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Published in: BMC Gastroenterology 1/2023

Open Access 01-12-2023 | Primary Biliary Cholangitis | Research

High neutrophil-lymphocyte ratio indicates a worse response to ursodeoxycholic acid in primary biliary cholangitis: a retrospective cohort study

Authors: Huiling Zhu, Mengyao Zheng, Haiyu He, Hongtao Lei, Wenlin Tai, Jinhui Yang

Published in: BMC Gastroenterology | Issue 1/2023

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Abstract

Background

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease characterized by inflammation of the interlobular bile ducts. Ursodeoxycholic acid (UDCA) is the only FDA approved first-line therapy for PBC, but up to 40% of patients with PBC have an incomplete response to UDCA. Neutrophil-to-lymphocyte (NLR) has been used to predict prognosis in various liver diseases. There is limited evidence on the treatment response to UDCA in PBC patients. Our study aimed to evaluate the relationship between NRL and the response to UDCA treatment in PBC patients.

Methods

A total of 257 primary biliary cholangitis (PBC) patients treated with UDCA (13–15 mg/kg/d) were enrolled in this retrospective study. The response to treatment was evaluated based on alkaline phosphatase levels ≤1.67 times the upper limit of the normal value after 12 months of UDCA treatment. Multivariable logistic regression analysis was performed to investigate the association between NLR at baseline and the response to 12 months of UDCA treatment after adjusting for important confounding variables. The stability of the results was evaluated by unadjusted and adjusted models.

Results

The results of multiple regression analysis showed that NLR at baseline was positively associated with the nonresponse to UDCA treatment after adjustments for potential confounders (age, sex, BMI, hypertension, arterial plaque, thyroid disease, jaundice, albumin, globulin, total bile acid, ALP, GGT, LDLC, total cholesterol, hemoglobin, and APTT) (OR = 1.370, 95% CI 1.066–1.761). These results reveal that NLR is an independent risk factor for UDCA treatment nonresponse.

