Results of Entecavir treatment in patients with chronic hepatitis B

Year 2013, Volume: 3 Issue: 04, 176 - 180, 01.12.2013

Şükran Köse Melda Turken Bengu Gireniz Tatar

https://doi.org/10.5799/ahinjs.02.2013.04.0104

Abstract

Objective: This study was designed to determine the efficacy and safety of Entecavir (ETV) after 96 weeks treatment in patients with chronic viral hepatitis B (CHB). Methods: Thirty-eight patients were included into the study. The criteria for starting ETV treatment were as follows: elevated ALT levels >upper limit of normal (ULN) two times, with HBV-DNA levels ≥5 log10 copies/ml (≥20000 IU/mL), in HBe Ag positive patients, ≥4log10 copies/ml (≥2000IU/mL) in HBe Ag negative patients and liver damage was confirmed by histopathology (Knodell HAI ≥4 or fibrosis ≥1). Patients were followed up every 12 weeks by virological and biochemical tests. Results: Twenty-four of 38 patients (63.2%) were male. Mean age of patients were 38.6 years, 14 of them were HBeAg positive (36.8%). At baseline, median ALT level was detected as 106.7 IU/ml, median HBV DNA levels were 4.8 x 107 copy/ml, and mean Knodell HAI score was nine. Eleven of 14 HBe Ag positive patients (78.6%) were treatment-naïve. No resistance mutation was determined during treatment. Biochemical responses (BR) at 48th and 96th week were 100% and virologic response (VR) were 57.1%, and 50%, respectively. Serological response (SR) at 48th and 96th weeks were 35.7% and 42.8% respectively. Fifteen (62.5%) of 24 HBe Ag negative patients were treatment-naïve; two patients were detected to have lamivudine resistance mutation. At 48th and 96th week, BR was 95.8%, and 100%, respectively; and VR were 83.3% both. Conclusion: In our study, virologic response was significantly high after two years of therapy with Entecavir in HBe Ag negative patients.

Keywords

Chronic hepatitis B, Entecavir, therapy

Results of Entecavir treatment in patients with chronic hepatitis B

Abstract

Amaç: Bu çalışmada kronik hepatit B hastalarında 96 haftalık Entekavir (ETV) tedavi etkinliğinin ve güvenliğinin değerlendirilmesi amaçlandı.Yöntemler: Kronik Hepatit B tanısıyla 38 hasta çalışmaya alındı. Entekavir tedavisine başlama kriterleri: yükselmiş ALT düzeyleri, (>normalin iki katında fazla), HBe Ag pozitif hastalarda HBV DNA ≥5 log10 kopya/ml (≥20000 IU/ml), HBe Ag negatif hastalarda ≥4 log10 kopya/ml (≥ 2000 IU/ml) karaciğer hasarının histopatolojik olarak gösterilmesi (Knodell HAİ ≥4, fibrozis ≥1). Hastalar 12 haftada bir biyokimyasal ve virolojik testlerle takip edildi. Bulgular: Hastaların 24’ü (%63,2) erkekti. Yaş ortalaması 38,6 yıldı. Tüm hastaların 14’ünde (%36,8) HBe Ag pozitifti. Başlangıç ortalama ALT düzeyleri 106,7 IU/ml, HBV DNA düzeyleri 4,8 x 107 kopya/ml ve Knodell HAI skoru dokuz idi. HBe Ag pozitif hastaların 11’i (%78,6) naivdi. Hiçbirinde direnç mutasyonu yoktu. Biyokimyasal yanıt (BY) 48. ve 96. haftalarda %100, virolojik yanıt (VY) sırasıyla %57,1 ve %50 idi. Serolojik yanıt (SY) sırasıyla %35,7 ve %42,8 olarak saptandı. HBeAg negatif hastaların 15’i (%62,5) naivdi; iki hastada lamuvidin direnç mutasyonu saptandı. Kırksekizinci ve 96. haftalarda sırasıyla BY %95,8 ve %100, VY %83,3 saptandı.Sonuç: Çalışmamızda iki yıllık entakavir tedavisi sonucunda, özellikle HBe Ag negatif hastalarda tedaviye yüksek oranda yanıt sağlanmıştır

