Role of Neopterin in Determining the Efficacy of Interferon Therapy in Chronic Hepatitis B and C

Öz

Neopterin (NP) is a pteridine derivative that is secreted as a response to gamma interferon stimulation. The purpose in this study was to investigate the relationship between the NP levels and the disease and determining the efficacy of an interferon (IFN) therapy in patients with chronic hepatitis B (CHB) and C (CHC). The study was conducted on 49 cases with CHB, 30 cases with CHC and 72 healthy individuals. Serum samples were taken from the patients receiving treatment at the beginning and at the end of the treatment and only once from the healthy individuals in the control group. The NP levels were found significantly higher in the patients with CHB and CHC than those in the control group. When the pre and post-treatment serum NP levels of the patients who received an interferon therapy were compared, the post-treatment NP levels of the patients who responded to the treatment were significantly higher. When a comparison was made before and after treatment, a decrease was seen in the NP levels in most of the infections due to decreased activation of the immune system. However, when the disease was treated with an IFN therapy, which is a treatment stimulating the immune system, the post-treatment NP level remained high.

Anahtar Kelimeler

• Neopterin, chronic hepatitis B, chronic hepatitis C

Role of Neopterin in Determining the Efficacy of Interferon Therapy in Chronic Hepatitis B and C

Öz

Neopterin (NP), hücresel immun sistemin aktivasyonu sonucu, gama interferon stimülasyonuna cevap olarak insan makrofaj ve monositlerinden sekrete edilen bir pteridin derivesidir. Hücresel immünutenin göstergesi olan NP pek çok kanser, infeksiyon hastalığı ve otoimmün hastalıkta vücut sıvılarında çalışılmış ve hücresel immün sistemin aktif durumda olduğu hastalıkların neredeyse tümünde yüksek olarak tespit edilmiştir. Bu çalışmada, kronik hepatit B (KHB) ve kronik hepatit C’li (KHC) hastalarda; NP düzeyleri ile hastalık arasındaki ilişki ve interferon (IFN) tedavisinin etkinliğini belirlemede neopterin rolünün araştırılması amaçlandı. Çalışma, 49 KHB ‘li olgu, 30 KHC’li olgu ve 72 sağlıklı birey üzerinde yapıldı. Serum örnekleri tedavi alan hastalardan tedavi başlangıcı ve bitiminde, kontrol grubundaki sağlıklı bireylerden ise bir kez alındı. Tedaviye yanıtsızlık virolojik ve/veya biyokimyasal cevap alınıp alınmamasına göre değerlendirildi. Kronik hepatit B ve KHC’li hastalarda NP düzeyleri kontrol grubundan anlamlı olarak yüksek saptandı. Pegile interferon tedavisi alan KHB’li ve KHC’li hastaların tedavi öncesi ve sonrası serum NP düzeyleri karşılaştırıldığında tedavi sonrası NP düzeyleri anlamlı olarak yüksek saptandı. Tedaviye yanıt veren??? KHB’li 16 hasta ve KHC’li 14 hastada tedavi sonrası NP düzeylerinde anlamlı yükseklik saptanırken, her iki hasta grubunda da tedaviye yanıtsız hastalarda tedavi öncesi ve sonrası serum NP düzeylerinde anlamlı değişiklik saptanmadı. İnfeksiyonların çoğunda infeksiyon tedavisi öncesi ve sonrasında bir kıyaslama yapıldığında tedavi sonunda immün sistemin aktivasyonu azaldığı için NP düzeylerinde azalma görülmektedir. Fakat immün sistemi uyarıcı bir tedavi olan IFN tedavisi ile hastalık tedavi edildiğinde, tedavi sonunda IFN tedavisine bağlı olarak NP düzeyi yüksek kalmaktadır

