Abstract
Among chronic viral infections, hepatitis C virus (HCV) infection is uniquely associated with an array of rheumatic manifestations and autoimmune laboratory findings. These include, among others, arthralgias, arthritis, fatigue, fibromyalgia, vasculitis, and sialadenitis (Sjögren-like). The mechanisms that are involved in the pathogenesis of these diverse manifestations have not yet been clarified. Regardless of the direct or indirect pathogenetic role of HCV in these clinical entities, the concomitant presence of a chronic viral infection creates a number of diagnostic and therapeutic problems. This is particularly true when immunosuppressive therapy is needed for control of disease activity (eg, HCV-associated cryoglobulinemic vasculitis). The emerging treatment options for chronic HCV offer a major chance for viral eradication and conceivably for cure of these HCV-associated conditions. In this review, the recent advances in the epidemiology, pathogenesis, clinical findings, and treatment of HCV-associated rheumatic conditions are presented.
Similar content being viewed by others
References and Recommended Reading
Lauer GM, Walker BD: Hepatitis C virus infection. N Engl J Med 2001, 45:41–52.
Ferri C, Zignego AL, Pileri SA: Cryoglobulins. J Clin Pathol 2002, 55:4–13.
Obermayer-Straub P, Manns MP: Hepatitis C and D, retroviruses and autoimmune manifestations. J Autoimmun 2001, 16:275–285.
Lovy MR, Starkebaum G: Rheumatic disorders associated with hepatitis C. Baillieres Best Pract Res Clin Rheumatol 2000, 14:535–557.
Herrine SK: Approach to the patient with chronic hepatitis C virus infection. Ann Intern Med 2002, 136:747–757.
Cacoub P, Poynard T, Ghillani P, et al.: Extrahepatic manifestations of chronic hepatitis C. Multi-department Virus C Group. Arthritis Rheum 1999, 42:2204–2212. The largest study in the literature with data on extrahepatic manifestations and laboratory findings in 1614 patients infected with HCV.
Cacoub P, Renou C, Rosenthal E, et al.: Extrahepatic manifestations associated with hepatitis C virus infection: a prospective multicenter study of 321 patients. Medicine (Baltimore) 2000, 79:47–56.
Buskila D: Hepatitis C-associated arthritis. Curr Opin Rheumatol 2000, 12:295–299.
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, 28:107–113.
Kessel A, Rosner I, Zuckerman E, et al.: Use of antikeratin antibodies to distinguish between rheumatoid arthritis and polyarthritis associated with hepatitis C infection. J Rheumatol 2000, 27:610–612.
Ioannou Y, Isenberg DA: Current evidence for the induction of autoimmune rheumatic manifestations by cytokine therapy. Arthritis Rheum 2000, 43:1431–1442.
Levesque MC, Ward FE, Jeffery DR, et al.: Interferon-beta1Ainduced polyarthritis in a patient with the HLA-DRB1*0404 allele. Arthritis Rheum 1999, 42:569–573.
Passos DS, Evangelista SP, Jose FF, et al.: Rheumatoid arthritis induced by alpha-interferon therapy. Clin Rheumatol 2002, 20:297–299.
Zuckerman E, Keren D, Rozenbaum M, et al.: Hepatitis C virusrelated arthritis: characteristics and response to therapy with interferon alpha. Clin Exp Rheumatol 2000, 18:579–584.
Goulding C, O’Connell P, Murray FE: Prevalence of fibromyalgia, anxiety and depression in chronic hepatitis C virus infection: relationship to RT-PCR status and mode of acquisition. Eur J Gastroenterol Hepatol 2001, 13:507–511.
Poynard T, Cacoub P, Ratziu V, et al.: Fatigue in patients with chronic hepatitis C. J Viral Hepat 2002, 9:295–303.
Wessely S, Pariante C: Fatigue, depression and chronic hepatitis C infection. Psychol Med 2002, 32:1–10.
