类风湿因子和免疫球蛋白 M 标记丙型肝炎相关性混合性冷球蛋白血症：一项 8 年的前瞻性研究。
Rheumatoid factor and immunoglobulin M mark hepatitis C-associated mixed cryoglobulinaemia: an 8-year prospective study.
机构信息
Liver Research Centre, Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Clinical Informatics and Medical Statistics Research Centre, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Emergency Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan.
出版信息
Clin Microbiol Infect. 2020 Mar;26(3):366-372. doi: 10.1016/j.cmi.2019.06.018. Epub 2019 Jun 20.
OBJECTIVES
The prevalence and factors of hepatitis C virus (HCV) -associated mixed cryoglobulinaemia in Asia remain elusive, and we aimed to investigate these topics.
METHODS
An 8-year prospective cohort study was conducted in 678 consecutive Taiwanese individuals with chronic HCV infection (438 completed an anti-HCV therapy course).
RESULTS
Of 678 individuals, 437 (64.5%) had mixed cryoglobulinaemia and 20 (2.9%) had mixed cryoglobulinaemic syndrome. At baseline, IgM (cut-off >122 mg/dL), triglycerides and IgG levels, and HCV genotype 3 were independently associated with mixed cryoglobulinaemia. Rheumatoid factor (RF) levels were associated with mixed cryoglobulinaemic syndrome (cut-off >12.2 IU/mL). At 24 weeks post-therapy, the 362 individuals with a sustained virological response (SVR) had higher cured (106/362 (29.3%) versus 10/76 (13.2%), p = 0.003) and lower persistent (100/362 (27.6%) versus 33/76 (43.4%), p = 0.003) mixed cryoglobulinaemia rates than non-SVR patients. Among SVR patients, compared with baseline levels, RF, IgG and IgM levels decreased, except in individuals with new mixed cryoglobulinaemia. Pre-therapy IgM levels were associated with 24-week post-therapy new (95% CI of OR 1.002-1.023) and persistent (95% CI of OR 1.004-1.015) mixed cryoglobulinaemia in SVR patients. After up to 8 years, 24-week post-therapy IgM levels were associated with mixed cryoglobulinaemia in SVR patients (9/51; 17.64%; 95% CI of HR 1.004-1.011). Among 17 SVR patients with pre-therapy mixed cryoglobulinaemic syndrome, 5 (29.4%) had long-term mixed cryoglobulinaemia and 4 (23.5%) had mixed cryoglobulinaemic syndrome.
CONCLUSIONS
Over 60% of chronic HCV-infected individuals had mixed cryoglobulinaemia, and 17.64% of SVR patients had mixed cryoglobulinaemia 8 years post-therapy. Pre-therapy RF and IgM levels marked HCV-associated mixed cryoglobulinaemic syndrome and mixed cryoglobulinaemia, respectively.
目的
亚洲丙型肝炎病毒（HCV）相关混合性冷球蛋白血症的流行情况和相关因素仍不明确，本研究旨在探讨这些问题。
方法
对 678 例连续的台湾慢性 HCV 感染个体（438 例完成了抗 HCV 治疗疗程）进行了 8 年的前瞻性队列研究。
结果
678 例个体中，437 例（64.5%）存在混合性冷球蛋白血症，20 例（2.9%）存在混合性冷球蛋白血症综合征。基线时，IgM（截断值>122mg/dL）、甘油三酯和 IgG 水平以及 HCV 基因型 3 与混合性冷球蛋白血症独立相关。类风湿因子（RF）水平与混合性冷球蛋白血症综合征相关（截断值>12.2IU/mL）。治疗 24 周后，362 例获得持续病毒学应答（SVR）的个体中，治愈的混合性冷球蛋白血症（106/362（29.3%）与未治愈的混合性冷球蛋白血症（10/76（13.2%）相比，差异具有统计学意义（p=0.003），持续性混合性冷球蛋白血症的发生率更低（100/362（27.6%）与未治愈的混合性冷球蛋白血症（33/76（43.4%）相比，差异具有统计学意义（p=0.003）。在 SVR 患者中，与基线水平相比，RF、IgG 和 IgM 水平降低，新发生混合性冷球蛋白血症的患者除外。治疗前 IgM 水平与 SVR 患者 24 周时新发生（95%CI的 OR 值为 1.002-1.023）和持续性（95%CI的 OR 值为 1.004-1.015）混合性冷球蛋白血症相关。随访 8 年后，24 周时 IgM 水平与 SVR 患者的混合性冷球蛋白血症相关（9/51；17.64%；95%CI 的 HR 值为 1.004-1.011）。在 17 例治疗前患有混合性冷球蛋白血症综合征的 SVR 患者中，5 例（29.4%）发生了持续性混合性冷球蛋白血症，4 例（23.5%）发生了混合性冷球蛋白血症综合征。
结论
超过 60%的慢性 HCV 感染者存在混合性冷球蛋白血症，在治疗后 8 年，17.64%的 SVR 患者存在混合性冷球蛋白血症。治疗前的 RF 和 IgM 水平分别提示 HCV 相关混合性冷球蛋白血症和混合性冷球蛋白血症综合征。
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