内科学肝硬化张顺财

Hepatic Cirrhosis,Professor Wang Ji-yao,Zhang Shuncai Department of Internal MedicineDivision 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.,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,1.Chronic viral hepatitis (慢性病毒性肝炎): HBV,HCV,HBV+HDV2. 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 cirrhosis4. Drugs and toxins(药物和毒物) toxic hepatitis-chronic active hepatitis-cirrhosis5. Nonalcoholic steatohepatitis (NASH)(非酒精性脂肪性肝炎),Etiology of cirrhosis(I),Etiology of cirrhosis(II),6. Hepatic venous outflow obstruction(肝血液循环障碍) veno-occlusive disease, Budd-Chiari syndrome, constrictive pericarditis7. Metabolic disorders (遗传代谢性疾病) hemochromatosis(血色病); Wilsons 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,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,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,Histopathologic classification,micronodular uniformly small nodules (250 neutrophils/mm3.,ComplicationsII,Hepatocellular carcinoma(肝细胞肝癌) Hepatic encephalopathy (肝性 脑病) Asterixis(扑翼样振颤) Disoriented(定向障碍) Coma(昏迷),ComplicationsIII,Hepatorenal syndrome(HRS): Oliguria(少尿), azotemia(氮质血 症), hypotension(低血压), dilutional hyponatremia(稀释性低钠血症), low urinary sodium(低钠尿),ComplicationsIV,Electrolyte and acid-base imbalance(电介质酸硷平衡失调) hyponatremia, hypokalemia And hypochloremic alkalosis,Laboratory findingsI,Blood and urine routinesLiver function tests -to estimate the severity of liver dysfunction：ALT,AST,AKP,GGT, serum total bilirubin, serum albumin, prothrombin time, globulin, cholesterol. - to differential diagnosis: Alcoholic: AST/ALT=2; PBC: AKP,GGTALT,AST -to refect hepatic fibrosis: PIIIP、HA、laminin -to quanlity liver function,Immunology,Cellular immune, hormonal immuneautoimmune liver disease: IgG,globulin ANA(+), SMA(+)PBC: IgM, AMA(+) Marker of virus AFP,Laboratory findingsII, Ascites paracentesis: routine, culture, ADA, LDH, SAAG (serum ascites albumin gradient) (血清腹水白蛋白梯度) 11g/L Ultrasonography, CT scanning： biliary obstruction, liver masses, splenomegaly, ascites. Endoscopy: the number, appearance, and size of any esophageal/gastric varix, portal hypertensive gastropathy (PHG),Laboratory findingsIII, Radionuclide: 99m TC-MIBI, H/L liver biopsy: to confirm the diagnosis Laparoscopy HVPG (hepatic vein pressure gradient)(肝静脉压力梯度) (wedged - free )hepatic venous pressure Normal: 5-6mmHg, 10mmHg: varices; 12mmHg:rupture,Diagnosis I, Etiology of cirrhosis Pathology of cirrhosis Evaluating of liver function: Child-Pugh classification Searching for complications,DiagnosisII, the history of disease contributes to identifying the cause of cirrhosis. history of viral hepatitis, blood transfusions, medication use, alcohol use, sexual practices should be carefully reviewed. signs and symptoms confirm to existence of portal hypertension and impared liver function. liver function tests: hypoalbuminemia,hyperbilirubinemia，the prolonged prothrombin time suggest hepatic decompensation. Imaging study: Ultrasound and CT readily identify the lesion, but have no characteristic findings.,Child-Pugh classification Scorea variable 1 2 3 Encephalopathy(degree) Nil Slight-Moderate Moderate-Severe Ascites(degree) Nil Slight Moderate-Severe Bilirubin(umol/L) 51 Albumin(g/L) 35 28-34 70 40-70 18 Prothrombin Time(INR) 1.5 * PBC: SB(mol/L) 1768 68170 170 aScores are summed to determine Childs class: class A=5-6 class B= 7-9 class C= 10-15,DiagnosisIII,Differential Diagnosis,Other condition of hepatomegaly or splenomegaly ： chronic virus hepatitis,Gauchers disease, lymphomas and leukaemias, congestive splenomegalyDifferebtial diagnosis of cirrhotic ascites and other types of ascites： malignant ascites, constrictive pericarditis, tuberculous peritonitis, et al.Portal hypertension:,Treatment of cirrhosisI,specific treatment for the underlying etiology of the liver disease antivirus therapy -viral hepatitis abstinence from alcohol-alcoholic Ursodeoxycholic acid(UDCA)(熊去氧胆酸)-PBC Penicillamine(青霉胺)Wilsons disease General Treatments: High calories (40 kcal/kg d)、 adequate protein (1-1.5g/kg d) 、vitamin、Herbal compounds.,Treatment of Ascites,a. Bed rest ,sodium and water restriction. 1. Fluid intake: 800-1000ml/d (hyponatremia, serum sodium1 Spironolactone(安体舒通) +furosemide(速尿) urinary sodium / urinary potassium 1 higher doses spironolactone，,Treatment of Ascites(III),c. Large-volume paracentesis associated with plasma volume expansiond. Ascites ultrafiltration and re-infusione. Peritoneo-venous (LeVeen) shuntsf. TIPS(transjugular intrahepatic porto-systemic stent)(经颈静脉门体分流术) g. Liver transplantation(肝移植),TIPS-stent positioned between the hepatic and portal veins,Treatment of cirrhosisIV,surgical treatment of portal hypertension portacaval shunt surgery： portacaval mesocaval distal splenorenal shunts Choice of patients： Child-Pugh: A, B bleeding from gastroesophageal varices, hypersplenism.,Treatment of cirrhosisV,Treatment complationsTreatment of acute variceal haemorrhage： -General management: abstain food, intensive care, volume and blood replacement, specific measures to stop the bleeding - Pharmacological therapy: vasopressin(垂体后叶素) somatostatin(生长抑素) Octreotide(奥曲肽),Treatment of acute variceal haemorrhage：,_Emergent endoscopy: after Patients hemodynamic status stabilized(usually within 2-12 hours) -Balloon tube tamponade( if bleeding continues) -Endoscopic variceal sclerotherapy and band ligation -Prophylactic therapy to prevent rebleeding: Beta-adrenergic antagonists(普奈洛尔), endoscopic sclerotherapy(硬化剂)/banding(套扎) (usually 3-6 sessions), portacaval shunting, TIPS,TIPS-stent positioned between the hepatic and portal veins,Treatment,portal hypertension(250/mm3 : antibiotic therapy should be initiated.2. Ascites PMN250/mm3 and ascitic fluid culture continues to be positive: initiation of antibiotic treatment. 3. Follow-up diagnostic paracentesis performed 48 hours after starting therapy allows assessment of response to treatment and the need to modify antibiotic coverage. 4. Long-term prophylaxis -Patients who have recovered from an episode of SBP are at a high risk of developing SBP recurrence.,Therapies for HRSI, Avoid use of nephrotoxic drugs: （1）Antibiotics ：aminoglycosides （2）NSAIDs：inhibit formation intrarenal prostaglandins -marked decline in renal function Avoid and treat factors to hypovolaemia: （1）active treatments of upper gastrointestinal bleeding （2）Judicious use of diuretics（weight loss0.5Kg/d） Rectify electrolyte and metabolic imbalance, Fluid intake restriction,Therapies for HRSII, Volume expansion: with IV dextrose, plasma, albumin or Concomitant plasma volume expansion with album