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Published in: BMC Infectious Diseases 1/2019

Open Access 01-12-2019 | Hepatitis B | Research article

Potential circulating biomarkers of circulating chemokines CCL5, MIP-1β and HA as for early detection of cirrhosis related to chronic HBV (hepatitis B virus) infection

Authors: Liangshan Hu, Yan Zhu, Jingqian Zhang, Wei Chen, Zeyong Li, Lihua Li, Liping Zhang, Donglin Cao

Published in: BMC Infectious Diseases | Issue 1/2019

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Abstract

Background

Due to no clinical symptoms in the compensated stage of cirrhosis, it is usually diagnosed when decompensated complications occur. In this study, the noninvasive circulating biomarkers for early detection to compensated stage of cirrhosis in patients with chronic HBV (hepatitis B virus) infection was explored.

Methods

According to the Guideline of Prevention and Treatment of Chronic Hepatitis B (2015 Update), 78 patients with CHB (chronic hepatitis B) were divided into mild group, moderate-to-advanced group, while 73 patients with HBV-related cirrhosis were divided into compensated group and decompensated group. Nineteen cytokines and chemokines, four serum liver fibrosis markers were measured using chemiluminescence. The expression of CCL5 in liver tissue was determined with immunohistochemistry.

Results

The CCL5 expression level in serum increased in CHB patients with aggravated liver injury and significantly decreased in cirrhosis patients with advanced liver fibrosis. ROC analysis revealed that the serum levels of CCL5, HA and MIP-1β were effective in distinguishing patients with cirrhosis from patients with CHB, especially for CCL5. Increasing serum level of CCL5 in CHB patients was severely associated with disease progression.

