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

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

Aim: 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.

___

  • 1. 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 donors in Kano, Nigeria. Turk J Med Sci 2012; 42: 337–41.
  • 5. Işıkgöz Taşbakan M, Önen Sertöz Ö, Pullukçu H, Özkören Çalık Ş, Sipahi OR, Yamazhan T. Comparison of quality of life in hepatitis B virus carriers versus chronic hepatitis B virus carriers versus the normal population. Turk J Med Sci 2010; 40: 575–83.
  • 6. Takkenberg RB, Weegink CJ, Zaaijer HL, Reesink HW. New developments in antiviral therapy for chronic hepatitis B. Vox Sang 2010; 98: 481–94.
  • 7. Perz JF, Armstrong GL, Farrington LA, Hutin YJ, Bell BP. The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol 2006; 45: 529–38.
  • 8. Yokosuka O, Kurosaki M, Imazeki F, Arase Y, Tanaka Y, Chayama K et al. Management of hepatitis B: consensus of the Japan Society of Hepatology 2009. Hepatol Res 2011; 41: 1–21.
  • 9. Tong MJ, Hsu L, Chang PW, Blatt LM. Evaluation of current treatment recommendations for chronic hepatitis B: a 2011 update. J Gastroenterol Hepatol 2011; 26: 829–35.
  • 10. Locarnini S. Molecular virology and the development of resistant mutants. Implications for therapy. Semin Liver Dis 2005; 25 (Suppl 1): 9–19.
  • 11. 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.
  • 12. Chien RN, Yeh CT, Tsai SL, Chu CM, Liaw YF. Determinants for sustained HBeAg response to lamivudine therapy. Hepatology 2003; 38: 1267–73.
  • 13. 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.
  • 14. 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.
  • 15. 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.
  • 16. Kubar A, Saygun I, Özdemir A, Yapar M, Slots J. Realtime 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.
  • 17. Hunt CM, McGill JM, Allen MI, Condreay LD. Clinical relevance of hepatitis B viral mutations. Hepatology 2000; 31: 1037–44.
  • 18. Zoulim F. Detection of hepatitis B virus resistance to antivirals. J Clin Virol 2001; 21: 243–53.
  • 19. Zoulim F. Assessing hepatitis B virus resistance in vitro and molecular mechanisms of nucleoside resistance. Semin Liver Dis 2002; 22: 23–31.
  • 20. 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.
  • 21. 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
Sayıdaki Diğer Makaleler

Dexmedetomidine infusion prevents postoperative shivering in patients undergoing gynecologic laparoscopic surgery

Yücel KARAMAN, Ahmet Mete ERGENOĞLU, Semra KARAMAN, Mustafa Arda CEYLAN, Esra Nur ÇETİN, İlkben GÜNÜŞEN, Abdurrahim DERBENT

The outcomes of the pregnancies of lactating women

Mahmut Kuntay KOKANALI, Ahmet Akın SİVASLIOĞLU, Işık ÜSTÜNER, Özlem ŞENGÜL, Ayşe Filiz AVŞAR

Evaluation of the relationship between dental erosion and scintigraphically detected gastroesophageal reflux in patients with cerebral palsy

Özlem Martı AKGÜN, Günseli POLAT GÜVEN, Ceyhan ALTUN, İlker TURAN, Zülfikar POLAT

Anterior segment morphometry and intraocular pressure change after uneventful phacoemulsification

Pınar KÖSEKAHYA, Piraye Zeynep KÜRKÇÜOĞLU, Tamer TAKMAZ

Comparison of the effects of intraarticular hyaluronic acid and antiinflammatory drug treatments on the surgical intervention rates in patients with gonarthrosis

Yalçın ERDOĞAN, İlhan GÜNAYDIN, Ayşe Yeşim GÖÇMEN, Murat KORKMAZ, Aylin OKUR

Polymorphisms in ABC transporters (ABCA1 and ABCC8) in metabolic syndrome

Yunus Emre YANDI, Mihriban AYVAZ, Arif Bayram HACIHASANOĞLU, Cihangir EREM, Orhan DEĞER

Decreasing blood loss and the need for transfusion after CABG surgery: a double-blind randomized clinical trial of topical tranexamic acid

Rahman GHAFARI, Narges SHARIFI, Mahmoud NOURAEI, Afshin BARADARI GHOLIPOUR, Mohammad Reza HABIBI2, Amir ZEYDI EMAMI

Immunohistochemical distribution and gene expression of transforming growth factor alpha in ovarian tissue of rats treated with capsaicin in puberty*

Gökhan NUR, Sevda YILDIZ ELİŞ, Mümtaz NAZLI

Evaluation of nonneoplastic findings on vaginal smears with comparison of intrauterine devices and oral contraceptive pill effects

Jale KARAKAYA, Ayşe Nurcan ÜNLÜER, Servet GÜREŞCİ, Rahime FINDIK BEDİR

The effects of short-acting analogue insulins on body weight in patients with type 2 diabetes mellitus

Ertuğrul TAŞAN, Cumali KARATOPRAK, Adnan YAY, Servet YOLBAŞ, Mustafa ÇAKIRCA, Mehmet Ali ÇIKRIKCIOĞLU, Mehmet ZORLU, Muharrem KISKAÇ, Reha ERKOÇ