine in liver tissue of chronic hepatitis B patients under lamivudine therapy

To demonstrate the genotypic lamivudine resistance in liver tissue of patients with negative serum hepatitis B virus (HBV) DNA under long-term lamivudine therapy. Materials and methods: Fourteen patients (10 patients with elevated alanine aminotransferase and 4 patients under long-term lamivudine therapy for severe liver disease) with undetected serum HBV DNA were included in the study. A liver biopsy was performed for each patient, and HBV DNA extracted from liver tissue was analyzed with TaqMan real-time polymerase chain reaction. Results: Mutations conferring lamivudine resistance were shown for all 14 patients in their liver tissue-extracted HBV DNA. One patient had rtM204V, 4 patients had rtL180M, 2 had rtL180M + rtM204V, 4 had rtL180M + rtM204I, and 3 had rtL180M + rtM204I + rtM204V substitutions. Conclusion: Analyzing mutation in liver tissues of these patients might help demonstrate resistance earlier and prevent delaying of therapeutic modification. Therefore, all liver biopsy specimens of patients with severe liver fibrosis should be analyzed using the molecular technique.

Demonstration of mutations conferring resistance to lamivudine in liver tissue of chronic hepatitis B patients under lamivudine therapy

To demonstrate the genotypic lamivudine resistance in liver tissue of patients with negative serum hepatitis B virus (HBV) DNA under long-term lamivudine therapy. Materials and methods: Fourteen patients (10 patients with elevated alanine aminotransferase and 4 patients under long-term lamivudine therapy for severe liver disease) with undetected serum HBV DNA were included in the study. A liver biopsy was performed for each patient, and HBV DNA extracted from liver tissue was analyzed with TaqMan real-time polymerase chain reaction. Results: Mutations conferring lamivudine resistance were shown for all 14 patients in their liver tissue-extracted HBV DNA. One patient had rtM204V, 4 patients had rtL180M, 2 had rtL180M + rtM204V, 4 had rtL180M + rtM204I, and 3 had rtL180M + rtM204I + rtM204V substitutions. Conclusion: Analyzing mutation in liver tissues of these patients might help demonstrate resistance earlier and prevent delaying of therapeutic modification. Therefore, all liver biopsy specimens of patients with severe liver fibrosis should be analyzed using the molecular technique.

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  • Dikici B, Uzun H, Gözü A, Fidan M. Prevalence of hepatitis B infection among schoolchildren in southeast Turkey. Turk J Med Sci 2009; 39: 289–93. 2. Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat 2004; 11: 97–107. 3.
  • Öner S, Yapıcı G, Şaşmaz CT, Kurt AÖ, Buğdaycı R. Hepatitis
  • B, hepatitis C, HIV, and VDRL seroprevalence of blood donors
  • in Mersin, Turkey. Turk J Med Sci 2011; 41: 335–41. 4.
  • Nwankwo E, Momodu I, Umar I, Musa B, Adeleke S.
  • Seroprevalence of major blood-borne infections among blood
  • Locarnini S. Molecular virology and the development of resistant mutants. Implications for therapy. Semin Liver Dis 2005; 25 (Suppl 1): 9–19.
  • Allen MI, Deslauriers M, Andrews CW, Tipples GA, Walters KA, Tyrrell DL et al. Identification and characterization of mutations in hepatitis B virus resistant to lamivudine. Lamivudine Clinical Investigation Group. Hepatology 1998; 27: 1670–7.
  • Chien RN, Yeh CT, Tsai SL, Chu CM, Liaw YF. Determinants for sustained HBeAg response to lamivudine therapy. Hepatology 2003; 38: 1267–73.
  • Damerow H, Yuen L, Wiegand J, Walker C, Bock CT, Locarnini S et al. Mutation pattern of lamivudine resistance in relation to hepatitis B genotypes: hepatitis B genotypes differ in their lamivudine resistance associated mutation pattern. J Med Virol 2010; 82: 1850–8.
  • Bozdayi AM, Eyigun CP, Turkyilmaz AR, Avci IY, Pahsa A, Yurdaydin C. A novel pattern (sW195a) in surface gene of HBV DNA due to YSDD (L180M plus M204S) mutation selected during lamivudine therapy and successful treatment with adefovir dipivoxil. J Clin Virol 2004; 31: 76–7.
  • Zhao P, Wang C, Huang L, Xu D, Li T. Comparison of rescue strategies in lamivudine-resistant patients with chronic hepatitis B. Antiviral Res 2012; 96: 100–4.
  • Kubar A, Saygun I, Özdemir A, Yapar M, Slots J. Real- time polymerase chain reaction quantification of human cytomegalovirus and Epstein-Barr virus in periodontal pockets and the adjacent gingiva of periodontitis lesions. J Periodont Res 2005; 40: 97–104.
  • Hunt CM, McGill JM, Allen MI, Condreay LD. Clinical relevance of hepatitis B viral mutations. Hepatology 2000; 31: 1037–44.
  • Zoulim F. Detection of hepatitis B virus resistance to antivirals. J Clin Virol 2001; 21: 243–53.
  • Zoulim F. Assessing hepatitis B virus resistance in vitro and molecular mechanisms of nucleoside resistance. Semin Liver Dis 2002; 22: 23–31.
  • Thompson AJV, Nguyen T, Iser D, Ayres A, Jackson K, Littlejohn M et al. 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 2010; 51: 1933–44.
  • Vivekanandan P, Singh OV. Molecular methods in the diagnosis and management of chronic hepatitis B. Expert Rev Mol Diagn 2010; 10: 921–35.
Turkish Journal of Medical Sciences-Cover
  • ISSN: 1300-0144
  • Yayın Aralığı: Yılda 6 Sayı
  • Yayıncı: TÜBİTAK
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