Conclusions

The serum levels of CCL5, HA and MIP-1β maybe used to distinguish cirrhosis from CHB patients, moreover, CCL5 was the most reliable marker. The increasing serum levels of CCL5 were significantly related to disease progression in CHB patients.
Literature
1.
go back to reference Van Tong H, Van Ba N, Hoan NX, Binh MT, Quyen DT, Son HA, Van Luong H, Quyet D, Meyer CG, Song LH, Toan NL, Velavan TP. Soluble fibrinogen-like protein 2 levels in patients with hepatitis B virus-related liver diseases. BMC Infect Dis. 2018;18(1):553.CrossRef Van Tong H, Van Ba N, Hoan NX, Binh MT, Quyen DT, Son HA, Van Luong H, Quyet D, Meyer CG, Song LH, Toan NL, Velavan TP. Soluble fibrinogen-like protein 2 levels in patients with hepatitis B virus-related liver diseases. BMC Infect Dis. 2018;18(1):553.CrossRef
2.
go back to reference Tsochatzis EA, Bosch J, Burroughs AK. Liver cirrhosis. Lancet. 2014;383(9930):1749–61.CrossRef Tsochatzis EA, Bosch J, Burroughs AK. Liver cirrhosis. Lancet. 2014;383(9930):1749–61.CrossRef
3.
go back to reference Marcellin P, Kutala BK. Liver diseases: a major, neglected global public health problem requiring urgent actions and large-scale screening. Liver Int. 2018;38(Suppl 1):2–6.CrossRef Marcellin P, Kutala BK. Liver diseases: a major, neglected global public health problem requiring urgent actions and large-scale screening. Liver Int. 2018;38(Suppl 1):2–6.CrossRef
4.
go back to reference Dohan A, Guerrache Y, Boudiaf M, Gavini JP, Kaci R, Soyer P. Transjugular liver biopsy: indications, technique and results. Diagn Interv Imaging. 2014;95(1):11–5.CrossRef Dohan A, Guerrache Y, Boudiaf M, Gavini JP, Kaci R, Soyer P. Transjugular liver biopsy: indications, technique and results. Diagn Interv Imaging. 2014;95(1):11–5.CrossRef
5.
go back to reference Boyum JH, Atwell TD, Schmit GD, Poterucha JJ, Schleck CD, Harmsen WS, Kamath PS. Incidence and risk factors for adverse events related to image-guided liver biopsy. Mayo Clin Proc. 2016;91(3):329–35.CrossRef Boyum JH, Atwell TD, Schmit GD, Poterucha JJ, Schleck CD, Harmsen WS, Kamath PS. Incidence and risk factors for adverse events related to image-guided liver biopsy. Mayo Clin Proc. 2016;91(3):329–35.CrossRef
6.
go back to reference Ou H, Cai S, Liu Y, Xia M, Peng J. A noninvasive diagnostic model to assess nonalcoholic hepatic steatosis in patients with chronic hepatitis B. Ther Adv Gastroenterol. 2017;10(2):207–17.CrossRef Ou H, Cai S, Liu Y, Xia M, Peng J. A noninvasive diagnostic model to assess nonalcoholic hepatic steatosis in patients with chronic hepatitis B. Ther Adv Gastroenterol. 2017;10(2):207–17.CrossRef
7.
go back to reference Zhu MY, Zou X, Li Q, Yu DM, Yang ZT, Huang D, Chen J, Gong QM, Zhang DH, Zhang Y, Chen L, Chen PZ, Zhang XX. A novel noninvasive algorithm for the assessment of liver fibrosis in patients with chronic hepatitis B virus infection. J Viral Hepat. 2017;24(7):589–98.CrossRef Zhu MY, Zou X, Li Q, Yu DM, Yang ZT, Huang D, Chen J, Gong QM, Zhang DH, Zhang Y, Chen L, Chen PZ, Zhang XX. A novel noninvasive algorithm for the assessment of liver fibrosis in patients with chronic hepatitis B virus infection. J Viral Hepat. 2017;24(7):589–98.CrossRef
8.
go back to reference Kim BK, Kim HS, Yoo EJ, Oh EJ, Park JY, Kim DY, Ahn SH, Han KH, Kim SU, Park YN. Risk assessment of clinical outcomes in Asian patients with chronic hepatitis B using enhance dliver fibrosis test. Hepatology. 2014;60(6):1911–9.CrossRef Kim BK, Kim HS, Yoo EJ, Oh EJ, Park JY, Kim DY, Ahn SH, Han KH, Kim SU, Park YN. Risk assessment of clinical outcomes in Asian patients with chronic hepatitis B using enhance dliver fibrosis test. Hepatology. 2014;60(6):1911–9.CrossRef
9.
go back to reference Vergniol J, Foucher J, Terrebonne E, Bernard PH, le Bail B, Merrouche W, Couzigou P, de Ledinghen V. Noninvasive tests for fibrosis and liver stiffness predict 5-year outcomes of patients with chronic hepatitis C. Gastroenterology. 2011;140(7):1970–9.CrossRef Vergniol J, Foucher J, Terrebonne E, Bernard PH, le Bail B, Merrouche W, Couzigou P, de Ledinghen V. Noninvasive tests for fibrosis and liver stiffness predict 5-year outcomes of patients with chronic hepatitis C. Gastroenterology. 2011;140(7):1970–9.CrossRef
