İbrahim BAŞARIR, Sevil İLİKHAN, Ferda HARMANDAR, Utku Erdem SOYALTIN, Selim AYDEMİR, Yücel ÜSTÜNDAĞ

Kronik aktif hepatit B tanılı hastalarımızın tedavi yanıtlarının değerlendirilmesi

Giriş ve Amaç:Bülent Ecevit Üniversitesi Tıp Fakültesi Gastorenteroloji Kliniğinde tedavi edilen kronik hepatit B olgularımızı retrospektif olarak değerlendirerek uygulanan ajanların; antiviral etkinliklerinin ve ilaç yan etkilerinin araştırılması planlanmıştır. Gereç ve Yöntem:Çalışmamızda 2001-2010 yılları arasında gastroenteroloji kliniğinde tedavi edilen 241 hastanın; tedaviye yanıt ve direnç oranları ile ilaç yan etkileri incelendi. Bulgular: Karakteristik özellikler açısından aralarında fark olmayan; entekavir kullanan 35 ve tenofovir kullanan 20 naiv hastanın, bir yıllık tedavi sonunda antiviral etkinlikleri benzer saptandı. Lamivudin direnci saptanan 2 hastada tenofovir monoterapisiyle HBV DNA saptanabilir düzeyin altına indi. İnterferon ve lamivudin ikili tedavi sonrası tenofovir monoterapisine geçilen 14 hastada HBV DNA'nın saptanabilir düzeyin altına inmesi oranı sırasıyla ilk yılda %81, 2. yılda %85'ti. Lamivudin sonrası, adefovir tedavisine geçilen ancak HBV DNA düzeyi 1 yıllık tedavi ile 300 kopya/ml'nin üzerinde olan 5 hastada tenofovir monoterapisine geçildi. 12 ve 24 aylık tedavi sonunda bu hastaların tamamında HBV DNA saptanabilir düzeyin altına indi. Sonuç:Entekavir ve tenofovir; naiv hastalarda antiviral etkinlik, yan etki ve komplians bakımından benzer özelliktedir. Tenofovir, lamivudin dirençli hastalarda yüksek etkinlikte olup ilk seçenek ilaçtır. Lamivudine direnç varlığı tenofovir cevabını etkilememektedir. Tenofovir monoterapisi; adefovire yanıtsız, suboptimal yanıtlı hastalarda dahi yüksek etkinliktedir

Anahtar Kelimeler:

Kronik hepatit B, tenofovir, entekavir

Assessment of treatment responses in patients with chronic active hepatitis B

Background and Aims:In this study, patients with chronic hepatitis B, treated in Bülent Ecevit University School of Medicine, Department of Gastroenterology, were evaluated retrospectively with respect to antiviral efficacy and adverse effects. Materials and Methods:Treatment responses, resistance rates and side effects of 241 patients treated between 2001 and 2010 in the gastroenterology clinic were examined retrospectively. Results:There were no statistically significant differences between 35 naive patients treated with entecavir and 20 naive patients treated with tenofovir regarding demographic characteristics. After a one-year period of treatment, similar antiviral activity was detected between these two groups. Two patients who had lamivudine resistance were switched to tenofovir, and their HBV DNA level became undetectable. For 14 patients with tenofovir treatment, which followed interferon and lamivudine combination treatment, the ratio of undetectable levels of HBV DNA was 81% at the first year and 85% at the second year. Five patients, treated with adefovir after lamivudine treatment and whose HBV DNA levels reached more than 300 copies/ml following one year with adefovir monotherapy, were switched to tenofovir monotherapy. Following 12 and 24 months' treatment, HBV DNA levels became undetectable in all five patients. Conclusions: Entecavir and tenofovir are similar in terms of antiviral activity, side effects and compliance in naive patients. Tenofovir is highly effective in lamivudine-resistant patients and should be the first choice in these patients. Lamivudine resistance does not affect the tenofovir treatment response. Tenofovir monotherapy is highly active in the adefovir- refractory or suboptimal response patients.

Keywords:

Chronic hepatitis B, tenofovir, entecavir,

PDF

___

Eddleston ALWF and Dixon B. Interferons in thetreatment of chron- ic viral infection of theliver, 1st edit, UK, Pennine Press. 1990; 56- 61.
Dienstag JL. Hepatitis B Virüs İnfection. N Eng J Med 2008; 359: 1486-500. 3. de Franchis R, Hadengue A, Lau G, et al. EASL International Con- sensus Conference on Hepatitis B. 13-14 September, 2002 Geneva, Switzerland. Consensus statement (long version). J Hepatol 2003; 39(Suppl 1): S3-25.
European Association For The Study Of The Liver. EASL Clinical Practice Guidelines: management of chronic hepatitis B. J Hepatol 2009; 50: 227-42.
Look ASF, Mc Mahon BJ. Chronic hepatitis B. Hepatology 2007; 45: 507-39.
Chang TT, Gish RG, de Man R, et al. A comparison of entecavir and lamivudin efor HBeAg-positive chronic hepatitis B. N Engl J Med 2006; 354: 1001-10.
Güzelbulut F, Ovünç AO, Çetinkaya ZA, et al. Comparison of the efficacy of entecavir and tenofovir in chronic hepatitis B. Hepato- gastroenterology 2012; 59: 477-80.
Keeffe EB, Dieterich DT, Han SH, et al. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States. Clin Gastroenterol Hepatol 2008; 6: 1315-41.
Osborne M. Safety and efficacy of entecavir for the treatment of chronic hepatitis B. Infect Drug Resist 2011; 4: 55-64.
Gish RG, Lok AS, Chang TT, et al. Entecavir the therapy for up to 96 weeks in patients with HBeAg-positive chronic hepatitis B. Gas- troenterology 2007; 133: 1437-44.
Marcellin P, Heathcote EJ, Buti M, et al. Tenofovir disoproxil fuma- rate versus adefovir dipivoxil for chronic hepatitis B. N Engl J Med 2008; 359: 2442-55.
Khungar V, Han SH. A systematic review of side effects of nucleo- side and nucleotide drugs used for treatment of chronic hepatitis B. Curr Hepatitis Rep 2010; 9: 75-90.
Demirtürk N, Demirdal T. Yüksek genetik bariyerli antivirallerle te- davi edilen kronik hepatit B hastalarında gözlenen yan etkiler. Yeni Tıp Dergisi 2011; 28: 146-9.
Zhang YY, Chen EQ, Yang J, et al. Treatment with lamivudine ver- sus lamivudine and thymosin alpha-1 for e antigen-positive chronic hepatitis B patients: a meta-analysis. Virol J 2009; 6: 63.
Lau GK, Piratvisuth T, Luo KX, et al. Peginterferon Alfa-2a, lamivu- dine, and the combination for HBeAg-positive chronic hepatitis B. N Engl J Med 2005; 352: 2682-95.
Van Bömmel F, Man R.A, Wedemeyer Het al. Long-termefficacy of tenofovir monotherapy for hepatitis B virus-monoinfected patients after failure of nucleoside/nucleotide analogues. Hepatology 2010; 51: 73-80.
Snow A, Thibault V, Qi X, ve ark. Combination of adefovir dipivoxil and lamivudine prevented of ADV resistence mutations in chronic hepatitis B patients with Lam resistant HBV. Gastroenteroloy 2005; 128: 945-53.
Van Bömmel F, Zöllner B, Sarrazin C, et al. Tenofovir for patients with lamivudine-resistant hepatitis B virus (HBV) infection and high HBV DNA level during adefovir therapy. Hepatology 2006; 44: 318- 25.