Araştırma Makalesi
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Kronik hepatit B hastalarında tiyol/ disülfit dengesi

Yıl 2020, Cilt: 12 Sayı: 2, 279 - 287, 01.06.2020
https://doi.org/10.21601/ortadogutipdergisi.752362

Öz

Amaç: Bu çalışmanın amacı, oksidatif stres belirteci olarak kullanılan tiyol / disülfit dengesi ile kronik hepatit B (KHB) arasındaki ilişkiyi değerlendirmektir.

Gereç ve Yöntem: Bu çalışma Mayıs 2016 - Temmuz 2016 tarihleri ​​arasında Erzurum Bölge Eğitim ve Araştırma Hastanesi Enfeksiyon Hastalıkları Polikliniğinde yapıldı. Çalışmaya KHB’li 63 hasta ve bilinen herhangi bir hastalığı olmayan 60 sağlıklı gönüllü dahil edildi. Dinamik tiyol /disülfit dengesini ölçmek için Erel ve Neselioğlu tarafından geliştirilen yeni otomatik analiz yöntemini kullanıldı. Doğal tiyolden (SH) sonra, toplam tiyol (toplam SH) ve disülfit (SS) seviyeleri belirlendi; SS/SH, SS/toplam SH ve SH/toplam SH gibi ölçüler hesaplandı.

Bulgular: KHB grubunda, SH seviyelerinin (P=0,041), toplam SH seviyelerinin (P = 0,043) kontrol grubundan düşük olduğunu tespit edildi. Anti-HBc toplam IgG ile toplam SH, SH, SH/toplam SH arasında negatif korelasyon vardı, Anti-HBc toplam IgG ile SS/SH, SS/toplam SH oranı arasında pozitif korelasyon vardı. BMX indeksi ile toplam SH, SH, SH/toplam SH arasında negatif, SS/total SH, SS/SH arasında pozitif korelasyon vardı. Toplam protein, albümin ve toplam SH, SH arasında pozitif korelasyon bulundu.

Sonuç: Çalışmamızda KHB hastalarında antioksidan olarak tiyol düzeyleri düşük bulundu. Hepatit B’de tiyol düzeyinin yeni bir belirteç olduğu tekrar vurgulandı. Gelecekte yapılacak daha geniş çalışmalarla KHB’de tiyol düzeyleri hem hastalığın seyrinin yavaşlatılması hemde yeni tedavi geliştirme çabalarına ışık tutacağı düşünülmektedir.

