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Published in: BMC Gastroenterology 1/2016

Open Access 01-12-2016 | Research article

Usefulness of ascitic fluid lactoferrin levels in patients with liver cirrhosis

Authors: Sang Soo Lee, Hyun Ju Min, Ja Yun Choi, Hyun Chin Cho, Jin Joo Kim, Jae Min Lee, Hong Jun Kim, Chang Yoon Ha, Hyun Jin Kim, Tae Hyo Kim, Jin Hyun Kim, Ok-Jae Lee

Published in: BMC Gastroenterology | Issue 1/2016

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Abstract

Background

Although elevated levels of lactoferrin provide a biomarker for inflammatory bowel diseases and colorectal cancer, the clinical significance of these elevated levels in ascitic fluid of patients with ascites caused by liver cirrhosis is limited. The aims of our study were to investigate the usefulness of ascitic fluid lactoferrin levels for the diagnosis of spontaneous bacterial peritonitis (SBP) in patients with cirrhosis and to evaluate the association between lactoferrin levels and the development of hepatocellular carcinoma (HCC).

Methods

A total of 102 patients with ascites caused by cirrhosis were consecutively enrolled into the study, from December 2008 to December 2011. Ascitic fluid lactoferrin levels were quantified using a human lactoferrin enzyme-linked immunosorbent assay kit.

Results

The median ascitic fluid lactoferrin levels were significantly higher in patients with SBP than in those without SBP (112.7 ng/mL vs. 0.6 ng/mL; p < 0.001). The area under the receiver operator characteristic curve for the diagnosis of SBP was 0.898 (95 % confidence interval, 0.839–0.957, p < 0.001), with a sensitivity and specificity for a cut-off level of 51.4 ng/mL of 95.8 % and 74.4 %, respectively. Moreover, the incidence of HCC in the 78 patients without SBP was significantly higher in patients with high ascitic fluid lactoferrin levels (≥35 ng/mL) than in those with low ascitic fluid lactoferrin level (<35 ng/mL).