Keywords

Kronik hepatit B, entekavir, tedavi

References

• World Health Organization. HepatitisB fact sheet WHO/204. Geneva: World Health Organization, October 2000. (Ac- cessed February 10, 2006, at http://www. who.int/mediacen- tre/factsheets/fs204/en.)
• Lee WM. Hepatitis B virus infection. N Engl J Med 1997;337:1733-1745.
• Liaw YF, Leung N, Kao JH et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2008 update. Hepatol Int 2008;2:263-283.
• European Association for the Study of the Liver. EASL clini- cal practice guidelines: management of chronic hepatitis B. J Hepatol 2009;50:227–242.
• Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hep- atology 2009;50:661-662.
• European Association For The Study Of The Liver. EASL Clini- cal Practice Guidelines: management of chronic hepatitis B. J Hepatol 2009;50:227-42.
• Niu C, Murakami E, Furman PA. Clevudine is efficiently phos- phorylated to the active triphosphate form in primary human hepatocytes. Antivir Ther 2008;13:263-269.
• Baraclude Package Insert. Wallingford, CT: Bristol-Myers Squibb.
• http://packageinserts.bms.com/pi/pi_baraclude.pdf. Accessed December 4, 2010.
• Seifer M, Hamatake RK, Colonno RJ, Standring DN. In vitro inhibition of hepadnavirus polymerases by the triphosphates of BMS-200475 and lobucavir. Antimicrob Agents Chemoth- er1998;42:3200–3208.
• Chang TT, Lai CL, Kew Yoon S, et al. Entecavir treatment for up to 5 years in patients with hepatitis B e antigen-positive chronic hepatitis B. Hepatology 2010;51:422–430.
• Tenney DJ, Rose RE, Baldick CJ, et al. Long-term monitoring shows hepatitis B virus resistance to Entecavir in nucleoside naive patients is rare through 5 years of therapy. Hepatology. 2009;49:1503–1514.
• Buster EH, van Erpecum KJ , Schalm SW. Treatment of chronic hepatitis B virus infection- Dutch national guidelines. Neth J Med 2008;66:292-306.
• Nagasaki F, Niitsuma H, Ueno Y. The high incidence of the emergence of Entecavir-resistant mutants among patients infected with Lamuvidine-resistant hepatitis B virus. Tohoku J Exp Med 2007;213:181-186.
• Dimou E, Papadimitropoulos V, Hadziyannis SJ. The role of Entecavir in the treatment of chronic hepatitis B. Therapeu- tics and Clinical Risk Management 2007;3:1077-1086.
• Chang TT, Gish RG, Man RD. A comparison of Entecavir and Lamuvidine for HBeAg-positive chronic hepatitis B. N Engl J Med 2006;354:1001-1010.
• Lai CL, Shouval D, Lok AS. Entecavir versus lamuvidine for patients with HBeAg-negative chronic hepatitis B. N Engl J Med.2006;354:1011-1020.
• Tillmann HL. Antiviral therapy and resistance with hepatitis B virus infection. World J Gastroenterol 2007;13:125-140.
• Sherman M, Yurdaydin C, Sollano. Entecavir for treatment of Lamuvidine- refractory, HBeAg-positive chronic hepatitis B. Gastroenterology 2006;130:2039-2049.
• Yao GB, Ren H, Xu DZ, et al. Virological, serological and bio- chemical outcomes through 3 years of Entecavir treatment in nucleoside-naive Chinese chronic hepatitis B patients. J Viral Hepat 2010;17 Suppl 1:51-58.
• Buti M, Morillas RM, Prieto M, et al. Efficacy and safety of Entecavir in clinical practice in treatment-naive Caucasian chronic hepatitis B patients. Eur J Gastroenterol Hepatol 2012;24:535-542.
• Chen EQ, Wang TT, Bai L, et al. Quantitative hepatitis B sur- face antigen titres in Chinese chronic hepatitis B patients over 4 years of Entecavir treatment. Antivir Ther 2013;2.