自身免疫性肝病(ALD)课件

ASCA
– 无麦胶饮食6-9月后抗体可消失
组织转氨酶抗体（TTG)
• 代替肌内膜抗体作为麦胶性肠病筛查.
ASCA
• Crohn’s 病
• Saccharomyces cerevisiae stained sequentially with the red fluorescent Rhodamine B hexyl ester, which selectively labels yeast mitochondria and the green fluorescent yeast vacuole membrane marker
AIH评分 +2
+2 0 -2 +3 +2 +1 0 +3 +2 +1 0 -4 -3/+3 -4/+1 +2/-2 +2 +2 +2/+3
AIH抗体谱
Antibody (prevalence)
ANA (60% to 80%) SMA (60% to 80%) LKM-1 (−4%) pANCA (−90%) SLA/LP (10% to 30%)
自身免疫性肝病 • 自身免疫性肝炎（AIH) • 原发性胆汁性肝硬化（PBC) • 原发性硬化性胆管炎（PSC)
AIH
AIH 临床表现
• 无症状－－－－暴发性肝衰竭 • 非特异 小关节痛 • CLUE: 伴其他自身免疫病：甲状腺炎，UC
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Female sex ALP:AST ratio – <1.5 – 1.5-3.0 – >3.0 Serum globulins or IgG above normal – >2.0 – 1.5-2.0 – 1.0-1.5 – <1.0 ANA, SMA, LKM-1 – >1:80 – 1:80 – 1:40 – <1:40 AMA positivity Hepatitis viral markers (+/-) Drug history (+/-) Average ETOH intake (<25/>60g/day) Liver histology Other autoimmune diseases Other autoantibodies Response to therapy (complete/relapse)
网硬蛋白抗体
• 鼠组织底物 • 麦胶性肠病，敏感特异均较差 • ANA screen
抗麦胶蛋白抗体
• 麦胶性肠病：敏感但不特异.
肌内膜抗体
• 肌内膜－－平滑肌纤维表 面覆盖的结缔组织 • 灵长类食道或人脐索组织
肌内膜抗体
• IgA抗体对麦胶性肠病及疱疹性皮炎>90% 敏感 性和特异性 • 滴度与肠损害相关
PBC, PSC, 慢性 HCV, NAFLD Acute viral hepatitis, 慢性 HCV, NAFLD 慢性 HCV PSC, PBC Hepatitis C
LC-1 (<5%)
ASGP-R (−90%)
Formiminotransferase cyclodeaminase
Asialoglycoprotein receptor
ห้องสมุดไป่ตู้
Target antigen
Multiple nuclear proteins Actin CYP 2D6 Lactoferrin, other unknown antigens UGA repressor tRNAassociated protein
Other diseaseassociations
自身免疫性肝病(ALD)
Portal vein Hepatic artery
Bile duct
Parenchyma: hepatocytes sinusoids endothelial cells Kupffer cells (resident macrophages) perisinusoidal stellate cells (fat storing/quiescent myofibroblasts)
hepatocytes
sinusoid
sinusoid
hepatocytes
Bile canaliculus
Sinusoidal endothelial cells fenestrated: permits passage of proteins
Hepatocyte: microvilli visible through fenestrae
慢性 HCV
慢性 HBV, HCV, ALD, PBC
SMA
• 慢活肝 – cytoskeletal蛋白 • actin – ALD. • tubulin – 传单 • vimentin- 感染，风湿病 等 • desmin – 心肌炎，CHD
SMA
– 70-90%患者，常伴ANA. • I型AIH – 对AIH不特异，感染、风湿病均可出现，50%PBC – 滴度与病情无关，个体差异大 – 结合AST/ALT，IgG升高－怀疑
抗LKM-1抗体
• II型AIH • LKM-1抗原：cytochrome P450 II D6 • 亦见于慢性HCV,隐源性肝硬 化，药物性肝病
“胃”相关抗体
• PCA
– 自身免疫性胃炎, PA (90%), PBC (10%), AIH (75%); CLD (30%) ; 自身免疫性甲状腺炎 (30%) 老年人(10-15%)
• 内因子抗体
– ELISA: PA特异性诊断，4050% of PA
“胃”相关抗体
• 抗网硬蛋白和麦胶蛋白抗体 • 抗肌内膜抗体 • 抗组织转氨酶 (TTG)抗体
– 麦胶性肠病1/100-1/300
• 抗Saccharomyces cerevisae抗体(ASCA) • ANCA
– Crohn病和UC
Bile canaliculus: apical domain of hepatocytes site of bile secretion: bile salts, phospholipid, cholesterol, bilirubin glucuronides, electrolytes, water