References

medsovet

Медицинский Совет

Meditsinskiy sovet = Medical Council

2079-701X2658-5790

REMEDIUM GROUP Ltd.

10.21518/2079-701X-2022-16-7-60-68

medsovet-6861

Research Article

Заболевания билиарной системы и печени

Liver diseases

Прогностическое и диагностическое значение показателя отношения нейтрофилов к лимфоцитам у пациентов с заболеваниями желудочно-кишечного тракта и печени

Prognostic and diagnostic value of the ratio of neutrophils to lymphocytes of patients with diseases of the gastrointestinal tract and liver

https://orcid.org/0000-0001-7263-2881

Саркарова

М. Р.

Sarkarova

M. R.

Саркарова Медина Рамидиновна - аспирант кафедры пропедевтики внутренних болезней, гастроэнтерологии и гепатологии Института клинической медицины имени Н.В. Склифосовского.

119991, Москва, ул. Погодинская, д. 1, корп. 1.

Medina R. Sarkarova - Postgraduate Student of Chair for Internal Diseases Propedeutics, Gastroenterology and Hepatology of the Sklifosovsky Clinical Medicine Institute, Sechenov First Moscow State Medical University (Sechenov University).

1, Bldg. 1, Pogodinskaya St., Moscow, 119991.

medsar88@mail.ru

https://orcid.org/0000-0001-8913-140X

Маевская

М. В.

Maevskaya

M. V.

Маевская Марина Викторовна - доктор медицинских наук, профессор, консультант лечебно-диагностического отделения №3 Университетской клинической больницы №2.

119991, Москва, ул. Погодинская, д. 1, корп. 1.

Marina V. Maevskaya - Dr. Sci. (Med.), Professor, Consultant of the Medical and Diagnostic Department No. 3 of the University Clinical Hospital No. 2, Sechenov First Moscow State Medical University (Sechenov University).

1, Bldg. 1, Pogodinskaya St., Moscow, 119991.

mvmaevskaya@me.com

Первый Московский государственный медицинский университет имени И.М. Сеченова (Сеченовский Университет)РоссияSechenov First Moscow State Medical University (Sechenov University)Russian Federation

2022

14052022

076068

2022

Саркарова М.Р., Маевская М.В.

Sarkarova M.R., Maevskaya M.V.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://www.med-sovet.pro/jour/article/view/6861

Цель данного обзора – провести анализ данных последних научных исследований, оценивающих диагностическую и прогностическую ценность показателя отношения нейтрофилов к лимфоцитам (ОНЛ) у пациентов с заболеваниями желудочно-кишечного тракта (ЖКТ) и печени. У пациентов с неалкогольной жировой болезнью печени (НАЖБП) повышенное значение показателя отношения нейтрофилов к лимфоцитам коррелировало со степенью выраженности фиброза и активностью заболевания, а также позволяло дифференцировать пациентов со стеатозом и неалкогольным стеатогепатитом (НАСГ). У пациентов с циррозом печени ОНЛ показало свою прогностическую значимость в развитии летального исхода, сопоставимую со шкалами MELD и Child – Pugh, а в некоторых исследованиях даже превосходило их. Противоречивые данные получены в отношении его прогностической ценности в риске развития инфекционных осложнений у данной категории больных. У пациентов с болезнью Крона (БК) и язвенным колитом (ЯК) повышенное значение показателя ОНЛ ассоциировалось с активностью заболевания. ОНЛ служит предиктором летального исхода и более тяжелого течения острого панкреатита. У пациентов с острым аппендицитом ОНЛ показало свою диагностическую значимость в выявлении его тяжелых форм и прогностическую ценность в развитии летального исхода у пацинтов с онкологическими заболеваниями ЖКТ. ОНЛ служит маркером системного воспаления, который можно рассчитать с помощью параметров простого клинического анализа крови, что доступно в повседневной клинической практике. Ценность ОНЛ обусловлена его неинвазивностью и низкой стоимостью. Анализ литературы показал его прогностическую и диагностическую ценность при определенных заболеваниях ЖКТ и печени: чем выше значение исследуемого показателя, тем хуже прогноз, однако нет единого мнения относительно градации ОНЛ, а уровни отсечения колеблются в различных исследованиях. Также большинство работ носит ретроспективный характер, в связи с чем необходимо проведение крупных проспективных исследований в этом направлении.

