Fibrosis-4 Index as a Predictor for Disease Severity and Mortality in Patients with COVID-19

Öz

Objective: The Fibrosis-4 (FIB-4) index is a noninvasive marker of liver fibrosis in various patient populations. We examined whether there is a relationship between the severity and prognosis of COVID-19 disease and the FIB-4 index. Materials and Methods: This stuy is a cross-sectional and retrospective. The patients were divided into two groups as those hospitalized in the intensive care unit (ICU) and those hospitalized in the clinic (non- ICU). Results: Of the total 158 cases,86(54%) were male. Age, total bilirubin, AST levels and FIB-4 index were higher in ICU patients compared to non-ICUs (p<0.001,p=0.002, p=0.003, p<0.001 respectively). FIB-4 index non-survivors were also higher (p=0.002). When the effect of the FIB-4 index on the severity of COVID-19 disease and mortality was evaluated by ROC analysis, both ICU and non-survivors were found to be significant (respectively FIB-4 score;AUC=0.705,95%CI:0.624-785,p<0.001;AUC=0.654,95%CI:0.566-742,p=0.002). When the FIB-4 index cut-off value for disease severity was taken as 2.19, 70.0% sensitivity and 60% specificity were found in predicting disease severity. Moreover, when the FIB-4 index cut-off value for mortality was taken as 2.19, 71.2% sensitivity and 53% specificity were found in predicting mortality. Conclusion: The FIB-4 index is an independent predictor of severity and mortality in COVID-19 patients requiring ICU.

Anahtar Kelimeler

• COVID-19
• FIB-4 index,
• mortality

COVID-19 Hastalarında Hastalık Şiddeti ve Mortalite için Bir Öngörücü Olarak Fibrozis-4 Indeksi

Öz

Amaç: Fibrosis 4 (FIB-4) index çeşitli hasta popülasyonlarında karaciğer fibrozisini gösteren non invaziv bir belirteçdir. Çalışmamızda COVİD-19 hastalığının ciddiyeti ve mortalite ile FIB-4 skoru arasında ilişki olup olmadığını incelemeyi planladık. Gereç ve Yöntem: Bu çalışma kesitsel retrospektiftir. COVID-19 tanısı doğrulanmış olup hastanede yatan 158 hastayı içermektedir. Hastalar yoğun bakım ünitesinde (ICU) yatanlar ve kliniğe yatırılanlar (non-ICU) olarak iki gruba ayrıldı. Bulgular: Toplam 158 olgunun 86 (50%)’sı erkek idi. Yaş, total bilirubin, AST ve FIB-4 index yoğun bakım ünitesinde yatanlarda yoğun bakımda yatmayanlarla karşılaştırıldığında sırasıyla (p<0,001, p=0,002, p=0,003, p<0,001 ) idi. FIB-4 index hayatta kalmayanlarda daha yüsekti (p=0,002). FIB-4 skorunun COVİD-19 ciddiyetini ve mortaliteyi öngörmedeki etkisi ROC analizi ile değerlendirildiğinde hem yoğun bakımda yatan hemde hayatta kalmayanlarda anlamlı bulundu (sırasıyla AUC=0,705, 95%CI: 0.624-785, p<0,001; AUC=0,654, 95%CI:0,566-742, p=0,002). Hastalık şiddeti için FIB-4 indeks için cut-off değeri 2,19 olarak alındığında hastalık şiddetini öngörmede %70,0 duyarlılık ve %60 özgüllük bulunmuştur. Ayrıca, mortalite için FIB-4 indeksi için cut-off değeri 2,19 olarak alındığında, mortaliteyi öngörmede %71,2 duyarlılık ve %53 özgüllük bulunmuştur. Sonuç: FIB-4 indeksi yoğun bakım gerektiren COVİD-19 hastalarının cidiyetini ve mortaliteyi belirlemede bağımsız bir öngördürücüdür.

Anahtar Kelimeler

• COVİD-19
• FİB-4 İNDEX
• mortalite

Kaynakça

1. 1. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel corona virus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507-513. doi:10.1016/S0140-6736(20)30211-7.
2. 2. Wu C, Chen X, Cai Y, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with corona virüs disease 2019 pneumonia in Wuhan, China. JAMA Intern Med. 2020; 180(7):934-943. doi: 10.1001/jamainternmed.2020.0994.
3. 3. Zhu N, Zhang D, Wang W, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020;20;382(8):727-733. doi.org/10.1056/NEJMoa2001017.
4. 4. Hundt MA, Deng Y, Ciarleglio MM, Nathanson M, Lim JK. Abnormal Liver Tests in COVID-19: A Retrospective Observational Cohort Study of 1,827 Patients in a Major U.S. Hospital Network. Hepatology. 2020; 72(4):1169-1176. doi.org/1 0.1002/hep.31487.
5. 5. Bloom PP, Meyerowitz EA, Reinus Z, et al. Liver biochemistries in hospitalized patients with COVID-19. Hepatology. 2020; 73(3):890-900. doi. org/10.1002/hep.31326. 6. Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of corona virus disease 2019 in China. N Engl J Med. 2020; 382:1708–1720. doi. org/10.1056/NEJMoa2002032.
6. 7. Eslam M, Sanyal AJ, George J. MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease. Gastroenterology. 2020; 158:1999–2014. doi:10.1053/j.gastro.2019.11.312
7. 8. Gines P, Graupera I, Lammert F, et al. Screening for liver fibrosis in the general population: a callforaction. Lancet Gastroenterol Hepatol. 2016; 1:256–60. doi:10.1016/s2468-1253(16)30081-4.
8. 9. Taylor RS, Taylor RJ, Bayliss S, et al. Association between fibrosis stage and outcomes of patients with nonalcoholic fatty liver disease: a systematic review and meta-analysis. Gastroenterology. 2020; 158:1611–1625. doi: 10.1053/j.gastro.2020.01.043.