Conclusions

Ascitic fluid lactoferrin level can be a useful diagnostic tool to identify SBP in patients with ascites caused by cirrhosis. Elevated ascitic fluid lactoferrin level in patients without SBP may be indicative of a developing hepatocellular carcinoma.
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Literature
1.
go back to reference Iyer S, Lonnerdal B. Lactoferrin, lactoferrin receptors and iron metabolism. Eur J Clin Nutr. 1993;47(4):232–41.PubMed Iyer S, Lonnerdal B. Lactoferrin, lactoferrin receptors and iron metabolism. Eur J Clin Nutr. 1993;47(4):232–41.PubMed
2.
go back to reference Baker EN, Baker HM. Molecular structure, binding properties and dynamics of lactoferrin. Cell Mol Life Sci. 2005;62(22):2531–9.CrossRefPubMed Baker EN, Baker HM. Molecular structure, binding properties and dynamics of lactoferrin. Cell Mol Life Sci. 2005;62(22):2531–9.CrossRefPubMed
3.
go back to reference Iigo M, Alexander DB, Long N, Xu J, Fukamachi K, Futakuchi M, Takase M, Tsuda H. Anticarcinogenesis pathways activated by bovine lactoferrin in the murine small intestine. Biochimie. 2009;91(1):86–101.CrossRefPubMed Iigo M, Alexander DB, Long N, Xu J, Fukamachi K, Futakuchi M, Takase M, Tsuda H. Anticarcinogenesis pathways activated by bovine lactoferrin in the murine small intestine. Biochimie. 2009;91(1):86–101.CrossRefPubMed
4.
go back to reference Birgens HS. Lactoferrin in plasma measured by an ELISA technique: evidence that plasma lactoferrin is an indicator of neutrophil turnover and bone marrow activity in acute leukaemia. Scand J Haematol. 1985;34(4):326–31.CrossRefPubMed Birgens HS. Lactoferrin in plasma measured by an ELISA technique: evidence that plasma lactoferrin is an indicator of neutrophil turnover and bone marrow activity in acute leukaemia. Scand J Haematol. 1985;34(4):326–31.CrossRefPubMed
5.
go back to reference Gibson RJ, Bowen JM. Biomarkers of regimen-related mucosal injury. Cancer Treat Rev. 2011;37(6):487–93.CrossRefPubMed Gibson RJ, Bowen JM. Biomarkers of regimen-related mucosal injury. Cancer Treat Rev. 2011;37(6):487–93.CrossRefPubMed
6.
go back to reference Kanwar JR, Roy K, Patel Y, Zhou SF, Singh MR, Singh D, Nasir M, Sehgal R, Sehgal A, Singh RS, et al. Multifunctional Iron Bound Lactoferrin and Nanomedicinal Approaches to Enhance Its Bioactive Functions. Molecules. 2015;20(6):9703–31.CrossRefPubMed Kanwar JR, Roy K, Patel Y, Zhou SF, Singh MR, Singh D, Nasir M, Sehgal R, Sehgal A, Singh RS, et al. Multifunctional Iron Bound Lactoferrin and Nanomedicinal Approaches to Enhance Its Bioactive Functions. Molecules. 2015;20(6):9703–31.CrossRefPubMed
7.
go back to reference Caccavo D, Garzia P, Sebastiani GD, Ferri GM, Galluzzo S, Vadacca M, Rigon A, Afeltra A, Amoroso A. Expression of lactoferrin on neutrophil granulocytes from synovial fluid and peripheral blood of patients with rheumatoid arthritis. J Rheumatol. 2003;30(2):220–4.PubMed Caccavo D, Garzia P, Sebastiani GD, Ferri GM, Galluzzo S, Vadacca M, Rigon A, Afeltra A, Amoroso A. Expression of lactoferrin on neutrophil granulocytes from synovial fluid and peripheral blood of patients with rheumatoid arthritis. J Rheumatol. 2003;30(2):220–4.PubMed
8.
go back to reference Hayakawa T, Jin CX, Ko SB, Kitagawa M, Ishiguro H. Lactoferrin in gastrointestinal disease. Intern Med. 2009;48(15):1251–4.CrossRefPubMed Hayakawa T, Jin CX, Ko SB, Kitagawa M, Ishiguro H. Lactoferrin in gastrointestinal disease. Intern Med. 2009;48(15):1251–4.CrossRefPubMed
9.
go back to reference Uchida K, Matsuse R, Tomita S, Sugi K, Saitoh O, Ohshiba S. Immunochemical detection of human lactoferrin in feces as a new marker for inflammatory gastrointestinal disorders and colon cancer. Clin Biochem. 1994;27(4):259–64.CrossRefPubMed Uchida K, Matsuse R, Tomita S, Sugi K, Saitoh O, Ohshiba S. Immunochemical detection of human lactoferrin in feces as a new marker for inflammatory gastrointestinal disorders and colon cancer. Clin Biochem. 1994;27(4):259–64.CrossRefPubMed
