Araştırma Makalesi
BibTex RIS Kaynak Göster

Testosteron Tedavisinin Hipogonad Hastalardaki Non-Alkolik Yağlı Karaciğer Hastalığı Üzerine Etkisinin Fibroscan ile Değerlendirilmesi

Yıl 2022, Cilt: 17 Sayı: 1, 186 - 192, 21.03.2022
https://doi.org/10.17517/ksutfd.1055412

Öz

Giriş: Hipogonadizm, metabolik sendrom ve non-alkolik yağlı karaciğer hastalığı (NAYKH) ile yakın ilişki içindedir. Çalışmamızda hipogonad hastalara uygulanan testesteron tedavisi ile non-alkolik yağlı karaciğer hastalığı ilişkisini Fibroscan ve laboratuar veriler ile incelemeyi amaçladık.
Materyal-Metod: Çalışmaya 18-60 yaş arasında, yeni tanı veya son 6 aydır androjen replasman tedavisi almayan 40 hipogonad erkek (hasta grubu) ve yaş, vücut kitle indeksi (VKİ) benzer 36 ögonad erkek (kontrol grubu) alındı. Tüm katılımcıların VKİ, bel çevresi ölçüldü. Laboratuvar parametrelerinden açlık plazma glukozu, açlık insülin değeri, karaciğer fonksiyon testleri, hormon ve lipid paneli ölçüldü. Ayrıca tüm katılımcıların Fibroscan® (transient elastografi) işlemi yapılarak, hepatosteatoz düzeyi (CAP skoru) değerlendirildi.
Bulgular: Çalışmamızda hipogonad grupta kontrol grubuna göre ortalama (CAP skoru) hepatosteatoz düzeyi daha yüksek izlendi (sırasıyla, 274.72±78.69 dB/m ve 207.41±52.82 dB/m, p=0,000). Testesteron tedavisi sonrası hipogonad grup ortalama bel çevresi, hepatosteatoz düzeyi ve laboratuar değerlerinde (AST, ALT, Açlık plazma glikoz, Total-K, LDL, TG, insülin) gerileme izlendi. Ancak bunlardan AST, ALT, LDL-K, TG, total testesteron düzeyi, bel çevresi ve ek olarak vücut kitle indeksi direk ortalama hepatosteatoz düzeyi ile korelasyon gösterdi. Lojistik regresyon analizi yapıldığında hepatosteatozu predikte eden en anlamlı parametre total testesteron düzeyi olduğu saptandı (OR: 0,004, %95 C.I: 0,988-0,998).
Sonuç: Hipogonadizmli erkek hastalarda ögonad erkeklere göre NAYKH sıklığı artmıştır. Total testesteron düzeyi, VKİ, Bel Çevresi artışı NAYKH gelişiminde bağımsız risk faktörleridir. Bu nedenle testesteron replasman tedavisinin NAYKH ve eşlik eden metabolik sendrom parametrelerini iyileştirebileceğini düşünmekteyiz.

