Title: Serum Apolipoprotein A-Iv Level in HCV Related Liver Diseases
Authors: Ibrahim E.H., Elyamany A.S., Dwedar F.I., Aly E.F.
DOI: http://dx.doi.org/10.18535/jmscr/v3i12.49
Abstract
Background: Hepatitis C virus (HCV) is a globally prevalent pathogen and chronic infection eventually causes cirrhosis leading to hepatocellular carcinoma (HCC) and ultimately death. Accurate assessment of liver fibrosis has become increasingly important as it allows for individualized management. Liver plays a key role in the metabolism of plasma apolipoproteins. Apolipoprotein A-IV (apoA-IV) is a component of intestinally derived, triglyceride-rich lipoproteins.
Objective: The present work was designed to study the level of apo A-IV in HCV related liver diseases.
Methods:Sixty treatment-naive patients with HCV related liver disease were enrolled in the study. They were classified as follow: twenty patients with chronic HCV infection (stage of fibrosis ≤ F3), twenty patients with HCV related liver cirrhosis, twenty patients with HCV related HCC and ten normal subjects as control. Serum level of apoA-IV was measured using enzyme linked immunosorbant assay (ELISA). Liver biopsies from patients with chronic HCV were examined to assess histological activity grade and fibrosis stage according to METAVIR scoring system and triphasic CT for HCC patients was performed.
Results: Apo A-IV level was significantly lower in liver cirrhosis than chronic hepatitis patients with a cutoff point of ˂36.4 (p<0.001). The receiver operating characteristic (ROC) curve showed an area under the curve (AUC) of 0.990 (P < 0.001), a sensitivity of 100% and a specificity of 90% for diagnosis of cirrhosis. Also, it was significantly lower in liver cirrhosis than HCC patients with a cutoff point ≤25.1 (p<0.001). The ROC showed AUC of 0.876, a sensitivity of 80.0 % and a specificity of 93.33% for diagnosis of HCC.
Conclusion: Serum apo A-IV showed bi-modal elevation in HCV related liver diseases and could be used as a noninvasive marker for liver cirrhosis in patients with chronic HCV infection and could be a promising marker for early detection of HCC in HCV hepatic cirrhosis.
Key words: (Apolipoprotein A-IV, Hepatitis C Virus, Liver cirrhosis, Hepatocellular carcinoma)
References
1. Cooke GS, Lemoine M, Thursz M, Gore C, Swan T, Kamarulzaman A, et al. Viral hepatitis and the Global Burden of Disease: a need to regroup. J Viral Hepat2013;20:600–1.
2. Mohd HK, Groeger J, Flaxman AD, Wiersma ST. Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence. Hepatol 2013; 57:1333–42.
3. HanafiahKM,GroegerJ,FlaxmanAD,WiersmaST. Global Epidemiology of Hepatitis C Virus Infection: New Estimates of Age-Specific Antibody to HCV Seroprevalence. Hepatol 2013; 57:1333-42.
4. Guerra J, Garenne M, Mohamed MK,Fontanet A. HCV burden of infection in Egypt: results from a nationwide survey. J Viral Hepat2012; 19:560–7.
5. Miller FD, Abu-Raddad LJ. Evidence of intense ongoing endemic transmission of hepatitis C virus in Egypt.ProcNatlAcadSciUSA2010;107(33):14757-6.
6. Kong F, Pan Y, Chi X, Wang X, Chen L, Lv J,etal. Factors Associated with Spontaneous Clearance of Hepatitis C Virus in Chinese Population. BioMed Research International2014; 1-6.
7. BengschB, ThimmeR, BlumHE. Role of Host Genetic Factors in the Outcome of Hepatitis C Virus Infection.Viruses 2009; 1:104-25.
8. Afzal M, Tahir S, Salman A, Baig T, Shafi T, Zaidi N, etal. Analysis of interleukin-10 gene polymorphisms and hepatitis C susceptibility in Pakistan. J Infect DevCtries 2011; 5(6):473-9.
9. MeraniS, PetrovicD, James I,Abha Chopra, Cooper D, FreitaE, et al. Effect of immune pressure on hepatitis C virus evolution: insights from a single-source outbreak. Hepatol 2011; 53:396–405.
10. Burdette D, Haskett A, Presser L, McRae S, Iqbal J, Waris G. Hepatitis C virus activates interleukin-1β via caspase-1-inflammasome complex. J Gen Virol2012;93:235–46.
11. Negash AA, Ramos HJ, Crochet N, Lau DT, Doehle B, Papic N, et al. IL-1β production through the NLRP3 inflammasome by hepatic macrophages links hepatitis C virus infection with liver inflammation and disease. PLoSPathog 2013;9:e1003330.
