ACR关于DMARDs在RA合并HBV感染患者中的应用.doc

American College of Rheumatology 2008Recommendations for the Use of Nonbiologic andBiologic Disease-Modifying Antirheumatic Drugsin Rheumatoid ArthritisLiver contraindications. Abnormal liver transaminases.When the levels of liver transaminases (aspartate aminotransferase or alanine aminotransferase) were greater than 2-fold the upper limit of normal, the TFP recommended that the initiation or resumption of leflunomide, methotrexate,and sulfasalazine was contraindicated (although recommendations on when to discontinue are not provided).There are a large number of studies addressing leflunomide (48,50,61,132,153,154), methotrexate (41,43,46,48,49,130132,134137,154179), and sulfasalazine(44,56,60,61,63,153,180,181). Acute hepatitis B or C. In the presence of acute hepatitis B or C, treatment with methotrexate, leflunomide, sulfasalazine,minocycline, and biologic agents was contraindicated by the TFP. Chronic hepatitis B or C. In the presence of chronic hepatitis B or C (treated or untreated), the severity of compromised liver function was considered by the TFP as a key factor in making therapeutic decisions. The Child-Pugh scoring system for chronic liver disease (182184) was used based on the advice of our expert advisor in the field of hepatology. This system is a liver disease severity instrument used to determine the prognosis of chronic liver disease. It is based on the serum albumin and total bilirubin levels, the prothrombin time, the presence or absence of ascites, and the presence or absence of encephalopathy. Child-Pugh class C is associated with a 1-year survival rate of 50%, whereas patients with Child-Pugh classes A or B have a 5-year survival rate of 7080%. The recommendations for nonbiologic DMARDs in patients with chronic hepatitis B or C were stratified based on the type of hepatitis, the Child-Pugh grade, and whether or not antiviral agents to treat hepatitis had been initiated (Table 2). When treating patients with chronic hepatitis B or C, physicians need to consider the risks and benefits for all DMARDs. For certain DMARDs, such as hydroxychloroquine, the TFP discussed uncommon but reported concerns about the use of these agents in thesetting of severe underlying liver injury, defined as Child-Pugh class C (185,186). In the setting of treated chronic hepatitis B, leflunomide and methotrexate were contraindicated by the TFP for all Child-Pugh classifications, and minocycline and sulfasalazine were contraindicated for Child-Pugh class C. In untreated chronic hepatitis B, leflunomide, methotrexate, minocycline, and sulfasalazine were contraindicated by the TFP for all Child-Pugh classifications, and hydroxychloroquine was contraindicated for Child-Pugh class C.In treated chronic hepatitis C, leflunomide and methotrexate were contraindicated for all Child-Pugh classifications, minocycline was contraindicated for Child-Pugh class C, and sulfasalazine was contraindicated for Child-Pugh classes B and C.In untreated chronic hepatitis C, leflunomide, methotrexate,and minocycline were contraindicated for all Child-Pugh classifications, sulfasalazine was contraindicated for Child-Pugh classes B and C, and hydroxychloroquine was contraindicated for Child-Pugh class C. The recommendations concerning biologic DMARDs in patients with chronic hepatitis B or C are as follows: although TNF_ blockade occasionally has been used in patients with chronic hepatitis, particularly when antiviraltherapy is used concomitantly (187,188), the TFP recommended that biologic agents were contraindicated in both chronic hepatitis B and C, whether treated or untreated for those with significant liver injury, defined as chronic Child-Pugh classes B or C (189,190).肝脏方面禁忌 肝脏转氨酶异常。当肝脏转氨酶水平高于正常上限2倍时，专责小组认为是开始或者恢复使用来氟米特、甲氨喋呤和柳氮磺胺吡啶的原因，禁用或停用（但是并未提出何时停药的建议）。目前已积累大量来氟米特、甲氨喋呤和柳氮磺胺吡啶的相关研究。急性乙型肝炎或丙型肝炎。患有急性乙型肝炎或丙型肝炎时，专责小组建议禁用来氟米特、甲氨喋呤和柳氮磺胺吡啶、米诺环素和生物制剂。慢性肝炎或丙型肝炎。存在已治疗或未治疗的慢性肝炎或丙型肝炎时，专责小组认为该功能损害的严重程度是决定治疗方案的关键性因素。根据肝病学专家的建议，采用慢性肝病的CHILD-Pugh评分系统，此系统是评价肝脏病变严重程度的一种手段，用于界定慢性肝病的预后。CHILD-Pugh评分取决于患者的血清白蛋白、总胆红素、凝血酶原时间、是否出现腹水和肝性脑病等指标，CHILD-Pugh分级为C级患者的一年生存率为50%，CHILD-Pugh分级为A级患者或B级患者一年生存率为70-80%.慢性乙型肝炎或丙型肝炎的患者是否能够使用非生物DMARD取决于肝炎的类型，CHILD-Pugh分级以及是否已经使用抗病毒药物治疗肝炎（表2）。当治疗慢性乙型肝炎或丙型肝炎的患者时,医生应考虑所有DMARD药物的风险和收益。对于某些DMARD药物，例如羟基氯喹，在伴有严重的原发性肝病患者中使用（CHILD-Pugh分级为C级），尽管这种情况不很常见，但令人担忧，专责小组就此方面进行了讨论。对已经接受治疗的慢性乙型肝炎患者，专责小组建议无论任何CHILD-Pugh分级均禁止使用来氟米特和甲氨喋呤；对于CHILD-Pugh分级为C级患者，禁止使用米诺环素和柳氮磺胺吡啶；对于未经接受治疗的乙型肝炎患者，专责小组建议无论任何CHILD-Pugh分级均限制使用来氟米特和甲氨喋呤；对于CHILD-Pugh分级为C级患者，禁止使用羟基氯喹。已经接受治疗的慢性丙型肝炎患者，专责小组建议无论任何CHILD-Pugh分级均禁止使用来氟米特和甲氨喋呤，对于CHILD-Pugh分级为C级患者，禁止使