Kaynakça

  • Lai CL, Ratziu V, Yuen MF, Poynard T. Viral hepatitis B. Lancet 2003; 362: 2089-94. (doi: 10.1016/S0140-6736(03)15108-2).
  • Dede F, Köş M, Bukan N, Şener D, Demir M, Aydın Ö, Arhan M, Eskioğlu E. The Evaluation of Oxidative Stress Parameters in Chronic Viral Hepatitis. İstanbul Tıp Derg- Istanbul Med J 2011;12(4):175-80. (doi: 10.5505/1304.8503.2011.28199).
  • Sırmatel F, Duygu F, Çelik H, Selek Ş, Sırmatel Ö, Gürsoy B, Eriş FN. Evaluation of Total Oxidative Level and Total Antioxidant Capacity in Cases with Chronic Viral Hepatitis. Klimik Dergisi 2009; 22(3): 92-6.
  • Sabitha KE, Shyamaladevi CS. Oxidant and antioxidant activity changes in patients with oral cancer and treated with radiotherapy. Oral Oncol. 1999; 35(3): 273-7. (doi: 10.1016/S1368-8375(98)00115-8).
  • McCord JM. Human disease, free radicals, and the oxidant /antioxidant balance. Clin Biochem 1993; 25: 354-7. (doi: 10.1016/0009-9120(93)90111-I).
  • Kundi H, Ates I, Kiziltunc E, Cetin M, Cicekcioglu H, et al. A Novel Oxidative Stress Marker In Acute Myocardial Infarction; Thiol/Disulphide Homeostasis, American Journal of Emergency Medicine. 2015; 33: 11. (doi: 10.1016/j.ajem.2015.06.016).
  • Guner R, Tasyaran MA, Keske S, Hasanoglu I, Kalem AK, Yapar D, et al. Relationship between total thiol status and thrombocytopenia in patients with Crimean-Congo hemorrhagic fever. Southeast Asian J Trop Med Public Health. 2012; 43: 1411-8.
  • Özşahin AE, Yazıcı C, Köse K, Utaş C, Tokgöz B. Malondialdehyde and Thiol Levels in Plasma of Hemodialysis Patients. Erciyes Üniversitesi Sağlık Bilimleri Dergisi (E.Ü. Journal of Health Sciences) 2004; 13(2): 8-14.
  • Erel O, Neselioglu S. A novel and automated assay for thiol/disulphide homeostasis. Clin Biochem 2014; 47: 326-32. (doi: 10.1016/j.clinbiochem.2014.09.026).
  • Gormez VA, Orengul C, Ozer FÖ, Uzuner S, Selek S. Thiol/Disulphide Homeostasis and Oxidative Stress Parameters in Children and Adolescents with Attention Deficit/ Hyperactivity Disorder. Anadolu Kliniği, Eylül 2016; 3: 12.
  • Robinson WS. Hepatitis B virus and hepatitis D virus. In: Mandell GL, Bennett JE, Dolin R.eds. Mandell, Douglas and Bennett’s Principles and Practice of Infectious Diseases. 5th ed. Philedelphia Pennnsylvania, Churchill Livingstone 2005; 1652-85.
  • Stehbens WE. Oxidative stres in viral hepatitis and AIDS. Experimental and Molecular Pathology 2004; 77: 121-32. (doi: 10.1016/j.yexmp.2004.04.007).
  • Acar A, Görenek L, Aydın A, Eyigün PC, Eken A,Sayal A, Pahsa A. İnvestigation of oxidative stress and antioxidant defense in patients with hepatitis B virus infection and the effect of interferon-plus lamivudin combination therapy on oxidative stres. Mikrobiyol Bul. 2009; 43: 411-23.
  • Schwarz KB. Oxidative stress during viral infection: a review. Free Radic Biol Med. 1996; 21: 641-9. (doi: 10.1016/0891-5849(96)00131-1).
  • Halliwell B, Aruoma OI. DNA damage by oxygen-derived species. Its mechanism and measurement in mammalian systems. FEBS Lett. 1991; 281(1-2): 9-19. (doi: 10.1016/0014-5793(91)80347-6).
  • Dikici I, Mehmetoglu I, Dikici N, Bitirgen M, Kurban S. Investigation of oxidative stress and some antioxidants in patients with acute and chronic viral hepatitis B and the effect of interferon-alpha treatment. Clin Biochem. 2005; 38(12): 1141-4. (doi: 10.1016/j.clinbiochem.2005. 10.006).
  • Duygu F, Karsen H, Aksoy N, Taskin A. Relationship of oxidative stress in hepatitis B infection activity with HBV DNA and fibrosis. Ann Lab Med. 2012; 32(2): 113-8. (doi: 10.3343/alm.2012.32.2.113).
  • Bolukbas C, Bolukbas FF, Horoz M, Aslan M, Celik H, Erel O. Increased oxidative stress associated with the severity of the liver disease in various forms of hepatitis B virus infection. BMC Infect Dis. 2005; 5: 95. (doi: 10.1186/1471-2334-5-95).
  • Yamamoto Y, Yamashita S, Fujisawa A, Kokura S, Yoshikawa T. Oxidative stress in patients with hepatitis, cirrhosis, and hepatoma evaluated by plasma antioxidants. Biochem Biophys Res Commun. 1998; 247(1): 166-70. (doi: 10.1006/bbrc.1998.8752).
