Publication: Kronik Hepatit B Hastalarında Lamivudin ve Adefovir Dipivoksil Tedavilerinin Etkinlikleri ve Güvenilirlikleri
Abstract
KHB tedavisinde iki grup ilaç kullanılmaktadır. Birinci grup INF alfa ve peg-INF ikinci grup ilaçlar ise nükleozid/ nükleotid anologlarıdır.Bu çalışmada 2000?2008 tarihleri arasında kliniğimizde KHB tanısı ile izlenenlamivudin ve adefovir dipivoksil tedavileri alan hastalar; tedavi yanıtı ve tedavi sırasındaortaya çıkan yan etkiler açısından değerlendirilmiştir.Çalışmaya lamivudin tedavisi verilen 62 hasta alınmıştır. Bu hastalardan 30'uHBeAg pozitif, 32 `si AntiHBe pozitifti. Hastalara en az 24 ay (maksimum 46 ay)lamivudin tedavisi verildi. Lamivudin tedavisi verilen hastalarda tedavinin 3., 6., 12., 24.ve tedavi sonrası 6.ay ortalama ALT, HBV DNA seviyelerinde tedavi başlangıcındakiortalama değerlere göre anlamlı azalma saptanmıştır (p<0,05). Tedavi sonu virolojikyanıt; HBeAg pozitif grupta %50, Anti HBe pozitif grupta %78,1, biyokimyasal yanıtHBeAg pozitif grupta %80, Anti HBe pozitif grupta %84,4 olarak tespit edilmiştir.Tedavi sonu 6.ayda kalıcı viral yanıt HBeAg pozitif grupta %30, Anti HBe pozitif grupta%53,1, biyokimyasal yanıt HBeAg pozitif grupta %43,3 Anti HBe pozitif grupta %56,6bulunmuştur.Lamivudin tedavisi sırasında HBeAg pozitif grupta %46,7, AntiHBe pozitifgrupta ise %12,5 virolojik breakthrough gelişmiştir. HBeAg pozitif grupta virolojikbreakthrough gelişimi Anti HBe pozitif gruba göre istatiksel olarak yüksek bulunmuştur(p=0,03). Lamivudin tedavisi sonrasında takiplerde HBeAg pozitif grupta %9,1, Anti-HBe pozitif grupta %33,3 relaps gelişmiştir. Relaps gelişimi Anti HBe pozitif grupta HBeAg pozitif gruba göre istatiksel olarak yüksek bulunmuştur (p=0,01).Tedavisi tamamlanan 62 hastanın 26 (%41,93) 'sında kalıcı yanıt elde edilmiştir.Adefovir dipivoksil tedavisi 27 hastaya verilmiştir. 13 hasta HBeAg pozitif, 14hasta Anti HBe pozitif idi. Hastalara en az 24 ay (maksimum 42 ay) adefovir dipivoksiltedavisi verildi. Adefovir dipivoksil tedavisi verilen hastalarda tedavinin 3.6.12.24. vetedavi sonrası 6.ay ortalama ALT, HBV DNA seviyelerinde başlangıçtaki ortalamadeğerlere göre anlamlı azalma saptanmıştır (p<0,05). Tedavi sonu virolojik yanıt;HBeAg pozitif grupta %53,8, Anti HBe pozitif grupta %64,3, biyokimyasal yanıtHBeAg pozitif grupta %69,2, Anti HBe pozitif grupta %82,9 olarak tespit edilmiştir.Tedavi sonu 6.ayda kalıcı viral yanıt oranları HBeAg pozitif grupta %38,5, Anti HBeVIpozitif grupta %42,9, biyokimyasal yanıt ise HBeAg pozitif grupta %46,2 Anti HBepozitif grupta %64,3 bulunmuştur.Adefovir dipivoksil tedavisi sırasında HBeAg pozitif grupta hastaların%7,7'sinde, Anti-HBe pozitif grupta ise %14,3'ünde virolojik breakthrough gelişti.Virolojik breakthrough açısından bu iki grup arasında istatiksel olarak anlamlı farkbulunmadı (p=0,5). Adefovir dipivoksil tedavisi sonrasında takiplerde HBeAg pozitifgrupta %16,7, Anti-HBe pozitif grupta %33,3 oranında relaps gelişimi saptandı. Relapsgelişimi açısından bu iki grup arasında istatiksel olarak anlamlı fark bulunamadı(p=0,4).Adefovir tedavisi verilen 27 hastanın %40,7'sinde kalıcı yanıt elde edildi.Her iki tedavi grubunda da tedavinin sonlandırılmasına neden olacak yan etkigelişmemiştir.Sonuç olarak Lamivudin ve adefovir dipivoksil tedavileri ile serum HBV DNAseviyelerinin baskılandığı, ALT normalizasyonunun sağlandığı söylenebilir.Bu iki ilacın aynı zamanda yan etki açısından güvenili olduğu saptanmıştır. Hiçbirvakada yan etki nedeniyle tedaviye ara vermek ya da kesmek zorunda kalınmamıştır.Ancak her iki antiviral ile tedavi sonrasında hedeflenen virolojik ve biyokimyasalyanıt oranlarına ulaşılamamıştır. Bu nedenle günümüzde KHB tedavisinde daha etkintedavi seçeneklerine ihtiyaç vardır.Anahtar kelimeler: Kronik hepatit B, lamivudin, adefovir dipivoksil, virolojikyanıt, biyokimyasal yanıt, yan etki
