Metabolik Disfonksiyonla İlişkili Steatotik Karaciğer Hastalığı Olan Hastalarda Subklinik Hipotiroidi Sıklığı ve Noninvaziv Fibrozis Skorları ile İlişkisi

Öz

Metabolik disfonksiyonla ilişkili steatotik karaciğer hastalığı (MASLD), obezite, insülin direnci ve diyabet gibi metabolik bozukluklarla yakından ilişkilidir. Tiroid hormonları lipid ve glukoz metabolizmasının düzenlenmesinde önemli rol oynamakta olup subklinik hipotiroidinin metabolik düzensizliklere katkıda bulunabileceği öne sürülmüştür. Bu çalışmada, MASLD tanısı olan hastalarda subklinik hipotiroidi sıklığının belirlenmesi ve non-invaziv karaciğer fibrozis skorları ile ilişkisinin değerlendirilmesi amaçlandı. Bu retrospektif kesitsel çalışmaya MASLD tanısı alan 200 erişkin hasta dahil edildi. Hastalar tiroid fonksiyon durumlarına göre subklinik hipotiroidi ve ötiroid olarak sınıflandırıldı. Demografik ve laboratuvar verileri kaydedildi. Karaciğer fibrozisi riski Fibrozis-4 (FIB-4) indeksi ve non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS) ile değerlendirildi. Serum tiroid uyarıcı hormon (TSH) düzeyleri ile fibrozis skorları arasındaki ilişkiler korelasyon analizi ile incelendi ve subklinik hipotiroidinin ileri fibrozis riski ile bağımsız ilişkisi çok değişkenli lojistik regresyon analizi ile değerlendirildi. Yaş ortalaması 54,2 ± 9,7 yıl olup hastaların %58’i kadındı ve subklinik hipotiroidi sıklığı %18 olarak saptandı. Subklinik hipotiroidi ve ötiroid gruplar arasında FIB-4 ve NFS değerleri açısından anlamlı fark izlenmedi. TSH düzeyleri ile FIB-4 arasında zayıf ancak istatistiksel olarak anlamlı korelasyon gözlenirken (r = 0,15, p = 0,034), NFS ile anlamlı ilişki saptanmadı. Çok değişkenli analizde, yaş, cinsiyet, vücut kitle indeksi, diyabet varlığı, homeostaz model değerlendirmesi ile insülin direnci (HOMA-IR) ve trigliserid/yüksek yoğunluklu lipoprotein (HDL) kolesterol oranı için düzeltme yapıldıktan sonra subklinik hipotiroidi ileri fibrozis riski ile bağımsız ilişkili bulunmadı. Sonuç olarak, subklinik hipotiroidi MASLD hastalarında görece sık görülmekle birlikte fibrozis riski ile bağımsız ilişkili değildir. Bu sonuçlar, MASLD’de fibrozis riskinin belirlenmesinde metabolik faktörlerin daha belirleyici olduğunu düşündürmektedir.

Anahtar Kelimeler

• subklinik hipotiroidi;
• karaciğer fibrozisi;
• FIB-4
• NAFLD fibrozis skoru

Prevalence of Subclinical Hypothyroidism and Its Association with Noninvasive Fibrosis Scores in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease

Öz

Metabolic dysfunction–associated steatotic liver disease (MASLD) is closely related to obesity, insulin resistance, and diabetes mellitus. Thyroid hormones play a key role in lipid and glucose metabolism, and subclinical hypothyroidism has been suggested to contribute to metabolic disturbances. This study aimed to determine the prevalence of subclinical hypothyroidism in patients with MASLD and evaluate its association with noninvasive fibrosis scores. This retrospective cross-sectional study included 200 adult patients diagnosed with MASLD. Patients were classified as having subclinical hypothyroidism or euthyroid status based on thyroid function tests. Demographic characteristics, metabolic parameters, and laboratory findings were recorded. Fibrosis risk was assessed using the Fibrosis-4 (FIB-4) index and the non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS). Group comparisons, correlation analyses, and multivariable logistic regression were performed. The mean age of the study population was 54.2 ± 9.7 years, 58% of patients were female, and the prevalence of subclinical hypothyroidism was 18%. No significant differences were observed between subclinical hypothyroid and euthyroid groups in FIB-4 or NFS values. A weak but statistically significant correlation was observed between TSH levels and the FIB-4 index (r = 0.15, p = 0.034), whereas no significant correlation was found with NFS. In multivariable analysis adjusted for age, sex, body mass index, diabetes mellitus, homeostasis model assessment of insulin resistance (HOMA-IR), and triglyceride-to-high-density lipoprotein (HDL) cholesterol ratio, subclinical hypothyroidism was not independently associated with advanced fibrosis risk. These findings indicate metabolic factors remain the primary determinants of fibrosis risk.

Anahtar Kelimeler

• Metabolic dysfunction–associated steatotic liver disease
• subclinical hypothyroidism
• ; liver fibrosis
• ; FIB-4
• ; NAFLD fibrosis score

Kaynakça

1. 1. Eslam M, Newsome PN, Sarin SK, Anstee QM, Targher G, Romero-Gomez M, et al. A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement. J Hepatol. 2020;73(1):202–9.
2. 2. Mantovani A, Scorletti E, Mosca A, Alisi A, Byrne CD, Targher G. Complications, morbidity and mortality of nonalcoholic fatty liver disease. Metabolism. 2020;111:154170.
3. 3. Younossi ZM, Golabi P, Paik JM, Henry A, Van Dongen C, Henry L. The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review. Hepatology. 2023;Publish Ahead of Print(4).
4. 4. Angulo P, Kleiner DE, Dam-Larsen S, Adams LA, Bjornsson ES, Charatcharoenwitthaya P, et al. Liver Fibrosis, but No Other Histologic Features, Is Associated With Long-term Outcomes of Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology. 2015;149(2):389-397.e10.
5. 5. Dulai PS, Singh S, Patel J, Soni M, Prokop LJ, Younossi Z, et al. Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: Systematic review and meta-analysis. Hepatology. 2017;65(5):1557–65.
6. 6. Lonardo A, Ballestri S, Marchesini G, Angulo P, Loria P. Nonalcoholic fatty liver disease: A precursor of the metabolic syndrome. Dig Liver Dis. 2015;47(3):181–90.
7. 7. Cooper DS, Biondi B. Subclinical thyroid disease. Lancet Lond Engl. 2012;379(9821):1142–54.
8. 8. Pearce SHS, Brabant G, Duntas LH, Monzani F, Peeters RP, Razvi S, et al. 2013 ETA Guideline: Management of Subclinical Hypothyroidism. Eur Thyroid J. 2013;2(4):215–28.