10.
go back to reference Balkwill FR. The chemokine system and cancer. J Pathol. 2012;226(2):148–57.CrossRef Balkwill FR. The chemokine system and cancer. J Pathol. 2012;226(2):148–57.CrossRef
11.
go back to reference Jang JW, Oh BS, Kwon JH, You CR, Chung KW, Kay CS, Jung HS. Serum interleukin-6 and C-reactive protein as a prognostic indicator in hepatocellular carcinoma. Cytokine. 2012;60(3):686–93.CrossRef Jang JW, Oh BS, Kwon JH, You CR, Chung KW, Kay CS, Jung HS. Serum interleukin-6 and C-reactive protein as a prognostic indicator in hepatocellular carcinoma. Cytokine. 2012;60(3):686–93.CrossRef
12.
go back to reference Xue H, Lin F, Tan H, Zhu ZQ, Zhang ZY, Zhao L. Overrepresentation of IL-10-expressing B cells suppresses cytotoxic CD4+ T cell activity in HBV-induced hepatocellular carcinoma. PLoS One. 2016;11(5):e0154815.CrossRef Xue H, Lin F, Tan H, Zhu ZQ, Zhang ZY, Zhao L. Overrepresentation of IL-10-expressing B cells suppresses cytotoxic CD4+ T cell activity in HBV-induced hepatocellular carcinoma. PLoS One. 2016;11(5):e0154815.CrossRef
13.
go back to reference Schwabe RF, Bataller R, Brenner DA. Human hepatic stellate cells express CCR5 and RANTES to induce proliferation and migration. Am J Physiol Gastrointest Liver Physiol. 2003;285(5):949–58.CrossRef Schwabe RF, Bataller R, Brenner DA. Human hepatic stellate cells express CCR5 and RANTES to induce proliferation and migration. Am J Physiol Gastrointest Liver Physiol. 2003;285(5):949–58.CrossRef
14.
go back to reference Mohs A, Kuttkat N, Reißing J, Zimmermann HW, Sonntag R, Proudfoot A, Youssef SA, de Bruin A, Cubero FJ, Trautwein C. Functional role of CCL5/RANTES for HCC progression during chronic liver disease. J Hepatol. 2017;66(4):743–53.CrossRef Mohs A, Kuttkat N, Reißing J, Zimmermann HW, Sonntag R, Proudfoot A, Youssef SA, de Bruin A, Cubero FJ, Trautwein C. Functional role of CCL5/RANTES for HCC progression during chronic liver disease. J Hepatol. 2017;66(4):743–53.CrossRef
15.
go back to reference Seki E, De Minicis S, Gwak GY, Kluwe J, Inokuchi S, Bursill CA, Llovet JM, Brenner DA, Schwabe RF. CCR1 and CCR5 promote hepatic fibrosis in mice. J Clin Invest. 2009;119(7):1858–70.PubMedPubMedCentral Seki E, De Minicis S, Gwak GY, Kluwe J, Inokuchi S, Bursill CA, Llovet JM, Brenner DA, Schwabe RF. CCR1 and CCR5 promote hepatic fibrosis in mice. J Clin Invest. 2009;119(7):1858–70.PubMedPubMedCentral
16.
go back to reference Castera L. Noninvasive assessment of liver fibrosis. Dig Dis. 2015;33(4):498–503.CrossRef Castera L. Noninvasive assessment of liver fibrosis. Dig Dis. 2015;33(4):498–503.CrossRef
17.
go back to reference Karagoz E, Ozturker C, Sivrioglu AK. Noninvasive evaluation of liver fibrosis: is acoustic radiation force impulse a useful tool for evaluating liver fibrosis in patients with chronic hepatitis B and C? J Ultrasound Med. 2016;35(3):668.CrossRef Karagoz E, Ozturker C, Sivrioglu AK. Noninvasive evaluation of liver fibrosis: is acoustic radiation force impulse a useful tool for evaluating liver fibrosis in patients with chronic hepatitis B and C? J Ultrasound Med. 2016;35(3):668.CrossRef
18.
go back to reference Lucero C, Brown RJ. Noninvasive measures of liver fibrosis and severity of liver disease. Gastroenterol Hepatol (NY). 2016;12(1):33–40. Lucero C, Brown RJ. Noninvasive measures of liver fibrosis and severity of liver disease. Gastroenterol Hepatol (NY). 2016;12(1):33–40.
19.
go back to reference Orăşan OH, Sava M, Iancu M, Cozma A, Saplonţai-Pop A, Sarlea Ţărmure S, Lungoci C, Orăşan RA, Patiu IM, Dumitraşcu DL. Serum hyaluronic acid in chronic viral hepatitis B and C: a biomarker for assessing liver fibrosis in chronic hemodialysis patients. Int Urol Nephrol. 2015;47(7):1209–17.CrossRef Orăşan OH, Sava M, Iancu M, Cozma A, Saplonţai-Pop A, Sarlea Ţărmure S, Lungoci C, Orăşan RA, Patiu IM, Dumitraşcu DL. Serum hyaluronic acid in chronic viral hepatitis B and C: a biomarker for assessing liver fibrosis in chronic hemodialysis patients. Int Urol Nephrol. 2015;47(7):1209–17.CrossRef
20.
