降脂药物诱导自身免疫性肝炎的系统评价

Lipid-lowering agents-induced autoimmune hepatitis: A systematic review

目的:系统评价国内外关于降脂药物诱导的自身免疫性肝炎(autoimmune hepatitis,AIH)的临床特点.方法:在中国生物医学文献光盘数据库、维普医药信息资源系统和PubMed数据库中检索1983-01/2014-10所有降脂药物诱导的AIH中英文病例资料进行分析.结果:多种降脂药物可诱导AIH发生,共检索到7种药物14例报道,女性占64.3%(9/14).与散发性AIH相比,临床表现及肝组织学改变相似,还可引起系统性红斑狼疮、横纹肌溶解等肝外表现.他汀类降脂药物之间可能存在交叉毒性,再用不同他汀类药物后仍可发生肝损害,潜伏期更短且症状更严重.确诊后需立即停药,6例停药后肝功能异常仍继续加重,其中28.6%(4/14)进展为不同程度肝硬化.92.9%(13/14)患者经免疫抑制治疗.该病较少复发,通常不需长期治疗.结论:降脂药物诱导的AIH特点与散发性AIH存在异同之处,监测肝功能和自身抗体的动态变化以及加强随访便于及时发现和诊治.

AIM： To identify the clinical characteristics of lipid-lowering agents-induced autoirnmunehepatitis （AIH） METHODS： The clinical data for patients with lipid-lowering agents-induced AIH were retrieved from Chinese Biomedical Database, VIP Medical information resource system and PubMed （January 1983 to October 2014） to conduct a systematic review. RESULTS： Multiple lipid-lowering agents could induce AIH. A total of 14 cases due to 7 kinds of drugs were identified, and 64.3% （9/14） of the patients were females. No significant differences were found in clinical manifestations or liver histology compared to sporadic AIH, and lipid-lowering agents- induced AIH patients might have extrahepatic manifestations such as systemic lupus erythematosus and rhabdomyolysis. Different statins might have cross-toxicity, liver injury with a shorter latency period and more serious symptoms could occur when other statins were reused. Discontinuation of offending drugs was the essential treatment when the diagnosis was established; however, liver function in 6 patients was even worse although the drugs were stopped and 28.6% （4/14） of the patients finally developed cirrhosis. Immunosuppressive therapy was needed in 92.9% （13/14） of patients. Most patients responded well and the liver function was gradually improved, while antinuclear antibody titer might also significantly decrease and even turn negative. Long-term immunosuppressive therapy was not needed generally because relapse seldom occurred. CONCLUSION： Different characteristics can be found in lipid-lowering agents-induced AIH patients compared to sporadic AIH patients. Liver function and antinuclear antibody tests with intensive follow-up may promote an immediate diagnosis and treatment.