Hepatic Cirrhosis Professor Wang Ji-yao Department of Internal Medicine Division of Gastroenterology, Zhongshan hospital, Fu Dan university
Hepatic Cirrhosis Professor Wang Ji-yao Department of Internal Medicine Division of Gastroenterology, Zhongshan hospital , Fu Dan university
Cirrhosis---definition chronic, progressed, diffuse hepatocellular injury fibrosis nodular regeneration Incidence: 17/100000/y Age: 20-50 yr
Cirrhosis---definition chronic, progressed, diffuse hepatocellular injury fibrosis nodular regeneration Incidence: 17/100000/y Age: 20-50 yr
Hepatic cirrhosis Etiology Diffuse, chronic liver injury Hepato-cellulai Formation of regenerative necrosis, collapse of diffuse fibrous septa nodules formation hepatic lobules Liver function Injury, Portal hypertension Complations: Upper GI Bleeding, Hepatic coma, infections, primary liver cancer, Functional renal failure
Hepatic cirrhosis 》 Etiology Liver function Injury,Portal hypertension Diffuse, chronic liver injury Hepato-cellular necrosis, collapse of hepatic lobules regenerative nodules formation Formation of diffuse fibrous septa Complations: Upper GI Bleeding, Hepatic coma, infections, primary liver cancer, Functional renal failure
Etiology of cirrhosis n) ± Chronic viral hepatitis(慢性病毒性肝炎) HBV,HCV,HBV+HDVI 2 Long-term alcoho|sm慢性酒精中毒) 80g/d,10y: 13Pro| onged cholestasis(长期胆汁郁积, intra-and extra-hepatic: primary biliary cirrhosis, PBCI /[secondary biliary cirrhosis] 4. Drugs and toxins(药物和毒物) Itoxic hepatitis---chronic active hepatitis cirrhosis 5. Nonalcoholic steatohepatitis( NASH)(非酒精性 脂肪性肝炎)
1.Chronic viral hepatitis (慢性病毒性肝炎): [HBV,HCV,HBV+HDV] 2. Long-term alcoholism(慢性酒精中毒) [80g/d, 10 yr.] 3. Prolonged cholestasis(长期胆汁郁积), intra-and extra-hepatic:[primary biliary cirrhosis, PBC] /[secondary biliary cirrhosis] 4. Drugs and toxins(药物和毒物) [toxic hepatitis---chronic active hepatitis--- cirrhosis] 5. Nonalcoholic steatohepatitis (NASH)(非酒精性 脂肪性肝炎) Etiology of cirrhosis(I)
Etiology of cirrhosis(In) 6. Hepatic venous outflow obstruction(肝血液循环 障碍) veno-occlusive disease, Budd-Chiari syndrome, constrictive pericarditis 7. Metabolic disorders(遗传代谢性疾病) hemochromatosis(血色病); Wilson 's disease(肝豆状核变性; 8. Autoimmune hepatitis(AH)自身免疫性肝炎) 9.5 schistosomiasis(血吸虫病) 10. Cryptogenic(隐原性) 11. Mixed; alcohol+virus, HBv+HCV, HBV+schistosomiasis
Etiology of cirrhosis(II) 6. Hepatic venous outflow obstruction(肝血液循环 障碍) veno-occlusive disease, Budd-Chiari syndrome, constrictive pericarditis 7. Metabolic disorders (遗传代谢性疾病) hemochromatosis(血色病);Wilson‘s disease(肝豆状核变性); 8. Autoimmune hepatitis (AIH)(自身免疫性肝炎) 9. Schistosomiasis (血吸虫病) 10. Cryptogenic (隐原性) 11. Mixed: alcohol+virus , HBV+HCV, HBV+schistosomiasis
Hepatic stellate cell activation Quiescent Activated HSC HSC Autocrine tokine roliferation Smooth muscle cytokine Retinoid Y-actin Proliferative droplets cytokines (PDGH Fib cytokines stimulus (GEb) from Fibrogenesis Type NV Matrix collagenase nduced Initiation Perpetuation activation Phase Phase
Hepatic stellate cell activation
Liver fibrosis accumulation of synthesis degradation of matrix extracellular of matrix matrix in liver proteins proteins Collagens type I andⅢ constitute more than 95% of the total content of increased collagen in fibrotic liver
Liver fibrosis accumulation of extracellular matrix in liver synthesis of matrix proteins degradation of matrix proteins Collagens type I and III constitute more than 95% of the total content of increased collagen in fibrotic liver
THE HEPATIC PERISINUSOIDAL (DISSE)SPACE NORMAL FIBROTIC Collagen fibers Sinusoid Endothelial cell Sinusoid Lipocyte: Myofibroblast Low density matrix High density matrix LIPOCYTE- MYOFIBROBLAST
ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY OF LIVER FUNCTION NORMAL Sinusoid Central veIn Bile duct Portal v Hepatocyte Hepatic a FIBROTIC Fibrillar matrix Collagen bundle Basement membrane F igu Distortion of Capillarization Central Vein figure Veins by Septa of Sinusoids Sclerosis pane/)
Pathogenesis: chronic, progressed, diffuse Hepatocyte injury leading to necrosis Chronic inflammation-(hepatitis) Capillarization(肝窦毛细血管化) of the space of Disse is a key event ° Bridging fibrosis Regeneration of remaining hepatocytes proliferate as round nodules surrounded by fibrous septa Loss of vascular arrangement results in regenerating hepatocytes ineffective. Cirrhosis may lead to liver failure, portal hypertension, or development of hepatocellular carcinoma
Pathogenesis: chronic, progressed, diffuse • Hepatocyte injury leading to necrosis. • Chronic inflammation - (hepatitis). • Capillarization (肝窦毛细血管化) of the space of Disse is a key event. • Bridging fibrosis. • Regeneration of remaining hepatocytes proliferate as round nodules surrounded by fibrous septa. • Loss of vascular arrangement results in regenerating hepatocytes ineffective. • Cirrhosis may lead to liver failure, portal hypertension, or development of hepatocellular carcinoma