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Current Rheumatology Reviews


ISSN (Print): 1573-3971
ISSN (Online): 1875-6360

Review Article

HCV and Autoimmunity in Rheumatic Diseases

Author(s): Alberto Altomare*, Addolorata Corrado, Nicola Maruotti, Daniela Cici and Francesco Paolo Cantatore

Volume 18, Issue 2, 2022

Published on: 12 August, 2021

Page: [101 - 107] Pages: 7

DOI: 10.2174/1573397117666210812141524

Price: $65


HCV is a global health problem affecting mainly the liver and is often characterized by extrahepatic manifestations mediated by autoimmune reactions. Among these, arthritis and arthralgia are most frequent, as well as the presence of cryoglobulinemia that may induce vasculitis and sicca syndrome. Thus, HCV appears to be a trigger for an autoimmune response, as demonstrated by the finding of autoantibody in a high percentage of serum of these patients. Therefore, it is important that clinicians recognize these autoimmune manifestations as symptoms due to an autoimmune activity triggered by HCV in order to give the correct diagnosis and start an effective therapeutic strategy. Therefore, clinical examination, searching of markers of infection, as well as autoantibody patterns should be performed to make a correct differential diagnosis. The treatment should be based on antiviral drugs associated with immunosuppressive drugs according to autoimmune manifestations.

Keywords: HCV, autoimmunity, arthritis, cryoglobulinemia, sjogren’s syndrome, rheumatic diseases.