Two drug groups are used in CHB treatment. First group is INF-alpha and peg-INF, second group drugs are nucleoside/nucleotid analogs.In this study, the patients who were followed up with CHB diagnosis in ourclinic and took Lamivudin and Adefovir Dipivoxil treatment between 2000-2008 wereevaluated in terms of treatment response and the adverse effects that occur during thetreatment.62 patients who were given lamivudin treatment included in the study.30 ofthese patients were HBeAg positive and 32 were AntiHbe positive. Lamivudintreatment was given to patients minimum 24 months (maximum 46 months). In patientswho were given lamivudin treatment, a significant decrease was determined at themedian ALT and HBV DNA levels at 3., 6., 12., 24. and 6 months after the treatmentcomparing to median values at the beginning of treatment (p<0,05). The virologicresponse at the end of the treatment was determined as 50% in HBeAg positive groupand 78% in Anti HBe positive group, also biochemical response was 80% in HBeAgpositive group and 84,4% in Anti HBe positive group.6 months after the treatment, thepermanent viral response was determined as 30% in HBeAg positive group and 53,1%in Anti HBe positive group, also biochemical response was 43,3% in HBeAg positivegroup and 56,6 % in Anti HBe positive group.During the lamivudin treatment, virologic breakthrough developed in %46,7 ofHBeAg positive group and12,5% of Anti HBe positive group. Virological breakthroughdevelopment in HBeAg positive group was found statistical significantly highcomparing to Anti HBe positive group (P=0.03). After the lamivudin treatment, duringthe following up, relapse developed in 9,1% of HBeAg positive group and 33.3% ofAnti HBe positive group. Relapse development in Anti HBe positive group was foundstatistically high comparing to HBeAg positive group (P=0,01).In 26 of 62 patients (41,93%) whose treatment was completed, permanentresponse was obtained.Adefovir dipivoxil treatment was given to 27 patients. 13 patients were HBeAgpositive, 14 patients were Anti HBe positive. Adefovir dipivoxil treatment was given topatients minimum 24 months (maximum 42 months). In patients who were givenVIIIAdefovir dipivoxil treatment, a significant decrease was determined at the median ALTand HBV DNA levels in 3., 6., 12., 24. and 6 months after the treatment comparing tomedian values at the beginning of treatment (p<0,05). The virologic response at the endof the treatment was determined as 53,8% in HBeAg positive group and 64,3% in AntiHBe positive group, also biochemical response was 69,2% in HBeAg positive groupand 82,9% in Anti HBe positive group.6 months after the treatment, the permanentviral response was determined as38,5% in HBeAg positive group and 42,9% in AntiHBe positive group, also biochemical response was 46,2% in HBeAg positive groupand 64,3% in Anti HBe positive group.During the Adefovir dipivoxil treatment, virologic breakthrough developed in7,7% of HBeAg positive group and 14,3% of Anti HBe positive group. No statisticalsignificant difference was found between two groups in terms of virologicalbreakthrough development (P=0.5). After the Adefovir dipivoxil treatment, during thefollowing up, relapse development was determined in 16,7% of HBeAg positive groupand 33.3% of Anti HBe positive group. No statistical significant difference was foundbetween two groups in terms of relapse development (P=0,4).In 40,7 % of 27 patients who were given adefovir treatment, permanentresponse was obtained.No adverse effect that cause to terminate the treatment developed in both of thetreatment groups.Finally, it can be said that, both lamivudin and adefovir dipivoxil treatmentsrepress serum HBV DNA levels and provide ALT normalization.Also it was determined that both these drugs are safe in terms of adverse effects.There was no need to terminate or interrupt the treatment in any case because of theadverse effects.But, after the both antiviral treatments, the aimed virologic and biochemicalresponse rates couldn?t have been obtained. Therefore, at the present day, moreefficacious treatment alternatives are needed in CHB treatment .Keywords: Chronic Hepatit B, lamivudin, adefovir dipivoxil, virologic response,biochemical response,adverse effect.
