1、American College of Rheumatology 2008 Recommendations for the Use of Nonbiologic and Biologic Disease-Modifying Antirheumatic Drugsin Rheumatoid ArthritisLiver contraindications. Abnormal liver transaminases.When the levels of liver transaminases (aspartate aminotransferase or alanine aminotransfera

2、se 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

3、(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 th

4、e 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 t

5、he 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 pres

6、ence 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

7、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, th

8、e 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 classif

9、ications, andminocycline 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

10、-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, leflunomi

11、de, 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 hepat

12、itis B or C are as follows: although TNF_ blockade occasionally has been used in patients with chronic hepatitis, particularly when antiviral therapy is used concomitantly (187,188, the TFP recommended that biologic agents were contraindicated in both chronic hepatitis B and C, whether treated or un

13、treated for those with significant liver injury, defined as chronic Child-Pugh classes B or C (189,190.肝臟方面禁忌肝臟轉氨酶異常。當肝臟轉氨酶水平高于正常上限2倍時,專責小組認為是開始或者恢復使用來氟米特、甲氨喋呤和柳氮磺胺吡啶的原因,禁用或停用(但是并未提出何時停藥的建議。目前已積累大量來氟米特、甲氨喋呤和柳氮磺胺吡啶的相關研究。急性乙型肝炎或丙型肝炎。患有急性乙型肝炎或丙型肝炎時,專責小組建議禁用來氟米特、甲氨喋呤和柳氮磺胺吡啶、米諾環素和生物制劑。慢性肝炎或丙型肝炎。存在已治療或未治療

14、的慢性肝炎或丙型肝炎時,專責小組認為該功能損害的嚴重程度是決定治療方案的關鍵性因素。根據肝病學專家的建議,采用慢性肝病的CHILD-Pugh評分系統,此系統是評價肝臟病變嚴重程度的一種手段,用于界定慢性肝病的預后。CHILD-Pugh評分取決于患者的血清白蛋白、總膽紅素、凝血酶原時間、是否出現腹水和肝性腦病等指標,CHILD-Pugh分級為C級患者的一年生存率為50%,CHILD-Pugh分級為A級患者或B級患者一年生存率為70-80%.慢性乙型肝炎或丙型肝炎的患者是否能夠使用非生物DMARD取決于肝炎的類型,CHILD-Pugh分級以及是否已經使用抗病毒藥物治療肝炎(表2。當治療慢性乙型肝炎

15、或丙型肝炎的患者時,醫生應考慮所有DMARD藥物的風險和收益。對于某些DMARD藥物,例如羥基氯喹,在伴有嚴重的原發性肝病患者中使用(CHILD-Pugh分級為C級,盡管這種情況不很常見,但令人擔憂,專責小組就此方面進行了討論。對已經接受治療的慢性乙型肝炎患者,專責小組建議無論任何CHILD-Pugh 分級均禁止使用來氟米特和甲氨喋呤;對于CHILD-Pugh分級為C級患者,禁止使用米諾環素和柳氮磺胺吡啶;對于未經接受治療的乙型肝炎患者,專責小組建議無論任何CHILD-Pugh分級均限制使用來氟米特和甲氨喋呤;對于CHILD-Pugh分級為C級患者,禁止使用羥基氯喹。已經接受治療的慢性丙型肝炎患者,專責小組建議無論任何CHILD-Pugh 分級均禁止使用來氟米特和甲氨喋呤,對于CHILD-Pugh分級為C級患者,禁止使用米