  • Gutteridge JM. Lipid peroxidation and antioxidants as biomarkers of tissue damage. Clin Chem. 1995; 41: 1819-28. (doi: 10.1093/clinchem/41.12.1819).
  • Coşkun C, Emre HÖ, Gümüş A, Uzun S, et al. Dynamic Thiol Disulphide Homeostasis and Advanced Oxidation Protein Products (Aopps) in Diabetic and Non-Diabetic Chronic Renal Failure Disease. Deneysel Tıp Dergisi 2016; 6(12).
  • Kloner RA, Przyklenk K, Whittaker P. Deleterious effects of oxygen radicals in ischemia/reperfusion. Resolved and unresolved issues. Circulation 1989; 80: 1115-27. (doi: 10.1161/01.CIR.80.5.1115).
  • Opie LH. Reperfusion injury and its pharmacologic modification. Circulation. 1989; 80: 1049-62. (doi: 10.1161/01.CIR.80.4.1049).
  • Bal C, Buyuksekerci M, Koca C, Agıs ER, Erdogan S, et al. The compromise of dynamic disulfide/thiol homeostasis as a biomarker of oxidative stres in trichloroethylene exposure. Hum Exp Toxicol. 2015; 49: 1-6.
  • Erel O. A new automated colorimetric method for measuring total oxidant status. Clinical Biochemistry. 2005; 9: 1-9. (doi: 10.1016/j.clinbiochem.2005.08.008).
  • Elmas B, Karacan M, Dervişoğlu P, Kösecik M, İşgüven ŞP, Bal C. Dynamic thiol/disulphide homeostasis as a novel indicator of oxidative stress in obese children and its relationship with inflammatory-cardiovascular markers. Anatol J Cardiol. 2017;18(5): 361-9. (doi: 10.14744/ AnatolJCardiol.2017.7740).
  • Ates I, Kaplan M, Inan B, Alisik M, Erel O, Yilmaz N, et al. How does thiol/disulfide homeostasis change in prediabetic patients? Diabetes Res Clin Pract. 2015; 110(2): 166-71. (doi: 10.1016/j.diabres.2015.09.011).
  • Ates I, Ozkayar N, Inan B, Yilmaz FM, Topcuoglu C, Neselioglu S, et al. Dynamic thiol/disulphide homeostasis in patients with newly diagnosed primary hypertension. J Am Soc Hypertens. 2016; 10(2): 159-66. (doi: 10.1016/j.jash.2015.12.008).
  • Erkenekli K, Sanhal CY, Yucel A, Bicer CK, Erel O, Uygur D. Thiol/disulfide homeostasis in patients with idiopathic recurrent pregnancy loss assessed by a novel assay: Report of a preliminary study. J Obstet Gynaecol Res. 2016; 42(2): 136-41. (doi: 10.1111/jog.12860).
  • Matteucci E, Giampietro O. Thiol signalling network with an eye to diabetes. Molecules. 2010; 15: 8890-903. (doi: 10.3390/molecules15128890).
  • Senyurt M, Neselioglu S, Bicer CK, Yildiz F, Gözcü H, Carlıoglu A. Decreased Thiol Levels, Increased Disulphide Levels Are Associated with Increased Blood Glucose Levels in Newly Diagnosed Type 2 Diabetes. West Indian Medical Journal.
  • Kundi H, Erel Ö, Balun A, Çiçekçioglu H, Cetin M, Kiziltunç E, et al. Association of thiol/disulfide ratio with syntax score in patients with NSTEMI. Scand Cardiovasc J. 2015; 49(2): 95-100. (doi: 10.3109/14017431.2015.1013153).
  • Eren Y, Dirik E, Neselioglu S, Erel Ö. Oxidative stress and decreased thiol level in patients with migraine: Cross-sectional study. Acta Neurol Belg. 2015; 115(4): 643-9. (doi: 10.1007/s13760-015-0427-y).
  • Erkus ME, Altiparmak IH, Akyuz AR, Demirbag R, Sezen Y, Gunebakmaz O, et al. The association between plasma thiol levels and left ventricular diastolic dysfunction in patient with hypertension. Scand J Clin Lab Invest. 2015; 75(8): 667-73. (doi: 10.1016/j.amjcard.2015.01.076).
  • Kaya S, Sütçü R, Çetin ES, Nigar Yılmaz N, Arıkan S, Arıdoğan BC, Delibaş N. Relationship Between Viral Load and Lipid Peroxidation and Antioxidant Enzymes in Patients Infected with Hepatitis B Virus. Türk Klinik Biyokimya Derg 2006; 4(2): 77-82.
  • Wang K, Wang B, Fan XP, Lin YJ, Shui WP. Oxidative stress in patients with chronic hepatitis B. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi 2004; 18: 172-4.
  • Schmilovitz-Weiss H, Tovar A, Halpern M., Sulkes J, Braun M, Rotman Y. et al. Predictive value of serum globulin levels for the extent of hepatic fibrosis in patients with chronic hepatitis B infection. J Viral Hepat 2006; 13: 671-7. (doi: 10.1111/j.1365-2893.2006.00744.x).
  • Kandemır Ö, Bayarslan C, Kaya A. Isolated Anti-Hbc positive subjects and their response to Hepatitis B vaccıne. Viral Hepatit Derg 2002; (1): 430-1.

