From January 1996 to January 1997, 321 patients with an average age of 46 +/- 16 years and chronically infected with hepatitis C virus (HCV) were prospectively enrolled in a study designed to determine the prevalence of extrahepatic manifestations associated with HCV
infection in a large cohort of HCV patients, to identify associations between clinical and
biologic manifestations, and to compare the results obtained in human immunodeficiency virus (HIV)-positive versus HIV-negative subsets. In a cross-sectional study, clinical extrahepatic manifestations, viral
coinfections with HIV and/or hepatitis B virus,
connective tissue diseases, and a wide panel of
autoantibodies were assessed. Thirty-eight percent (122/321) of patients presented at least 1 clinical extrahepatic manifestation including
arthralgia (60/321, 19%),
skin manifestations (55/321, 17%),
xerostomia (40/321, 12%),
xerophthalmia (32/321, 10%), and sensory neuropathy (28/321, 9%). Main
biologic abnormalities were mixed
cryoglobulins (110/196, 56%),
thrombocytopenia (50/291, 17%), and the presence of the following
autoantibodies: antinuclear (123/302, 41%),
rheumatoid factor (107/280, 38%), anticardiolipin (79/298, 27%),
antithyroglobulin (36/287, 13%) and antismooth muscle cell (27/288, 9%). At least 1
autoantibody was present in 210/302 (70%) of sera. By multivariate logistic regression analysis, 4 parameters were significantly associated with
cryoglobulin positivity:
systemic vasculitis (p = 0.01, odds ratio OR[ = 17.3), HIV positivity (p = 0.0006, OR = 10.2),
rheumatoid factor positivity (p = 0.01, OR = 2.8), and
sicca syndrome (p = 0.03, OR = 0.27). A definite
connective tissue disease was noted in 44 patients (14%), mainly symptomatic mixed
cryoglobulinemia and
systemic vasculitis,
HIV coinfection (23%) was associated with 3 parameters: anticardiolipin (p = 0.003, OR = 4.18),
thrombocytopenia (p = 0.01, OR = 3.56), and
arthralgia or
myalgia (p = 0.017, OR = 0.23). HIV-positive patients presented more severe histologic lesions (p = 0.0004). Extrahepatic clinical manifestations in HCV patients involve primarily the skin and joints. The most frequent immunologic abnormalities include mixed
cryoglobulins,
rheumatoid factor, antinuclear, anticardiolipin, and
antithyroglobulin antibodies.
Cryoglobulin positivity is associated with
systemic vasculitis and
rheumatoid factor and HIV positivity.
HIV coinfection is associated with
arthralgia or
myalgia,
anticardiolipin antibodies, and
thrombocytopenia.