ANA-H and/or SMA-AA does not exclude AIH, the character-Antibodies to nuclei (ANA), smooth muscle (SMA), and ization of ANA and SMA may help to discriminate between liver/kidney microsomes type 1 (anti-LKM1) may occur in the two conditions. As compared with the seronegative counchronic hepatitis C. Distinct subspecificities, including ANA terpart, autoantibody-positive chronic hepatitis C is more with the homogeneous pattern (ANA-H) and SMA with anticommon in females and exhibits a more severe biochemical actin specificity (SMA-AA), are found in autoimmune hepatiand histological activity. The response to IFN therapy, howtis (AIH). This study was performed to characterize the hepaever, is similar. (HEPATOLOGY 1997;26:561-566.) titis C virus (HCV)-associated autoantibodies and to evaluate their influence on the profile of the disease. Two hundred ninety consecutive patients with chronic hepatitis C and 35
A variety of immunological abnormalities has been decontrol cases with AIH were screened for autoantibodies by scribed in patients with chronic hepatitis C. In particular, indirect immunofluorescence (IFL) at 1:40 serum dilution. the occurrence of serum non-organ-specific autoantibodies The ANA pattern was defined by IFL on HEp-2 cells and the has been extensively studied: smooth muscle (SMA) and anti-SMA-AA identified by the presence of at least two of the nuclear (ANA) antibodies have been detected in approxifollowing elements: 1) SMA T or SMA G pattern by IFL on mately one third of the cases, 1,2 while antibodies to liver/ kidney sections; 2) XR 1 precipitating system by counterimmukidney microsomes type 1 (anti-LKM1) have been found noelectrophoresis; or 3) typical pattern by IFL on liver secmore rarely (from 0% to 5%). [2][3][4] Variations in the autoantitions from phalloidin-intoxicated rats. ANA, SMA, and antibody prevalence among the reports so far published 1-7 have LKM1 occurred in 9%, 20%, and 6% of chronic hepatitis C been attributed both to different experimental conditions in cases, respectively. The overall prevalence of autoantibodies the immunofluorescence (IFL) procedure and to ethnical and was 30% (87 of 290). Compared with AIH, HCV-associated geographical differences in the study populations.
ANA and SMA exhibited ANA-H and SMA-AA at a lower
Most reports agree that the autoantibody positivity does prevalence (38% vs. 71%, P Γ
.04 and 8% vs. 87%, P Γ΅ not influence either the clinical and biochemical profile of .000001, respectively) and had a lower median titer (1:80 vs. chronic hepatitis C or the response to interferon (IFN) alfa. 1:320, P Γ΅ .001 and 1:40 vs. 1:320, P Γ΅ .000001, respec-Some data, however, have been published on the occurrence tively). The concomitant positivity for ANA-H and SMA-AA of disease activity exacerbations in patients with serum autowas detected in none of the HCV cases, but in 46% of AIH antibodies during IFN treatment. 8-10 sera (P Γ΅ .000001). Two parameters were independently as-
The major impact of the above autoantibodies in the hepasociated with the autoantibodies in chronic hepatitis C: high tological area relies on their well-recognized role as diagnosalanine transaminase (ALT) serum levels (F Γ
14.04) and tic markers of type 1 (ANA and/or SMA) 11 and type 2 (antifemale gender (F Γ
5.03). At the univariate analysis, patients LKM1) 12 autoimmune hepatitis (AIH), respectively. It must with autoantibodies had a more severe portal-periportal nebe taken into account that each of the three reactivities does croinflammation (median Scheuer's score: 2.05 vs. 1.64, P Γ
actually include antigenically heterogeneous antibodies. [13][14][15] .003). The presence of autoantibodies did not influence the Within ANA and SMA, subspecificities have been identified, response to interferon (IFN). In chronic hepatitis C, serum such as ANA with homogeneous IFL pattern (ANA-H) and autoantibodies are common, but their subspecificities are dis-SMA with anti-actin specificity (SMA-AA), which are more tinct from those occurring in AIH. Whereas the absence of closely associated to AIH. 16 Other ANA and SMA subspecificities have been conversely reported in association with viral liver disorders, 17,18 in particular, chronic posttransfusion non Abbreviations: SMA, smooth muscle antibodies; ANA, antinuclear antibodies; anti-A, non B hepatitis, 19 subsequently identified as chronic hepa-LKM1, liver/kidney microsome type 1 antibodies; IFL, immunofluorescence; IFN, intertitis C. feron; AIH, autoimmune hepatitis; HCV, hepatitis C virus; ALT, alanine transaminase.