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1、内科学 肝硬化张顺财第1页，共67页，编辑于2022年，星期五Cirrhosis-definition chronic,progressed,diffuse hepatocellular injury fibrosis nodular regeneration Incidence:17/100000/y Age:20-50 yr.第2页，共67页，编辑于2022年，星期五Hepatic cirrhosisEtiologyLiver function Injury,Portal hypertensionDiffuse,chronic liver injuryHepato-cellular nec
2、rosis,collapse of hepatic lobulesregenerative nodulesformationFormation of diffuse fibrous septaComplations:Upper GI Bleeding,Hepatic coma,infections,primary liver cancer,Functional renal failure第3页，共67页，编辑于2022年，星期五1.Chronic viral hepatitis(慢性病毒性肝炎慢性病毒性肝炎):HBV,HCV,HBV+HDV2.Long-term alcoholism(慢性酒精
3、中毒慢性酒精中毒)80g/d,10 yr.3.Prolonged cholestasis(长期胆汁郁积长期胆汁郁积),intra-and extra-hepatic:primary biliary cirrhosis,PBC/secondary biliary cirrhosis4.Drugs and toxins(药物和毒物物和毒物)toxic hepatitis-chronic active hepatitis-cirrhosis5.Nonalcoholic steatohepatitis(NASH)(非酒精性脂肪非酒精性脂肪性肝炎性肝炎)Etiology of cirrhosis(I)第
4、4页，共67页，编辑于2022年，星期五Etiology of cirrhosis(II)6.Hepatic venous outflow obstruction(肝血液循环障肝血液循环障碍碍)veno-occlusive disease,Budd-Chiari syndrome,constrictive pericarditis7.Metabolic disorders(遗传代谢性疾病遗传代谢性疾病)hemochromatosis(血色病血色病);Wilsons disease(肝豆状核变性肝豆状核变性);8.Autoimmune hepatitis(AIH)(自身免疫性肝炎自身免疫性肝炎)
5、9.Schistosomiasis(血吸虫病血吸虫病)10.Cryptogenic(隐原性隐原性)11.Mixed:alcohol+virus,HBV+HCV,HBV+schistosomiasis第5页，共67页，编辑于2022年，星期五Hepatic stellate cell activation第6页，共67页，编辑于2022年，星期五Liver fibrosisaccumulation of extracellular matrix in liversynthesisofmatrixproteinsdegradationofmatrixproteinsCollagenstypeIan
6、dIIIconstitutemorethan95%ofthetotalcontentofincreasedcollageninfibroticliver第7页，共67页，编辑于2022年，星期五第8页，共67页，编辑于2022年，星期五第9页，共67页，编辑于2022年，星期五Pathogenesis:chronic,progressed,diffuseHepatocyte injury leading to necrosis.Chronic inflammation-(hepatitis).Capillarization(肝窦毛细血管化肝窦毛细血管化)of the space of Diss
7、e 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 carc
8、inoma 第10页，共67页，编辑于2022年，星期五Histopathologic classificationmicronodular uniformlysmallnodules(250 neutrophils/mm3.第31页，共67页，编辑于2022年，星期五ComplicationsIIHepatocellular carcinoma(肝细胞肝细胞肝癌肝癌)Hepatic encephalopathy(肝性肝性 脑病脑病)Asterixis(扑翼样振颤扑翼样振颤)Disoriented(定向障碍定向障碍)Coma(昏迷昏迷)第32页，共67页，编辑于2022年，星期五Complic
9、ationsIII Hepatorenal syndrome(HRS):Oliguria(少尿少尿),azotemia(氮质血氮质血 症症),hypotension(低血压低血压),dilutional hyponatremia(稀释性低钠血症稀释性低钠血症),low urinary sodium(低钠尿低钠尿)第33页，共67页，编辑于2022年，星期五ComplicationsIVElectrolyte and acid-base imbalance(电介质酸硷平衡失调)hyponatremia,hypokalemia And hypochloremic alkalosis 第34页，共6
10、7页，编辑于2022年，星期五Laboratory findingsIBlood 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
11、 fibrosis:PIIIP、HA、laminin -to quanlity liver function第35页，共67页，编辑于2022年，星期五ImmunologyCellular immune,hormonal immune autoimmune liver disease:IgG,globulin ANA(+),SMA(+)PBC:IgM,AMA(+)Marker of virus AFP第36页，共67页，编辑于2022年，星期五Laboratory findingsII Ascites paracentesis:routine,culture,ADA,LDH,SAAG (ser
12、um ascites albumin gradient)(血清腹水白蛋白梯度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)第37页，共67页，编辑于2022年，星期五Laboratory findingsIII Radionucli
13、de:99m TC-MIBI,H/L liver biopsy:to confirm the diagnosis Laparoscopy HVPG(hepatic vein pressure gradient)(肝静脉压力梯肝静脉压力梯度度)(wedged-free)hepatic venous pressure Normal:5-6mmHg,10mmHg:varices;12mmHg:rupture第38页，共67页，编辑于2022年，星期五第39页，共67页，编辑于2022年，星期五第40页，共67页，编辑于2022年，星期五第41页，共67页，编辑于2022年，星期五第42页，共67页，
14、编辑于2022年，星期五Diagnosis I Etiology of cirrhosis Pathology of cirrhosis Evaluating of liver function:Child-Pugh classification Searching for complications第43页，共67页，编辑于2022年，星期五DiagnosisIIthe history of disease contributes to identifying the cause of cirrhosis.history of viral hepatitis,blood transfusio
15、ns,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:Ul