go back to reference Crawford DH, Murphy TL, Ramm LE, Fletcher LM, Clouston AD, Anderson GJ, Subramaniam VN, Powell LW, Ramm GA. Serum hyaluronic acid with serum ferritin accurately predicts cirrhosis and reduces the need for liver biopsy in C282Y hemochromatosis. Hepatology. 2009;49(2):418–25.CrossRef Crawford DH, Murphy TL, Ramm LE, Fletcher LM, Clouston AD, Anderson GJ, Subramaniam VN, Powell LW, Ramm GA. Serum hyaluronic acid with serum ferritin accurately predicts cirrhosis and reduces the need for liver biopsy in C282Y hemochromatosis. Hepatology. 2009;49(2):418–25.CrossRef
21.
go back to reference Zhang Z, Wang G, Kang K, Wu G, Wang P. The diagnostic accuracy and clinical utility of three noninvasive models for predicting liver fibrosis in patients with HBV infection. PLoS One. 2016;11(4):e0152757.CrossRef Zhang Z, Wang G, Kang K, Wu G, Wang P. The diagnostic accuracy and clinical utility of three noninvasive models for predicting liver fibrosis in patients with HBV infection. PLoS One. 2016;11(4):e0152757.CrossRef
22.
go back to reference Lan T, Chang L, Wu L, Yuan YF. IL-6 plays a crucial role in HBV infection. J Clin Transl Hepatol. 2015;3(4):271–6.CrossRef Lan T, Chang L, Wu L, Yuan YF. IL-6 plays a crucial role in HBV infection. J Clin Transl Hepatol. 2015;3(4):271–6.CrossRef
23.
go back to reference Tan A, Gao Y, Yao Z, Su S, Jiang Y, Xie Y, Xian X, Mo Z. Genetic variants in IL12 influence both hepatitis B virus clearance and HBV-related hepatocellular carcinoma development in a Chinese male population. Tumour Biol. 2016;37(5):6343–8.CrossRef Tan A, Gao Y, Yao Z, Su S, Jiang Y, Xie Y, Xian X, Mo Z. Genetic variants in IL12 influence both hepatitis B virus clearance and HBV-related hepatocellular carcinoma development in a Chinese male population. Tumour Biol. 2016;37(5):6343–8.CrossRef
25.
go back to reference Li BH, He FP, Yang X, Chen YW, Fan JG. Steatosis induced CCL5 contributes to early-stage liver fibrosis in nonalcoholic fatty liver disease progress. Transl Res. 2016;180:103–17.CrossRef Li BH, He FP, Yang X, Chen YW, Fan JG. Steatosis induced CCL5 contributes to early-stage liver fibrosis in nonalcoholic fatty liver disease progress. Transl Res. 2016;180:103–17.CrossRef
26.
go back to reference Soria G, Ben-Baruch A. The inflammatory chemokines CCL2 and CCL5 in breast cancer. Cancer Lett. 2008;267(2):271–85.CrossRef Soria G, Ben-Baruch A. The inflammatory chemokines CCL2 and CCL5 in breast cancer. Cancer Lett. 2008;267(2):271–85.CrossRef
27.
go back to reference Chenoweth MJ, Mian MF, Barra NG, Alain T, Sonenberg N, Bramson J, Lichty BD, Richards CD, Ma A, Ashkar AA. IL-15 can signal via IL-15Ralpha, JNK, and NF-kappaB to drive RANTES production by myeloid cells. J Immunol. 2012;188(9):4149–57.CrossRef Chenoweth MJ, Mian MF, Barra NG, Alain T, Sonenberg N, Bramson J, Lichty BD, Richards CD, Ma A, Ashkar AA. IL-15 can signal via IL-15Ralpha, JNK, and NF-kappaB to drive RANTES production by myeloid cells. J Immunol. 2012;188(9):4149–57.CrossRef
28.
go back to reference Stock MK, Hammerich L, do ONT, Berres ML, Alsamman M, Heinrichs D, Nellen A, Trautwein C, Tacke F, Wasmuth HE, Sahin H. Met-CCL5 modifies monocyte subpopulations during liver fibrosis regression. Int J Clin Exp Pathol. 2013;6(4):678–85.PubMedPubMedCentral Stock MK, Hammerich L, do ONT, Berres ML, Alsamman M, Heinrichs D, Nellen A, Trautwein C, Tacke F, Wasmuth HE, Sahin H. Met-CCL5 modifies monocyte subpopulations during liver fibrosis regression. Int J Clin Exp Pathol. 2013;6(4):678–85.PubMedPubMedCentral
29.
go back to reference Bedossa P, Dargere D, Paradis V. Sampling variability of liver fibrosis in chronic hepatitis C. Hepatology. 2003;38(6):1449–57.CrossRef Bedossa P, Dargere D, Paradis V. Sampling variability of liver fibrosis in chronic hepatitis C. Hepatology. 2003;38(6):1449–57.CrossRef
Metadata
Title
Potential circulating biomarkers of circulating chemokines CCL5, MIP-1β and HA as for early detection of cirrhosis related to chronic HBV (hepatitis B virus) infection
Authors
Liangshan Hu
Yan Zhu
Jingqian Zhang
Wei Chen
Zeyong Li
Lihua Li
Liping Zhang
Donglin Cao
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2019
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-019-4130-0

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