Conclusions

Our results suggest that PBC patients with a high NLR had a worse response to UDCA therapy.
Literature
1.
go back to reference Giannini EG, Pieri G, Labanca S, et al. Characteristics and survival of patients with primary biliary cholangitis and hepatocellular carcinoma. Dig Liver Dis. 2022;54:1215–21.PubMedCrossRef Giannini EG, Pieri G, Labanca S, et al. Characteristics and survival of patients with primary biliary cholangitis and hepatocellular carcinoma. Dig Liver Dis. 2022;54:1215–21.PubMedCrossRef
2.
3.
go back to reference Han E, Jo SJ, Lee H, et al. Clinical relevance of combined anti-mitochondrial M2 detection assays for primary biliary cirrhosis. Clin Chim Acta. 2017;464:113–7.PubMedCrossRef Han E, Jo SJ, Lee H, et al. Clinical relevance of combined anti-mitochondrial M2 detection assays for primary biliary cirrhosis. Clin Chim Acta. 2017;464:113–7.PubMedCrossRef
4.
go back to reference Dahlqvist G, Gaouar F, Carrat F, et al. Large-scale characterization study of patients with antimitochondrial antibodies but nonestablished primary biliary cholangitis. Hepatology. 2017;65:152–63.PubMedCrossRef Dahlqvist G, Gaouar F, Carrat F, et al. Large-scale characterization study of patients with antimitochondrial antibodies but nonestablished primary biliary cholangitis. Hepatology. 2017;65:152–63.PubMedCrossRef
5.
go back to reference Granito A, Muratori P, Quarneti C, et al. Antinuclear antibodies as ancillary markers in primary biliary cirrhosis. Expert Rev Mol Diagn. 2012;12:65–74.PubMedCrossRef Granito A, Muratori P, Quarneti C, et al. Antinuclear antibodies as ancillary markers in primary biliary cirrhosis. Expert Rev Mol Diagn. 2012;12:65–74.PubMedCrossRef
6.
go back to reference Zeng N, Duan W, Chen S, et al. Epidemiology and clinical course of primary biliary cholangitis in the Asia-Pacific region: a systematic review and meta-analysis. Hepatol Int. 2019;13:788–99.PubMedCrossRef Zeng N, Duan W, Chen S, et al. Epidemiology and clinical course of primary biliary cholangitis in the Asia-Pacific region: a systematic review and meta-analysis. Hepatol Int. 2019;13:788–99.PubMedCrossRef
7.
go back to reference Lu M, Zhou Y, Haller IV, et al. Increasing prevalence of primary biliary cholangitis and reduced mortality with treatment. Clin Gastroenterol Hepatol. 2018;16:1342-1350.e1.PubMedCrossRef Lu M, Zhou Y, Haller IV, et al. Increasing prevalence of primary biliary cholangitis and reduced mortality with treatment. Clin Gastroenterol Hepatol. 2018;16:1342-1350.e1.PubMedCrossRef
8.
go back to reference Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69:394–419.PubMedCrossRef Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69:394–419.PubMedCrossRef
9.
go back to reference Goel A, Kim WR. Natural history of primary biliary cholangitis in the Ursodeoxycholic acid era: role of scoring systems. Clin Liver Dis. 2018;22:563–78.PubMedCrossRef Goel A, Kim WR. Natural history of primary biliary cholangitis in the Ursodeoxycholic acid era: role of scoring systems. Clin Liver Dis. 2018;22:563–78.PubMedCrossRef
10.
go back to reference John BV, Khakoo NS, Schwartz KB, et al. Ursodeoxycholic acid response is associated with reduced mortality in primary biliary cholangitis with compensated cirrhosis. Am J Gastroenterol. 2021;116:1913–23.PubMedPubMedCentralCrossRef John BV, Khakoo NS, Schwartz KB, et al. Ursodeoxycholic acid response is associated with reduced mortality in primary biliary cholangitis with compensated cirrhosis. Am J Gastroenterol. 2021;116:1913–23.PubMedPubMedCentralCrossRef
11.
go back to reference Yoon CI, Kim D, Ahn SG, et al. Radiotherapy-induced high neutrophil-to-lymphocyte ratio is a negative prognostic factor in patients with breast Cancer. Cancers (Basel). 2020;12. Yoon CI, Kim D, Ahn SG, et al. Radiotherapy-induced high neutrophil-to-lymphocyte ratio is a negative prognostic factor in patients with breast Cancer. Cancers (Basel). 2020;12.
12.
go back to reference Flores-Bustamante A, Hernández-Regino L, Castillejos-López MD, et al. Changes in the neutrophil to lymphocyte ratio as predictors of outcome in pediatric patients with central nervous system tumors undergoing surgical resection. Cancer Biomark. 2022;33:291–8.PubMedCrossRef Flores-Bustamante A, Hernández-Regino L, Castillejos-López MD, et al. Changes in the neutrophil to lymphocyte ratio as predictors of outcome in pediatric patients with central nervous system tumors undergoing surgical resection. Cancer Biomark. 2022;33:291–8.PubMedCrossRef
13.