The purpose of the review is to analyze the data of the latest scientific studies assessing the diagnostic and predictive value of the indicator of the ratio of neutrophils to lymphocytes (NLR) in patients with diseases of the gastrointestinal tract and liver. Patients with non-alcoholic fatty liver disease (NAFLD) have the increased ratio of neutrophils to lymphocytes correlated with the severity of fibrosis and the activity of the disease, and also made it possible to differentiate patients with steatosis and non-alcoholic steatohepatitis (NASH). NLR of patients with liver cirrhosis has shown its prognostic significance in the development of death, comparable to the MELD and Child – Pugh scales, and in some studies even surpassed them. Contradictory data have been obtained regarding its predictive value at risk of infectious complications in this category of patients. In patients with Crohn’s disease (CD) and ulcerative colitis (UC), an increased value of NLR was associated with the activity of the disease. NLR serves as a predictor of death and a more severe course of acute pancreatitis. In patients with acute appendicitis, NLR has shown its diagnostic significance in identifying its severe forms. NLR has also shown its prognostic value in the development of death among patients with gastrointestinal cancer. NLR serves as a marker of systemic inflammation, which can be calculated using the parameters of the simple clinical bloode test, which is available in everyday clinical practice. The value of NLR is due to its non-invasiveness and low cost. The analysis of the literature showed its predictive and diagnostic value in certain diseases of the gastrointestinal tract and liver. The higher the indicator under study, the worse the prognosis of the disease and/or life of the patient. However, there is no consensus on the gradation of NLR and cut-off levels fluctuate in various studies, and their results are often contradictory. Also, most studies are retrospective, so it is necessary to conduct major prospective studies in this direction.

отношение нейтрофилов к лимфоцитаммаркер системного воспаленияжелудочно-кишечный трактпеченьзаболевания

ratio of neutrophils to lymphocytesmarker of systemic inflammationgastrointestinal tractliverdiseases

References1

Cupp M., Cariolou M., Tzoulaki I., Aune D., Evangelou E., Berlanga-Taylor A.J. Neutrophil to lymphocyte ratio and cancer prognosis: an umbrella review of systematic reviews and meta-analyses of observational studies. BMC Med. 2020;18(1):360. https://doi.org/10.1186/s12916-020-01817-1.

Afari M.E., Bhat T. Neutrophil to lymphocyte ratio (NLR) and cardiovascu lar diseases: an update. Expert Rev Cardiovasc Ther. 2016;14(5):573–577. https://doi.org/10.1586/14779072.2016.1154788.

Hao X., Li D., Wu D., Zhang N. The Relationship between Hematological Indices and Autoimmune Rheumatic Diseases (ARDs), a Meta-Analysis. Sci Rep. 2017;7(1):10833. https://doi.org/10.1038/s41598-017-11398-4.

Russell C.D., Parajuli A., Gale H.J., Bulteel N.S., Schuetz P., de Jager C.P.C. et al. The utility of peripheral blood leucocyte ratios as biomarkers in infectious diseases: A systematic review and meta-analysis. J Infect. 2019;78(5):339–348. https://doi.org/10.1016/j.jinf.2019.02.006.

Pascual-González Y., López-Sánchez M., Dorca J., Santos S. Defining the role of neutrophil-to-lymphocyte ratio in COPD: a systematic literature review. Int J Chron Obstruct Pulmon Dis. 2018;13:3651–3662. https://doi.org/10.2147/COPD.S178068.

Kuyumcu M.E., Yesil Y., Oztürk Z.A., Kizilarslanoğlu C., Etgül S., Halil M., Arıoğul S. The evaluation of neutrophil-lymphocyte ratio in Alzheimer’s disease. Dement Geriatr Cogn Disord. 2012;34(2):69–74. https://doi.org/10.1159/000341583.

D’Amico E., Zanghì A., Romano A., Sciandra M., Palumbo G.A.M., Patti F. The Neutrophil-to-Lymphocyte Ratio is Related to Disease Activity in Relapsing Remitting Multiple Sclerosis. Cells. 2019;8(10):1114. https://doi.org/10.3390/cells8101114.

Steiner J., Frodl T., Schiltz K., Dobrowolny H., Jacobs R., Fernandes B.S. et al. Innate Immune Cells and C-Reactive Protein in Acute First-Episode Psychosis and Schizophrenia: Relationship to Psychopathology and Treatment. Schizophr Bull. 2020;46(2):363–373. https://doi.org/10.1093/schbul/sbz068.

