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慢性丙型肝炎中的血清自身抗体:与自身免疫性肝炎的比较及其对疾病特征的影响。

Serum autoantibodies in chronic hepatitis C: comparison with autoimmune hepatitis and impact on the disease profile.

作者信息

Cassani F, Cataleta M, Valentini P, Muratori P, Giostra F, Francesconi R, Muratori L, Lenzi M, Bianchi G, Zauli D, Bianchi F B

机构信息

Semeiotica Medica II, Department of Internal Medicine, Cardioangiology and Hepatology, Azienda Ospedaliera S. Orsola-Malpighi, University of Bologna, Italy.

出版信息

Hepatology. 1997 Sep;26(3):561-6. doi: 10.1002/hep.510260305.

DOI:10.1002/hep.510260305
PMID:9303483
Abstract

Antibodies to nuclei (ANA), smooth muscle (SMA), and liver/kidney microsomes type 1 (anti-LKM1) may occur in chronic hepatitis C. Distinct subspecificities, including ANA with the homogeneous pattern (ANA-H) and SMA with antiactin specificity (SMA-AA), are found in autoimmune hepatitis (AIH). This study was performed to characterize the hepatitis 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 control cases with AIH were screened for autoantibodies by indirect immunofluorescence (IFL) at 1:40 serum dilution. The ANA pattern was defined by IFL on HEp-2 cells and the SMA-AA identified by the presence of at least two of the following elements: 1) SMA(T) or SMA(G) pattern by IFL on kidney sections; 2) XR1 precipitating system by counterimmunoelectrophoresis; or 3) typical pattern by IFL on liver sections from phalloidin-intoxicated rats. ANA, SMA, and anti-LKM1 occurred in 9%, 20%, and 6% of chronic hepatitis C cases, respectively. The overall prevalence of autoantibodies was 30% (87 of 290). Compared with AIH, HCV-associated ANA and SMA exhibited ANA-H and SMA-AA at a lower prevalence (38% vs. 71%, P = .04 and 8% vs. 87%, P < .000001, respectively) and had a lower median titer (1:80 vs. 1:320, P < .001 and 1:40 vs. 1:320, P < .000001, respectively). The concomitant positivity for ANA-H and SMA-AA was detected in none of the HCV cases, but in 46% of AIH sera (P < .000001). Two parameters were independently associated with the autoantibodies in chronic hepatitis C: high alanine transaminase (ALT) serum levels (F = 14.04) and female gender (F = 5.03). At the univariate analysis, patients with autoantibodies had a more severe portal-periportal necroinflammation (median Scheuer's score: 2.05 vs. 1.64, P = .003). The presence of autoantibodies did not influence the response to interferon (IFN). In chronic hepatitis C, serum autoantibodies are common, but their subspecificities are distinct from those occurring in AIH. Whereas the absence of ANA-H and/or SMA-AA does not exclude AIH, the characterization of ANA and SMA may help to discriminate between the two conditions. As compared with the seronegative counterpart, autoantibody-positive chronic hepatitis C is more common in females and exhibits a more severe biochemical and histological activity. The response to IFN therapy, however, is similar.

摘要

核抗体(ANA)、平滑肌抗体(SMA)和1型肝肾微粒体抗体(抗LKM1)可能出现在慢性丙型肝炎中。自身免疫性肝炎(AIH)中发现了不同的亚特异性,包括均质型ANA(ANA-H)和具有抗肌动蛋白特异性的SMA(SMA-AA)。本研究旨在对丙型肝炎病毒(HCV)相关自身抗体进行特征分析,并评估其对疾病特征的影响。通过间接免疫荧光法(IFL)在血清稀释度为1:40时,对290例连续的慢性丙型肝炎患者和35例AIH对照病例进行自身抗体筛查。ANA模式通过在HEp-2细胞上的IFL确定,SMA-AA通过以下至少两个要素的存在来识别:1)在肾切片上通过IFL呈现的SMA(T)或SMA(G)模式;2)通过对流免疫电泳的XR1沉淀系统;或3)在来自鬼笔环肽中毒大鼠的肝切片上通过IFL呈现的典型模式。ANA、SMA和抗LKM1分别出现在9%、20%和6%的慢性丙型肝炎病例中。自身抗体的总体患病率为30%(290例中的87例)。与AIH相比,HCV相关的ANA和SMA表现出ANA-H和SMA-AA的患病率较低(分别为38%对71%,P = 0.04和8%对87%,P < 0.000001),且中位滴度较低(分别为1:80对1:320,P < 0.001和1:40对1:320,P < 0.000001)。在HCV病例中未检测到ANA-H和SMA-AA的同时阳性,但在46%的AIH血清中检测到(P < 0.000001)。在慢性丙型肝炎中,有两个参数与自身抗体独立相关:高血清丙氨酸转氨酶(ALT)水平(F = 14.04)和女性性别(F = 5.03)。在单因素分析中,有自身抗体的患者有更严重的门脉周围坏死性炎症(中位Scheuer评分:2.05对1.64,P = 0.003)。自身抗体的存在不影响对干扰素(IFN)的反应。在慢性丙型肝炎中,血清自身抗体很常见,但其亚特异性与AIH中出现的不同。虽然ANA-H和/或SMA-AA的缺失并不排除AIH,但ANA和SMA的特征分析可能有助于区分这两种情况。与血清阴性的患者相比,自身抗体阳性的慢性丙型肝炎在女性中更常见,并且表现出更严重的生化和组织学活性。然而,对IFN治疗的反应相似。

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