Thiol/disulfide homeostasis in patients with chronic hepatitis B

Yıl 2020, Cilt: 12 Sayı: 2, 279 - 287, 01.06.2020
https://doi.org/10.21601/ortadogutipdergisi.752362

Öz

Aim: The purpose of this study was to evaluate the relation between chronic hepatitis B (CHB) and the thiol/disulfide balance, used as a marker of oxidative stress.

Materials and Methods: This study was conducted between May 2016 and July 2016 at the Erzurum Regional Training and Research Hospital Infectious Diseases Polyclinic. 63 subjects with CHB and 60 healthy volunteers without any known diseases were included in the study. In term of measuring dynamic thiol/disulfide homeostasis, we used the novel automated assay method developed by Erel and Neselioglu.

Results: Native thiol (SH), total thiol (total SH) and disulfide (SS) levels were determined; measures such as SS/SH, SS/total SH, and SH/total SH were calculated. It is determined that CHB group’s SH levels (P=0.041), total SH levels (P=0.043) were lower than the control group’s. There is negative correlation between Anti-HBc total IgG and total SH, SH, SH/total SH, there is positive correlation between Anti-HBc total IgG and SS/SH, SS/total SH ratio. There is negative correlation between BMX index and total SH, SH, SH/total SH and positive correlation between SS/total SH, SS/SH. Positive correlation is determined between total protein, albumin and total SH, SH.

Conclusions: In our study thiol levels as an antioxidant were found to be low in CHB patients. Thiol levels were again emphasized as a new marker in hepatitis B. Thiol levels in CHB are thought to shed light to slowing of disease course and improving new treatment efforts with more wide studies.