Moutchia J., Pokharel P., Kerri A., McGaw K., Uchai S., Nji M., Goodman M. Clinical laboratory parameters associated with severe or critical novel coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis. PLoS ONE. 2020;15(10):e0239802. https://doi.org/10.1371/journal.pone.0239802.

Ивашкин В.Т., Маевская М.В., Шупелькова Ю.О., Буеверов А.О., Драпкина О.М., Морозова М.А. Диагностика и лечение неалкогольной жировой болезни печени. М.; 2012. 32 с.

Ivashkin V.T., Maevskaya M.V., Shupelkova Yu.O., Buyeverov A.O., Drapkina О. М., Morozova M.A. Diagnosis and treatment of nonalcoholic fatty liver disease. Moscow; 2012. 32 p (In Russ.)

Peng Y., Li Y., He Y., Wei Q., Xie Q., Zhang L. et al. The role of neutrophil to lymphocyte ratio for the assessment of liver fibrosis and cirrhosis: a systematic review. Expert Rev Gastroenterol Hepatol. 2018;12(5):503–513. https://doi.org/10.1080/17474124.2018.1463158.

Yilmaz H., Yalcin K.S., Namuslu M., Celik H.T., Sozen M., Inan O. et al. Neutrophil-Lymphocyte Ratio (NLR) Could Be Better Predictor than C-reactive Protein (CRP) for Liver Fibrosis in Non-alcoholic Steatohepatitis (NASH). Ann Clin Lab Sci. 2015;45(3):278–286. Available at: https://pubmed.ncbi.nlm.nih.gov/26116591.

Alkhouri N., Morris-Stiff G., Campbell C., Lopez R., Tamimi T.A., Yerian L. et al. Neutrophil to lymphocyte ratio: a new marker for predicting steatohepatitis and fibrosis in patients with nonalcoholic fatty liver disease. Liver Int. 2012;32(2):297–302. https://doi.org/10.1111/j.1478-3231.2011.02639.x.

Wu L., Gao X., Guo Q., Li J., Yao J., Yan K. et al. The role of neutrophils in innate immunity-driven nonalcoholic steatohepatitis: lessons learned and future promise. Hepatol Int. 2020;14(5):652–666. https://doi.org/10.1007/s12072-020-10081-7.

Kamari Y., Shaish A., Vax E., Shemesh S., Kandel-Kfir M., Arbel Y. et al. Lack of interleukin-1α or interleukin-1β inhibits transformation of steatosis to steatohepatitis and liver fibrosis in hypercholesterolemic mice. J Hepatol. 2011;55(5):1086–1094. https://doi.org/10.1016/j.jhep.2011.01.048.

Fujii H., Kawada N. Inflammation and fibrogenesis in steatohepatitis. J Gastroenterol. 2012;47(3):215–225. https://doi.org/10.1007/s00535-012-0527-x.

Tarantino G., Conca P., Pasanisi F., Ariello M., Mastrolia M., Arena A. et al. Could inflammatory markers help diagnose nonalcoholic steatohepatitis? Eur J Gastroenterol Hepatol. 2009;21(5):504–511. https://doi.org/10.1097/MEG.0b013e3283229b40.

Yoneda M., Uchiyama T., Kato S., Endo H., Fujita K., Yoneda K. et al. Plasma Pentraxin3 is a novel marker for nonalcoholic steatohepatitis (NASH). BMC Gastroenterol. 2008;8:53. https://doi.org/10.1186/1471-230X-8-53.

Paterson J.M., Morton N.M., Fievet C., Kenyon C.J., Holmes M.C., Staels B. et al. Metabolic syndrome without obesity: Hepatic overexpression of 11beta-hydroxysteroid dehydrogenase type 1 in transgenic mice. Proc Natl Acad Sci U S A. 2004;101(18):7088–9703. https://doi.org/10.1073/pnas.0305524101.

Candia R., Riquelme A., Baudrand R., Carvajal C.A., Morales M., Solís N. et al. Overexpression of 11β-hydroxysteroid dehydrogenase type 1 in visceral adipose tissue and portal hypercortisolism in non-alcoholic fatty liver disease. Liver Int. 2012;32(3):392–399. https://doi.org/10.1111/j.1478-3231.2011.02685.x.

Ahmed A., Rabbitt E., Brady T., Brown C., Guest P., Bujalska I.J. et al A switch in hepatic cortisol metabolism across the spectrum of non alcoholic fatty liver disease. PLoS ONE. 2012;7(2):e29531. https://doi.org/10.1371/journal.pone.0029531.