10.
go back to reference Sugi K, Saitoh O, Hirata I, Katsu K. Fecal lactoferrin as a marker for disease activity in inflammatory bowel disease: comparison with other neutrophil-derived proteins. Am J Gastroenterol. 1996;91(5):927–34.PubMed Sugi K, Saitoh O, Hirata I, Katsu K. Fecal lactoferrin as a marker for disease activity in inflammatory bowel disease: comparison with other neutrophil-derived proteins. Am J Gastroenterol. 1996;91(5):927–34.PubMed
11.
go back to reference Hirata I, Hoshimoto M, Saito O, Kayazawa M, Nishikawa T, Murano M, Toshina K, Wang FY, Matsuse R. Usefulness of fecal lactoferrin and hemoglobin in diagnosis of colorectal diseases. World j gastroenterology. 2007;13(10):1569–74.CrossRef Hirata I, Hoshimoto M, Saito O, Kayazawa M, Nishikawa T, Murano M, Toshina K, Wang FY, Matsuse R. Usefulness of fecal lactoferrin and hemoglobin in diagnosis of colorectal diseases. World j gastroenterology. 2007;13(10):1569–74.CrossRef
12.
go back to reference Parsi MA, Shen B, Achkar JP, Remzi FF, Goldblum JR, Boone J, Lin D, Connor JT, Fazio VW, Lashner BA. Fecal lactoferrin for diagnosis of symptomatic patients with ileal pouch-anal anastomosis. Gastroenterology. 2004;126(5):1280–6.CrossRefPubMed Parsi MA, Shen B, Achkar JP, Remzi FF, Goldblum JR, Boone J, Lin D, Connor JT, Fazio VW, Lashner BA. Fecal lactoferrin for diagnosis of symptomatic patients with ileal pouch-anal anastomosis. Gastroenterology. 2004;126(5):1280–6.CrossRefPubMed
13.
go back to reference Proctor MJ, Talwar D, Balmar SM, O’Reilly DS, Foulis AK, Horgan PG, Morrison DS, McMillan DC. The relationship between the presence and site of cancer, an inflammation-based prognostic score and biochemical parameters. Initial results of the Glasgow Inflammation Outcome Study. Br J Cancer. 2010;103(6):870–6.CrossRefPubMedPubMedCentral Proctor MJ, Talwar D, Balmar SM, O’Reilly DS, Foulis AK, Horgan PG, Morrison DS, McMillan DC. The relationship between the presence and site of cancer, an inflammation-based prognostic score and biochemical parameters. Initial results of the Glasgow Inflammation Outcome Study. Br J Cancer. 2010;103(6):870–6.CrossRefPubMedPubMedCentral
14.
go back to reference Nagaoka S, Yoshida T, Akiyoshi J, Akiba J, Torimura T, Adachi H, Kurogi J, Tajiri N, Inoue K, Niizeki T, et al. Serum C-reactive protein levels predict survival in hepatocellular carcinoma. Liver int. 2007;27(8):1091–7.CrossRefPubMed Nagaoka S, Yoshida T, Akiyoshi J, Akiba J, Torimura T, Adachi H, Kurogi J, Tajiri N, Inoue K, Niizeki T, et al. Serum C-reactive protein levels predict survival in hepatocellular carcinoma. Liver int. 2007;27(8):1091–7.CrossRefPubMed
15.
go back to reference Hashimoto K, Ikeda Y, Korenaga D, Tanoue K, Hamatake M, Kawasaki K, Yamaoka T, Iwatani Y, Akazawa K, Takenaka K. The impact of preoperative serum C-reactive protein on the prognosis of patients with hepatocellular carcinoma. Cancer. 2005;103(9):1856–64.CrossRefPubMed Hashimoto K, Ikeda Y, Korenaga D, Tanoue K, Hamatake M, Kawasaki K, Yamaoka T, Iwatani Y, Akazawa K, Takenaka K. The impact of preoperative serum C-reactive protein on the prognosis of patients with hepatocellular carcinoma. Cancer. 2005;103(9):1856–64.CrossRefPubMed
16.
go back to reference Xiao WK, Chen D, Li SQ, Fu SJ, Peng BG, Liang LJ. Prognostic significance of neutrophil-lymphocyte ratio in hepatocellular carcinoma: a meta-analysis. BMC Cancer. 2014;14:117.CrossRefPubMedPubMedCentral Xiao WK, Chen D, Li SQ, Fu SJ, Peng BG, Liang LJ. Prognostic significance of neutrophil-lymphocyte ratio in hepatocellular carcinoma: a meta-analysis. BMC Cancer. 2014;14:117.CrossRefPubMedPubMedCentral
17.