9. 10. Sterling RK, Lissen E, Clumeck N, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006; 43(6):1317-1325. doi.org/10.1002/hep.21178.
10. 11. Kim BK, Kim DY, Park JY, et al Validation of FIB-4 and comparison with other simple noninvasive indices for predicting liver fibrosis and cirrhosis in hepatitis B virus-infected patients. Liver Int. 2010; 30(4):546-53. doi: 10.1111/j.1478-3231.2009.02192.x.
11. 12. Ibáñez-Samaniego L, Bighelli F, Usón C, et al. Elevation of Liver Fibrosis Index FIB-4 Is Associated With Poor Clinical Outcomes in Patients With COVID-19. J Infect Dis. 2020;222(5):726-733. doi: 10.1093/infdis/jiaa355.
12. 13. Park JG, Kang MK, Lee YR, et al. Fibrosis-4 Index as a Predictor for Mortality in Hospitalized Patients with COVID-19: a retrospective multicenter cohort study. BMJ Open. 2021;10(11):e041989. doi:10.1136/bmjopen-2020-041989.
13. 14. Li Y, Regan J, Fajnzylber J, et al. Liver Fibrosis Index FIB-4 Is Associated With Mortality in COVID-19. Hepatology Communications. 2021; 5(3):434-445. doi:10.1002/hep4.1650.
14. 15. COVID-19 clinical management: living guidance, 25 january 2021,COVID-19:Clinical care. https://www. who.int/ publications/i/item/WHO-2019-nCoV-clinical-2021-1 (World health organisation, clinical management of COVID-19: interim guidance, 27 May 2020).
15. 16. Grasselli G, Zangrillo A, Zanella A, et al. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy. JAMA. 2020; 323:1574–1581. doi:10.1001/jama.2020.5394.
16. 17. Cattelan AM, Di Meco E, Trevenzoli M, et al. Clinical characteristics and laboratory biomarkers changes in COVID-19 patients requiring or not intensive or sub-intensive care:a comparative study. BMC Infect Dis. 2020; 20:934. doi.org/10.1186/s1287 9-020-05647 -7.
17. 18. Wu Z, Mc Googan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020; 323:1239–1242. doi:10.1001/jama.2020.2648.
18. 19. Nalbant A, Demirci T, Kaya T, Aydın A, Altındiş M, Güçlü E. Can prognostic nutritional index and systemic immune‐inflammatory index predict disease severity in COVID‐19? International Journal of Clinical Practice. 2021;75: 1-8.e14544. doi.org: 10.1111/ijcp.14544.
19. 20. Henry BM, de Oliveira MHS, Benoit S, Plebani M, Lippi G. Hematologic, biochemical and immune biomarker abnormalities associated withsevere illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. Clin Chem Lab Med. 2020;58:1021–1028. doi.org/10.1515/cclm-2020-0369.
20. 21. Ghahramani S, Tabrizi R, Lankarani KB, et al. Laboratory features of severe vs. non-severe COVID-19 patients in Asian populations: a systematic review and meta-analysis. Eur J Med Res. 2020; 25:1–10. doi.org/10.1186/s4000 1-020-00432 -3.
21. 22. Huang C, Wang Y, Li X, et al . Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506. doi.org/10.1159/000513400.
22. 23. Ali N, Hossain K. Liver injury in severe COVID-19 infection: current insights and challenges. Expert Rev Gastroenterol Hepatol. 2020; 14:879-884. doi.org/10.1080/17474124.2020.1794812.
23. 24. Albillos A, Lario M, Álvarez-Mon M. Cirrhosis-associated immune dysfunction: distinctive features and clinical relevance. J Hepatol. 2014;61:1385–1396.doi: 10.1016/j.jhep.2014.08.010. doi: 10.1016/j.jhep.2014.08.010.
24. 25. Zhou Z, Xu MJ, Gao B. Hepatocytes: a key cell type for innate immunity. Cell Mol Immunol. 2016; 13:301–315. doi: 10.1038/cmi.2015.97.