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Rosenthal E, Cacoub P. Extrahepatic manifestations in chronic hepatitis C virus carriers. Lupus 2015; 24: 469-82.
Kuna L, Jakab J, Smolic R, Wu GY, Smolic M. HCV extrahepatic manifestations. J Clin Transl Hepatol 2019; 7(2): 172-82.
[PMID: 31293918]
Buskila D, Shnaider A, Neumann L, et al. Musculoskeletal manifestations and autoantibody profile in 90 hepatitis C virus infected Israeli patients. Semin Arthritis Rheum 1998; 28(2): 107-13.
[] [PMID: 9806371]
Pawlotsky J-M, Ben Yahia M, Andre C, et al. Immunological disorders in C virus chronic active hepatitis: A prospective case-control study. Hepatology 1994; 19(4): 841-8.
[] [PMID: 8138255]
Muratori P, Muratori L, Stroffolini T, et al. Prevalence of non-organ specific autoantibodies in HCV-infected subjects in the general population. Clin Exp Immunol 2003; 131(1): 118-21.
[] [PMID: 12519394]
Lee YH, Ji JD, Yeon JE, Byun KS, Lee CH, Song GG. Cryoglobulinaemia and rheumatic manifestations in patients with hepatitis C virus infection. Ann Rheum Dis 1998; 57(12): 728-31.
[] [PMID: 10070272]
Bayraktar Y, Bayraktar M, Gurakar A, Hassanein TI, Van Thiel DH. A comparison of the prevalence of autoantibodies in individuals with chronic hepatitis C and those with autoimmune hepatitis: the role of interferon in the development of autoimmune diseases. Hepatogastroenterology 1997; 44(14): 417-25.
[PMID: 9164512]
Zein NN, Persing DH, Czaja AJ. Viral genotypes as determinants of autoimmune expression in chronic hepatitis C. Mayo Clin Proc 1999; 74(5): 454-60.
[] [PMID: 10319074]
Palazzi C, Buskila D, D’Angelo S, D’Amico E, Olivieri I. Autoantibodies in patients with chronic hepatitis C virus infection: pitfalls for the diagnosis of rheumatic diseases. Autoimmun Rev 2012; 11(9): 659-63.
[] [PMID: 22155016]
Palazzi C, Canelli A, Ursitti G, Capani F. Anti-ENA antibodies in patients with chronic hepatitis c virus infection. 2002; 47: pp. (4)755-9.
Wu Y, Hsu T, Chen T, Liu T, Liu G, Lee Y. Proteinase 3 and dihydrolipoamide dehydrogenase (E3) are major autoantigens in hepatitis C virus (HCV) infection. 2002; 347-52.
Omagari K, Ohba K, Kadokawa Y, et al. Anti-extractable nuclear antigens (ENA) antibodies in patients with chronic hepatitis C before and after treatment with interferon. Autoimmunity 2003; 36(5): 269-73.
[] [PMID: 14567556]
Lamprecht P, Schmitt WH, Gross WL. Mixed cryoglobulinaemia, glomerulonephritis, and ANCA: Essential cryoglobulinaemic vasculitis or ANCA-associated vasculitis? Nephrol Dial Transplant 1998; 13(1): 213-21.
[] [PMID: 9481747]
Clifford BD, Donahue D, Smith L, et al. High prevalence of serological markers of autoimmunity in patients with chronic hepatitis C. Hepatology 1995; 21(3): 613-9.
[PMID: 7533120]
Andrade LJ, Melo PR, Atta AM, et al. Smooth muscle antibodies and cryoglobulinemia are associated with advanced liver fibrosis in Brazilian hepatitis C virus carriers. Braz J Infect Dis 2011; 15(1): 66-8.
[] [PMID: 21412592]
Prieto J, Yuste JR, Beloqui O, et al. Anticardiolipin antibodies in chronic hepatitis C: Implication of hepatitis C virus as the cause of the antiphospholipid syndrome. Hepatology 1996; 23(2): 199-204.
[] [PMID: 8591841]
Zuckerman E, Yeshurun D, Rosner I. Management of hepatitis C virus-related arthritis. BioDrugs 2001; 15(9): 573-84.
[] [PMID: 11580301]
Palazzi C, D’Angelo S, Olivieri I. Hepatitis C virus-related arthritis. Autoimmun Rev 2008; 8(1): 48-51.
[] [PMID: 18707027]
Iagnocco A, Coari G, Mammarella A, et al. Joint sonography in asymptomatic patients with HCV correlated hepatitis. Clin Exp Rheumatol 2004; 22(1): 43-8.
[PMID: 15005003]
Wener MH, Hutchinson K, Morishima C, Gretch DR. Absence of antibodies to cyclic citrullinated peptide in sera of patients with hepatitis C virus infection and cryoglobulinemia. Arthritis Rheum 2004; 50(7): 2305-8.
[] [PMID: 15248231]
Ezzat WM, Raslan HM, Aly AA, Emara NA, El Menyawi MM, Edrees A. Anti-cyclic citrullinated peptide antibodies as a discriminating marker between rheumatoid arthritis and chronic hepatitis C-related polyarthropathy. Rheumatol Int 2011; 31(1): 65-9.
[] [PMID: 19882340]
Kessel A, Rosner I, Zuckerman E, Golan TD, Toubi E. Use of antikeratin antibodies to distinguish between rheumatoid arthritis and polyarthritis associated with hepatitis C infection. J Rheumatol 2000; 27(3): 610-2.
[PMID: 10743797]
Palazzi C, Olivieri I, Cacciatore P, Pennese E, D’Amico E. Management of hepatitis C virus-related arthritis. Expert Opin Pharmacother 2005; 6(1): 27-34.
[] [PMID: 15709880]
Fadda P, La Civita L, Zignego AL, Ferri C. [Hepatitis C virus infection and arthritis. A clinico-serological investigation of arthritis in patients with or without cryoglobulinemic syndrome]. Reumatismo 2002; 54(4): 316-23.
[PMID: 12563365]
Nissen MJ, Fontanges E, Allam Y, Zoulim F, Trépo C, Miossec P. Rheumatological manifestations of hepatitis C: Incidence in a rheumatology and non-rheumatology setting and the effect of methotrexate and interferon. Rheumatology (Oxford) 2005; 44(8): 1016-20.
[] [PMID: 15855185]
Mok MY, Ng WL, Yuen MF, Wong RW, Lau CS. Safety of disease modifying anti-rheumatic agents in rheumatoid arthritis patients with chronic viral hepatitis. Clin Exp Rheumatol 2000; 18(3): 363-8.