go back to reference Gines P, Quintero E, Arroyo V, Teres J, Bruguera M, Rimola A, Caballeria J, Rodes J, Rozman C. Compensated cirrhosis: natural history and prognostic factors. Hepatology. 1987;7(1):122–8.CrossRefPubMed Gines P, Quintero E, Arroyo V, Teres J, Bruguera M, Rimola A, Caballeria J, Rodes J, Rozman C. Compensated cirrhosis: natural history and prognostic factors. Hepatology. 1987;7(1):122–8.CrossRefPubMed
18.
go back to reference Fernandez J, Bauer TM, Navasa M, Rodes J. Diagnosis, treatment and prevention of spontaneous bacterial peritonitis. Baillieres Best Pract Res Clin Gastroenterol. 2000;14(6):975–90.CrossRefPubMed Fernandez J, Bauer TM, Navasa M, Rodes J. Diagnosis, treatment and prevention of spontaneous bacterial peritonitis. Baillieres Best Pract Res Clin Gastroenterol. 2000;14(6):975–90.CrossRefPubMed
19.
go back to reference Parsi MA, Saadeh SN, Zein NN, Davis GL, Lopez R, Boone J, Lepe MR, Guo L, Ashfaq M, Klintmalm G, et al. Ascitic fluid lactoferrin for diagnosis of spontaneous bacterial peritonitis. Gastroenterology. 2008;135(3):803–7.CrossRefPubMed Parsi MA, Saadeh SN, Zein NN, Davis GL, Lopez R, Boone J, Lepe MR, Guo L, Ashfaq M, Klintmalm G, et al. Ascitic fluid lactoferrin for diagnosis of spontaneous bacterial peritonitis. Gastroenterology. 2008;135(3):803–7.CrossRefPubMed
20.
go back to reference Moore KP, Wong F, Gines P, Bernardi M, Ochs A, Salerno F, Angeli P, Porayko M, Moreau R, Garcia-Tsao G, et al. The management of ascites in cirrhosis: report on the consensus conference of the International Ascites Club. Hepatology. 2003;38(1):258–66.CrossRefPubMed Moore KP, Wong F, Gines P, Bernardi M, Ochs A, Salerno F, Angeli P, Porayko M, Moreau R, Garcia-Tsao G, et al. The management of ascites in cirrhosis: report on the consensus conference of the International Ascites Club. Hepatology. 2003;38(1):258–66.CrossRefPubMed
21.
go back to reference Korean Liver Cancer Study Group and National Cancer Center, Korea. Practice guidelines for management of hepatocellular carcinoma 2009. Korean J Hepatol. 2009;15(3):391–423. Korean. Korean Liver Cancer Study Group and National Cancer Center, Korea. Practice guidelines for management of hepatocellular carcinoma 2009. Korean J Hepatol. 2009;15(3):391–423. Korean.
22.
go back to reference FM A, Shehata IH, Elsalam AEA ME-A. Diagnostic value of lactoferrin ascitic fluid levels in spontaneous bacterial peritonitis. Egyptian Liver Jl. 2013;3:54–61.CrossRef FM A, Shehata IH, Elsalam AEA ME-A. Diagnostic value of lactoferrin ascitic fluid levels in spontaneous bacterial peritonitis. Egyptian Liver Jl. 2013;3:54–61.CrossRef
23.
go back to reference Tuccari G, Villari D, Giuffre G, Simone A, Squadrito G, Raimondo G, Barresi G. Immunohistochemical evidence of lactoferrin in hepatic biopsies of patients with viral or cryptogenetic chronic liver disease. Histol Histopathol. 2002;17(4):1077–83.PubMed Tuccari G, Villari D, Giuffre G, Simone A, Squadrito G, Raimondo G, Barresi G. Immunohistochemical evidence of lactoferrin in hepatic biopsies of patients with viral or cryptogenetic chronic liver disease. Histol Histopathol. 2002;17(4):1077–83.PubMed
24.
go back to reference Azzam HS, Goertz C, Fritts M, Jonas WB. Natural products and chronic hepatitis C virus. Liver Int. 2007;27(1):17–25.CrossRefPubMed Azzam HS, Goertz C, Fritts M, Jonas WB. Natural products and chronic hepatitis C virus. Liver Int. 2007;27(1):17–25.CrossRefPubMed
Metadata
Title
Usefulness of ascitic fluid lactoferrin levels in patients with liver cirrhosis
Authors
Sang Soo Lee
Hyun Ju Min
Ja Yun Choi
Hyun Chin Cho
Jin Joo Kim
Jae Min Lee
Hong Jun Kim
Chang Yoon Ha
Hyun Jin Kim
Tae Hyo Kim
Jin Hyun Kim
Ok-Jae Lee
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Gastroenterology / Issue 1/2016
Electronic ISSN: 1471-230X
DOI
https://doi.org/10.1186/s12876-016-0546-9

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