9. 9. R M, Yy L, Ga B. Physiological reviews [Internet]. 2014. Thyroid Hormone Regulation of Metabolism. Available from: https://pubmed.ncbi.nlm.nih.gov/24692351/
10. 10. Sinha RA, Singh BK, Yen PM. Thyroid hormone regulation of hepatic lipid and carbohydrate metabolism. Trends Endocrinol Metab. 2014;25(10):538–45. doi:10.1016/j.tem.2014.07.001
11. 11. Brenta G. Why Can Insulin Resistance Be a Natural Consequence of Thyroid Dysfunction? J Thyroid Res. 2011;2011:1–9.
12. 12. Cappola AR, Ladenson PW. Hypothyroidism and Atherosclerosis. J Clin Endocrinol Metab. 2003;88(6):2438–44.
13. 13. Lai Y, Wang J, Jiang F, Wang B, Chen Y, Li M, et al. The relationship between serum thyrotropin and components of metabolic syndrome. Endocr J. 2011;58(1):23–30.
14. 14. Sinha RA, You SH, Zhou J, Siddique MM, Bay BH, Zhu X, et al. Thyroid hormone stimulates hepatic lipid catabolism via activation of autophagy. J Clin Invest. 2012;122(7):2428–38.
15. 15. Ferrandino G, Kaspari RR, Spadaro O, Reyna-Neyra A, Perry RJ, Cardone R, et al. Pathogenesis of hypothyroidism-induced NAFLD is driven by intra- and extrahepatic mechanisms. Proc Natl Acad Sci. 2017;114(43).
16. 16. Pagadala MR, Zein CO, Dasarathy S, Yerian LM, Lopez R, McCullough AJ. Prevalence of Hypothyroidism in Nonalcoholic Fatty Liver Disease. Dig Dis Sci. 2011;57(2):528–34.
17. 17. Kim D, Won Ho Kim, Sae Kyung Joo, Jeong Mo Bae, Jung Hyun Kim, Ahmed A. Subclinical Hypothyroidism and Low-Normal Thyroid Function Are Associated With Nonalcoholic Steatohepatitis and Fibrosis. Vol. 16. 2018;16(1):123-131.e1.
18. 18. Chung GE, Kim D, Kim W, Yim JY, Park MJ, Kim YJ, et al. Non-alcoholic fatty liver disease across the spectrum of hypothyroidism. J Hepatol. 2012;57(1):150–6.
19. 19. Xiang L lan, Cao Y tian, Sun J, Li R han, Qi F, Zhang Y juan, et al. Association between thyroid function and nonalcoholic fatty liver disease: a dose-response meta-analysis. Front Endocrinol. 2024;15.
20. 20. Sterling RK, Lissen E, Clumeck N, Sola R, Correa MC, Montaner J, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006;43(6):1317–25.
21. 21. Angulo P, Hui JM, Marchesini G, Bugianesi E, George J, Farrell GC, et al. The NAFLD fibrosis score: A noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology. 2007;45(4):846–54.
22. 22. Shah AG, Lydecker A, Murray K, Tetri BN, Contos MJ, Sanyal AJ. Comparison of Noninvasive Markers of Fibrosis in Patients With Nonalcoholic Fatty Liver Disease. Clin Gastroenterol Hepatol. 2009;7(10):1104–12.
23. 23. McPherson S, Stewart SF, Henderson E, Burt AD, Day CP. Simple non-invasive fibrosis scoring systems can reliably exclude advanced fibrosis in patients with non-alcoholic fatty liver disease. Gut. 2010;59(9):1265–9.
24. 24. Castera L, Friedrich-Rust M, Loomba R. Noninvasive Assessment of Liver Disease in Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology. 2019;156(5):1264-1281.e4.
25. 25. Adams LA, Vlad Ratziu. Non-alcoholic fatty liver – Perhaps not so benign. Vol. 62. 2015;62(5):1002–4.
26. 26. Rinella ME, Lazarus JV, Vlad Ratziu, Francque SM, Sanyal AJ, Kanwal F, et al. A multi-society Delphi consensus statement on new fatty liver disease nomenclature. J Hepatol. 2023;79(6).
27. 27. Stefan N, Häring HU, Cusi K. Non-alcoholic fatty liver disease: causes, diagnosis, cardiometabolic consequences, and treatment strategies. Lancet Diabetes Endocrinol. 2019;7(4):313–24.
28. 28. Bano A, Chaker L, Plompen EPC, Hofman A, Dehghan A, Franco OH, et al. Thyroid Function and the Risk of Nonalcoholic Fatty Liver Disease: The Rotterdam Study. J Clin Endocrinol Metab. 2016;101(8):3204–11.
29. 29. Brent GA. Mechanisms of Thyroid Hormone Action. J Clin Invest. 2012;122(9):3035–43.
30. 30. Kil Yeon Lee, Ki Bae Bang, Rhee EJ, Kwon HJ, Mi Woo Lee, Yong Soo Cho. Impact of hypothyroidism on the development of non-alcoholic fatty liver disease: A 4-year retrospective cohort study. Clin Mol Hepatol. 2015;21(4):372–372.