Two drug groups are used in CHB treatment. First group is INF-alpha and peg-INF, second group drugs are nucleoside/nucleotid analogs.In this study, the patients who were followed up with CHB diagnosis in ourclinic and took Lamivudin and Adefovir Dipivoxil treatment between 2000-2008 wereevaluated in terms of treatment response and the adverse effects that occur during thetreatment.62 patients who were given lamivudin treatment included in the study.30 ofthese patients were HBeAg positive and 32 were AntiHbe positive. Lamivudintreatment was given to patients minimum 24 months (maximum 46 months). In patientswho were given lamivudin treatment, a significant decrease was determined at themedian ALT and HBV DNA levels at 3., 6., 12., 24. and 6 months after the treatmentcomparing to median values at the beginning of treatment (p<0,05). The virologicresponse at the end of the treatment was determined as 50% in HBeAg positive groupand 78% in Anti HBe positive group, also biochemical response was 80% in HBeAgpositive group and 84,4% in Anti HBe positive group.6 months after the treatment, thepermanent viral response was determined as 30% in HBeAg positive group and 53,1%in Anti HBe positive group, also biochemical response was 43,3% in HBeAg positivegroup and 56,6 % in Anti HBe positive group.During the lamivudin treatment, virologic breakthrough developed in %46,7 ofHBeAg positive group and12,5% of Anti HBe positive group. Virological breakthroughdevelopment in HBeAg positive group was found statistical significantly highcomparing to Anti HBe positive group (P=0.03). After the lamivudin treatment, duringthe following up, relapse developed in 9,1% of HBeAg positive group and 33.3% ofAnti HBe positive group. Relapse development in Anti HBe positive group was foundstatistically high comparing to HBeAg positive group (P=0,01).In 26 of 62 patients (41,93%) whose treatment was completed, permanentresponse was obtained.Adefovir dipivoxil treatment was given to 27 patients. 13 patients were HBeAgpositive, 14 patients were Anti HBe positive. Adefovir dipivoxil treatment was given topatients minimum 24 months (maximum 42 months). In patients who were givenVIIIAdefovir dipivoxil treatment, a significant decrease was determined at the median ALTand HBV DNA levels in 3., 6., 12., 24. and 6 months after the treatment comparing tomedian values at the beginning of treatment (p<0,05). The virologic response at the endof the treatment was determined as 53,8% in HBeAg positive group and 64,3% in AntiHBe positive group, also biochemical response was 69,2% in HBeAg positive groupand 82,9% in Anti HBe positive group.6 months after the treatment, the permanentviral response was determined as38,5% in HBeAg positive group and 42,9% in AntiHBe positive group, also biochemical response was 46,2% in HBeAg positive groupand 64,3% in Anti HBe positive group.During the Adefovir dipivoxil treatment, virologic breakthrough developed in7,7% of HBeAg positive group and 14,3% of Anti HBe positive group. No statisticalsignificant difference was found between two groups in terms of virologicalbreakthrough development (P=0.5). After the Adefovir dipivoxil treatment, during thefollowing up, relapse development was determined in 16,7% of HBeAg positive groupand 33.3% of Anti HBe positive group. No statistical significant difference was foundbetween two groups in terms of relapse development (P=0,4).In 40,7 % of 27 patients who were given adefovir treatment, permanentresponse was obtained.No adverse effect that cause to terminate the treatment developed in both of thetreatment groups.Finally, it can be said that, both lamivudin and adefovir dipivoxil treatmentsrepress serum HBV DNA levels and provide ALT normalization.Also it was determined that both these drugs are safe in terms of adverse effects.There was no need to terminate or interrupt the treatment in any case because of theadverse effects.But, after the both antiviral treatments, the aimed virologic and biochemicalresponse rates couldn?t have been obtained. Therefore, at the present day, moreefficacious treatment alternatives are needed in CHB treatment .Keywords: Chronic Hepatit B, lamivudin, adefovir dipivoxil, virologic response,biochemical response,adverse effect.
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