Kumar, Abbas, Abui K. Fausto. Robbins and Cotran Pathologic Basis of Disease. 7th ed. New York; 2005.

Jalan R., Gines P., Olson J.C., Mookerjee R.P., Moreau R., Garcia-Tsao G. et al. Acute-on chronic liver failure. J Hepatol. 2012;57(6):1336–1348. https://doi.org/10.1016/j.jhep.2012.06.026.

Liu H., Zhang H., Wan G., Sang Y., Chang Y., Wang X., Zeng H. Neutrophillymphocyte ratio: a novel predictor for short-term prognosis in acute-onchronic hepatitis B liver failure. J Viral Hepat. 2014;21(7):499–507. https://doi.org/10.1111/jvh.12160.

Fan Z., EnQiang C., Yao D.L., LiBo Y., Hong L., Lang B. et al. Neutrophil– lymphocyte ratio predicts short term mortality in patients with hepatitis B virus-related acute-on-chronic liver failure treated with an artificial liver support system. PLoS ONE. 2017;12(4):e0175332. https://doi.org/10.1371/journal.pone.0175332.

Cai J., Wang K., Han T., Jiang H. Evaluation of prognostic values of inflammation-based makers in patients with HBV-related acute-onchronic liver failure. Medicine (Baltimore). 2018;97(46):e13324. https://doi.org/10.1097/MD.0000000000013324.

Lin L., Yang F., Wang Y., Su S., Su Z., Jiang X. et al. Prognostic nomogram incorporating neutrophil-to-lymphocyte ratio for early mortality in decompensated liver cirrhosis. Int Immunopharmacol. 2018;56(3):58–64. https://doi.org/10.1016/j.intimp.2018.01.007.

Cai Y.J., Dong J.J., Dong J.Z., Chen Y., Lin Z., Song M. et al. A nomogram for predicting prognostic value of inflammatory response biomarkers in decompensated cirrhotic patients without acute-on-chronic liver failure. Aliment Pharmacol Ther. 2017;45(11):1413–1426. https://doi.org/10.1111/apt.14046.

Chen L., Lou Y., Chen Y., Yang J. Prognostic value of the neutrophil-to-lymphocyte ratio in patients with acute-on-chronic liver failure. Int J Clin Pract. 2014;68(8):1034–1040. https://doi.org/10.1111/ijcp.12408.

Луньков В.Д., Маевская М.В., Цветаева Е.К., Мендез А.Г., Жаркова М.С., Ткаченко П.Е., Ивашкин В.Т. Отношение нейтрофилов к лимфоцитам как предиктор неблагоприятного исхода у пациентов с декомпенсированным циррозом печени. Российский журнал гастроэнтерологии, гепато логии, колопроктологии. 2019;(1):47–61. https://doi.org/10.22416/1382-4376-2019-29-1-47-61.

Lunkov V.D., Maevskaya M.V., Tsvetaeva E.K., Mendez A.G., Zharkova M.S., Tkachenko P.E., Ivashkin V.T. Neutrophil to Lymphocyte Ratio as a Predictor of Adverse Outcome in Patients with Decompensated Liver Cirrhosis. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2019;(1):47–61. (In Russ.) https://doi.org/10.22416/1382-4376-2019-29-1-47-61.

Wedd J., Bambha K.M., Stotts M., Laskey H., Colmenero J., Gralla J., Biggins S.W. Stage of cirrhosis predicts the risk of liver-related death in patients with low Model for End-Stage Liver Disease scores and cirrhosis awaiting liver transplantation. Liver Transpl. 2014;20(10):1193–1201. https://doi.org/10.1002/lt.23929.

Biggins S.W., Bambha K. MELD-based liver allocation: who is underserved? Semin Liver Dis. 2006;26(3):211–220. https://doi.org/10.1055/s-2006-947291.

Zhang H., Sun Q., Mao W., Fan J., Ye B. Neutrophil-to-Lymphocyte Ratio Predicts Early Mortality in Patients with HBV-Related Decompensated Cirrhosis. Gastroenterol Res Pract. 2016;2016:4394650. https://doi.org/10.1155/2016/4394650.

Biyik M., Ucar R., Solak Y., Gungor G., Polat I., Gaipov A. et al. Blood neutrophil–to-lymphocyte ratio independently predicts survival in patients with liver cirrhosis. Eur J Gastroenterol Hepatol. 2013;25(4):435–441. https://doi.org/10.1097/MEG.0b013e32835c2af3.