Kaynakça

  • Lai CL, Ratziu V, Yuen MF, Poynard T. Viral hepatitis B. Lancet 2003; 362: 2089-94. (doi: 10.1016/S0140-6736(03)15108-2).
  • Dede F, Köş M, Bukan N, Şener D, Demir M, Aydın Ö, Arhan M, Eskioğlu E. The Evaluation of Oxidative Stress Parameters in Chronic Viral Hepatitis. İstanbul Tıp Derg- Istanbul Med J 2011;12(4):175-80. (doi: 10.5505/1304.8503.2011.28199).
  • Sırmatel F, Duygu F, Çelik H, Selek Ş, Sırmatel Ö, Gürsoy B, Eriş FN. Evaluation of Total Oxidative Level and Total Antioxidant Capacity in Cases with Chronic Viral Hepatitis. Klimik Dergisi 2009; 22(3): 92-6.
  • Sabitha KE, Shyamaladevi CS. Oxidant and antioxidant activity changes in patients with oral cancer and treated with radiotherapy. Oral Oncol. 1999; 35(3): 273-7. (doi: 10.1016/S1368-8375(98)00115-8).
  • McCord JM. Human disease, free radicals, and the oxidant /antioxidant balance. Clin Biochem 1993; 25: 354-7. (doi: 10.1016/0009-9120(93)90111-I).
  • Kundi H, Ates I, Kiziltunc E, Cetin M, Cicekcioglu H, et al. A Novel Oxidative Stress Marker In Acute Myocardial Infarction; Thiol/Disulphide Homeostasis, American Journal of Emergency Medicine. 2015; 33: 11. (doi: 10.1016/j.ajem.2015.06.016).
  • Guner R, Tasyaran MA, Keske S, Hasanoglu I, Kalem AK, Yapar D, et al. Relationship between total thiol status and thrombocytopenia in patients with Crimean-Congo hemorrhagic fever. Southeast Asian J Trop Med Public Health. 2012; 43: 1411-8.
  • Özşahin AE, Yazıcı C, Köse K, Utaş C, Tokgöz B. Malondialdehyde and Thiol Levels in Plasma of Hemodialysis Patients. Erciyes Üniversitesi Sağlık Bilimleri Dergisi (E.Ü. Journal of Health Sciences) 2004; 13(2): 8-14.
  • Erel O, Neselioglu S. A novel and automated assay for thiol/disulphide homeostasis. Clin Biochem 2014; 47: 326-32. (doi: 10.1016/j.clinbiochem.2014.09.026).
  • Gormez VA, Orengul C, Ozer FÖ, Uzuner S, Selek S. Thiol/Disulphide Homeostasis and Oxidative Stress Parameters in Children and Adolescents with Attention Deficit/ Hyperactivity Disorder. Anadolu Kliniği, Eylül 2016; 3: 12.
  • Robinson WS. Hepatitis B virus and hepatitis D virus. In: Mandell GL, Bennett JE, Dolin R.eds. Mandell, Douglas and Bennett’s Principles and Practice of Infectious Diseases. 5th ed. Philedelphia Pennnsylvania, Churchill Livingstone 2005; 1652-85.
  • Stehbens WE. Oxidative stres in viral hepatitis and AIDS. Experimental and Molecular Pathology 2004; 77: 121-32. (doi: 10.1016/j.yexmp.2004.04.007).
  • Acar A, Görenek L, Aydın A, Eyigün PC, Eken A,Sayal A, Pahsa A. İnvestigation of oxidative stress and antioxidant defense in patients with hepatitis B virus infection and the effect of interferon-plus lamivudin combination therapy on oxidative stres. Mikrobiyol Bul. 2009; 43: 411-23.
  • Schwarz KB. Oxidative stress during viral infection: a review. Free Radic Biol Med. 1996; 21: 641-9. (doi: 10.1016/0891-5849(96)00131-1).
  • Halliwell B, Aruoma OI. DNA damage by oxygen-derived species. Its mechanism and measurement in mammalian systems. FEBS Lett. 1991; 281(1-2): 9-19. (doi: 10.1016/0014-5793(91)80347-6).
  • Dikici I, Mehmetoglu I, Dikici N, Bitirgen M, Kurban S. Investigation of oxidative stress and some antioxidants in patients with acute and chronic viral hepatitis B and the effect of interferon-alpha treatment. Clin Biochem. 2005; 38(12): 1141-4. (doi: 10.1016/j.clinbiochem.2005. 10.006).
  • Duygu F, Karsen H, Aksoy N, Taskin A. Relationship of oxidative stress in hepatitis B infection activity with HBV DNA and fibrosis. Ann Lab Med. 2012; 32(2): 113-8. (doi: 10.3343/alm.2012.32.2.113).
  • Bolukbas C, Bolukbas FF, Horoz M, Aslan M, Celik H, Erel O. Increased oxidative stress associated with the severity of the liver disease in various forms of hepatitis B virus infection. BMC Infect Dis. 2005; 5: 95. (doi: 10.1186/1471-2334-5-95).
  • Yamamoto Y, Yamashita S, Fujisawa A, Kokura S, Yoshikawa T. Oxidative stress in patients with hepatitis, cirrhosis, and hepatoma evaluated by plasma antioxidants. Biochem Biophys Res Commun. 1998; 247(1): 166-70. (doi: 10.1006/bbrc.1998.8752).
  • Gutteridge JM. Lipid peroxidation and antioxidants as biomarkers of tissue damage. Clin Chem. 1995; 41: 1819-28. (doi: 10.1093/clinchem/41.12.1819).
  • Coşkun C, Emre HÖ, Gümüş A, Uzun S, et al. Dynamic Thiol Disulphide Homeostasis and Advanced Oxidation Protein Products (Aopps) in Diabetic and Non-Diabetic Chronic Renal Failure Disease. Deneysel Tıp Dergisi 2016; 6(12).