go back to reference Toya K, Tomimaru Y, Kobayashi S, et al. Preoperative neutrophil-to-lymphocyte ratio predicts healing time for postoperative pancreatic fistula after distal pancreatectomy. Ann Gastroenterol Surg. 2022;6:169–75.PubMedCrossRef Toya K, Tomimaru Y, Kobayashi S, et al. Preoperative neutrophil-to-lymphocyte ratio predicts healing time for postoperative pancreatic fistula after distal pancreatectomy. Ann Gastroenterol Surg. 2022;6:169–75.PubMedCrossRef
14.
go back to reference Lin L, Piao M, Jiang X, et al. Does neutrophil-to-lymphocyte ratio predict 1-year mortality in patients with primary biliary cholangitis? Results from a retrospective study with validation cohort. BMJ Open. 2017;7:e015304.PubMedPubMedCentralCrossRef Lin L, Piao M, Jiang X, et al. Does neutrophil-to-lymphocyte ratio predict 1-year mortality in patients with primary biliary cholangitis? Results from a retrospective study with validation cohort. BMJ Open. 2017;7:e015304.PubMedPubMedCentralCrossRef
15.
go back to reference Dong FC, Tan WT, Wang XB, et al. The neutrophil-to-lymphocyte ratio represents a systemic inflammation marker and reflects the relationship with 90-day mortality in non-cirrhotic chronic severe hepatitis. J Dig Dis. 2022;23:587–96.PubMedCrossRef Dong FC, Tan WT, Wang XB, et al. The neutrophil-to-lymphocyte ratio represents a systemic inflammation marker and reflects the relationship with 90-day mortality in non-cirrhotic chronic severe hepatitis. J Dig Dis. 2022;23:587–96.PubMedCrossRef
16.
go back to reference Shavakhi M, Nourigheimasi S, Dioso E, et al. Prognostic role of neutrophil to lymphocyte ratio in nonalcoholic fatty liver disease: a systematic review and Meta-analysis. Can J Gastroenterol Hepatol. 2022;2022:1554079.PubMedPubMedCentralCrossRef Shavakhi M, Nourigheimasi S, Dioso E, et al. Prognostic role of neutrophil to lymphocyte ratio in nonalcoholic fatty liver disease: a systematic review and Meta-analysis. Can J Gastroenterol Hepatol. 2022;2022:1554079.PubMedPubMedCentralCrossRef
17.
go back to reference Cusi K, Isaacs S, Barb D, et al. American Association of Clinical Endocrinology Clinical Practice Guideline for the diagnosis and Management of Nonalcoholic Fatty Liver Disease in primary care and endocrinology clinical settings: co-sponsored by the American Association for the Study of Liver Diseases (AASLD). Endocr Pract. 2022;28:528–62.PubMedCrossRef Cusi K, Isaacs S, Barb D, et al. American Association of Clinical Endocrinology Clinical Practice Guideline for the diagnosis and Management of Nonalcoholic Fatty Liver Disease in primary care and endocrinology clinical settings: co-sponsored by the American Association for the Study of Liver Diseases (AASLD). Endocr Pract. 2022;28:528–62.PubMedCrossRef
18.
go back to reference European Association for the Study of the liver, Electronic address eee, European Association for the Study of the L. EASL clinical practice guidelines: the diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017;67:145–72.CrossRef European Association for the Study of the liver, Electronic address eee, European Association for the Study of the L. EASL clinical practice guidelines: the diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017;67:145–72.CrossRef
19.
go back to reference Yang Y, Sun G, Diao S, et al. Diagnostic performances of neutrophil to lymphocyte ratio and lymphocyte to monocyte ratio in acute ischemic stroke caused by cervicocranial arterial dissection. J Clin Lab Anal. 2020;34:e23515.PubMedPubMedCentralCrossRef Yang Y, Sun G, Diao S, et al. Diagnostic performances of neutrophil to lymphocyte ratio and lymphocyte to monocyte ratio in acute ischemic stroke caused by cervicocranial arterial dissection. J Clin Lab Anal. 2020;34:e23515.PubMedPubMedCentralCrossRef
20.
go back to reference Dunn GP, Old LJ, Schreiber RD. The immunobiology of cancer immunosurveillance and immunoediting. Immunity. 2004;21:137–48.PubMedCrossRef Dunn GP, Old LJ, Schreiber RD. The immunobiology of cancer immunosurveillance and immunoediting. Immunity. 2004;21:137–48.PubMedCrossRef
21.
go back to reference Li Y, Zhao Y, Feng L, et al. Comparison of the prognostic values of inflammation markers in patients with acute pancreatitis: a retrospective cohort study. BMJ Open. 2017;7:e013206.PubMedPubMedCentralCrossRef Li Y, Zhao Y, Feng L, et al. Comparison of the prognostic values of inflammation markers in patients with acute pancreatitis: a retrospective cohort study. BMJ Open. 2017;7:e013206.PubMedPubMedCentralCrossRef
22.