Kalra A., Wedd J.P., Bambha K.M., Gralla J., Golden-Mason L., Collins C. et al. Neutrophil-to-lymphocyte ratio correlates with proinflammatory neutrophils and predicts death in low model for end-stage liver disease patients with cirrhosis. Liver Transpl. 2017;23(2):155–165. https://doi.org/10.1002/lt.24702.

Leithead J.A., Rajoriya N., Gunson B.K., Ferguson J.W. Neutrophil-to-lymphocyte ratio predicts mortality in patients listed for liver transplantation. Liver Int. 2015;35(2):502–509. https://doi.org/10.1111/liv.12688.

Motomura T., Shirabe K., Mano Y., Muto J., Toshima T., Umemoto Y. et al. Neutrophil-lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment. J Hepatol. 2013;58(1):58–64. https://doi.org/10.1016/j.jhep.2012.08.017.

Xue T.C., Zhang L., Xie X.Y., Ge N.L., Li L.X., Zhang B.H. et al. Prognostic significance of the neutrophil-to-lymphocyte ratio in primary liver cancer: a meta-analysis. PLoS ONE. 2014;9:e96072. https://doi.org/10.1371/journal.pone.0096072.

Zhang M., Zhang Y., Liu L., Prithweeraj M., Xu H., Wu R. et al. Neutrophil-to-Lymphocyte Ratio and Albumin: New Serum Biomarkers to Predict the Prognosis of Male Alcoholic Cirrhosis Patients. Biomed Res Int. 2020;2020:7268459. https://doi.org/10.1155/2020/7268459.

Kwon J.H., Jang J.W., Kim Y.W., Lee S.W., Nam S.W., Jaegal D. et al. The usefulness of C-reactive protein and neutrophil-to-lymphocyte ratio for predicting the outcome in hospitalized patients with liver cirrhosis. BMC Gastroenterol. 2015;15:146. https://doi.org/10.1186/s12876-015-0378-z.

Cai Y.J., Dong J.J., Dong J.Z., Yang N.B., Song M., Wang Y.Q. et al. Neutrophil-lymphocyte ratio predicts hospital-acquired bacterial infections in decompensated cirrhosis. Clin Chim Acta. 2017;469:201–207. https://doi.org/10.1016/j.cca.2017.04.011.

Thabut D., Massard J., Gangloff A., Carbonell N., Francoz C., Nguyen-Khac E. et al. Model for endstage liver disease score and systemic inflammatory response are major prognostic factors in patients with cirrhosis and acute functional renal failure. Hepatology. 2007;46(6):1872–1882. https://doi.org/10.1002/hep.21920.

Cazzaniga M., Dionigi E., Gobbo G., Fioretti A., Monti V., Salerno F. The systemic inflammatory response syndrome in cirrhotic patients: relationship with their in-hospital outcome. J Hepatol. 2009;51(3):475–482. https://doi.org/10.1016/j.jhep.2009.04.017.

Dirchwolf M., Ruf A.E. Role of systemic inflammation in cirrhosis: From pathogenesis to prognosis. World J Hepatol. 2015;7(16):1974–1981. https://doi.org/10.4254/wjh.v7.i16.1974.

Albillos A., Lario M., Álvarez-Mon M. Cirrhosis-associated immune dysfunction: distinctive features and clinical relevance. J Hepatol. 2014;61(6):1385–1396. https://doi.org/10.1016/j.jhep.2014.08.010.

Jalan R., Fernandez J., Wiest R., Schnabl B., Moreau R., Angeli P. et al. Bacterial infections in cirrhosis: a position statement based on the EASL Special Conference. J Hepatol. 2013;60(6):1310–1324. https://doi.org/10.1016/j.jhep.2014.01.024.

Jalan R., Gines P., Olson J.C., Mookerjee R.P., Moreau R., Garcia-Tsao G. et al. Acute-on chronic liver failure. J Hepatol. 2012;57(6):1336–1348. https://doi.org/10.1016/j.jhep.2012.06.026.

Bruns T., Zimmermann H.W., Stallmach A. Risk factors and outcome of bacterial infections in cirrhosis. World J Gastroenterol. 2014;20(10):2542–2554. https://doi.org/10.3748/wjg.v20.i10.2542.

