Tedavi alan kronik hepatit B hastalarında serum kantitatif HBsAg düzeyi ile viral yük arasındaki ilişkinin araştırılması

Yıl 2020, Cilt: 13 Sayı: 3, 569 - 578, 18.09.2020

Meryem Demirelli , Necla Tülek , Fatih Temoçin , Doğan Yücel , Şebnem Erdinç , Gunay Ertem

https://doi.org/10.31362/patd.691645

Öz

ÖZET
Amaç: Yakın geçmişe kadar HBsAg sadece hepatit B enfeksiyonun tanısında kullanılırken, günümüzde serum HBsAg kantitasyonu (qHBsAg)’nun, hepatit B virüsü (HBV) enfeksiyonunun viral monitörizasyonunda kullanılabileceğine dair veriler artmaya başlamıştır. Bu çalışmada inaktif hepatit B taşıyıcıları ile kronik aktif hepatit B hastaları arasındaki qHBsAg ile HBV DNA düzeyleri karşılaştırılmış ve tedavi başlanmış hastalarda tedavi süresince qHBsAg ile HBVDNA seyri izlenerek aralarındaki ilişki değerlendirilmiştir.
Materyal ve Metod: Çalışma Ankara Eğitim ve Araştırma Hastanesi Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji kliniği’nde yapılmıştır. Kronik hepatit B (KHB) tanısıyla tedavi alan 71 hasta ve inaktif HBsAg taşıyıcısı 74 hasta çalışmaya dahil edildi. Bu hastalarda serum qHBsAg düzeyleri Elecsys HBsAg II cihazı ile çalışıldı.
Bulgular: Nükleoz(t)id analoğu ile tedavi edilen hastalarda 6. ve 12. aydaki serum qHBsAg düzeyi ile HBV-DNA arasında pozitif yönde bir korelasyon görüldü ve her iki parametrenin altı ay ve bir yıllık izlemindeki düşüş istatiksel olarak anlamlı bulundu (qHBsAg 6ay p=0,03, qHBsAg 12 ay p=0,001, HBV DNA 6 ay p=0,001, HBV DNA 12 ay p=0,001). Peg-IFN tedavisi alan kronik hepatit B hastalarında ise serum qHBsAg düzeyi ile HBV-DNA arasında tedavi başlangıcı ve 6. ayında anlamlı bir ilişki olmayıp tedavi sonunda pozitif yönde korelasyon görüldü. PEG-IFN tedavisi alan hasta grubunda ise qHBsAg seviyeleri ile HBV DNA arasındaki korelasyon tedavi sonunda anlamlı (p=0,01) olarak saptandı.
Sonuç: Bizim bulgularımız qHBsAg’nin, inaktif HBsAg taşıyıcıları ve KHB hastalarını ayırmada HBV-DNA düzeyleri birlikte kullanıldığında oldukça faydalı bir test olabileceği ve tedavi kararında ve takibinde qHBSAg seviyelerinin kullanılabileceğini düşündürmektedir.

Anahtar Kelimeler

Kronik Hepatit B, inaktif HBsAg taşıyıcılığı, qHBsAg, PEG-IFN, nükleoz(t)id analogları

Investigation of the association of serum quantitative HBsAg levels with viral load in chronic hepatitis B Patients receiving treatment

Öz

Study Aims: The Hepatitis B surface antigen (HBsAg) test was only used for diagnosis of hepatitis B infection, whereas now there is growing evidence favoring utilization of serum HBsAg quantitation (qHBsAg) for monitoring of infection with hepatitis B virus (HBV). In our study, we examined the courses of qHBsAg and HBV-DNA levels throughout the treatment course of patients receiving treatment for chronic hepatitis B infection and evaluated their correlation with each other.
Material and Methods: The study was performed Ankara Training and Research Hospital. A total of 71 patients receiving treatment for the diagnosis of chronic hepatitis B (CHB) infection were included in the study. Serum qHBsAg levels of these patients were analyzed with an Elecsys HBsAg II assay.
Results: When we evaluated the correlation of serum qHBsAg levels with the HBV-DNA levels among patients treated with nucleotide analogues, there was a positive correlation. The decline in both parameters at sixth and 12 month follow-up was found to be statistically significant (qHBsAg decline at 6th month: p = 0.03; qHBsAg decline at 12th month: p = 0.001; HBV-DNA decline at 6th month: p = 0.001; HBV-DNA decline at12th month: p = 0.001). In the group of patients receiving PEG-IFN treatment, there was positive correlation between the two at the end of the treatment (p = 0.01).
Conclusion: Our findings suggest that qHBsAg may be used for both the treatment decision and monitoring of treatment.

Anahtar Kelimeler

Chronic Hepatitis B, qHBsAg, PEG-IFN, , Nucleotide analogues.