Anahtar Kelimeler

• Neopterin, kronik hepatit B, kronik hepatit C

Kaynakça

1. Berdowska A, Zwirska-Korczala K. Neopterin measurement in clinical diagnosis. J Clin Phar Ther 2001;26:319-29
2. Hoffmann G, Wirleitner B, Fuchs D. Potential role of im- mun system activation associated production of NP de- rivatives in humans. Inflamm Res 2003;52:313-21
3. Hamerlinck FFV. Neopterin: a review. Exp Dermatol 1999;8:167–76
4. Murr C, Widner B, Wirleitner B and Fuchs D. Neopterin as a Marker for Immune System Activation Current Drug. Metabolism 2002;3:175-87
5. Müller MM, Curtius HC, Herold M, Huber CH. Neopterin in Clinical Practice. Clinica Chmica Acta 1991;201:1-16
6. Fuchs D, Weiss G, Wachter H. Neopterin, biochemistry and clinical use as a marker for celluler immune reac- tions. International Archives of Allergy and Immunology 1993;101:16
7. Fuchs D, Weiss G, Reibnegger G, Wachter H. The role of neopterin as a monitor of cellular immune activation in transplantation, inflammatory, infectious and malignant disease. Crit Rev Clin Lab Sci 1992;29:307-41
8. Murr C, Bergant A, Widschwendter M, Heim K, Schröcksnadel H, Fuchs D. Neopterin is an independent prognostic variable in females with breast cancer. Clin Chem 1999;45:1998-2004

9. Schennach H, Hessenberger G, Mayersbach P, Schonitzer D, Fuchs D. Acute cytomegalovirus infections in blood do- nors are indicated by increased serum neopterin concen- trations. Med Microbiol Immunol (Berl) 2002;191:115-8
10. Eddleston ALWF and Dixon B: Interferons in the treatment of chronic viral infection of the liver,1. Edit, UK, Pennine Press 1990
11. Balik I. The course of chronic hepatitis B and interferon therapy. In Viral Hepatitis 2003. Tekeli E, Balik I edt. Viral Hepatitis Struggle Association. First edition. P:135-55
12. Dianzani F, Antonelli G, Capobianchi MR. The biologi- cal basis fort he clinical use of interferon . J Hepatol 1990;(suppl 1):5-10
13. Murr C, Bergant A, Widschwendter M, Heim K, Schröcksnadel H, Fuchs D. Neopterin is an independent prognostic variable in females with breast cancer. Clin Chem 1999;45:1998-2004
14. Schennach H, Hessenberger G, Mayersbach P, Schonitzer D, Fuchs D. Acute cytomegalovirus infections in blood do- nors are indicated by increased serum neopterin concen- trations. Med Microbiol Immunol (Berl) 2002;191:115-8
15. Kalkan A, Ozden M, Akbulut H. Serum Neopterin Levels in Patients with Chronic Hepatitis B. Jpn J Infect Dis 2005:58;107-109
16. Grungreiff K, Reinhold D, Ansorge S. Serum concentra- tions of sIL-2R, IL-6, TGF-beta1, neopterin, and zinc in chronic hepatitis C patients treated with interferon-al- pha. Cytokine 1999;11:1076-80
17. Demirtürk N, Demirdal T, Aktepe OC, Aykin N, Orhan S, Cevik F. Serum Neopterin Levels in Patients with HBV Infection at Various Stages. Hepato-Gastroenterology 2007;54:903-5
18. Gelderblom HC, Zeuzem S, Weegınk CJ, et al. Inflammatory markers neopterin and alanine amino- transferase in HCV patients treated with HCV NS3+4A protease inhibitor telaprevir (VX-950) and/or peginter- feron alfa-2a. Scandinavian Journal of Gastroenterology, 2008;43:1122-7
19. Daito K, Suou T, Kawasaki H. Serum and urinary neop- terin levels in patients with chronic hepatitis B treated with interferon. Res Commun Chem Pathol Pharmacol 1994;83:303-16
20. Oxenkrug GF, Requintina PJ, Mikolich DL, et al. Neopterin as aMarker of Response to Antiviral Therapy in Hepatitis C Virus Patients. Hepatitis Res Treat 2012;2012:1-4.