Attar B.M., Moore C.M., George M., Ion-Nedelcu N., Turbay R., Zachariah A. et al. Procalcitonin, and cytokines document a dynamic inflammatory state in non-infected cirrhotic patients with ascites. World J Gastroenterol. 2014;20(9):2374–2382. https://doi.org/10.3748/wjg.v20.i9.2374.

Sipeki N., Antal-Szalmas P., Lakatos P.L., Papp M. Immune dysfunction in cirrhosis. World J Gastroenterol. 2014;20(10):2564–2577. https://doi.org/10.3748/wjg.v20.i10.2564.

Tiegs G., Lohse A.W. Immune tolerance: what is unique about the liver. J Autoimmun. 2010;34(1):1–6. https://doi.org/10.1016/j.jaut.2009.08.008.

Wasmuth H.E., Kunz D., Yagmur E., Timmer-Stranghöner A., Vidacek D., Siewert E. et al. Patients with acute on chronic liver failure display “sepsis-like” immune paralysis. J Hepatol. 2005;42(2):195–201. https://doi.org/10.1016/j.jhep.2004.10.019.

Acarturk G., Acay A., Demir K., Ulu M.S., Ahsen A., Yuksel S. Neutrophil-to-lymphocyte ratio in inflammatory bowel disease – as a new predictor of disease severity. Bratisl Lek Listy. 2015;116(4):213–217. Available at: https://pubmed.ncbi.nlm.nih.gov/25773946.

Gao S.Q., Huang L.D., Dai R.J., Chen D.D., Hu W.J., Shan Y.F. Neutrophil-lymphocyte ratio: a controversial marker in predicting Crohn’s disease severity. Int J Clin Exp Pathol. 2015;8(11):14779–14785. Available at: https://pubmed.ncbi.nlm.nih.gov/26823804.

Kang W.M., Zhu C.Z., Yang X.X., Yu J.C., Ma Z.Q., Ye X. et al. Application of the Onodera prognostic nutrition index and neutrophil-to-lymphocyte ratio in risk evaluation of postoperative complications in Crohn’s disease. Sci Rep. 2017;7(1):8481. https://doi.org/10.1038/s41598-017-09265-3.

Argeny S., Stift A., Bergmann M., Mittlböck M., Maschke S., Yang Y. et al. Prognostic value of preoperative neutrophil-to-lymphocyte ratio in Crohn’s disease. Wien Klin Wochenschr. 2018;130(11–12):398–403. https://doi.org/10.1007/s00508-018-1322-3.

Posul E., Yilmaz B., Aktas G., Kurt M. Does neutrophil-tolymphocyte ratio-predict active ulcerative colitis? Wien Klin Wochenschr. 2015;127(7–8):262–265. https://doi.org/10.1007/s00508-014-0683-5.

Celikbilek M., Dogan S., Ozbakir O., Zararsız G., Kücük H., Gürsoy S. et al. Neutrophil-lymphocyte ratio as a predictor of disease severity in ulcerative colitis. J Clin Lab Anal. 2013;27(1):72–76. https://doi.org/10.1002/jcla.21564.

Demir A.K., Demirtas A., Kaya S.U., Tastan I., Butun I., Sagcan M. et al. The relationship between the neutrophil-lymphocyte ratio and disease activity in patients with ulcerative colitis. Kaohsiung J Med Sci. 2015;31(11):585–590. https://doi.org/10.1016/j.kjms.2015.10.001.

Torun S., Tunc B.D., Suvak B., Yildiz H., Tas A., Sayilir A. et al. Assessment of neutrophil-lymphocyte ratio in ulcerative colitis: a promising marker in predicting disease severity. Clin Res Hepatol Gastroenterol. 2012;36(5):491–497. https://doi.org/10.1016/j.clinre.2012.06.004.

Nishida Y., Hosomi S., Yamagami H., Yukawa T., Otani K., Nagami Y. et al. Neutrophil-to-Lymphocyte Ratio for Predicting Loss of Response to Infliximab in Ulcerative Colitis. PLoS ONE. 2017;12(1):e0169845. https://doi.org/10.1371/journal.pone.0169845.

Qin X. Etiology of inflammatory bowel disease: A unified hypothesis. World J Gastroenterol. 2012;18(15):1708–1722. https://doi.org/10.3748/wjg.v18.i15.1708.

Selby W.S., Janossy G., Bofill M., Jewell D.P. Intestinal lymphocyte subpopulations in inflammatory bowel disease: an analysis by immunohistological and cell isolation techniques. Gut. 1984;25(1):32–40. https://doi.org/10.1136/gut.25.1.32.

