【正文】 s of diuretics cannot be achieved because of diureticinduced plications ? Diureticresistant ascites No response to maximal diuretic therapy (400 mg spironolactone + 160 mg furosemide/day) 20% 80% Arroyo et al. Hepatology 1996。 319:983 Variceal hemorrhage Varix with red signs PROGNOSTIC INDICATORS OF FIRST VARICEAL HEMORRHAGE Tension (T) Wall thickness (w) Groszmann, Gastroenterology 1984。38:266 VARICES INCREASE IN DIAMETER PROGRESSIVELY A Threshold Portal Pressure of ~12 mmHg is Necessary for Varices to Form P 5 10 12 15 25 30 35 20 Hepatic Venous Pressure Gradient (mmHg) GarciaTsao et. al., Hepatology 1985。ARCHITECTURAL LIVER DISRUPTION IS THE MAIN MECHANISM THAT LEADS TO AN INCREASED INTRAHEPATIC RESISTANCE Hepatic cirrhosis Ma Xiong, ., Associate Professor Shanghai Institute of Digestive Disease, Renji Hospital Shanghai Jiao Tong University School of Medicine Hepatic Cirrhosis ? End stage of any chronic liver disease ? Characterized histologically by regenerative nodules surrounded by fibrous tissue ? Clinically there are two types of cirrhosis: ? Compensated ? Depensated DEFINITION OF CIRRHOSIS Cirrhosis Normal Nodules Irregular surface GROSS IMAGE OF A NORMAL AND A CIRRHOTIC LIVER Cirrhotic liver Nodular, irregular surface Nodules GROSS IMAGE OF A CIRRHOTIC LIVER Cirrhosis Normal Nodules surrounded by fibrous tissue HISTOLOGICAL IMAGE OF A NORMAL AND A CIRRHOTIC LIVER HISTOLOGICAL IMAGE OF CIRRHOSIS Fibrosis Regenerative nodule PATHOGENESIS OF LIVER FIBROSIS Hepatocytes Space of Disse Sinusoidal endothelial cell Hepatic stellate cell Fenestrae Normal Hepatic SInusoid Retinoid droplets PATHOGENESIS OF LIVER FIBROSIS Alterations in Microvasculature in Cirrhosis ? Activation of stellate cells ? Collagen deposition in space of Disse ? Constriction of sinusoids ? Defenestration of sinusoids Compensated cirrhosis Depensated cirrhosis Death Chronic liver disease Natural History of Chronic Liver Disease Development of plications: ? Variceal hemorrhage ? Ascites ? Encephalopathy ? Jaundice NATURAL HISTORY OF CHRONIC LIVER DISEASE 60 40 80 100 120 140 160 0 40 60 80 20 20 0 100 Months Probability of survival All patients with cirrhosis Depensated cirrhosis 180 Depensation Shortens Survival Gines et. al., Hepatology 1987。7:122 Median survival ~ 9 years Median survival ~ years SURVIVAL TIMES IN CIRRHOSIS 10 Liver insufficiency Variceal hemorrhage Complications of Cirrhosis Result from Portal Hypertension or Liver Insufficiency Cirrhosis Ascites Encephalopathy Jaundice Portal hypertension Spontaneous bacterial peritonitis Hepatorenal syndrome COMPLICATIONS OF CIRRHOSIS Cirrhosis Diagnosis ? Cirrhosis is a histological diagnosis ? However, in patients with chronic liver disease the presence of various clinical features suggests cirrhosis ? The presence of these clinical features can be followed by noninvasive testing, prior to liver biopsy DIAGNOSIS OF CIRRHOSIS In Whom Should We Suspect Cirrhosis? ? Any patient with chronic liver disease ? Chronic abnormal aminotransferases and/or alkaline phosphatase ? Physical exam findings ? Stigmata of chronic liver disease (muscle wasting, vascular spiders, palmar erythema) ? Palpable left lobe of the liver ? Small liver span ? Splenomegaly ? Signs of depensation (jaundice, ascites, asterixis) DIAGNOSIS OF CIRRHOSIS – CLINICAL FINDINGS Laboratory ? Liver insufficiency ? Low albumin ( g/dL) ? Prolonged prothrombin time (INR ) ? High bilirubin ( mg/dL) ? Portal hypertension ? Low platelet count ( 175 x1000/ml) ? AST / ALT ratio 1 In Whom Should We Suspect Cirrhosis? DIAGNOSIS OF CIRRHOSIS – LABORATORY STUDIES CT Scan in Cirrhosis Liver with an irregular surface Splenomegaly Collaterals DIAGNOSIS OF CIRRHOSIS – CAT SCAN No Yes Diagnostic Algorithm Patient with chronic liver disease and any of the following: ? Variceal hemorrhage ? Ascites ? Hepatic encephalopathy Liver biopsy not necessary for the diagnosis of cirrhosis Physical findings: Enlarged left hepatic lobe Splenomegaly Stigmata of chronic liver disease Laboratory findings: Thrombocytopenia Impaired hepatic synthetic function Radiological findings: ? Small nodular liver ? Intraabdominal collaterals ? Ascites ? Splenomegaly ? Colloid shift to spleen and/or bone marrow Yes No Yes No Liver biopsy DIAGNOSTIC ALGORITHM Mechanisms of Portal Hypertension ? Pressure (P) results from the interaction of resistance (R) and flow (F): P = R x F ?Portal hyperte