go back to reference Dong CH, Wang ZM, Chen SY. Neutrophil to lymphocyte ratio predict mortality and major adverse cardiac events in acute coronary syndrome: a systematic review and meta-analysis. Clin Biochem. 2018;52:131–6.PubMedCrossRef Dong CH, Wang ZM, Chen SY. Neutrophil to lymphocyte ratio predict mortality and major adverse cardiac events in acute coronary syndrome: a systematic review and meta-analysis. Clin Biochem. 2018;52:131–6.PubMedCrossRef
23.
go back to reference Bannaga A, Arasaradnam RP. Neutrophil to lymphocyte ratio and albumin bilirubin grade in hepatocellular carcinoma: a systematic review. World J Gastroenterol. 2020;26:5022–49.PubMedPubMedCentralCrossRef Bannaga A, Arasaradnam RP. Neutrophil to lymphocyte ratio and albumin bilirubin grade in hepatocellular carcinoma: a systematic review. World J Gastroenterol. 2020;26:5022–49.PubMedPubMedCentralCrossRef
24.
go back to reference Xue TC, Zhang L, Xie XY, et al. Prognostic significance of the neutrophil-to-lymphocyte ratio in primary liver cancer: a meta-analysis. PLoS One. 2014;9:e96072.PubMedPubMedCentralCrossRef Xue TC, Zhang L, Xie XY, et al. Prognostic significance of the neutrophil-to-lymphocyte ratio in primary liver cancer: a meta-analysis. PLoS One. 2014;9:e96072.PubMedPubMedCentralCrossRef
25.
go back to reference Zhao Z, Liu J, Wang J, et al. Platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) are associated with chronic hepatitis B virus (HBV) infection. Int Immunopharmacol. 2017;51:1–8.PubMedCrossRef Zhao Z, Liu J, Wang J, et al. Platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) are associated with chronic hepatitis B virus (HBV) infection. Int Immunopharmacol. 2017;51:1–8.PubMedCrossRef
26.
go back to reference Kuo MT, Hu TH, Lu SN, et al. Neutrophil-to-lymphocyte ratio as a predictor of response to peginterferon plus ribavirin therapy for chronic hepatitis C. Dis Markers. 2014;2014:462958.PubMedPubMedCentralCrossRef Kuo MT, Hu TH, Lu SN, et al. Neutrophil-to-lymphocyte ratio as a predictor of response to peginterferon plus ribavirin therapy for chronic hepatitis C. Dis Markers. 2014;2014:462958.PubMedPubMedCentralCrossRef
27.
go back to reference Abdel-Razik A, Mousa N, Shabana W, et al. A novel model using mean platelet volume and neutrophil to lymphocyte ratio as a marker of nonalcoholic steatohepatitis in NAFLD patients: multicentric study. Eur J Gastroenterol Hepatol. 2016;28:e1–9.PubMedCrossRef Abdel-Razik A, Mousa N, Shabana W, et al. A novel model using mean platelet volume and neutrophil to lymphocyte ratio as a marker of nonalcoholic steatohepatitis in NAFLD patients: multicentric study. Eur J Gastroenterol Hepatol. 2016;28:e1–9.PubMedCrossRef
28.
go back to reference Yoo JJ, Cho EJ, Lee B, et al. Prognostic value of biochemical response models for primary biliary cholangitis and the additional role of the neutrophil-to-lymphocyte ratio. Gut Liver. 2018;12:714–21.PubMedPubMedCentralCrossRef Yoo JJ, Cho EJ, Lee B, et al. Prognostic value of biochemical response models for primary biliary cholangitis and the additional role of the neutrophil-to-lymphocyte ratio. Gut Liver. 2018;12:714–21.PubMedPubMedCentralCrossRef
29.
go back to reference Webb GJ, Hirschfield GM. Primary biliary cholangitis in 2016: high-definition PBC: biology, models and therapeutic advances. Nat Rev Gastroenterol Hepatol. 2017;14:76–8.PubMedCrossRef Webb GJ, Hirschfield GM. Primary biliary cholangitis in 2016: high-definition PBC: biology, models and therapeutic advances. Nat Rev Gastroenterol Hepatol. 2017;14:76–8.PubMedCrossRef
30.
go back to reference Liaskou E, Hirschfield GM, Gershwin ME. Mechanisms of tissue injury in autoimmune liver diseases. Semin Immunopathol. 2014;36:553–68.PubMedCrossRef Liaskou E, Hirschfield GM, Gershwin ME. Mechanisms of tissue injury in autoimmune liver diseases. Semin Immunopathol. 2014;36:553–68.PubMedCrossRef
31.
go back to reference Isse K, Harada K, Nakanuma Y. IL-8 expression by biliary epithelial cells is associated with neutrophilic infiltration and reactive bile ductules. Liver Int. 2007;27:672–80.PubMedCrossRef Isse K, Harada K, Nakanuma Y. IL-8 expression by biliary epithelial cells is associated with neutrophilic infiltration and reactive bile ductules. Liver Int. 2007;27:672–80.PubMedCrossRef
32.
go back to reference Cao H, Zhu B, Qu Y, et al. Abnormal expression of ERα in Cholangiocytes of patients with primary biliary cholangitis mediated intrahepatic bile duct inflammation. Front Immunol. 2019;10:2815.PubMedPubMedCentralCrossRef Cao H, Zhu B, Qu Y, et al. Abnormal expression of ERα in Cholangiocytes of patients with primary biliary cholangitis mediated intrahepatic bile duct inflammation. Front Immunol. 2019;10:2815.PubMedPubMedCentralCrossRef
33.
