自身免疫性肝炎与药物性肝损伤-鉴别诊断和处理.pdf

自身免疫性肝炎与药物性肝损伤：鉴别诊断和处理苗琪马雄 关键词 肝炎，自身免疫性;肝炎，慢性，药物性;鉴别诊断；治疗D i f f e r e n t i a l d i a g n o s i s a n d t h e r a p y f o r a u t o i m m u n e h e p a t i t i s a n d d r u g-i n d u c e d l i v e r i n j u r yM I A O Q iM A X i o n g K e y w o r d s H e p a t i t i s,a u t o i m m u n e；H e p a t i t i s,c h r o n i c,d r u g-I n d u c e d；D i f f e r e n t i a l d i a g n o s i s；T h e r a p y F i r s t a u t h o r s a d d r e s s D e p a r t m e n t o f G a s t r o e n t e r o l o g y,R e n j i H o s p i t a l,S h a n g h a i J i a o t o n g U n i v e r s i t y S c h o o l o f M e d i c i n e S h a n g h a i I n s t i t u t e o f D i g e s t i v e D i s e a s e,S h a n g h a i 2 0 0 0 0 1,C h i n a C o r r e s p o n d i n g a u t h o r:M A X i o n g,E m a i l:m a x i o n g m d h o t m a i l.c o m 自身免疫性肝炎(A I H)是由异常自身免疫反应介导的肝实质炎症性病变，多发于女性，以高丙种球蛋白血症、血清自身抗体阳性和对免疫抑制剂治疗应答为特点。药物性肝损伤(d r u g-i n d u c e d l i v e ri n j u r y,D I L I)是与用药相关的肝功能损伤，同样多见于女性，有时可出现自身抗体阳性，严重病例需免疫抑制剂治疗。两者究竟存在怎样的关系，如何在初诊时予以鉴别和适当治疗是临床医生需要重视的问题。一、A I H 和D I L I 的关系 在临床工作中存在这样的现象：D I L I 患者恢复后再次使用相同或相似的药物可出现A I H 样表现。L u c e n a 等 1 从西班牙药物性肝损中心选取9 例两次出现D I L I 的患者(9/7 4 2)，其中8 例第二次肝损伤的类型和第一次相同（肝细胞型为主），4 例患者两次肝损伤前后使用药物的结构相似，2 例作用靶点相似。1 0.3 7 6 0/c m a.j.i s s n.1 0 0 7-3 4 1 8.2 0 1 2.0 5.0 0 3 作者单位：2 0 0 0 0 1 上海交通大学医学院附属仁济医院消化科上海市消化疾病研究所激素对两者均有 1 L u c e n a M I,K a p l o w i t z N,H a l l a l H,e t a l.R e c u r r e n t d r u g-i n d u c e d l i v e r i n j u r y (D I L I)w i t h d i f f e r e n t d r u g s i n t h e S p a n i s h r e g i s t r y:t h e d i l e m m a o f t h e r e l a t i o n s h i p t o a u t o i m m u n e h e p a t i t i s.J H e p a t o l,2 0 1 1,5 5:8 2 0-8 2 7.2 A l v a r e z F,B e r g P A,B i a n c h i F B,e t a l.I n t e r n a t i o n a l a u t o i m m u n e h e p a t i t i s g r o u p r e p o t:r e v i e w o f c r i t e r i a f o r d i a g n o s i s o f a u t o i m m u n e h e p a t i t i s.J H e p a t o l,1 9 9 9,3 1:9 2 9-9 3 8.3 H e n n e s E M,Z e n i y a M,C z a j a A J,e t a l.S i m p l i f i e d c r i t e r i a f o r t h e d i a g n o s i s o f a u t o i m m u n e h e p a t i t i s.H e p a t o l o g y,2 0 0 8,4 8:1 6 9-1 7 6.4 W e i l e r-N o r m a n n C,S c h r a m m C.D r u g i n d u c e d l i v e r i n j u r y a n d i t s r e l a t i o n s h i p t o a u t o i m m u n e h e p a t i t i s.J H e p a t o l,2 0 1 1,5 5:7 4 7-7 4 9.5 C z a j a A J.D r u g-i n d u c e d a u t o i m m u n e-l i k e h e p a t i t i s.D i g D i s S c i,2 0 1 1,5 6:9 5 8-9 7 6.6 B j r n s s o n E,T a l w a l k a r J,T r e e p r a s e r t s u k S,e t a l.D r u g-i n d u c e d a u t o i m m u n e h e p a t i t i s:c l i n i c a l c h a r a c t e r i s t i c s a n d p r o g n o s i s.H e p a t o l o g y,2 0 1 0,5 1:2 0 4 0-2 0 4 8.7 B o g d a n o s D P,M i e l i-V e r g a n i G,V e r g a n i D.A u t o a n t o b o d i e s a n d t h e i r a n t i g e n s i n a u t o h m m u n e h e p a t i t i s.S e m i n L i v e r D i s,2 0 0 9,2 9:2 4 1-2 5 3.8 L e c o