Destekleyen Kurum

yok

Kaynakça

  • 1. Loomba R. & Sanyal A. J. The global NAFLD epidemic. Nat Rev Gastroenterol Hepatol. 2013 Nov; 10(11), 686–690.
  • 2. Fernando B, Kenneth C. Nonalcoholic Fatty Liver Disease: The New Complication of Type 2 Diabetes Mellitus. Endocrinol Metab Clin North Am. 2016 Dec; 45(4):765-781.
  • 3. Blachier M, Leleu H, Peck M, Valla D, Roudot F. The burden of liver disease in Europe: A review of available epidemiological data. J Hepatol. 2013; 58, 593–608.
  • 4. Targher G, Day CP, Bonora E. Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N Engl J Med. 2010; 363, 1341–1350.
  • 5. Stefan N, Kantartzis K, Haring HU. Causes and metabolic consequences of Fatty liver. Endocr Rev. 2008 Dec; 29(7): 939–960.
  • 6. Anstee QM, Targher G, Day CP. Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nat Rev Gastroenterol Hepatol. 2013; 10(6), 330–344.
  • 7. Polyzos SA, Kang ES, Boutari C, Rhee EC, Mantzoros CS. Current and emerging pharmacological options for the treatment of non-alcoholic steatohepatitis. Metabolism (2020), Article 154203, 10. 1016/j. metabol. 2020. 54203154203.
  • 8. Eslam M, Newsome PN, Sarin SK, Anstee QM, Targher G, Gomez MR, et al. A new definition for metabolic dysfunction-associated fatty liver disease: an international expert consensus statement. J Hepatol, 73 (1) (2020), pp. 202-209.
  • 9. Eslam M, Sanyal AJ, George J. MAFLD: A consensus- driven proposed nomenclature for metabolic associated fatty liver disease Gastroenterology, 2020;158 (7): pp. 1999- 2014.
  • 10. Polyzos SA, Mantzoros CS. Making progress in nonalcoholic fatty liver disease (NAFLD) as we are transitioning from the era of NAFLD to dys-metabolism associated fatty liver disease (DAFLD). Metabolism (2020), Article 154318, 10. 1016/j. metabol. 2020. 154318.
  • 11. Polyzos SA: Endocrine and metabolic disorders interplaying with non-alcoholic fatty liver disease. Minerva Endocrinol, 42 (2) (2017), pp. 89-91.
  • 12. Mintziori G, Poulakos P, Tsametis C, Goulis DG. Hypogonadism and non-alcoholic fatty liver disease. Minerva Endocrinol, 42 (2) (2017), pp. 145-150.
  • 13. Lonardo A, Mantovani A, Lugari S, Targher G. NAFLD in some common endocrine diseases: prevalence, pathophysiology, and principles of diagnosis and management. Int J Mol Sci,2019; 20 (11):p. 2841.
  • 14. Snyder PJ, Causes of primary hypogonadism in males. 2020 UpToDate. www.uptodate.com. Date of Access: Dec 13, 2019.
  • 15. Brand JS, Rovers MM, Yeap BB, Schneider HJ, Tuomainen TP, Haring R, et al. Testosterone, sex hormone-binding globulin and the metabolic syndrome in men: An individual participant data meta-analysis of observational studies. PLoS One 2014;9(7): doi: 10. 1371/journal. pone.0100409.
  • 16. Derby CA, Zilber S, Brambilla D, Morales H, McKinlay JB. Body mass index, waist circumference and waist to hip ratio and change in sex steroid hormones: The Massachusetts Male Ageing Study. Clin Endocrinol (Oxf) 2006;65(1):125-131.
  • 17. Rao PM, Kelly DM, Jones TH. Testosterone and insülin resistance in the metabolic syndrome and T2DM in men. Nat Rev Endocrinol. 2013; 9(8): 479-493.
  • 18. Barbonetti A, Vassallo MRC, Cotugno M, Felzani G, Francavilla S, Francavilla F. Low testosterone and non- alcoholic fatty liver disease: evidence for their independent association in men with chronic spinal cord injury. J Spinal Cord Med, 2016;39 (4): p. 443-449.
  • 19. Kim S, Kwon H, Park JH, Cho B, Kim D, Oh SW, et al. A low level of serum total testosterone is independently associated with nonalcoholic fatty liver disease. BMC Gastroenterol, 2012;12: p. 69.
  • 20. Yim JY, Kim J, Kim D, Ahmed A. Serum testosterone and non-alcoholic fatty liver disease in men and women in the US. Liver Int, 2018; 38 (11): pp. 2051-2059.
  • 21. Polyzos A, Mantzoros CS. Necessity for timely noninvasive diagnosis of nonalcoholic fatty liver disease Metabolism,2014; 63 (2):pp. 161-167.
