HLA-DRB1 Polymorphisms and Rheumatologic Manifestations in Chronic Hepatitis C

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Abstract

Background/Aims: Hepatitis C has been associated with rheumatologic manifestations (HCV-related RM). Clinically, HCV-related RM may be indistinguishable from the symptoms that occur in diffuse connective tissue diseases (DCTD-related RM), making the differential diagnosis difficult. Host genetic factors, such as the Human Leukocyte Antigens (HLA) polymorphisms were associated with HCV infection, however, there are no studies that discriminate between HCVrelated RM and DCTD-related RM. This study focused on verifying associations between HLADRB1 and RM in patients with chronic hepatitis C, aiming to distinguish between DCTD-related RM and HCV-related RM.

Methods: The participants were 152 individuals, of both sexes, aged between 18 and 80 years, and affected by chronic hepatitis C. The patients underwent rheumatologic physical examination and HLA-class II (HLA-DRB1) typing was performed by PCR-SSO (Polymerase Chain Reactionsequence Specific Oligonucleotides).

Results: A significant number of patients with rheumatologic complaints (73%) not attributed to other causes was observed. DRB1*08 allele seems to confer protection against RM in chronic hepatitis C. There is no susceptibility association between HLA-DRB1 alleles and RM.

Conclusion: The absence of association between HLA-DRB1 and the rheumatologic manifestations studied suggests that the pathophysiological pathways of DCTD-related RM and HCV-related RM are distinct.

Keywords: HCV, hepatitis C, rheumatologic manifestations, HLA, DRB1, PCR-SSO.