e u r S,A n d r C,B e a u n e P H.T i e n i l i c a c i d-i n d u c e d a u t o i m m u n e h e p a t i t i s:a n t i-l i v e r a n d-k i d n e y m i c r o s o m a l t y p e 2 a u t o a n t i b o d i e s r e c o g n i z e a t h r e e-s i t e c o n f o r m a t i o n a l e p i t o p e o n c y t o c h r o m e P 4 5 0 2 C 9.M o l P h a r m a c o l,1 9 9 6,5 0:3 2 6-3 3 3.9 Z i m m e r m a n H J.D r u g-i n d u c e d l i v e r d i s e a s e.C l i n L i v e r D i s,2 0 0 0,4:7 3-9 6.1 0 E f e C,P u r n a k T,O z a s l a n E,e t a l.D r u g-i n d u c e d a u t o i m m u n e h e p a t i t i s c a u s e d b y a n t i-t u m o r n e c r o s i s f a c t o r a g e n t s.H e p a t p l o g y,2 0 1 0,5 2:2 2 4 6-2 2 4 7.1 1 v o n K a l c k r e u t h V,L o h s e A W,S c h r a m m C.U n m a s k i n g a u t o i m m u n e h e p a t i t i s u n d e r i m m u n o m o d u l a t o r y t r e a t m e n t o f m u l t i p l e s c l e r o s i s n o t o n l y b e t a i n t e r f e r o n.A m J G a s t r o e n t e r o l,2 0 0 8,1 0 3:2 1 4 7-2 1 4 8.1 2 W a t k i n s P B,S e e f f L B.D r u g-i n d u c e d l i v e r i n j u r y:s u m m a r y o f a s i n g l e t o p i c c l i n i c a l r e s e a r c h c o n f e r e n c e.H e p a t o l o g y,2 0 0 6,4 3:6 1 8-6 3 1.1 3 F o n t a n a R J,S e e f f L B,A n d r a d e R J,e t a l.S t a n d a r d i z a t i o n o f n o m e n c l a t u r e a n d c a u s a l i t y a s s e s s m e n t i n d r u g-i n d u c e d l i v e r i n j u r y:.s u m m a r y o f a c l i n i c a l r e s e a r c h w o r k s h o p.H e p a t o l o g y,2 0 1 0,5 2:7 3 0-7 4 2.1 4 S u z u k i A,B r u n t E M,K l e i n e r D E,e t a l.T h e u s e o f l i v e r b i o p s y e v a l u a t i o n i n d i s c r i m i n a t i o n o f i d i o p a t h i c a u t o i m m u n e h e p a t i t i s v e r s u s d r u g-i n d u c e d l i v e r i n j u r y.H e p a t o l o g y,2 0 1 1,5 4:9 3 1-9 3 9.1 5 L e w i s J H.D i a g n o s i s:l i v e r b i o p s y d i f f e r e n t i a t e s D I L I f r o m a u t o i m m u n e h e p a t i t i s.N a t R e v G a s t r o e n t e r o l H e p a t o l,2 0 1 1,8:5 4 0-5 4 2.1 6 M a n n s M P,C z a j a A J,G o r h a m H D,e t a l.D i a g n o s i s a n d m a m a g e m e n t o f a u t o i m m u n e h e p a t i t i s.H e p a t o l o g y,2 0 1 0,5 1:2 1 9 3-2 2 1 3.1 7 B j(o)r n s s o n E,K a l a i t z a k i s E,A v K l i n t e b e r g V,e t a l.L o n g-t e r m f o l l o w-u p o f p a t i e n t s w i t h m i l d t o m o d e r a t e d r u g-i n d u c e d l i v e r i n j u r y.A l i m e n t P h a r m a c o l T h e r,2 0 0 7,2 6:7 9-8 5.1 8 B j(o)r n s s o n E,D a v i d s d o t t i r L.T h e l o n g-t e r m f o l l o w-u p a f t e r i d i o s y n c r a t i c d r u g-i n d u c e d l i v e r i n j u r y w i t h j a u n d i c e.J H e p a t o l,2 0 0 9,5 0:5 1 1-5 1 7.2 0 1 2-0 2-1 5自身免疫性肝炎与药物性肝损伤:鉴别诊断和处理自身免疫性肝炎与药物性肝损伤:鉴别诊断和处理作者：苗琪，马雄，MIAO Qi，MA Xiong作者单位：200001,上海交通大学医学院附属仁济医院消化科上海市消化疾病研究所刊名：中华肝脏病杂志英文刊名：Chinese Journal of 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