  • 22. Hernaez R, Lazo M, Bonekamp S, Kamel I, Brancati FL, Guallar E, et al. Diagnostic accuracy and reliability of ultrasonography for the detection of fatty liver: a meta-analysis. Hepatology 2011, 54(3):1082–1090. doi: 10. 1002/hep.24452.
  • 23. Sasso M, Beaugrand M, Ledinghen V, Douvin C, Marcellin P, Poupon R, et al. “Controlled attenuation parameter (CAP): a novel VCTE™ guided ultrasonic attenuation measurement for the evaluation of hepatic steatosis: preliminary study and validation in a cohort of patients with chronic liver disease from various causes,” Ultrasound in Medicine & Biology,2010;36(11): pp. 1825–1835.
  • 24. Myers RP, Pollett A, Kirsch R, Pomier-Layrargues G, Beaton M, Levstik M, et al. Controlled Attenuation Parameter (CAP): a noninvasive method for the detection of hepatic steatosis based on transient elastography. Liver Int 2012, 32(6):902–910. doi: 10. 1111/ j.1478-3231.2012.02781.x
  • 25. Kwak MS, Chung GE, Yang JI, Yim JY, Chung SJ, Jung SY, et al. Clinical implications of controlled attenuation parameter in a health check-up cohort. Liver Int 2018, 38(5):915–923. doi: 10. 1111/ liv.13558.
  • 26. Karlas T, Petroff D, Sasso M, Fan JG, Mi YQ, de Lédinghen V, et al. Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis. Journal of hepatology 2017, 66(5):1022–1030. doi: 10. 1016/j. jhep. 2016.12.022.
  • 27. Wong VW, Vergniol J, Wong G, Foucher J, Chan H, Le Bail B, et al. Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease. Hepatology. 2010;51(12): 454–462. doi: 10. 1002/hep.23312.
  • 28. Karlas T, Petroff D., Garnov N., Böhm S, Tenckhoff H, Wittekind C, et al. Non-invasive assessment of hepatic steatosis in patients with NAFLD using controlled attenuation parameter and H-MR spectroscopy. PLoS ONE. 2014;9: doi: 10. 1371/ journal. pone. 0091987.
  • 29. Bellentani Stefano. The epidemiology of nonalcoholic fatty liver disease. Liver international. 2017;37: 81–84.
  • 30. Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, et al. The diagnosis and management of nonalcoholic fatty liver disease: practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. 2012;55(6): 2005-2023.
  • 31. Nikolaenko L, Jia Y, Wang C, Arjonilla MD, Yee JK, French SW, et al. Testosterone Replacement Ameliorates Nonalcoholic Fatty Liver Disease in Castrated Male Rats. Endocrinology. 2014;155(2): 417–428.
  • 32. Velde FV, Bekaert M, Hoorens A, Geerts A, T’Sjoen G, Fiers T, et al. Histologically proven hepatic steatosis associates with lower testosterone levels in men with obesity. Asian Journal of Andrology. 2020; 2(3):252– 257.
  • 33. Jensen TK, Andersson AM, Jorgensen N, Andersen AG, Carlsen E, Petersen JH, et al.. Body mass index in relation to semen quality and reproductive hormones among 1,558 Danish men. Ferti Steril. 2004;82(4): 863–870.
  • 34. Li C, Ford ES, Li B, Giles WH, Liu S, et al. Association of testosterone and sex hormone-binding globulin with metabolic syndrome and insülin resistance in men. Diabetes Care. 2010; 33(7): 1618-1624.
  • 35. Osuna JA, Gómez-Pérez R, Arata-Bellabarba G, Villaroel V, et al. Relationship between BMI, total testosterone, sex hormonebinding-globulin, leptin, insulin and insulin resistance in obese men. Arch Androl. 2006; 52(5): 355-361.
  • 36. Marchesini G, Brizi M, Bianchi G, Tomassetti S, Bugianesi E, Lenzi M, et al. Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes 2001;50(8): 1844 –1850.
  • 37. Cnop M, Landchild MJ, Vidal J, Havel PJ, Knowles NG, Carr DB, et al. The concurrent accumulation of intra- abdominal and subcutaneous fat explains the association between insulin resistance and plasma leptin concentrations: distinct metabolic effects of two fat compartments. Diabetes 2002;51(4): 1005-1015.
  • 38. Tavaglione F, De Vincentis A, Bruni V, Gallo IF, Carotti S, Tuccinardi D, et al. Accuracy of controlled attenuation parameter for assessing liver steatosis in individuals with morbid obesity before bariatric surgery. Liver Int. 2021 10. doi: 10. 1111/liv.15127.

