Kronik hepatit b enfeksiyonu olan çocuklarda çeşitli tedaviler ve immün yanıtla ilişkisi
Hepati̇t b olan çocuklarda çeşi̇tli̇ tedavi̇ler i̇le bağişikli si̇stemi̇ olan i̇li̇şki̇si̇
Yazar: MURAT KARAOĞLAN
Danışman: PROF. DR. MEHMET YAVUZ COŞKUN
Gaziantep Üniversitesi / Tıp Fakültesi / Çocuk Sağlığı ve Hastalıkları Ana Bilim Dalı
Derece: Tıpta Uzmanlık, 2000
Konu: Çocuk Sağlığı ve Hastalıkları = Child Health and Diseases
Dizin: Hepatit B antijenleri = Hepatitis B antigens ; Reseptörler-lenfosit yerine yerleştirme = Receptors-lymphocyte homing ; Viral hepatit aşıları = Viral hepatitis vaccines

Özet:
Kronik B hepatiti, kendine Ozgu klinik, biyokimyasal, seroloji ye histopatolojik Ozellikleri plan karacigerin uzun sUreli (en az alti ay) iltihabi (inflamatuar) hastaligidir. Kroniklesmeye egilimden kisinin immun yapisinin sorumlu oldugu belirtilmektedir.
Bu calismada kronik B hepatit'li hastalann tedavisinde kullanilan immunmodulatOr ilaclardan levamizol ve HBsAg asisinin cocuk hastalarda kullanimi ve buna bagli olarak kantitatif bazi immun parametreler ile viral replikasyonda meydana gelen degisimler incelenerek degerlendirildi.
Hastalann lenfosit alt gruplanndan CD3, CD19, CD4, CD8, CD4/CD8 CD16/56 degerleri flowsitometrik yOntemle; serum IgG, IgA, IgM, C3, C4 duzeyleri nefelometnk yentemle, HBV DNA dUzeyleri mikrokolon DNA prop RIA (Abbot) yOntemi ile, HBV markerleri ELIZA yOntemi ile,serum ALT,AST degerleri OlympusAU800 otoanalyzer cihazinda kendi kiti ile calisildi.
Klinigimizde kronik B hepatiti tanisi alms; 93 cocuk hastanin tedavi oncesi ve sonrasi hucresel ye humoral immun parametrelerdeki bulgular su sekilde idi:
Hastalann %6,04'unde absolu lenfosit sayisi, %12,8'inde total T lenfosit sayisi(CD3), %22,5'inde total B lenfosit sayisi (CD19), %3,22'sinde helper T lenfosit sayisi(CD4), %2,15'inde sitotoksik/supresor T lenfosit sayisi (CD8), (%6,04) natural killer lenfosit sayisi yasa gore normal degerlerin altinda saptandi. Tedavi sonrasi bu oranlann sirasi Ile % 3,22 -%3,22-%13,9 —%0,9-
%0-%0	degerlerine dustUgti gozlendi. Levamizol ve/veya asinin KBH'Il
hastalann absolu lenfosit sayisi, absolu	CD19 saps!, absolu CD16/56
sayilannda sagladigi artisin anlamli olmadigi belirlendi (p>0,05). Absolu CD3 sayisinda gorulen artis uzerine etkili olduklan saptandi. Asi kullanan kronik aktif hepatit'li hastalarda CD4'de arils ve CD8'de ise azalmaya neden oldugu gozlendi (p<0,05). Ayni hastalarda levamizolUn tedavi oncesi ve sonrasi degisim uzerine etkili olmadigi belirlendi (p>0,05). Tedavi oncesi 2 hastada IgM yap gore normal degerlerin altinda saptandi. Tedavi sonrasi bu durumun degismedigi gozlendi. Levamizol ve/veya asi C3 duzeyi uzerine etkili olmazken, C4 dUzeyinde azalmaya neden oldugu belidenmistir.
