METHODS: All patients were screened for cryoglobulins, rheumatoid factor (RF), C3, C4, antinuclear antibody (ANA), anti-smooth muscle (ASMA), anti-liver kidney microsome type 1 (anti-LKM1), anti-mitochondrial antibodies (AMA), anti-neutrophil cytoplasmic antibodies (ANCA), and anti-liver cytosol type 1/soluble liver antigen (anti-LC1/SLA) autoantibodies before therapy and 12, 48 and 96 weeks after treatment. They were then grouped according to the expression of laboratory findings and related autoimmune diseases.
RESULTS: At baseline, autoimmune manifestations were found in 70 patients: 83% of them were cryoglobulinemic, whereas ANA, AMA, perinuclear ANCA (pANCA) and LKM/LC1 autoantibodies were found in the remaining 17%. An autoimmune disease was diagnosed in 9 cases, two of them featuring an autoimmune liver disease (AILD). At the end of follow-up, despite viral clearance and regression of vasculitis, cryoglobulins persisted in 12 patients (21%), and autoantibodies disappeared or decreased in most of cases but, with the exception of the 2 patients diagnosed as AILD, associated autoimmune diseases remained stable. In one patient with relapsing cryoglobulinemia and ANA positivity, type-1 autoimmune hepatitis was defined. Conversely, autoantibodies first appeared after viral clearance in 5 patients, of whom one was diagnosed with type-1 autoimmune hepatitis and one with pANCA+ primary sclerosing cholangitis.
CONCLUSIONS: Following DAA-induced viral clearance, cryoglobulins may persist or reappear. Autoantibodies changed dynamically in step with the disappearance of a previously diagnosed or the occurrence of a new AILD. A longer follow-up will be necessary to establish the possible diagnosis of a newly onset AILD, the reactivation of cryoglobulinemic vasculitis and even its progression to non-Hodgkin lymphoma.
方法:所有患者均接受冷球蛋白筛查,类风湿因子(RF),C3,C4,抗核抗体(ANA),抗平滑肌(ASMA),抗肝肾微粒体1型(抗LKM1),抗线粒体抗体(AMA),抗中性粒细胞胞浆抗体(ANCA),治疗前和治疗后12、48和96周的抗肝细胞溶胶1型/可溶性肝抗原(抗LC1/SLA)自身抗体。然后根据实验室发现和相关自身免疫性疾病的表达对它们进行分组。
结果:在基线时,在70例患者中发现了自身免疫性表现:其中83%是冷球蛋白血症,而ANA,AMA,在剩余的17%中发现了核周ANCA(pANCA)和LKM/LC1自身抗体。9例诊断为自身免疫性疾病,其中两个以自身免疫性肝病(AILD)为特征。在后续行动结束时,尽管病毒清除和血管炎消退,冷球蛋白在12例患者中持续存在(21%),在大多数情况下,自身抗体消失或减少,但是,除了诊断为AILD的2例患者外,相关的自身免疫性疾病保持稳定。在一名复发性冷球蛋白血症和ANA阳性的患者中,1型自身免疫性肝炎的定义。相反,自身抗体首次出现在5例患者的病毒清除后,其中1人被诊断为1型自身免疫性肝炎,1人被诊断为pANCA+原发性硬化性胆管炎。
结论:在DAA诱导的病毒清除后,冷球蛋白可能持续存在或重新出现.自身抗体随着先前诊断的消失或新的AILD的发生而动态变化。需要更长的随访以确定新发作的AILD的可能诊断。冷球蛋白血症性血管炎的再激活,甚至进展为非霍奇金淋巴瘤。