Pavlidis T.E., Pavlidis E.T., Sakantamis A.K. Advances in prognostic factors in acute pancreatitis: a mini-review. Hepatobiliary Pancreat Dis Int. 2010;9(5):482–486. Available at: https://pubmed.ncbi.nlm.nih.gov/20943456.

Suppiah A., Malde D., Arab T., Hamed M., Allgar V., Smith A.M., Morris-Stiff G. The prognostic value of the neutrophil-lymphocyte ratio (NLR) in acute pancreatitis: identification of an optimal NLR. J Gastrointest Surg. 2013;17(4):675–681. https://doi.org/10.1007/s11605-012-2121-1.

Gülen B., Sonmez E., Yaylacı S., Serinken M., Eken C., Dur A. et al. Effect of harmless acute pancreatitis score, red cell distribution width and neutrophil to lymphocyte ratio on the mortality of patients with nontraumatic acute pancreatitis at the emergency department. World J Emerg Med. 2015;6(1):29–33. https://doi.org/10.5847/wjem.j.1920-8642.2015.01.005.

Zhang Y., Wu W., Dong L., Yang C., Fan P., Wu H. Neutrophil to lymphocyte ratio predicts persistent organ failure and in-hospital mortality in an Asian Chinese population of acute pancreatitis. Medicine (Baltimore). 2016;95(37):e4746. https://doi.org/10.1097/MD.0000000000004746.

Kokulu K., Günaydın Y.K., Akıllı N.B., Köylü R., Sert E.T., Köylü Ö., Cander B. Relationship between the neutrophil-to-lymphocyte ratio in acute pancreatitis and the severity and systemic complications of the disease. Turk J Gastroenterol. 2018;29(6):684–691. https://doi.org/10.5152/tjg.2018.17563.

Jeon T.J., Park J.Y. Clinical significance of the neutrophil-lymphocyte ratio as an early predictive marker for adverse outcomes in patients with acute pancreatitis. World J Gastroenterol. 2017;23(21):3883–3889. https://doi.org/10.3748/wjg.v23.i21.3883.

Felderbauer P., Muller C., Bulut K., Belyaev O., Schmitz F., Uhl W. et al. Pathophysiology and treatment of acute pancreatitis: new therapeutic targets-a ray of hope? Basic Clin Pharmacol Toxicol. 2005;97(6):342–350. https://doi.org/10.1111/j.1742-7843.2005.pto_274.x.

Wittel U.A., Rau B., Gansauge F., Gansauge S., Nussler A.K., Beger H.G., Poch B. Influence of PMN leukocyte-mediated pancreatic damage on the systemic immune response in severe acute pancreatitis in rats. Dig Dis Sci. 2004;49(7–8): 1348–1357. https://doi.org/10.1023/b:ddas.0000037833.16433.77.

De Jager C.P., van Wijk P.T., Mathoera R.B., de Jongh-Leuvenink J., van der Poll T., Wever P.C. Lymphocytopenia and neutrophil-lymphocyte count ratio predict bacteremia better than conventional infection markers in an emergency care unit. Crit Care. 2010;14(5):R192. https://doi.org/10.1186/cc9309.

Zahorec R. Ratio of neutrophil to lymphocyte counts-rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl Lek Listy. 2001;102(1):5–14. Available at: https://pubmed.ncbi.nlm.nih.gov/11723675.

Le Tulzo Y., Pangault C., Gacouin A., Guilloux V., Tribut O., Amiot L. et al. Early circulating lymphocyte apoptosis in human septic shock is associated with poor outcome. Shock. 2002;18(6):487–494. https://doi.org/10.1097/00024382-200212000-00001.

Pavlov P., Uchikov P., Murdzheva M., Tuleva S., Tsvetkova T. Main lymphocyte populations and their subpopulations in patients with acute pancreatitis studied in the course of disease. Khirurgiia (Sofiia). 2001;57(5–6):4–11. Available at: https://pubmed.ncbi.nlm.nih.gov/12122758.

Pezzilli R., Billi P., Beltrandi E., Maldini M., Mancini R., Morselli Labate A.M., Miglioli M. Circulating lymphocyte subsets in human acute pancreatitis. Pancreas. 1995;11(1):95–100. https://doi.org/10.1097/00006676-199507000-00010.

