Study of host and virological factors of patients with chronic HCV infection and associated laboratory or clinical autoimmune manifestations

D. Vassilopoulos¹, Z.M. Younossi², E. Hadziyannis³, N. Boparai², B. Yen-Lieberman³, E. Hsi³, A. Villa-Forte¹, E. Ball⁴, R.P. Kimberly⁵, L.H. Calabrese¹

¹Department of Rheumatic and Immunologic Diseases, ²Department of Gastroenterology, ³Department of Pathology and Laboratory Medicine, and ⁴Allogen Laboratories, The Cleveland Clinic Foundation, Cleveland, Ohio; ⁵Division of Clinical Immunology and Rheumatology, Departments of Medicine and Microbiology, 
University of Alabama at Birmingham, Birmingham, Alabama, USA.

ABSTRACT
Objective
Chronic hepatitis C virus (HCV) infection is associated with an array of autoimmune laboratory and clinical manifestations. The goals of our study were to identify host and/or virological factors that are implicated in the pathogenesis of these manifestations.

Methods
We performed a detailed prospective study of various demographic, virological, biochemical, immunological (including lymphocyte subsets, Fcg-receptor and HLA class-II genotyping), histological and host genetic parameters in 3 well defined subgroups of HCV patients (n = 40): patients with liver disease only (group I, n = 11) or with laboratory (group II, n = 20) and clinical (group III, n = 9) autoimmune manifestations.

Results
Group III patients, mainly with features of mixed cryoglobulinemia, were older, with higher levels of rheumatoid factor and circulating cryoglobulins while they tended to have a longer estimated disease duration compared to the other two groups of patients. We did not identify any specific immunological features that could differentiate symptomatic versus asymptomatic patients, except from the elevated soluble interleukin-2 receptor levels. An increased frequency of the R/R131 FcRgIIIA and the NA1/NA1 FcgRIIIB genotypes was observed in our total HCV population, regardless of autoimmune manifestations, compared to historical controls. No statistically significant differences in HLA class II allele frequencies was detected between patient subgroups or in comparison to healthy controls.

Conclusions
Chronically infected HCV patients with symptomatic mixed cryoglobulinemia display a number of unique characteristics that differentiate them from asymptomatic patients with chronic hepatitis C.

Key words
Hepatitis C virus, hepatitis C, cryoglobulinemia.

Please address correspondence to: Leonard H. Calabrese, D.O., Vice Chairman, Department of Rheumatic and Immunologic Diseases/A50, R.J. Fasenmeyer Chair of Clinical Immunology, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195-5028, USA. E-mail: calabrl@ccf.org

Clin Exp Rheumatol 2003; 21: (Suppl. 32): S101-S111.
© Copyright Clinical and Experimental Rheumatology 2003.