Document Type : Research articles
Authors
1 Dalian Blood Center, Dalian, Liaoning, China
2 Department of Cell Biology, Dalian Medical University, Dalian, China
Abstract
Background and Objectives: Most patients with untreated chronic hepatitis C virus (HCV) infection develop hepatic fibrosis. Hepatic disease progression is monitored with hematological markers (alanine aminotransferase [ALT], aspartate aminotransferase [AST], albumin and platelet [PLT] count, AST/ALT ratio, AST/PLT ratio index [APRI], and fibrosis 4 score [FIB-4]) and FibroScan. The present study aimed to investigate the association between Duffy antigen/chemokines receptor (DARC) polymorphisms and clinical parameters in the Han people with chronic hepatitis C infection in Dalian, China.
Materials and Methods: This cohort study was performed on 245 Han people with chronic HCV at Dalian infectious hospital during April-December 2015. The participants of the research were selected using the consecutive sampling method. The DARC genotyping was performed using the TaqMan probe method and transient elastography was measured by FibroScan.
Results: Based on the findings, DARC polymorphisms correlated with ALT concentrations (FY*A/FY*A vs. FY*A/FY*B, P=0.025). However, the DARC polymorphism did not have an association with HCV RNA titers (FY*A/FY*A vs. FY*A/FY*B, P=0.241) or hepatic fibrosis (FY*A/FY*A vs. FY*A/FY*B, P=0.325). Moreover, correlation analyses showed that APRI (P<0.001, rho=0.603) and FIB-4 (P<0.001, rho=0.698) were useful predictors of hepatic fibrosis in chronic HCV infection. Besides, HCV RNA titers (P=0.327) and hepatic injury markers (P=0.814, 0.198, 0.767, and 0.171 for ALT, AST, ALB, and AST/ALT, respectively) were not useful for the estimation of the fibrosis stage in patients with chronic hepatitis C.
Conclusion: The FY*A allele is a potentially valuable protective factor against hepatocyte damage in chronic HCV-infected patients.
Keywords
- Cosset FL, Mialon C, Boson B, Granier C, Denolly S. HCV interplay with lipoproteins: inside or outside the cells? Viruses. 2020;12(4):434. doi:10.3390/v12040434. [PubMed: 32290553].
- Karsdal MA, Daniels SJ, Holm Nielsen S, Bager C, Rasmussen DGK, Loomba R, et al. Collagen biology and non-invasive biomarkers of liver fibrosis. Liver Int. 2020;40(4):736-50. doi: 10.1111/liv.14390. [PubMed: 31997561].
- Höher G, Rodrigues MMO, Waskow G, Agnes G, Von Burg PV, Onsten T, et al. Identification of ACKR1 variants associated with altered Duffy phenotype expression in blood donors from southern Brazil. Transfus Apher Sci. 2020;59(4)102768. doi: 10.1016/j.transci.2020.102768. [PubMed: 32276863].
- Morein D, Erlichman N, Ben-Baruch A. Beyond cell motility: the expanding roles of chemokines and their receptors in malignancy. Front Immunol. 2020;11:952. doi: 10.3389/fimmu.2020.00952. [PubMed: 32582148].
- Jenkins BD, Martini RN, Hire R, Brown A, Bennett B, Brown I, et al. Atypical chemokine receptor 1 (DARC/ACKR1) in breast tumors is associated with survival, circulating chemokines, tumor-infiltrating immune cells, and african ancestry. Cancer Epidemiol Biomarkers Prev. 2019;28(4):690-700. doi: 10.1158/1055-9965.epi-18-0955. [PubMed: 30944146].
- Höher G, Fiegenbaum M, Almeida S. Molecular basis of the Duffy blood group system. Blood Transfus. 2018;16(1):93-100. doi: 10.2450/2017.0119-16. [PubMed: 28151395].
- Davis MB, Walens A, Hire R, Mumin K, Brown AM, Ford D, et al. Distinct transcript isoforms of the atypical chemokine receptor 1 (ACKR1)/Duffy antigen receptor for chemokines (DARC) gene are expressed in lymphoblasts and altered isoform levels are associated with genetic ancestry and the duffy-null allele. PLoS One. 2015;10(10):e0140098. doi: 10.1371/journal.pone.0140098. [PubMed: 26473357].