16、trasound and CT readily identify the lesion,but have no characteristic findings.第44页，共67页，编辑于2022年，星期五Child-Pugh classificationScoreavariable 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 40
17、 Prothrombin Time(s)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=10-15DiagnosisIII第45页，共67页，编辑于2022年，星期五Differential Diagnosis Other condition of hepatomegaly or splenomegaly：chronic virus hepatitis,Gauchers dis
18、ease,lymphomas and leukaemias,congestive splenomegalyDifferebtial diagnosis of cirrhotic ascites and other types of ascites：malignant ascites,constrictive pericarditis,tuberculous peritonitis,et al.Portal hypertension:第46页，共67页，编辑于2022年，星期五Treatment of cirrhosisIspecific treatment for the underlying
19、 etiology of the liver disease antivirus therapy-viral hepatitis abstinence from alcohol-alcoholic Ursodeoxycholic acid(UDCA)(熊去氧胆酸熊去氧胆酸)-PBC Penicillamine(青霉胺青霉胺)Wilsons diseaseGeneral Treatments:High calories(40 kcal/kg d)、adequate protein(1-1.5g/kg d)、vitamin、Herbal compounds.第47页，共67页，编辑于2022年，星
20、期五Treatment of Ascitesa.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，第49页，共67页，编辑于2022年，星期五Treatment of Ascites(III)c.Large-volume paracentesis associated
21、 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经颈静脉门体分流术)g.Liver transplantation(肝移植肝移植)第50页，共67页，编辑于2022年，星期五第51页，共67页，编辑于2022年，星期五TIPS-stent positioned between the hepatic and por
22、tal veins第52页，共67页，编辑于2022年，星期五Treatment of cirrhosisIVsurgical treatment of portal hypertension portacaval shunt surgery：portacaval mesocaval distal splenorenal shunts Choice of patients：Child-Pugh:A,B bleeding from gastroesophageal varices,hypersplenism.第53页，共67页，编辑于2022年，星期五Treatment of cirrhosis
23、VTreatment complationsTreatment of acute variceal haemorrhage：-General management:abstain food,intensive care,volume and blood replacement,specific measures to stop the bleeding -Pharmacological therapy:vasopressin(垂体后叶素垂体后叶素)somatostatin(生生长抑素抑素)Octreotide(奥曲肽奥曲肽)第54页，共67页，编辑于2022年，星期五Treatment of
24、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(普奈普奈洛洛尔),en
25、doscopic sclerotherapy(硬化硬化剂)/banding(套扎套扎)(usually 3-6 sessions),portacaval shunting,TIPS第55页，共67页，编辑于2022年，星期五第56页，共67页，编辑于2022年，星期五第57页，共67页，编辑于2022年，星期五第58页，共67页，编辑于2022年，星期五第59页，共67页，编辑于2022年，星期五第60页，共67页，编辑于2022年，星期五TIPS-stent positioned between the hepatic and portal veins第61页，共67页，编辑于2022年，星
26、期五Treatmentportalhypertension(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 treat
27、ment 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.第63页，共67页，编辑于2022年，星期五Therapies for HRSI Avoid use of nephrotoxic drugs:（1）Antibiotics：aminoglycosides （2）NSAIDs：inhibit formatio
28、n 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第64页，共67页，编辑于2022年，星期五The
29、rapies for HRSII Volume expansion:with IV dextrose,plasma,albumin or Concomitant plasma volume expansion with albumin has been used with LVP to correct decreased effective arterial volume that leads to sodium retention,TIPS Vasoactive drugs:terlipressin(可利新可利新),ornipressin,dopamine,-increasing renal
30、 plasma flow Elimination of endotoxaemia and control infections Liver transplantation:the most effective treatment for patients with HRS 第65页，共67页，编辑于2022年，星期五Indications for Liver transplantation(irreversible,progressive chronic liver diseases)Primary biliary cirrhosisSclerosing cholangitisFulminan
31、t liver failureMetabolic liver diseasesAlcoholic cirrhosisPostnecrotic cirrhosisAutoimmune liver diseaseBudd-Chiari syndromeHepatocellular carcinoma第66页，共67页，编辑于2022年，星期五Indications for Liver transplantation(cirrhosis)Refractory ascitesRecurrent variceal bleedingHepatic encephalopathyspontaneous bacterial peritonitisWorsening functional status,rising bilirubin,decreasing albumin,worsening coagulopathy(Child-Pugh C)第67页，共67页，编辑于2022年，星期五