Graphical Abstract

[1]
Preciado MV, Valva P, Escobar-Gutierrez A, et al. Hepatitis C virus molecular evolution: Transmission, disease progression and antiviral therapy. World J Gastroenterol 2014; 20(43): 15992-6013.
[http://dx.doi.org/10.3748/wjg.v20.i43.15992] [PMID: 25473152]
[2]
Messina JP, Humphreys I, Flaxman A, et al. Global distribution and prevalence of hepatitis C virus genotypes. Hepatology 2015; 61(1): 77-87.
[http://dx.doi.org/10.1002/hep.27259] [PMID: 25069599]
[3]
Global Hepatitis Report 2017. Geneva: World Health Organization 2017. Available from: https://www.who.int/hepatitis/publications/global-hepatitis-report2017/en/
[4]
Gumber SC, Chopra S. Hepatitis C: A multifaceted disease. Review of extrahepatic manifestations. Ann Intern Med 1995; 123(8): 615-20.
[http://dx.doi.org/10.7326/0003-4819-123-8-199510150-00008] [PMID: 7677303]
[5]
Ferri C, Ramos-Casals M, Zignego AL, et al. International diagnostic guidelines for patients with HCV-related extrahepatic manifestations. A multidisciplinary expert statement. Autoimmun Rev 2016; 15(12): 1145-60.
[http://dx.doi.org/10.1016/j.autrev.2016.09.006] [PMID: 27640316]
[6]
Rocha OM, Batista AAP, Medolago N, Silva GF. Manifestações reumatológicas da hepatite C. JBM 2010; 98(2): 37-42.
[7]
Treppo E, Quartuccio L, Ragab G. DE Vita S. Rheumatologic manifestations of Hepatitis C Virus. Minerva Med 2021; 112(2): 201-14.
[http://dx.doi.org/10.23736/S0026-4806.20.07158-X] [PMID: 33263372]
[8]
Bombardieri M, Alessandri C, Labbadia G, et al. Role of anti-cyclic citrullinated peptide antibodies in discriminating patients with rheumatoid arthritis from patients with chronic hepatitis C infection-associated polyarticular involvement. Arthritis Res Ther 2004; 6(2): R137-41.
[http://dx.doi.org/10.1186/ar1041] [PMID: 15059277]
[9]
Sayiner ZA, Haque U, Malik MU, Gurakar A. Hepatitis C virus infection and its rheumatologic implications. Gastroenterol Hepatol (N Y) 2014; 10(5): 287-93.
[PMID: 24987312]
[10]
Cacoub P, Poynard T, Ghillani P, et al. Extrahepatic manifestations of chronic hepatitis C. MULTIVIRC Group. Multidepartment Virus C Arthritis Rheum 1999; 42(10): 2204-12.
[http://dx.doi.org/10.1002/1529-0131(199910)42:10<2204::AID-ANR24>3.0.CO;2-D] [PMID: 10524695]
[11]
Buskila D, Hepatitis C. Hepatitis C-associated rheumatic disorders. Rheum Dis Clin North Am 2009; 35(1): 111-23.
[http://dx.doi.org/10.1016/j.rdc.2009.03.005] [PMID: 19481000]
[12]
Ali A, Zein NN. Hepatitis C infection: A systemic disease with extrahepatic manifestations. Cleve Clin J Med 2005; 72(11): 1005-1008, 1010-1014, 1016 passim.
[http://dx.doi.org/10.3949/ccjm.72.11.1005] [PMID: 16315439]
[13]
Cacoub P, Renou C, Kerr G, et al. Influence of HLA-DR phenotype on the risk of hepatitis C virus-associated mixed cryoglobulinemia. Arthritis Rheum 2001; 44(9): 2118-24.
[http://dx.doi.org/10.1002/1529-0131(200109)44:9<2118::AID-ART364>3.0.CO;2-X] [PMID: 11592376]
[14]
Czaja AJ, Carpenter HA, Santrach PJ, Moore SB. Immunologic features and HLA associations in chronic viral hepatitis. Gastroenterology 1995; 108(1): 157-64.
[http://dx.doi.org/10.1016/0016-5085(95)90020-9] [PMID: 7806037]
[15]
Giannitti C. Viral genotype and HLA class II alleles influence on extra-hepatic manifestations of chronic HCV infection. C. Reumatismo 2008; 60(3): 192-8.
[PMID: 18854880]
[16]
Louzada-Júnior P, Freitas MVC, Oliveira RDR, et al. A majority of Brazilian patients with rheumatoid arthritis HLA-DRB1 alleles carry both the HLA-DRB1 shared epitope and anti-citrunillated peptide antibodies. Braz J Med Biol Res 2008; 41(6): 493-9.
[http://dx.doi.org/10.1590/S0100-879X2008005000021] [PMID: 18560674]
[17]
Bodis G, Toth V, Schwarting A. Role of Human Leukocyte Antigens (HLA) in autoimmune diseases. Rheumatol Ther 2018; 5(1): 5-20.
[http://dx.doi.org/10.1007/s40744-018-0100-z] [PMID: 29516402]