Cacoub P, Ratziu V, Myers RP, et al.: Impact of treatment on extra hepatic manifestations in patients with chronic hepatitis C. J Hepatol 2002, 36:812–818. Retrospective analysis of the impact of antiviral treatment to a variety of HCV-associated extrahepatic manifestations.
Vassilopoulos D, Calabrese LH: Hepatitis C virus infection and vasculitis: implications of antiviral and immunosuppressive therapies. Arthritis Rheum 2002, 46:585–597.
Lamprecht P, Gause A, Gross WL: Cryoglobulinemic vasculitis. Arthritis Rheum 1999, 42:2507–2516.
Garini G, Allegri L, Carnevali L, et al.: Interferon-alpha in combination with ribavirin as initial treatment for hepatitis C virus-associated cryoglobulinemic membranoproliferative glomerulonephritis. Am J Kidney Dis 2001, 38:E35.
Misiani R, Bellavita P, Baio P, et al.: Successful treatment of HCV-associated cryoglobulinaemic glomerulonephritis with a combination of interferon-alpha and ribavirin. Nephrol Dial Transplant 1999, 14:1558–1560.
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, 27:2172–2178. First report in the literature of nine patients with HCV-associated CV treated with combination antiviral therapy (standard IFNá and ribavirin).
Boonyapisit K, Katirji B: Severe exacerbation of hepatitis Cassociated vasculitic neuropathy following treatment with interferon alpha: a case report and literature review. Muscle Nerve 2002, 25:909–913. Review of reported cases of HCV-associated neuropathy that deteriorated after treatment with IFNá.
Thiel J, Peters T, Mas MA, et al.: Kinetics of hepatitis C (HCV) viraemia and quasispecies during treatment of HCV associated cryoglobulinaemia with pulse cyclophosphamide. Ann Rheum Dis 2002, 61:838–841.
Zaja F, De Vita S, Russo D, et al.: Rituximab for the treatment of type II mixed cryoglobulinemia. Arthritis Rheum 2002, 46:2252–2254. Preliminary report on the efficacy of rituximab in three patients with HCV-associated type II mixed cryoglobulinemia.
Cacoub P, Maisonobe T, Thibault V, et al.: Systemic vasculitis in patients with hepatitis C. J Rheumatol 2001, 28:109–118.
Costedoat-Chalumeau N, Cacoub P, Maisonobe T, et al.: Renal microaneurysms in three cases of hepatitis C virus-related vasculitis. Rheumatology (Oxford) 2002, 41:708–710.
Ramos-Casals M, Garcia-Carrasco M, Cervera R, et al.: Sjogren’s syndrome and hepatitis C virus. Clin Rheumatol 1999, 18:93–100.
Ramos-Casals M, Garcia-Carrasco M, Cervera R, et al.: Hepatitis C virus infection mimicking primary Sjogren syndrome: a clinical and immunologic description of 35 cases. Medicine (Baltimore) 2001, 80:1–8. A comparative study of the clinical and laboratory findings between patients with primary SS and HCV-associated sialadenitis.
Loustaud-Ratti V, Riche A, Liozon E, et al.: Prevalence and characteristics of Sjogren’s syndrome or Sicca syndrome in chronic hepatitis C virus infection: a prospective study. J Rheumatol 2001, 28:2245–2251.
Arrieta JJ, Rodriguez-Inigo E, Ortiz-Movilla N, et al.: In situ detection of hepatitis C virus RNA in salivary glands. Am J Pathol 2001, 158:259–264. First report on the presence of replicating HCV in the epithelial cells of the salivary glands of patients with HCV-associated sialadenitis using sensitive molecular and hybridization techniques.
Hadziyannis SJ, Vassilopoulos D: Complex management issues: management of HCV in the atypical patient. Baillieres Best Pract Res Clin Gastroenterol 2000, 14:277–291.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Vassilopoulos, D., Calabrese, L.H. Rheumatic manifestations of hepatitis C infection. Curr Rheumatol Rep 5, 200–204 (2003). https://doi.org/10.1007/s11926-003-0067-8
Issue Date:
DOI: https://doi.org/10.1007/s11926-003-0067-8