胆汁淤积在原发性干燥综合征中的意义

Sjogren's syndrome and cholestasis,highlight of primary Sjogren's syndrome cholangitis

目的探讨胆汁淤积在原发性干燥综合征(pSS)中的意义及其与原发性胆汁性肝硬化(PBC)的关联。方法将81例肯定的pSS患者按抗线粒体抗体(AMA)阳性与否分为两组,前瞻性地追随观察其临床表现、病程、实验室检查、转归有无异同。胆汁淤积标准定为血总胆红素(TBil)、碱性磷酸酶(ALP)、酌-谷氨酰转移酶(酌-GT)至少两项较正常增高1倍以上。结果AMA(+)组(46例)与AMA(-)组(35例)比较,在性别、年龄、血TBil、ALP、酌-GT,单项IgG、单项IgM增高及血抗核抗体(ANA)、类风湿因子(RF)、抗SSA和/或SSB抗体,抗着丝点抗体阳性例数上差异均无显著性。两组患者一般情况较好,皆有肝功能异常史长达20年的病例。两组皆有患者有干燥综合征(SS)症状或确诊为SS已多年,而只近年才出现胆汁淤积。20例AMA(+)及14例AMA(-)者查血核周型抗中性粒细胞胞质抗体(pANCA),前组1例阳性,后组3例阳性,其中2例行逆行胆管造影,皆示有硬化性胆管炎。9例AMA(+)及10例AMA(-)者行肝活检,除1例未见足够汇管区难作结论外,余均示汇管区及胆管炎症存在。81例皆予熊去氧胆酸、泼尼松、免疫抑制剂联合治疗,胆汁淤积很难完全消退,但前瞻性追随观察(最长者6年),绝大多数病例情况维持良好。结论①pSS所致胆管炎引起胆汁淤积可能并不少见。

Objective To study the significance of cholestasis in primary Sj?gren′s syndrome (pSS) and to clarify the relationship between pSS cholangitis and primary biliary cirrhosis (PBC).Method Eighty-one cases of pSS were studied prospectively and divided into 2 groups,the anti-mitochondrial antibodies(AMA) positive group and the AMA(-) group.The two groups were compared in terms of clinical manifestations,disease course,laboratory examinations and outcome.Cholestasis was categorized as two-fold increases of at least 2 of the blood bilirubin (TBil),alkaline phosphotase (ALP) and (-glutamyltranspeptidase ((-GT) determinations.Results No difference was found between AMA(+) and AMA(-) group in terms of sex,age,blood TBil,ALP, (-GT,single increase of IgG or IgM,ANA,RF,anti-SSA and/or SSB and anti-centromere antibodies.General condition of patients in both groups were relatively good.In both groups there were patients having had history of abnormal liver function tests for as long as 20 years,as well as patients with long history of SS symptoms (or having been diagnosed as SS) who only developed cholestasis in recent years.One of 20 AMA(+) and 3 of 14 AMA(-) patients showed positive pANCA.In 2 of the latter 3 patients,endoscopic retrograde cholangiography showed the presence of sclerosing cholangitis.Liver biopsy was done in 9 AMA(+) and 10 AMA(-) patients;all except one (not enough portal area seen) showed presence of pathological findings of bile ducts and of portal area.Eighty-one cases were subjected to combined treatment of ursodeoxycholic acid and corticosteroid and immunosuppressive agents.Cholestasis may improve but none totally recovered.Prospective follow-up examinations(the longest 6 years) showed all patients remained stationary.Conclusions ① Cholestasis due to cholangitis of pSS may not be a rarity and should be diagnosed as pSS cholangitis but not autoimmune hepatitis;②pSS cholangitis may be more commonly seen than 'classical' PBC.SS patients with cholestasis and AMA(+) should not all be randomly diagnosed as PBC.Similarly,SS in PBC should not all be considered as secondary SS.In fact,pSS may be one of the diseases that may cause 'PBC';③ pSS may be one of the causative factors of sclerosing cholangitis;④ Generally speaking,prognosis of pSS cholangitis is much better than 'classical' PBC.Differential diagnosis of these 2 conditions awaits immunological research in depth.Combined treatment of ursodeoxycholic acid and corticosteroid and immunosuppressive agents can not totally revert the cholestasis,yet may retard the progression of pSS cholangitis.One case has been followed up prospectively for 6 years,the patient′s general condition remained well.