Kaynakça

• 1. World Health Organization (WHO), Hepatitis B. Last accessed date 2017 Jan 5. http://www.who.int/mediacentre/factsheets/fs204/en/
• 2. Chen CJ, Yang HI, Su J, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295(1):65-73.
• 3. Kohmoto M, Enomoto M, Tamori A, et al. Quantitative detection of hepatitis B surface antigen by chemiluminescent microparticle immunoassay during lamivudine treatment of chronic hepatitis B virus carriers. J Med Virol. 2005;75(2):235-9.
• 4. Moucari R, Mackiewicz V, Lada O, et al. Early serum HBsAg drop: a strong predictor of sustained virological response to pegylated interferon alfa-2a in HBeAg-negative patients. Hepatology. 2009;49(4):1151-7.
• 5. Brunetto MR, Moriconi F, Bonino F, et al. Hepatitis B virus surface antigen levels: a guide to sustained response to peginterferon alfa-2a in HBeAg-negative chronic hepatitis B. Hepatology. 2009;49(4):1141-50.
• 6. Manesis EK, Schina M, Le Gal F, et al. Quantitative analysis of hepatitis D virus RNA and hepatitis B surface antigen serum levels in chronic delta hepatitis improves treatment monitoring. Antiviral therapy. 2007;12(3):381-8.
• 7. EASL Clinical Practice Guidelines: Management of chronic hepatitis B virus infection. Journal of Hepatology 2012 vol. 57; 167–185
• 8. Health Application Declaration of Ministry of Health in Turkey, Last accessed date 2013 Jan 11, http://www.tkhk.gov.tr/Dosyalar/51ccde8184fb474fb89d1c6ce5d651ba.rar,
• 9. Tseng TC, Liu CJ, Chen CL, et al. Risk stratification of hepatocellular carcinoma in hepatitis B virus e antigen-negative carriers by combining viral biomarkers. J Infect Dis. 2013;208(4):584-93.
• 10. Tseng TC, Liu CJ, Yang HC, et al. Serum hepatitis B surface antigen levels help predict disease progression in patients with low hepatitis B virus loads. Hepatology. 2013;57(2):441-50.
• 11. Tseng TC, Liu CJ, Yang HC, et al. High levels of hepatitis B surface antigen increase risk of hepatocellular carcinoma in patients with low HBV load. Gastroenterology. 2012;142(5):1140-9 e3; quiz e13-4.
• 12. Heathcote EJ, Marcellin P, Buti M, et al. Three-year efficacy and safety of tenofovir disoproxil fumarate treatment for chronic hepatitis B. Gastroenterology. 2011;140(1):132-43.
• 13. Gane E, Heathcote EJ, Marcellin P, et al. HBsAg kinetics of decay and baseline characteristics of HBsAg-positive patients with chronic hepatitis B following 3 years of tenofovir disoproxil fumarate (TDF) treatment. Journal of Hepatology. 2010;52:388.
• 14. Wursthorn K JM, Manns MP, Lopez P, Wedemeyer H, Naoumov N. Kinetics of HBsAg decline in HBeAg+ chronic hepatitis B patients with 3 years of telbivudine treatment during the Globe stud emelin tezi 153.kaynak. 2009.
• 15. Chevaliez S, Hezode C, Bahrami S, Grare M, Pawlotsky JM. Long-term hepatitis B surface antigen (HBsAg) kinetics during nucleoside/nucleotide analogue therapy: finite treatment duration unlikely. J Hepatol. 2013;58(4):676-83.
• 16. Zoutendijk R, Hansen BE, van Vuuren AJ, Boucher CA, Janssen HL. Serum HBsAg decline during long-term potent nucleos(t)ide analogue therapy for chronic hepatitis B and prediction of HBsAg loss. J Infect Dis. 2011;204(3):415-8.
• 17. Tseng TC, Kao JH. Clinical utility of quantitative HBsAg in natural history and nucleos(t)ide analogue treatment of chronic hepatitis B: new trick of old dog. Journal of gastroenterology. 2013;48(1):13-21.
• 18. Gheorghita VI, Caruntu FA, Curescu M, et al. Use of quantitative serum HBsAg for optimization of therapy in chronic hepatitis B patients treated with pegylated interferon alfa-2a: a Romanian cohort study. J Gastrointestin Liver Dis. 2013;22(1):27-32.
• 19. Peng CY, Lai HC, Li YF, at al.Early serum HBsAg level as a strong predictor of sustained response to peginterferon alfa-2a in HBeAg-negative chronic hepatitis B. Alimentary pharmacology & therapeutics. 2012;35(4):458-68.
• 20. Sonneveld MJ, Hansen BE, Piratvisuth T, et al. Response-guided peginterferon therapy in hepatitis B e antigen-positive chronic hepatitis B using serum hepatitis B surface antigen levels. Hepatology. 2013;58(3):872-80.
• 21. Chan HL, Thompson A, Martinot-Peignoux M, Piratvisuth T, Cornberg M, Brunetto MR, et al. Hepatitis B surface antigen quantification: why and how to use it in 2011 - a core group report. J Hepatol. 2011;55(5):1121-31.
• 22. Marcellin P, Bonino F, Yurdaydin C, et al. Hepatitis B surface antigen levels: association with 5-year response to peginterferon alfa-2a in hepatitis B e-antigen-negative patients. Hepatol Int. 2013;7(1):88-97.
• 23. Rijckborst V, Hansen BE, Cakaloglu Y, et al. Early on-treatment prediction of response to peginterferon alfa-2a for HBeAg-negative chronic hepatitis B using HBsAg and HBV DNA levels. Hepatology. 2010;52(2):454-61.