Kronik hepatit B ve hepatit C infeksiyonunun anti-viral tedavisinin değerlendirilmesi

Abstract

ÖZET Kronik hepatitler tüm dünyada önemli bir halk sağlığı probleminidir. Bu çalışmada 1996-2002 tarihleri arasında tedavi verilen toplam 186 kronik HBV ve kronik HCV hastasının sonuçlan değerlendirilmiştir. Kronik HBV tanısı ile 99 (68 erkek, 31 kadın) hastaya tedavi verildi. Hastaların yaş ortalaması 33.3 ±11.6 idi. Bu hastaların 36'sında (% 36.3) HBeAg pozitif, 63'ünde (% 63.6) anti-HBe pozitif idi. Kronik HBV'li hastalarda tedavi sonu virolojik yanıt; IFN monoterapisi, IFN+lamivudin kombinasyonu ve lamivudin alanlarda sırasıyla % 60.7, % 79,1 ve % 66.6 idi. Biyokimyasal yanıt ise monoterapi, kombine tedavi grubu ve lamivudin alanlarda sırasıyla % 39.2, % 58.3 ve % 45.8 idi. Kalıcı yanıt ise; monoterapi, kombine tedavi grubu ve lamivudin alanlarda sırasıyla % 35.2, % 43.7 ve % 1 1.1 idi. Uzun süreli kalıcı yanıt aynı gruplarda; % 21.5, % 25.0 ve % 1 1.1 idi. Kalıcı ve uzun süreli kalıcı yanıt açısından gruplar arasında istatistiksel bir fark yoktu (p>0.05). Non-mutant kronik HBV'li hastalarda kalıcı yanıt monoterapi grubunda % 18.7, kombine tedavi grubunda % 33.3 idi. Prekor mutant kronik HBV'li hastalarda kalıcı yanıt ise IFN monoterapi grubunda % 42.8, kombine tedavi grubunda % 50.0 idi. Prekor mutant kronik HBV'li hastalarda her iki tedavi grubunda da kalıcı yanıt daha yüksek ise de aradaki fark istatistiksel olarak anlamlı değildi (p>0.05). Genel olarak kalıcı yanıt kadın cinsiyette daha yüksekti (p<0.05). HBeAg serokonversiyonu; IFN monoterapi grubunda 3 hasta (% 18.7), kombine tedavi grubunda 4 hastada (% 33.3), lamivudin grubunda da 1 hastada (% 11.1) gözlenmişti. HBsAg serokonversiyonu sadece IFN monoterapi grubundan 2 hastada (% 3.9) gözlendi. Lamivudin monoterapisi alan hastalarda 12. ayda; virolojik ve biyokimyasal yanıt % 63.6, tedavide 24. ayı tamamlayan hastalarda virolojik ve biyokimyasal yanıt sırasıyla % 66.6 ve % 45.8 idi, 24. ayda tedavisi kesilen hastaların % 88.9'mda relaps gözlendi, sadece hastaların % 1 1.l'inde uzun süreli yanıt elde edildi. Kronik HCV tanısı ile 87 (36 erkek, 51 kadın) hastaya tedavi verildi. Hastaların yaş ortalaması 48.8 ±11.6. Kronik HCV'li hastalarda tedavi sonu virolojik yanıt; IFN monoterapisi ve kombine tedavi grubunda sırasıyla % 37.5 ve % 60.0 idi. Biyokimyasal yanıt ise monoterapi ve kombine tedavi grubunda sırasıyla % 43.7 ve % 78.1 idi. Tedavi sonu biyokimyasal yanıt kombine tedavi grubunda istatistiksel olarak daha yüksekti (p<0.01). 51Kalıcı yanıt ise; IFN monoterapisi alanlarda % 21.8, IFN+ribavirin tedavi grubunda % 57.1 idi. Uzun süreli yanıt her iki grupta sırasıyla; % 15.6 ve % 35.4 idi. Kalıcı yanıt kombine tedavi alanlarda daha yüksek olup istatistiksel olarak anlamlıydı (p<0.01). Uzun süreli yanıt ise kombine tedavi grubunda daha yüksek olsada aradaki fark istatistiksel olarak anlamdı değildi (p>0.05). Kalıcı yanıt veren hastalarda cinsiyet, yaş, serum ALT düzeyi, histolojik aktivite indeksi, muhtemel infeksiyon yaşı ve viral yük gibi değişkenlerle kalıcı yanıt arasında istatistiksel olarak anlamlı fark bulunamadı. IFN+ribavirin kombinasyonu ile; daha önce IFN monoterapi tedavisi alan ve sonrasında nüks gelişen hastaların % 60.0'ında (5 hastanın 3'ünde) ve önceki tedaviye yanıtsız hastaların % 33.3'ünde (3 hastanın 1 'inde) kalıcı yanıt elde edilmiştir. Kronik HBV ve HCV'li hastalarda tedavi; serum ALT düzeyini istatistiksel olarak anlamlı düşürdü (pO.001). Hastalarda tedavi iyi tolere edilmiştir. Sonuç olarak; bizim çalışmamızda kronik HBV hastalarında IFN monoterapi, IFN+lamivudin ve tek başına lamivudin tedavi grupları arasında kalıcı yanıt açısından istatistiksel olarak anlamlı fark bulunamadı. Çalışmamızda, kronik HCV'li hastalarda kalıcı yanıt açısından IFN+ribavirin tedavisi BFN monoterapisinden daha etkili bulunmuştur. 52