  • Kloner RA, Przyklenk K, Whittaker P. Deleterious effects of oxygen radicals in ischemia/reperfusion. Resolved and unresolved issues. Circulation 1989; 80: 1115-27. (doi: 10.1161/01.CIR.80.5.1115).
  • Opie LH. Reperfusion injury and its pharmacologic modification. Circulation. 1989; 80: 1049-62. (doi: 10.1161/01.CIR.80.4.1049).
  • Bal C, Buyuksekerci M, Koca C, Agıs ER, Erdogan S, et al. The compromise of dynamic disulfide/thiol homeostasis as a biomarker of oxidative stres in trichloroethylene exposure. Hum Exp Toxicol. 2015; 49: 1-6.
  • Erel O. A new automated colorimetric method for measuring total oxidant status. Clinical Biochemistry. 2005; 9: 1-9. (doi: 10.1016/j.clinbiochem.2005.08.008).
  • Elmas B, Karacan M, Dervişoğlu P, Kösecik M, İşgüven ŞP, Bal C. Dynamic thiol/disulphide homeostasis as a novel indicator of oxidative stress in obese children and its relationship with inflammatory-cardiovascular markers. Anatol J Cardiol. 2017;18(5): 361-9. (doi: 10.14744/ AnatolJCardiol.2017.7740).
  • Ates I, Kaplan M, Inan B, Alisik M, Erel O, Yilmaz N, et al. How does thiol/disulfide homeostasis change in prediabetic patients? Diabetes Res Clin Pract. 2015; 110(2): 166-71. (doi: 10.1016/j.diabres.2015.09.011).
  • Ates I, Ozkayar N, Inan B, Yilmaz FM, Topcuoglu C, Neselioglu S, et al. Dynamic thiol/disulphide homeostasis in patients with newly diagnosed primary hypertension. J Am Soc Hypertens. 2016; 10(2): 159-66. (doi: 10.1016/j.jash.2015.12.008).
  • Erkenekli K, Sanhal CY, Yucel A, Bicer CK, Erel O, Uygur D. Thiol/disulfide homeostasis in patients with idiopathic recurrent pregnancy loss assessed by a novel assay: Report of a preliminary study. J Obstet Gynaecol Res. 2016; 42(2): 136-41. (doi: 10.1111/jog.12860).
  • Matteucci E, Giampietro O. Thiol signalling network with an eye to diabetes. Molecules. 2010; 15: 8890-903. (doi: 10.3390/molecules15128890).
  • Senyurt M, Neselioglu S, Bicer CK, Yildiz F, Gözcü H, Carlıoglu A. Decreased Thiol Levels, Increased Disulphide Levels Are Associated with Increased Blood Glucose Levels in Newly Diagnosed Type 2 Diabetes. West Indian Medical Journal.
  • Kundi H, Erel Ö, Balun A, Çiçekçioglu H, Cetin M, Kiziltunç E, et al. Association of thiol/disulfide ratio with syntax score in patients with NSTEMI. Scand Cardiovasc J. 2015; 49(2): 95-100. (doi: 10.3109/14017431.2015.1013153).
  • Eren Y, Dirik E, Neselioglu S, Erel Ö. Oxidative stress and decreased thiol level in patients with migraine: Cross-sectional study. Acta Neurol Belg. 2015; 115(4): 643-9. (doi: 10.1007/s13760-015-0427-y).
  • Erkus ME, Altiparmak IH, Akyuz AR, Demirbag R, Sezen Y, Gunebakmaz O, et al. The association between plasma thiol levels and left ventricular diastolic dysfunction in patient with hypertension. Scand J Clin Lab Invest. 2015; 75(8): 667-73. (doi: 10.1016/j.amjcard.2015.01.076).
  • Kaya S, Sütçü R, Çetin ES, Nigar Yılmaz N, Arıkan S, Arıdoğan BC, Delibaş N. Relationship Between Viral Load and Lipid Peroxidation and Antioxidant Enzymes in Patients Infected with Hepatitis B Virus. Türk Klinik Biyokimya Derg 2006; 4(2): 77-82.
  • Wang K, Wang B, Fan XP, Lin YJ, Shui WP. Oxidative stress in patients with chronic hepatitis B. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi 2004; 18: 172-4.
  • Schmilovitz-Weiss H, Tovar A, Halpern M., Sulkes J, Braun M, Rotman Y. et al. Predictive value of serum globulin levels for the extent of hepatic fibrosis in patients with chronic hepatitis B infection. J Viral Hepat 2006; 13: 671-7. (doi: 10.1111/j.1365-2893.2006.00744.x).
  • Kandemır Ö, Bayarslan C, Kaya A. Isolated Anti-Hbc positive subjects and their response to Hepatitis B vaccıne. Viral Hepatit Derg 2002; (1): 430-1.
Toplam 38 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Sağlık Kurumları Yönetimi
Bölüm Araştırma makaleleri
Yazarlar

Neslihan Çelik 0000-0003-4543-9247

Cemile Biçer Bu kişi benim 0000-0001-7937-4475

Onur Çelik Bu kişi benim 0000-0002-9000-4851

Ayşe Çarlıoğlu 0000-0002-5622-9563

Murat Alışık 0000-0003-0434-3206

Yayımlanma Tarihi 1 Haziran 2020
Yayımlandığı Sayı Yıl 2020 Cilt: 12 Sayı: 2

Kaynak Göster

Vancouver Çelik N, Biçer C, Çelik O, Çarlıoğlu A, Alışık M. Thiol/disulfide homeostasis in patients with chronic hepatitis B. otd. 12(2):279-87.

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