- Kano FS, de Souza AM, de Menezes Torres L, Costa MA, Souza-Silva FA, Sanchez BAM, et al. susceptibility to plasmodium vivax malaria associated with darc (Duffy antigen) polymorphisms is influenced by the time of exposure to malaria. Sci Rep. 2018;8(1):13851. doi: 10.1038/s41598-018-32254-z. [PubMed: 30218021].
- Namdar A, Dunsmore G, Shahbaz S, Koleva P, Xu L, Jovel J, et al. CD71(+) erythroid cells exacerbate HIV-1 susceptibility, mediate trans-infection, and harbor infective viral particles. mBio. 2019;10(6) :e02767-19. doi: 10.1128/mBio.02767-19. [PubMed: 31772057].
- Li DD, Yang C, Shao ZM, Yu KD. Effect of functional genetic variants in chemokine decoy receptors on the recurrence risk of breast cancer. Cancer Med. 2018;7(11):5497-504. doi: 10.1002/cam4.1823. [PubMed: 30358125].
- Martins ML, da Silva AR, Santos HC, Alves MT, Schmidt LC, Vertchenko SB, et al. Duffy blood group system: New genotyping method and distribution in a Brazilian extra-Amazonian population. Mol Cell Probes. 2017;35:20-6. doi: 10.1016/j.mcp.2017.06.001. [PubMed: 28587995].
- Chaudhry S, Emond J, Griesemer A. Immune cell trafficking to the liver. Transplantation. 2019;103(7):1323-37. doi: 10.1097/tp.0000000000002690. [PubMed: 30817405].
- Chalin A, Lefevre B, Devisme C, Barget N, Amiot L, Samson M. Circulating levels of CXCL11 and CXCL12 are biomarkers of cirrhosis in patients with chronic hepatitis C infection. Cytokine. 2019;117:72-8. doi: 10.1016/j.cyto.2019.02.006. [PubMed: 30826602].
- Zhang ST, Shi M, Shao LN, Zhou SH, Yu WJ, Chen M, et al. Atypical chemokine receptor 1 polymorphism can not affect susceptibility to hepatitis C virus. Balkan Med J. 2017;34(4):308-12. doi: 10.4274/balkanmedj.2016.0766. [PubMed: 28443566].
- Viitasalo A, Eloranta AM, Atalay M, Romeo S, Pihlajamäki J, Lakka TA. Association of MBOAT7 gene variant with plasma ALT levels in children: the PANIC study. Pediatr Res. 2016;80(5):651-5. doi: 10.1038/pr.2016.139. [PubMed: 27411039].
- Liu Z, Ning H, He X, Que S, Zhou L. Meta-analysis reveals a specific association of the PNPLA3 I148M polymorphism with ALT level in adolescents. Per Med. 2015;12(2):67-82. doi: 10.2217/pme.14.72. [PubMed: 29754542].
- Larrieta-Carrasco E, Flores YN, Macías-Kauffer LR, Ramírez-Palacios P, Quiterio M, Ramírez-Salazar EG, et al. Genetic variants in COL13A1, ADIPOQ and SAMM50, in addition to the PNPLA3 gene, confer susceptibility to elevated transaminase levels in an admixed Mexican population. Exp Mol Pathol. 2018;104(1):50-8. doi: 10.1016/j.yexmp.2018.01.001. [PubMed: 29307798].
- Gounder PP, Haering C, Bruden DJT, Townshend-Bulson L, Simons BC, Spradling PR, et al. Does incorporating change in APRI or FIB-4 indices over time improve the accuracy of a single index for identifying liver fibrosis in persons with chronic hepatitis c virus infection? J Clin Gastroenterol. 2018;52(1):60-6. doi: 10.1097/mcg.0000000000000753. [PubMed: 27875352].
- Tseng CH, Chang CY, Mo LR, Lin JT, Tai CM, Perng DS, et al. Acoustic radiation force impulse elastography with Apri and FIB-4 to identify significant liver fibrosis in chronic hepatitis B patients. Ann Hepatol. 2018;17(5):789-94. doi: 10.5604/01.3001.0012.3137. [PubMed: 30145564].
- Lim JK, Flamm SL, Singh S, Falck-Ytter YT. American gastroenterological association institute guideline on the role of elastography in the evaluation of liver fibrosis. Gastroenterology. 2017;152(6):1536-43. doi: 10.1053/j.gastro.2017.03.017. [PubMed: 28442119].
