Background/Aims: Immune mechanisms may modulate disease severity in ch
ronic hepatitis C and the DR human leukocyte antigens may affect these
mechanisms. Our aims were to evaluate the association between the DR
antigens and disease severity at presentation and to seek correlation
between these antigens, disease severity and autoantibodies in this co
ndition. Methods: Sixty-four patients were assessed prospectively and
classified as having mild, moderate and severe disease by clinical, la
boratory and histologic criteria. Fourteen DR antigens were determined
by restriction fragment length polymorphism or polymerase chain react
ion-sequence specific primers. Eighty normal subjects were typed in a
similar fashion. Results: Patients with mild (16), moderate (32) and s
evere (16) disease at presentation were indistinguishable from each ot
her and from normal subjects by the frequencies of each DR antigen. Su
bsets of patients with different laboratory and histologic findings ha
d DR frequencies comparable to those without these findings and to tho
se of normal subjects, Patients with autoantibodies and/or concurrent
immunologic diseases had mild (19% versus 32%, p=0.4), moderate (50% v
ersus 50%) and severe (31% versus 18%, p=0.4) disease as commonly as o
ther patients. The frequencies of the DR antigens were similar in each
category of disease severity. Patients with autoimmune features diffe
red from patients without these features (3% versus 32%, p=0.002) and
normal subjects (3% versus 25%, p=0.003) by having a lower frequency o
f HLA DR1. Conclusions: The DR antigens are not associated with any in
dex of disease severity at presentation. Immunologic manifestations do
not identify patients with a different disease severity or a distinct
ive genetic predisposition for disease activity. The presence of DR 1
is associated with a lower frequency of immune manifestations.