Evaluation of the Effect of Testosterone Treatment on Non-Alcoholic Fatty Liver Disease in Hypogonad Patients with Fibroscan

Yıl 2022, Cilt: 17 Sayı: 1, 186 - 192, 21.03.2022
https://doi.org/10.17517/ksutfd.1055412

Öz

Introduction: It is closely associated with hypogonadism, metabolic syndrome and non-alcoholic fatty liver disease (NAFLD). In our study, we aimed to examine the relationship between testosterone treatment applied to hypogonad patients and non-alcoholic fatty liver disease using Fibroscan and laboratory data.
Material-method: Forty hypogonads and 36 eugonads aged 8-60 years without treatment were included in the study. BMI, waist circumference and laboratory measurements (glucose, liver function tests, hormone and lipid panel) of all participants were measured. In addition, hepatosteatosis level was evaluated with Fibroscan® (transient elastography) procedure.
Results: In our study, the mean (CAP score) hepatosteatosis level of the hypogonad group was higher than the control group (274. 72±78.69 dB/m and 207. 41±52.82 dB/m, p=0.000, respectively). After testosterone treatment, a decrease was observed in the mean waist circumference, hepatosteatosis level and laboratory values (AST, ALT, Fasting plasma glucose, Total-C, LDL, TG, insulin) of the hypogonad group. However, of these, AST, ALT, LDL-C, TG, total testosterone level, waist circumference and additionally body mass index were directly correlated with the mean hepatosteatosis level. When logistic regression analysis was performed, the most significant parameter predicting hepatosteatosis was found to be total testosterone level (OR: 0.004, 95% CI: 0.988-0.998).
Conclusion: The incidence of NAFLD is increased in male patients with hypogonadism compared to eugonad males. Total testosterone level, BMI, Waist Circumference are independent risk factors for the development of NAFLD. Therefore, we think that testosterone replacement therapy can improve NAFLD and accompanying metabolic syndrome parameters.

