丙型肝炎病毒慢性感染相关的系统性自身免疫病分析

Analysis of Clinical Manifestations and Treatment Response in Patients with Chronic Hepatitis C Virus Infection Related Systemic Autoimmune Diseases

目的描述和分析丙型肝炎病毒(HCV)慢性感染相关系统性自身免疫病(SAD)患者的临床表现、实验室检查特征、治疗及预后。方法对1989年至2009年北京协和医院收治的12例HCV慢性感染相关SAD患者的临床表现、实验室检查特征及治疗情况进行统计和分析。结果 12例患者在发现慢性HCV感染后发生SAD,其中5例系统性红斑狼疮(SLE)、2例冷球蛋白血症、1例显微镜下多血管炎(MPA)、1例结节性多动脉炎(PAN)、1例系统性硬化(SSc)、1例类风湿关节炎(RA)合并多发性肌炎(PM)、1例皮肌炎(DM)。男女比例为1:11,发现慢性HCV感染时平均年龄为39.8岁(18～62岁),SAD平均发病年龄为41.5岁(23～62岁)。所有患者都符合相应SAD的分类标准,最常见临床表现为血液系统受累(83.3%)和皮肤受累(66.7%),最常见实验室检查特征为抗核抗体(ANA)阳性(83.3%),红细胞沉降率增快(83.3%)和低补体血症(75.0%)。对5例SLE患者进行亚组分析显示,其临床表现和实验室检查结果与一般SLE患者差异无显著性。此外,12例伴发SAD的慢性HCV感染者中,11例(91.7%)丙氨酸转氨酶(ALT)水平正常,ALT正常率显著高于慢性HCV感染患者的平均水平(P<0.01)。SAD的治疗,除1例患者拒绝治疗自行出院外,其余11例患者采用糖皮质激素联合免疫抑制剂治疗均可有效控制SAD。慢性HCV感染的治疗,1例治疗前ALT水平升高患者拒绝干扰素联合利巴韦林抗病毒治疗,剩余11例ALT水平正常患者中3例接受治疗,其中1例由于干扰素使用后白细胞数下降而停用,余2例均获得了持续病毒学应答(SVR)。接受抗病毒治疗的3例患者中,有2例因SAD活动再次入院治疗;未接受抗病毒治疗的9例患者有3例因SAD活动再次入院(P>0.05)。结论 HCV慢性感染相关的SAD在临床表现及实验室检查特征上与未合并HCV慢性感染时相比无差异,使用糖皮质激素联合免疫抑制剂治疗仍安全有效。出现SAD的HCV慢性感染患者的肝炎表现较轻微,ALT大多处于正常范围,是否使用抗病毒治疗需根据个体情况确定。

Objective To describe the clinical, immunologic characteristics and treatment response of patients with chronic hepatitis C virus （HCV） infection related systemic autoimmune diseases （SAD）. Methods We retrospectively analyzed 12 patients with chronic HCV infection related SAD in Peking Union Medical College Hospital during the last 20 years. The clinical, immunologic characteristics and treatment responses were documented and analyzed. Results All 12 patients with chronic HCV infection developed the following SAD： Systemic lupus erythematosus （SLE, n = 5 ）, cryoglobulinaemia （n = 2 ）, microscopic polyangitis （MPA, n = 1 ）, polyarteritis nodosa （PAN, n = 1 ）, systemic sclerosis （SSc, n = 1 ）, rheumatoid arthritis （RA） co-existing with polymyositis （ PM, n = 1 ）, dermatomyositis （ DM, n = 1 ）. Eleven （91.7%） patients were female and 1 （8.3%） male, with a mean age of chronic HCV infection detection of 39.8 （18-62） years and a mean age of SAD onset of 41.5（23-62） years. All patients fulfilled the corresponding SAD classification criteria. The major clinical manifestations were hematological involvement （83.3%） and cutaneous involvement （66. 7% ） ; the main laboratory features were antinuclear antibodies（ANA） in 83.3% of patients, increase of erythrocyte sedimentation rate（ESR） in 83.3% of patients and hypocomplementaemia in 75.0%. Subgroup analysis of 5 patients revealed that there was no significant difference between HCV infection related SLE and general SLE patients. For the 12 patients with chronic HCV infection, the hepatitis related manifestations were mild and 11 （91.7%） had normal alanine aminotransferase（ALT） levels, a rate which was significantly higher than that of the patients with chronic HCV in the general population （ P 〈 0. 05 ）. As for SAD treatment, one patient refused treatment after diagnosis, all the others received glucocorticoids plus immunosuppressive agents with good treatment response. As for HCV infection treatment, one patient with elevated ALT level refused interferon plus ribavirin therapy; as for those 11 patients with normal ALT levels, 3 started anti-viral therapy. One discontinued the therapy because of drug-induced leucopenia; the other patients who completed the therapy both achieved sustained virologic response. For patients who received anti-viral therapy, 2/3 were rehospitalized due to flare of SAD ; for patients who did not start anti-viral treatment, 3/9 were re-hospitalized for SAD flare（P 〉 0. 05 ）. Conclusions The clinical and immunological characteristics of chronic HCV infection related SAD were classical. And glucocorticoids-based immunosuppressive therapy was still effective and safe for this category of patients. Those chronic： HCV patients who developed SAD often had mild hepatitis related manifestations and a significantly higher rate of normal ALT level; anti-viral treatment should be individualized after carefully weighing the balance between cost and effectiveness.