12. Sugimoto K, Shiraki K, Takei Y, Ito M, Nobori T, Suzuki H, et al. Serum protein isoform profiles indicate the progression of hepatitis C virus-induced liver diseases. Intern J Mole Med 2013; 31(4):943-50.
13. Bedossa P, Poynard T. An algorithm for grading activity in chronic hepatitis C. the French METAVIR Cooperative Study Group.Hepatology 1996;24:289-93.
14. Kotz S, Balakrishnan N, Read CB, Vidakovic B. Encyclopedia of statistical sciences. 2nd ed. Hoboken, N.J. Wiley-Interscience; 2006.
15. Kirkpatrick LA, Feeney BC. A simple guide to IBM SPSS statistics for version 20.0. Student ed. Belmont, Calif. Wadsworth, Cengage Learning; 2013.
16. Seishima M, Usui T, Naganawa S, Nishimura M, Moriwaki H, Muto Y, et al. Reduction of intestinal apo A-IV mRNA levels in the cirrhotic rat. J Gastroenterol Hepatol 1996;11(8):746-51.
17. Pleguezuelo M, Lopez-Sanchez LM, Rodriguez-Ariza A, Montero JL, Briceno J, Ciria R, et al. Proteomic analysis for developing new biomarkers of hepatocellular carcinoma. World J Hepatol 2010; 2(3): 127–35.
18. Teng CF, Hsieh WC, Yang CW, Su HM, Tsai TF, Sung WC, et al. A biphasic response pattern of lipid metabolomics in the stage progression of hepatitis B virus X tumorigenesis. Mol Carcinog 2015; In Press
19. Michiel DF, Oppenheim JJ. Cytokines as positive and negative regulators of tumor promotion and progression.Semin Cancer Biol 1992; 3(1):3-15.
20. Argiles JM, Lopez-Soriano FJ, Evans RD, Williamson DH. Interleukin-1and lipid metabolism in the rat. Biochem J 1989; 259(3):673-8.
21. Navasa M, Gordon DA, Hariharan N, Jamil H, Shigenaga JK, Moser A, et al. Regulation of microsomal triglyceride transfer protein mRNA expression by endotoxin and cytokines. J Lipid Res 1998; 39(6):1220-30.
22. Zervos EE, Tanner SM, Osborne DA, Bloomston M, Rosemurgy AS, Ellison EC et al. Differential gene expression in patients genetically predisposed to pancreatic cancer. J Surg Res 2006; 135(2):317-22.
23. Li X, Li Z, Yan J, Tso P. ApoA-IV Regulates Cytokine Responsiveness in LPS-challenged Macrophage Cells.FASEB J2015; 29: Suppl LB197.
24. Negro F. Abnormalities of lipid metabolism in hepatitis C virus infection. Gut 2010;59(9):1279-87.
25. Jiang JT, Wu CP, Xu N, Zhang XG. Mechanisms and significance of lipoprotein (a) in hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 2009;8:25–8.
26. Wong WR, Stephens JW, Acharya J, Hurel SJ, Humphries SE, Talmud PJ. TheAPOA4T347S variant is associated with reduced plasma TAOS in subjects with diabetes mellitus and cardiovascular disease Journal of Lipid Research2004;45: 1565-71.
27. Recalde D, Ostos MA, Badell E, Garcia-Otin AL, Pidoux J, Castro G, et al. Human Apolipoprotein A-IV Reduces Secretion of Proinflammatory Cytokines and Atherosclerotic Effects of a Chronic Infection Mimicked by Lipopolysaccharide. Arteriosclerosis, Thrombosis, and Vascular Biology2004; 24: 756-61.
28. Khovidhunkita W, Duchateauc PN, Medzihradszkyd KF, Mosera AH, Naya-Vignec J, Shigenagaa JK, etal. Apolipoproteins A-IV and A-V are acute-phase proteins in mouse HDL. Atherosclerosis 2004; 176(1): 37–44.
29. Spaulding HL, Saijo F, Turnage RH, Alexander JS, Aw TY, Kalogeris TJ. Apolipoprotein A-IV attenuates oxidant-induced apoptosis in mitotic competent, undifferentiated cells by modulating intracellular glutathione redox balance. Am J Physiol Cell Physiol2006; 290 ( 1): 95-103.
30. Evert M, Schneider-Stock R, Dombrowski F. Apolipoprotein A-IV mRNA Overexpression in Early Preneoplastic Hepatic Foci Induced by Low-number Pancreatic Islet Transplants in Streptozotocin-diabetic Rats. Pathol Res Pract 2003;199(6):373-9.