Goodman D.A., Goodman C.B., Monk J.S. Use of the neutrophil:lymphocyte ratio in the diagnosis of appendicitis. Am Surg. 1995;61(3):257–259. Available at: https://pubmed.ncbi.nlm.nih.gov/7887542.

Markar S.R., Karthikesalingam A., Falzon A., Kan Y. The diagnostic value of neutrophil: lymphocyte ratio in adults with suspected acute appendicitis. Acta Chir Belg. 2010;110:543–547. Available at: https://pubmed.ncbi.nlm.nih.gov/21158332.

Ishizuka M., Shimizu T., Kubota K. Neutrophil-to-lymphocyte ratio has a close association with gangrenous appendicitis in patients undergoing appendectomy. Int Surg. 2012;97(4):299–304. https://doi.org/10.9738/CC161.1.

Kahramanca Ş., Özgehan G., Şeker D., Gökce E.I., Seker G., Tunç G. et al. Neutrophil-to-lymphocyte ratio as a predictor of acute appendicitis. Ulus Travma Acil Cerrahi Derg. 2014;20(1):19–22. https://doi.org/10.5505/tjtes.2014.20688.

Kucuk A., Erol M.F., Senel S., Eroler E., Yumun H.A., Uslu A.U. et al. The role of neutrophil lymphocyte ratio to leverage the differential diagnosis of familial Mediterranean fever attack and acute appendicitis. Korean J Intern Med. 2016;31(2):386–391. https://doi.org/10.3904/kjim.2015.039.

Bowen R.C., Little N.A.B., Harmer J.R., Ma J., Mirabelli L.G., Roller K.D. et al. Neutrophil-to-lymphocyte ratio as prognostic indicator in gastrointestinal cancers: a systematic review and meta-analysis. Oncotarget. 2017;8(19):32171–32189. https://doi.org/10.18632/oncotarget16291.

Templeton A.J., McNamara M.G., Seruga B., Vera-Badillo F.E., Aneja P., Ocaña A. et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst. 2014;106(6):dju124. https://doi.org/10.1093/jnci/dju124.

Nora I., Shridhar R., Huston J., Meredith K. The accuracy of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio as a marker for gastrointestinal malignancies. J Gastrointest Oncol. 2018;9(5):972–978. https://doi.org/10.21037/jgo.2018.08.05.

Kitamura T., Qian B.Z., Pollard J.W. Immune cell promotion of metastasis. Nat Rev Immunol. 2015;15(2):73–86. https://doi.org/10.1038/nri3789.

Karki R., Man S.M., Kanneganti T.D. Inflammasomes and Cancer. Cancer Immunol Res. 2017;5(2):94 –99. https://doi.org/10.1158/2326-6066.CIR-16-0269.

Fridlender Z.G., Albelda S.M. Tumor-associated neutrophils: friend or foe? Carcinogenesis. 2012;33(5):949– 955. https://doi.org/10.1093/carcin/bgs123.

Singhal S., Bhojnagarwala P.S., O’Brien S., Moon E.K., Garfall A.L., Rao A.S. et al. Origin and role of a subset of tumor-associated neutrophils with antigen-presenting cell features in early-stage human lung cancer. Cancer Cell. 2016;30(1):120–135. https://doi.org/10.1016/j.ccell.2016.06.001.

Долгушин И.И. Нейтрофильные гранулоциты: новые лица старых знакомых. Бюллетень сибирской медицины. 2019;(1):30–37. https://doi.org/10.20538/1682-0363-2019-1-30-37.

Dolgushin I.I. Neutrophil granulocytes: new faces of old acquaintances. Bulletenʹ Sibirskoj Mediciny. 2019;(1):30–37. (In Russ.) https://doi.org/10.20538/1682-0363-2019-1-30-37.

Nicolás-Ávila J.Á., Adrover J.M., Hidalgo A. Neutrophils in homeostasis, immunity, and cancer. Immunity. 2017;46(1):15–28. https://doi.org/10.1016/j.immuni.2016.12.012.

Powell D.R., Huttenlocher A. Neu-trophils in the tumor microenvironment. Trends Immunol. 2016;37(1):41–52. https://doi.org/10.1016/j.it.2015.11.008.

Shaul M.E., Fridlender Z.G. Cancer related circulating and tumor-associated neutrophils – subtypes, sources and function. FEBS J. 2018;285(23):4316–4342. https://doi.org/10.1111/febs.14524.

The authors declare that there are no conflicts of interest present.