SUMMARY Chronic hepatitis is an important public health problem around the world. The results of total 186 chronic hepatitis B and hepatitis C patients whom treatment was given between 1996 and 2002, were evaluated in this study. Treatment was given to 99 patients (68 men, 31 women) with chronic hepatitis B. The age average was 33.3 ± 1 1.6. HBeAg and anti-HBe was positive in 36 (36.3%) and 63 (63.6%) of these patients respectively. The end-treatment virologic response rates to IFN monotherapy, IFN plus lamivudin therapy group and lamivudine in the patients with chronic hepatitis B were 60.7%, 79.1% and 66.6% respectively. The biochemical response rates in monotherapy, combined therapy and lamivudin groups were 39.2%, 58.3%, and 45.8% respectively. The sustained response rates in monotherapy, combined therapy and lamivudine groups were 35.2%, 43.7%, and 11.1% respectively. The long- term sustained response rates in the same groups were 21.5%, 25.0% and 11.1%, respectively. There was no significant statistical difference between the groups related to sustained and long-term sustained response rates (p>0.05). The sustained response rate in the patients with non-mutant chronic hepatitis B was 18.7% for monotherapy group and 33.3% for the combined therapy group. The sustained response rate in the patients with precore mutant chronic hepatitis B was 42.8% for IFN monotherapy group and 50.0% for the combined therapy group. Although the sustained response rate in the patients with precore mutant chronic hepatitis B was high for both of the therapy groups, the difference between the groups was not statistically significant (p>0.05). The HBeAg seroconversion was observed in 3 patients (18.7%) of IFN monotherapy group, 4 patients (33.3%) of combined therapy group, and 1 patient (11.1%) of lamivudine group. HBsAg seroconversion was found only in 2 patients (3.9%) of IFN monotherapy group. The virologic and biochemical response rate in the patients treated with lamivudine monotherapy was 63.5% in 12th month and was 66.6% and 45.8% respectively in the patients who completed 24th month of the therapy. Relapse was seen in 88.9% of the patients whose treatments were stopped in 24* month, and a long-term response was obtained in only 1 1. 1 % of the patients. Eighty-seven patients (36 men, 51 women) with chronic hepatitis C were treated. The age average was 48.8 ± 11.6. The end-treatment virologic response rates in the patients with chronic hepatitis C were 37.5% and 60.0% for IFN monotherapy and combined therapy respectively. The biochemical response rates to monotherapy and 53combined therapy were 43.7% and 78.1% respectively. The end-treatment biochemical response rates was higher statistically in the combined therapy group (p<0.01). The sustained response rate was 21.8% in IFN monotherapy group and 57.1% in IFN plus ribavirin therapy group. The long-term response rate was 15.6% and 35.4% in those two groups respectively. The sustained response rate was significantly higher in the combined therapy group (p<0.01). Although the long-term response rate was higher in the combined therapy group it was not statistically important (p>0.05). No statistical significant difference was found in the patients who had sustained response, between the response and the variables such as gender, age, serum ALT level, histologic activity index, probable infection age, and viral load. Sustained response was obtained in 60.0% (5 of 3 patients) of the patients who have been treated with IFN monotherapy and then relapse have developed, and in 33.3% (1 of 3 patients) of the patients who have not have any response to previous therapy. The treatment decreased ALT levels statistically significant in the patients with chronic hepatitis B and C (p<0.001). The patients tolerated the treatment well. In conclusion, we found no significant difference between IFN monotherapy, IFN+lamivudine and lamivudine alone treatment groups related to sustained response in chronic hepatitis B patients. In our study, IFN+ribavirin treatment was found more effective than IFN monotherapy regarding sustained response in chronic hepatitis C patients. 54