ANA-H and/or SMA-AA does not exclude AIH, the characterAntibodies 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 35A 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 counterimmu-kidney microsomes type 1 (anti-LKM1) have been found noelectrophoresis; or 3) typical pattern by IFL on liver sec-more rarely (from 0% to 5%). [2][3][4] Variations in the autoantitions from phalloidin-intoxicated rats. ANA, SMA, and anti-body 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 Å .04 and 8% vs. 87%, P õ 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 õ .001 and 1:40 vs. 1:320, P õ .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 õ .000001). Two parameters were independently asThe major impact of the above autoantibodies in the hepasociated with the autoantibodie...

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basis the cases are defined autoimmune, in particular there Perinuclear anti-neutrophil cytoplasmic antibodies is no mention of the autoantibody profile. This is relevant (pANCA) have been recently defined as the most sensibecause it is fairly well accepted that AIH is not a unique tive autoantibody of type 1 autoimmune hepatitis (AIHentity. The classification recently proposed by Czaja and 1). Their prevalence in type 2 autoimmune hepatitis Manns 6 includes at least three types of AIH, each character-(AIH-2) has not yet been evaluated. The aim of the presized by distinct autoantibody markers as follows: high titre ent study was to verify the association of pANCA with smooth muscle antibody (SMA) and/or antinuclear antibody AIH-1 in an Italian series and to investigate the preva-(ANA) in type 1 (AIH-1), liver/kidney microsomal type 1 lence of the antibodies in AIH-2 and in proper control (LKM1) and/or liver cytosol type 1 (LC1) antibodies in type groups represented by cases of chronic hepatitis C (CH-2 (AIH-2), and soluble liver antigen antibody in type 3 (AIH-C) with similar autoimmune features. pANCA were 3). This immunopathological classification, although not acfound in 30 of 46 (65%) AIH-1 and in 4 of 30 (13%) ANA/ cepted by all hepatologists, allows comparison of data among smooth muscle antibody (SMA) positive CH-C (P Å different study groups and may influence the significance of .0000006). Nineteen AIH-2, 29 liver kidney microsomal new putative seroimmunological markers. antibody type 1/liver cytosol antibody type 1 (LKM1/LC1)A substantial proportion of ANA/SMA and LKM1/LC1 posipositive CH-C cases and 50 healthy controls were all negtive cases has evidence of concomitant hepatitis C virus infecative. In AIH-1, pANCA were significantly (P Å .009) more tion, at least in the Mediterranean area. 7,8 These intriguing frequent in males (8 of 9, 89%) than in females (22 of 37, cases are generally referred to as chronic hepatitis C (CH-C) 59%). All pANCA positive sera showed SMA of the antiwith autoimmune features and, although the term of unclasactin type. The present data confirm that pANCA, alsified chronic hepatitis as to viral or autoimmune origin has though less prevalent in our series than in other reports, been proposed, 9,10 we will use this current, less confusing do associate with AIH-1 also in the Mediterranean area jargon. Because no data are at present available concerning and show that it can identify a small subgroup (13%) of the prevalence of pANCA in these cases and in AIH type 2, ANA/SMA positive chronic hepatitis C, in which autoimthe present study was aimed both to validate the association mune reactions might play a more relevant role than of pANCA with AIH-1 in the Mediterranean area and to evalviral infection. They also show the antibodies are absent uate their occurrence in AIH-2 and in two groups of CH-C in AIH-2. In conclusion, pANCA appear to be mutually with identical autoantibodies. exclusive of LKM1 positivity, either hepatitis C virusrelated or not, thus representing a further val...