[PMID: 10895374]
Zuckerman E, Keren D, Slobodin G, et al. Treatment of refractory, symptomatic, hepatitis C virus related mixed cryoglobulinemia with ribavirin and interferon-alpha. J Rheumatol 2000; 27(9): 2172-8.
[PMID: 10990230]
Poynard T, Marcellin P, Lee SS, et al. Randomised trial of interferon alpha2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. Lancet 1998; 352(9138): 1426-32.
[] [PMID: 9807989]
Ferri C, Sebastiani M, Giuggioli D, et al. Mixed cryoglobulinemia: demographic, clinical, and serologic features and survival in 231 patients. Semin Arthritis Rheum 2004; 33(6): 355-74.
[] [PMID: 15190522]
Lener A, Watson C. Studies of cryoglobulins I. Unusual purpura associated with the presence of a high concentration of cryoglobulin (cold precipitable serum globulin). 1947; pp. 410-5.
Ramos-Casals M, Stone JH, Cid MC, Bosch X. The cryoglobulinaemias. Lancet 2012; 379(9813): 348-60.
[] [PMID: 21868085]
Schott E, Witt H, Neumann K, et al. A Toll-like receptor 7 single nucleotide polymorphism protects from advanced inflammation and fibrosis in male patients with chronic HCV-infection. J Hepatol 2007; 47(2): 203-11.
[] [PMID: 17512627]
Schott E, Witt H, Neumann K, et al. Association of TLR7 single nucleotide polymorphisms with chronic HCV-infection and response to interferon-a-based therapy. J Viral Hepat 2008; 15(1): 71-8.
[PMID: 18088248]
Alpers CE, Smith KD. Cryoglobulinemia and renal disease. Curr Opin Nephrol Hypertens 2008; 17(3): 243-9.
[] [PMID: 18408474]
Rosa D, Saletti G, De Gregorio E, et al. Activation of naïve B lymphocytes via CD81, a pathogenetic mechanism for hepatitis C virus-associated B lymphocyte disorders. Proc Natl Acad Sci USA 2005; 102(51): 18544-9.
[] [PMID: 16339892]
Wong VS, Egner W, Elsey T, Brown D, Alexander GJM. Incidence, character and clinical relevance of mixed cryoglobulinaemia in patients with chronic hepatitis C virus infection. Clin Exp Immunol 1996; 104(1): 25-31.
[] [PMID: 8603528]
Dammacco F, Sansonno D. Hepatitis C virus infection and mixed cryoglobulinemia: A striking association. Clin Exp Immunol 1992; 87: 352-6.
[] [PMID: 1311992]
Lunel F, Musset L. Hepatitis C virus infection and cryoglobulinemia. J Hepatol 1998; 29(5): 848-55.
[] [PMID: 9833927]
Kessel A, Rosner I, Zuckerman E, Golan TD, Toubi E. Rheumatoid arthritis and polyarthritis associated. 2001; 53: pp. (2)156-7.
Wörnle M, Schmid H, Banas B, et al. Novel role of toll-like receptor 3 in hepatitis C-associated glomerulonephritis. Am J Pathol 2006; 168(2): 370-85.
[] [PMID: 16436653]
Roccatello D, Fornasieri A, Giachino O, et al. Multicenter study on hepatitis C virus-related cryoglobulinemic glomerulonephritis. Am J Kidney Dis 2007; 49(1): 69-82.
[] [PMID: 17185147]
Bonetti B, Invernizzi F, Rizzuto N, et al. T-cell-mediated epineurial vasculitis and humoral-mediated microangiopathy in cryoglobulinemic neuropathy. J Neuroimmunol 1997; 73(1-2): 145-54.
[] [PMID: 9058770]
Sise ME, Bloom AK, Wisocky J, et al. Treatment of hepatitis C virus-associated mixed cryoglobulinemia with direct-acting antiviral agents. Hepatology 2016; 63(2): 408-17.
[] [PMID: 26474537]
Saadoun D, Resche Rigon M, Sene D, et al. Rituximab plus peg-interferon-alpha/ribavirin compared with Peg-interferon-alpha/ribavirin in hepatitis C-related mixed cryoglobulinemia. Blood 2010; 116(3): 326-34.
[] [PMID: 20439619]
Verbaan H, Carlson J, Eriksson S, et al. Extrahepatic manifestations of chronic hepatitis C infection and the interrelationship between primary Sjögren’s syndrome and hepatitis C in Swedish patients. J Intern Med 1999; 245(2): 127-32.
[] [PMID: 10081515]
Haddad J, Deny P, Munz-Gotheil C, et al. Lymphocytic sialadenitis of Sjögren’s syndrome associated with chronic hepatitis C virus liver disease. Lancet 1992; 339(8789): 321-3.
[] [PMID: 1346409]
Marrone A, Di Bisceglie AM, Fox P. Absence of hepatitis C viral infection among patients with primary Sjögren’s syndrome. J Hepatol 1995; 22(5): 599.
[] [PMID: 7650344]
Arrieta JJ, Rodríguez-Iñigo E, Ortiz-Movilla N, et al. In situ detection of hepatitis C virus RNA in salivary glands. Am J Pathol 2001; 158(1): 259-64.
[] [PMID: 11141499]
Toussirot E, Le Huédé G, Mougin C, Balblanc JC, Bettinger D, Wendling D. Presence of hepatitis C virus RNA in the salivary glands of patients with Sjögren’s syndrome and hepatitis C virus infection. J Rheumatol 2002; 29(11): 2382-5.
[PMID: 12415596]
Ohoka S, Tanaka Y, Amako Y, et al. Sialadenitis in patients with chronic hepatitis C is not directly related to hepatitis C virus. Hepatol Res 2003; 27(1): 23-9.
[] [PMID: 12957203]
De Vita S, Damato R, De Marchi G, Sacco S, Ferraccioli G. True primary Sjögren’s syndrome in a subset of patients with hepatitis C infection: A model linking chronic infection to chronic sialadenitis. Isr Med Assoc J 2002; 4(12): 1101-5.
[PMID: 12516900]
Ramos-Casals M, Loustaud-Ratti V, De Vita S, et al. Sjögren syndrome associated with hepatitis C virus: A multicenter analysis of 137 cases. Medicine (Baltimore) 2005; 84(2): 81-9.
[] [PMID: 15758837]

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