Abstract：
BACKGROUND: Hepatitis C virus (HCV) chronic infection is frequently associated to autoimmune manifestations. The aim of this study was to prospectively evaluate the occurrence of clinical and/or laboratory features of autoimmunity in a cohort of 140 consecutive HCV chronically infected patients treated with direct-acting antiviral agents (DAAs) and followed-up for 96 weeks.
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.
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.
摘要：
背景：丙型肝炎病毒（HCV）慢性感染通常与自身免疫表现有关。这项研究的目的是前瞻性评估140例接受直接作用抗病毒药物（DAA）治疗并随访96周的连续HCV慢性感染患者中自身免疫的临床和/或实验室特征的发生。
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。
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。