go back to reference Zimmermann HW, Seidler S, Gassler N, et al. Interleukin-8 is activated in patients with chronic liver diseases and associated with hepatic macrophage accumulation in human liver fibrosis. PLoS One. 2011;6:e21381.PubMedPubMedCentralCrossRef Zimmermann HW, Seidler S, Gassler N, et al. Interleukin-8 is activated in patients with chronic liver diseases and associated with hepatic macrophage accumulation in human liver fibrosis. PLoS One. 2011;6:e21381.PubMedPubMedCentralCrossRef
34.
go back to reference Tsuneyama K, Baba H, Morimoto Y, et al. Primary biliary cholangitis: its pathological characteristics and Immunopathological mechanisms. J Med Investig. 2017;64:7–13.CrossRef Tsuneyama K, Baba H, Morimoto Y, et al. Primary biliary cholangitis: its pathological characteristics and Immunopathological mechanisms. J Med Investig. 2017;64:7–13.CrossRef
36.
go back to reference Yu K, Li P, Xu T, et al. Decreased infiltration of CD4(+) Th1 cells indicates a good response to ursodeoxycholic acid (UDCA) in primary biliary cholangitis. Pathol Res Pract. 2021;217:153291.PubMedCrossRef Yu K, Li P, Xu T, et al. Decreased infiltration of CD4(+) Th1 cells indicates a good response to ursodeoxycholic acid (UDCA) in primary biliary cholangitis. Pathol Res Pract. 2021;217:153291.PubMedCrossRef
37.
go back to reference Tang L, Zhong R, He X, et al. Evidence for the association between IgG-antimitochondrial antibody and biochemical response to ursodeoxycholic acid treatment in primary biliary cholangitis. J Gastroenterol Hepatol. 2017;32:659–66.PubMedCrossRef Tang L, Zhong R, He X, et al. Evidence for the association between IgG-antimitochondrial antibody and biochemical response to ursodeoxycholic acid treatment in primary biliary cholangitis. J Gastroenterol Hepatol. 2017;32:659–66.PubMedCrossRef
38.
go back to reference Wen M, Men R, Fan X, et al. Worse response to Ursodeoxycholic acid in primary biliary cholangitis patients with autoimmune hepatitis features. Dig Dis. 2021;39:366–74.PubMedCrossRef Wen M, Men R, Fan X, et al. Worse response to Ursodeoxycholic acid in primary biliary cholangitis patients with autoimmune hepatitis features. Dig Dis. 2021;39:366–74.PubMedCrossRef
39.
go back to reference Carbone M, Mells GF, Pells G, et al. Sex and age are determinants of the clinical phenotype of primary biliary cirrhosis and response to ursodeoxycholic acid. Gastroenterology. 2013;144:560-569.e7 quiz e13–4.PubMedCrossRef Carbone M, Mells GF, Pells G, et al. Sex and age are determinants of the clinical phenotype of primary biliary cirrhosis and response to ursodeoxycholic acid. Gastroenterology. 2013;144:560-569.e7 quiz e13–4.PubMedCrossRef
40.
go back to reference Muratori P, Granito A, Pappas G, et al. The serological profile of the autoimmune hepatitis/primary biliary cirrhosis overlap syndrome. Am J Gastroenterol. 2009;104:1420–5.PubMedCrossRef Muratori P, Granito A, Pappas G, et al. The serological profile of the autoimmune hepatitis/primary biliary cirrhosis overlap syndrome. Am J Gastroenterol. 2009;104:1420–5.PubMedCrossRef
41.
go back to reference Quarneti C, Muratori P, Lalanne C, et al. Fatigue and pruritus at onset identify a more aggressive subset of primary biliary cirrhosis. Liver Int. 2015;35:636–41.PubMedCrossRef Quarneti C, Muratori P, Lalanne C, et al. Fatigue and pruritus at onset identify a more aggressive subset of primary biliary cirrhosis. Liver Int. 2015;35:636–41.PubMedCrossRef
42.
go back to reference Jones DE, Al-Rifai A, Frith J, et al. The independent effects of fatigue and UDCA therapy on mortality in primary biliary cirrhosis: results of a 9 year follow-up. J Hepatol. 2010;53:911–7.PubMedCrossRef Jones DE, Al-Rifai A, Frith J, et al. The independent effects of fatigue and UDCA therapy on mortality in primary biliary cirrhosis: results of a 9 year follow-up. J Hepatol. 2010;53:911–7.PubMedCrossRef
43.
go back to reference Raj A, Shah KVK. Current and potential treatments for primary biliary cholangitis. Lancet Gastroenterol Hepatol. 2019;5. Raj A, Shah KVK. Current and potential treatments for primary biliary cholangitis. Lancet Gastroenterol Hepatol. 2019;5.
Metadata
Title
High neutrophil-lymphocyte ratio indicates a worse response to ursodeoxycholic acid in primary biliary cholangitis: a retrospective cohort study
Authors
Huiling Zhu
Mengyao Zheng
Haiyu He
Hongtao Lei
Wenlin Tai
Jinhui Yang
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Gastroenterology / Issue 1/2023
Electronic ISSN: 1471-230X
DOI
https://doi.org/10.1186/s12876-023-03031-8

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