Kaynakça

  • 1. Loomba R. & Sanyal A. J. The global NAFLD epidemic. Nat Rev Gastroenterol Hepatol. 2013 Nov; 10(11), 686–690.
  • 2. Fernando B, Kenneth C. Nonalcoholic Fatty Liver Disease: The New Complication of Type 2 Diabetes Mellitus. Endocrinol Metab Clin North Am. 2016 Dec; 45(4):765-781.
  • 3. Blachier M, Leleu H, Peck M, Valla D, Roudot F. The burden of liver disease in Europe: A review of available epidemiological data. J Hepatol. 2013; 58, 593–608.
  • 4. Targher G, Day CP, Bonora E. Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N Engl J Med. 2010; 363, 1341–1350.
  • 5. Stefan N, Kantartzis K, Haring HU. Causes and metabolic consequences of Fatty liver. Endocr Rev. 2008 Dec; 29(7): 939–960.
  • 6. Anstee QM, Targher G, Day CP. Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nat Rev Gastroenterol Hepatol. 2013; 10(6), 330–344.
  • 7. Polyzos SA, Kang ES, Boutari C, Rhee EC, Mantzoros CS. Current and emerging pharmacological options for the treatment of non-alcoholic steatohepatitis. Metabolism (2020), Article 154203, 10. 1016/j. metabol. 2020. 54203154203.
  • 8. Eslam M, Newsome PN, Sarin SK, Anstee QM, Targher G, Gomez MR, et al. A new definition for metabolic dysfunction-associated fatty liver disease: an international expert consensus statement. J Hepatol, 73 (1) (2020), pp. 202-209.
  • 9. Eslam M, Sanyal AJ, George J. MAFLD: A consensus- driven proposed nomenclature for metabolic associated fatty liver disease Gastroenterology, 2020;158 (7): pp. 1999- 2014.
  • 10. Polyzos SA, Mantzoros CS. Making progress in nonalcoholic fatty liver disease (NAFLD) as we are transitioning from the era of NAFLD to dys-metabolism associated fatty liver disease (DAFLD). Metabolism (2020), Article 154318, 10. 1016/j. metabol. 2020. 154318.
  • 11. Polyzos SA: Endocrine and metabolic disorders interplaying with non-alcoholic fatty liver disease. Minerva Endocrinol, 42 (2) (2017), pp. 89-91.
  • 12. Mintziori G, Poulakos P, Tsametis C, Goulis DG. Hypogonadism and non-alcoholic fatty liver disease. Minerva Endocrinol, 42 (2) (2017), pp. 145-150.
  • 13. Lonardo A, Mantovani A, Lugari S, Targher G. NAFLD in some common endocrine diseases: prevalence, pathophysiology, and principles of diagnosis and management. Int J Mol Sci,2019; 20 (11):p. 2841.
  • 14. Snyder PJ, Causes of primary hypogonadism in males. 2020 UpToDate. www.uptodate.com. Date of Access: Dec 13, 2019.
  • 15. Brand JS, Rovers MM, Yeap BB, Schneider HJ, Tuomainen TP, Haring R, et al. Testosterone, sex hormone-binding globulin and the metabolic syndrome in men: An individual participant data meta-analysis of observational studies. PLoS One 2014;9(7): doi: 10. 1371/journal. pone.0100409.
  • 16. Derby CA, Zilber S, Brambilla D, Morales H, McKinlay JB. Body mass index, waist circumference and waist to hip ratio and change in sex steroid hormones: The Massachusetts Male Ageing Study. Clin Endocrinol (Oxf) 2006;65(1):125-131.
  • 17. Rao PM, Kelly DM, Jones TH. Testosterone and insülin resistance in the metabolic syndrome and T2DM in men. Nat Rev Endocrinol. 2013; 9(8): 479-493.
  • 18. Barbonetti A, Vassallo MRC, Cotugno M, Felzani G, Francavilla S, Francavilla F. Low testosterone and non- alcoholic fatty liver disease: evidence for their independent association in men with chronic spinal cord injury. J Spinal Cord Med, 2016;39 (4): p. 443-449.
  • 19. Kim S, Kwon H, Park JH, Cho B, Kim D, Oh SW, et al. A low level of serum total testosterone is independently associated with nonalcoholic fatty liver disease. BMC Gastroenterol, 2012;12: p. 69.
  • 20. Yim JY, Kim J, Kim D, Ahmed A. Serum testosterone and non-alcoholic fatty liver disease in men and women in the US. Liver Int, 2018; 38 (11): pp. 2051-2059.
  • 21. Polyzos A, Mantzoros CS. Necessity for timely noninvasive diagnosis of nonalcoholic fatty liver disease Metabolism,2014; 63 (2):pp. 161-167.
  • 22. Hernaez R, Lazo M, Bonekamp S, Kamel I, Brancati FL, Guallar E, et al. Diagnostic accuracy and reliability of ultrasonography for the detection of fatty liver: a meta-analysis. Hepatology 2011, 54(3):1082–1090. doi: 10. 1002/hep.24452.