Levamizol ve/veya asi, HBeAg (%34) kaybi ve anti-HBe'ye serokonversiyon (%25) ve ALT normallesmesi uzerine etkili (%28) bulunurken HBV DNA duzeylerinde belirgin bir yukselmeye neden olmaktadir.
Sonuc olarak; KHB tanisi Ile izlenen hastalann, call Ilan immun parametreler agisindan bir kisminda kantitatif bir yetmezlik bulunmaktadir. Levamizol ve HBV asisi bu hastalann bir bOlumOnde bu parametrelerin normal degerlere yukselmesini saglamaktadir HBV'nin persistansinda ve klirensinde temel rol oynayan helper T lenfosit (CD4) ye sitotoksik T lenfosit (CD8) dUzeyleri uzerine levamizolun onemli bir etkisi gozukmezken HBV a§.151, CD4 T lenfosit savisinda belirgin bir artisa, CD8 T lenfosit sayisinda da belirgin bir şekilde düşer

Abstract:
Chronic hepatitis B that has spesific clinical, biochemical, serologic and histopathologic charecteristics is a long term (at least six month) inflammatuar disease of the liver. It is strongly suggested Immunity plays a key role in chronicity of the disease.
Ninety three patients (59 males and 34 female) diagnosed as having chronic hepatitis B, aged between 2-18 years were studied. In this study, the relationship between two immunomodulator drugs, levamisole and HBsAg vaccine, which are used in child patients with Chronic hepatitis B, and the immune response to these drugs (as well as how some of the immune parameters can be affected quantitatively) including viral replication were investigated.
The lymphocyte subgroups; CD3, CD19, CD4, CD8, CD4/CD8, CD16/56, serum immunoglobulins; IgG, IgA, IgM and complement components; C3, C4 and HBV DNA, HBV markers, serum ALT, AST were assessed by using flow cytometric methods, nephelometric method, microcolon DNA probe RIA (Abbot) and ELISA, Olympus AU 800 autoanalyzer, respectively.
Before treatment the quantitative investigation results of immunological parameters of 93 patients were as follows; of the patients, absolute lymphocyte in %6,04, total T lymphocyte (CD3) in %12,8, total B lymphocyte (CD19) in %22.5, helper T lymphocyte (CD4), in %3,22, cytotoxic/supressor T lymphocyte (CD8) in %2,15 and natural killer lymphocyte in %6,04 were found to be below than their age matched controls. While the same values were 3,22%- 3,22%- 13,9%- 0,9%- 0% and 0% respectively, after treatment. The increase seen in levamisole and/or vaccine groups in absolute lymphocyte count, absolute CD19 and absolute CD16/56 were not statistically significant (p>0,05). However, the treatment in all groups seemed to be effective in increasing the absolute CD3 count (p<0,05). The vaccine was found to increase CD4 subset in patients while it caused a decrease in CD8 subset in with choronic active hepatitis 13 patients (p<0,05), but levamisole showed no effect in the same patients group. Two patients' serum IgM levels were below the standart deviation of normals. This condition remained unchanged after treatment. The treatment of levamisole and/or vaccine had no effect on C3 levels while they leaded to a decrease in C4 levels.
The study suggested that levamisole and/or vaccine had an important effect in the loss of HBeAg antigen (34%), in occurence of anti•HBe antibody (25%) and in the normalization ALT levels (28%) while these drugs result in marked elevation in HBV DNA levels
As in conclusion, the patients with choronic hepatitis B possess quantitative deficiencies in the immune parameters investigated. Levamisole and/or HBV vaccine is likely to be very effective in the normalization immune status in some of the patients. while levamisole does not exert a substantive effect on T-helper (CD4) and cytotoxic T lymphocytes (CD8) which eventually participates in the clearence and persistance of HBV, vaccination with HBV gives rise to substantial in increase in CD4 T lymphocytes and to decrease CD8 T subsets.
Key word: HBV, immune parameters, lymphocyte subpopulation, levamisole, HBsAg vaccine