Choi Su Hyun, Choi Gwang Hyeon, Jang Eun Sun, Lee Youn Jae, Kim Young Seok, Kim In Hee, Cho Sung Bum, Lee Byung Seok, Kim Kyung-Ah, Chung Woo Jin, Baik Dahye, Ki Moran, Jeong Sook-Hyang
Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.
Department of Internal Medicine, Inje University Busan Paik Hospital, Busan, Republic of Korea.
Transl Gastroenterol Hepatol. 2025 Apr 10;10:24. doi: 10.21037/tgh-24-134. eCollection 2025.
Hepatitis C virus (HCV) infection causes extrahepatic manifestations involving B-cell dysregulation and autoantibody production. This study aimed to elucidate the positivity rates of four autoantibodies [anti-nuclear antibody (ANA), anti-smooth muscle antibody (ASMA), anti-liver kidney microsomal type 1 (anti-LKM1), and anti-mitochondrial antibody (AMA)] in patients with chronic hepatitis C (CHC) before and after direct-acting antiviral (DAA) therapy compared to those in healthy controls.
This study enrolled prospectively collected plasma samples from 201 CHC patients [median age, 62 years; 49.8% women; 100% sustained virological response (SVR)] from eight hospitals before and after DAA therapy and 127 healthy individuals. Autoantibodies were detected using indirect immunofluorescence.
The positivity rate of ANA was higher in CHC patients than in healthy controls (32.3% 21.3%, P=0.03) at pretreatment (PreTx) and decreased at SVR (32.3% 23.9%, P=0.009). Female sex and higher globulin levels were related to ANA positivity in the control and CHC patient groups. Thirty-seven (57%) of 65 patients with ANA-positive HCV at PreTx maintained ANA-positivity at SVR. Among the 136 ANA-negative patients at PreTx, 11 (8%) showed newly positive ANA conversion at SVR. Patients with ANA positivity at SVR (n=48) were older and had a higher proportion of advanced liver disease than ANA-negative patients (n=153).
ANA positivity was observed in one-third of CHC patients at PreTx, which was significantly higher than that in healthy controls and decreased after SVR. CHC patients with ANA positivity after SVR were older and had more advanced liver disease than those with ANA negativity, suggesting persistent immune dysregulation after cure.
丙型肝炎病毒（HCV）感染会引发肝外表现，包括B细胞失调和自身抗体产生。本研究旨在阐明慢性丙型肝炎（CHC）患者在直接抗病毒（DAA）治疗前后四种自身抗体[抗核抗体（ANA）、抗平滑肌抗体（ASMA）、抗肝肾微粒体1型抗体（抗-LKM1）和抗线粒体抗体（AMA）]的阳性率，并与健康对照者进行比较。
本研究前瞻性收集了来自八家医院的201例CHC患者[中位年龄62岁；49.8%为女性；100%获得持续病毒学应答（SVR）]在DAA治疗前后的血浆样本以及127名健康个体的血浆样本。采用间接免疫荧光法检测自身抗体。
CHC患者在治疗前（PreTx）ANA阳性率高于健康对照者（32.3%对21.3%，P = 0.03），在SVR时下降（32.3%对23.9%，P = 0.009）。在对照组和CHC患者组中，女性和较高的球蛋白水平与ANA阳性相关。65例PreTx时ANA阳性的HCV患者中有37例（57%）在SVR时仍保持ANA阳性。在PreTx时136例ANA阴性的患者中，11例（8%）在SVR时出现新的ANA阳性转换。SVR时ANA阳性的患者（n = 48）比ANA阴性的患者（n = 153）年龄更大，晚期肝病比例更高。
三分之一的CHC患者在PreTx时ANA呈阳性，显著高于健康对照者，且在SVR后下降。SVR后ANA阳性的CHC患者比ANA阴性的患者年龄更大，肝病更严重，提示治愈后存在持续的免疫失调。