  • 23. Sasso M, Beaugrand M, Ledinghen V, Douvin C, Marcellin P, Poupon R, et al. “Controlled attenuation parameter (CAP): a novel VCTE™ guided ultrasonic attenuation measurement for the evaluation of hepatic steatosis: preliminary study and validation in a cohort of patients with chronic liver disease from various causes,” Ultrasound in Medicine & Biology,2010;36(11): pp. 1825–1835.
  • 24. Myers RP, Pollett A, Kirsch R, Pomier-Layrargues G, Beaton M, Levstik M, et al. Controlled Attenuation Parameter (CAP): a noninvasive method for the detection of hepatic steatosis based on transient elastography. Liver Int 2012, 32(6):902–910. doi: 10. 1111/ j.1478-3231.2012.02781.x
  • 25. Kwak MS, Chung GE, Yang JI, Yim JY, Chung SJ, Jung SY, et al. Clinical implications of controlled attenuation parameter in a health check-up cohort. Liver Int 2018, 38(5):915–923. doi: 10. 1111/ liv.13558.
  • 26. Karlas T, Petroff D, Sasso M, Fan JG, Mi YQ, de Lédinghen V, et al. Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis. Journal of hepatology 2017, 66(5):1022–1030. doi: 10. 1016/j. jhep. 2016.12.022.
  • 27. Wong VW, Vergniol J, Wong G, Foucher J, Chan H, Le Bail B, et al. Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease. Hepatology. 2010;51(12): 454–462. doi: 10. 1002/hep.23312.
  • 28. Karlas T, Petroff D., Garnov N., Böhm S, Tenckhoff H, Wittekind C, et al. Non-invasive assessment of hepatic steatosis in patients with NAFLD using controlled attenuation parameter and H-MR spectroscopy. PLoS ONE. 2014;9: doi: 10. 1371/ journal. pone. 0091987.
  • 29. Bellentani Stefano. The epidemiology of nonalcoholic fatty liver disease. Liver international. 2017;37: 81–84.
  • 30. Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, et al. The diagnosis and management of nonalcoholic fatty liver disease: practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. 2012;55(6): 2005-2023.
  • 31. Nikolaenko L, Jia Y, Wang C, Arjonilla MD, Yee JK, French SW, et al. Testosterone Replacement Ameliorates Nonalcoholic Fatty Liver Disease in Castrated Male Rats. Endocrinology. 2014;155(2): 417–428.
  • 32. Velde FV, Bekaert M, Hoorens A, Geerts A, T’Sjoen G, Fiers T, et al. Histologically proven hepatic steatosis associates with lower testosterone levels in men with obesity. Asian Journal of Andrology. 2020; 2(3):252– 257.
  • 33. Jensen TK, Andersson AM, Jorgensen N, Andersen AG, Carlsen E, Petersen JH, et al.. Body mass index in relation to semen quality and reproductive hormones among 1,558 Danish men. Ferti Steril. 2004;82(4): 863–870.
  • 34. Li C, Ford ES, Li B, Giles WH, Liu S, et al. Association of testosterone and sex hormone-binding globulin with metabolic syndrome and insülin resistance in men. Diabetes Care. 2010; 33(7): 1618-1624.
  • 35. Osuna JA, Gómez-Pérez R, Arata-Bellabarba G, Villaroel V, et al. Relationship between BMI, total testosterone, sex hormonebinding-globulin, leptin, insulin and insulin resistance in obese men. Arch Androl. 2006; 52(5): 355-361.
  • 36. Marchesini G, Brizi M, Bianchi G, Tomassetti S, Bugianesi E, Lenzi M, et al. Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes 2001;50(8): 1844 –1850.
  • 37. Cnop M, Landchild MJ, Vidal J, Havel PJ, Knowles NG, Carr DB, et al. The concurrent accumulation of intra- abdominal and subcutaneous fat explains the association between insulin resistance and plasma leptin concentrations: distinct metabolic effects of two fat compartments. Diabetes 2002;51(4): 1005-1015.
  • 38. Tavaglione F, De Vincentis A, Bruni V, Gallo IF, Carotti S, Tuccinardi D, et al. Accuracy of controlled attenuation parameter for assessing liver steatosis in individuals with morbid obesity before bariatric surgery. Liver Int. 2021 10. doi: 10. 1111/liv.15127.
Toplam 38 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Sağlık Kurumları Yönetimi
Bölüm Araştırma Makaleleri
Yazarlar

Murat İspiroğlu 0000-0002-0655-7235

Yayımlanma Tarihi 21 Mart 2022
Gönderilme Tarihi 9 Ocak 2022
Kabul Tarihi 25 Ocak 2022
Yayımlandığı Sayı Yıl 2022 Cilt: 17 Sayı: 1

Kaynak Göster

AMA İspiroğlu M. Testosteron Tedavisinin Hipogonad Hastalardaki Non-Alkolik Yağlı Karaciğer Hastalığı Üzerine Etkisinin Fibroscan ile Değerlendirilmesi. KSÜ Tıp Fak Der. Mart 2022;17(1):186-192. doi:10.17517/ksutfd.1055412