[18]
Dieudé P. Rheumatic diseases: Environment and genetics. Joint Bone Spine 2009; 76(6): 602-7.
[http://dx.doi.org/10.1016/j.jbspin.2009.10.002] [PMID: 19926510]
[19]
Mourad J, Monem F. Associação do alelo HLA-DRB1 com suscetibilidade a artrite reumatoide e gravidade da doença na Síria. Rev Bras Reumatol 2013; 53(1): 51-6.
[http://dx.doi.org/10.1590/S0482-50042013000100005] [PMID: 23588515]
[20]
De Silvestri A, Capittini C, Poddighe D, et al. HLA-DRB1 alleles and juvenile idiopathic arthritis: Diagnostic clues emerging from a meta-analysis. Autoimmun Rev 2017; 16(12): 1230-6.
[http://dx.doi.org/10.1016/j.autrev.2017.10.007] [PMID: 29037901]
[21]
Villeneuve E, Nam J, Emery P. 2010 ACR-EULAR classification criteria for rheumatoid arthritis. Rev Bras Reumatol 2010; 50(5): 481-3.
[http://dx.doi.org/10.1590/S0482-50042010000500001] [PMID: 21125184]
[22]
Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. Hepatology 1996; 24(2): 289-93.
[http://dx.doi.org/10.1002/hep.510240201] [PMID: 8690394]
[23]
Jadali Z, Alavian SM. Autoimmune diseases co-existing with hepatitis C virus infection. Iran J Allergy Asthma Immunol 2010; 9(4): 191-206.
[PMID: 21131699]
[24]
Aydeniz A, Namiduru M, Karaoglan I, Altindag O, Yagiz E, Gursoy S. Rheumatic manifestations of hepatitis B and C and their association with viral load and fibrosis of the liver. Rheumatol Int 2010; 30(4): 515-7.
[http://dx.doi.org/10.1007/s00296-009-1010-8] [PMID: 19536545]
[25]
Vassilopoulos D, Manolakopoulos S. Rheumatic manifestations of hepatitis. Curr Opin Rheumatol 2010; 22(1): 91-6.
[http://dx.doi.org/10.1097/BOR.0b013e328333ba5d] [PMID: 19864952]
[26]
Gohar NAE, Abdalla MA, Mehasseb MK, Saleb WAE. Impact of hepatitis C virus infection on disease activity, functional status and ultrasonography findings in Egyptian rheumatoid arthritis patients. Egypt Rheumatol 2018; 40(2): 79-83.
[http://dx.doi.org/10.1016/j.ejr.2017.07.002]
[27]
Mohammed RHA, ElMakhzangy HI, Gamal A, et al. Prevalence of rheumatologic manifestations of chronic hepatitis C virus infection among Egyptians. Clin Rheumatol 2010; 29(12): 1373-80.
[http://dx.doi.org/10.1007/s10067-010-1463-x] [PMID: 20411290]
[28]
Talsania M, Scofield RH. Menopause and rheumatic disease. Rheum Dis Clin North Am 2017; 43(2): 287-302.
[http://dx.doi.org/10.1016/j.rdc.2016.12.011] [PMID: 28390570]
[29]
Paradowska-Gorycka A, Stypińska B, Olesińska M, et al. Association of HLA-DRB1 alleles with susceptibility to mixed connective tissue disease in Polish patients. HLA 2016; 87(1): 13-8.
[http://dx.doi.org/10.1111/tan.12698] [PMID: 26818120]
[30]
Hassan AB, Nikitina-Zake L, Padyukov L, et al. MICA4/HLA-DRB1*04/TNF1 haplotype is associated with mixed connective tissue disease in Swedish patients. Hum Immunol 2003; 64(2): 290-6.
[http://dx.doi.org/10.1016/S0198-8859(02)00776-0] [PMID: 12559632]
[31]
Flåm ST, Gunnarsson R, Garen T, Lie BA, Molberg Ø. The HLA profiles of mixed connective tissue disease differ distinctly from the profiles of clinically related connective tissue diseases. Rheumatology (Oxford) 2015; 54(3): 528-35.
[http://dx.doi.org/10.1093/rheumatology/keu310] [PMID: 25187641]
[32]
Weyand CM, Goronzy JJ. Association of MHC and rheumatoid arthritis. HLA polymorphisms in phenotypic variants of rheumatoid arthritis. Arthritis Res 2000; 2(3): 212-6.
[http://dx.doi.org/10.1186/ar90] [PMID: 11094432]
[33]
Cacoub P, Comarmond C. New insights into HCV-related rheumatologic disorders: A review. J Adv Res 2017; 8(2): 89-97.
[http://dx.doi.org/10.1016/j.jare.2016.07.005] [PMID: 28149645]
[34]
Fabris M, Quartuccio L, Sacco S, et al. B-Lymphocyte stimulator (BLyS) up-regulation in mixed cryoglobulinaemia syndrome and hepatitis-C virus infection. Rheumatology (Oxford) 2007; 46(1): 37-43.
[http://dx.doi.org/10.1093/rheumatology/kel174] [PMID: 16735452]