- Xiao G, Zhu S, Xiao X, Yan L, Yang J, Wu G. Comparison of laboratory tests, ultrasound, or magnetic resonance elastography to detect fibrosis in patients with nonalcoholic fatty liver disease: A meta-analysis. Hepatology. 2017;66(5):1486-501. doi: 10.1002/hep.29302. [PubMed: 28586172].
- Guo L, Zheng L, Hu L, Zhou H, Yu L, Liang W. Transient elastography (fibroscan) performs better than non-invasive markers in assessing liver fibrosis and cirrhosis in autoimmune hepatitis patients. Med Sci Monit. 2017;23:5106-12. doi: 10.12659/msm.907300. [PubMed: 29073121].
- Shao LN, Zhang ST, Zhou SH, Yu WJ, Liu M. Atypical chemokine receptor 1 polymorphism cannot be used as an indicator of liver fibrosis progression in Hepatitis C virus positive patients. Pak J Med Sci. 2017;33(5):1134-7. doi: 10.12669/pjms.335.12590. [PubMed: 29142552].
- Lettow I, Berres ML, Schmitz P, Muller T, Berg T, Neumann UP, et al. A Duffy antigen receptor for chemokines (DARC) polymorphism that determines pro-fibrotic chemokine serum concentrations is not directly associated with severity of hepatitis C infection. Hum Immunol. 2011;72(3):273-7. doi: 10.1016/j.humimm.2010.12.002. [PubMed: 21156192].
- Jimenez-Sousa MA, Gomez-Moreno AZ, Pineda-Tenor D, Sanchez-Ruano JJ, Artaza-Varasa T, Martin-Vicente M, et al. Impact of DARC rs12075 variants on liver fibrosis progression in patients with chronic hepatitis C: A retrospective study. Biomolecules. 2019;9(4):143. doi: 10.3390/biom9040143. [PubMed: 30970632].
- Rappoport N, Simon AJ, Amariglio N, Rechavi G. The Duffy antigen receptor for chemokines, ACKR1,- 'Jeanne DARC' of benign neutropenia. Br J Haematol. 2019;184(4):497-507. doi: 10.1111/bjh.15730. [PubMed: 30592023].
- Fragiadaki I, Papadakis S, Sevastaki G, Sfyridaki K, Mavroudi I, Goulielmos GN, et al. Increased frequency of the single nucleotide polymorphism of the DARC/ACKR1 gene associated with ethnic neutropenia in a cohort of European patients with chronic idiopathic neutropenia. Am J Hematol. 2020;95(7):E163-6. doi: 10.1002/ajh.25813. [PubMed: 32243614].
- Yosry A, Fouad R, Alem SA, Elsharkawy A, El-Sayed M, Asem N, et al. FibroScan, APRI, FIB4, and GUCI: Role in prediction of fibrosis and response to therapy in Egyptian patients with HCV infection. Arab J Gastroenterol. 2016;17(2):78-83. doi: 10.1016/j.ajg.2016.05.002. [PubMed: 27353055].
- Cheng CH, Chu CY, Chen HL, Lin IT, Wu CH, Lee YK, et al. Subgroup analysis of the predictive ability of aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 (FIB-4) for assessing hepatic fibrosis among patients with chronic hepatitis C. J Microbiol Immunol Infect. 2020;53(4):542-9. doi: 10.1016/j.jmii.2019.09.002. [PubMed: 31831303].
- Guéchot J, Boisson RC, Zarski JP, Sturm N, Calès P, Lasnier E. AST/ALT ratio is not an index of liver fibrosis in chronic hepatitis C when aminotransferase activities are determinate according to the international recommendations. Clin Res Hepatol Gastroenterol. 2013;37(5):467-72. doi: 10.1016/j.clinre.2013.07.003. [PubMed: 23932706].
- Eminler AT, Ayyildiz T, Irak K, Kiyici M, Gurel S, Dolar E, et al. AST/ALT ratio is not useful in predicting the degree of fibrosis in chronic viral hepatitis patients. Eur J Gastroenterol Hepatol. 2015;27(12):1361-6. doi: 10.1097/meg.0000000000000468. [PubMed: 26352130].
- Al-Khurri LE, Al-Khafaji KR, Al-Salihi SA, Alwaysi SA, Al-Akayshi RJ. Serum HCV-RNA levels in patients with chronic hepatitis C: Correlation with histological features. Arab J Gastroenterol. 2009;10(1):10-3. doi: 10.1016/j.ajg.2009.03.003. [PubMed: 24842130].
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