【正文】 n ? Transjugular intrahepatic portosystemic shunt (TIPS) ? Vasoconstrictor + TIPS ? Extracorporeal albumin dialysis (ECAD) Ineffective ? Renal vasodilators (prostaglandin, dopamine) ? Hemodialysis MANAGEMENT OF HEPATORENAL SYNDROME HEPATIC ENCEPHALOPATHY Hepatic Encephalopathy 60 Hepatic Encephalopathy Nomenclature ? Type A Associated with Acute liver failure ? Type B Associated with portosystemic Bypass without intrinsic hepatocellular disease ? Type C Associated with Cirrhosis and portosystemic shunting Ferenci et al., Hepatology 2022。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。 35:716 HEPATIC ENCEPHALOPATHY – NOMENCLATURE ? Treatment: rarely effective short of liver transplant Characteristics of Type A vs. Type C Hepatic Encephalopathy ? Gradual onset ? Rarely fatal ? Main cause: shunting / toxin ? Precipitant ? Treatment: usually effective ? Rapid onset ? Frequently fatal ? Main cause: cerebral edema Type A Type C CHARACTERISTICS OF TYPE A VS. TYPE C ENCEPHALOPATHY Type C Hepatic Encephalopathy is the Encephalopathy of Cirrhosis ? Neuropsychiatric plication of cirrhosis ? Results from spontaneous or surgical / radiological portalsystemic shunt + chronic liver failure ? Failure to metabolize neurotoxic substances ? Alterations of astrocyte morphology and function (Alzheimer type II astrocytosis) TYPE C HEPATIC ENCEPHALOPATHY IS THE ENCEPHALOPATHY OF CIRRHOSIS Hepatic Encephalopathy Pathogenesis Bacterial action Protein load Failure to metabolize NH3 NH3 Shunting GABABD receptors Toxins PATHOPHYSIOLOGY OF HEPATIC ENCEPHALOPATHY Hepatic Encephalopathy Is A Clinical Diagnosis ? Clinical findings and history important ? Ammonia levels are unreliable ? Ammonia has poor correlation with diagnosis ? Measurement of ammonia not necessary ? Number connection test ? Slow dominant rhythm on EEG HEPATIC ENCEPHALOPATHY IS A CLINICAL DIAGNOSIS Stage Mental state Neurologic signs 1 Mild confusion: limited attention Incoordination, tremor, span, irritability, inverted sleep impaired handwriting pattern 2 Drowsiness, personality changes, Asterixis, ataxia, dysarthria intermittent disorientation 3 Somnolent, gross disorientation, Hyperreflexia, muscle marked confusion, slurred speech rigidity, Babinski sign 4 Coma No response to pain, decerebrate posture Stages of Hepatic Encephalopathy STAGES OF HEPATIC ENCEPHALOPATHY STAGES OF HEPATIC ENCEPHALOPATHY Confusion Drowsiness Somnolence Coma 1 2 3 4 Stage Stages of Hepatic Encephalopathy Asterixis ASTERIXIS IS THE HALLMARK IN THE DIAGNOSIS OF HEPATIC ENCEPHALOPATHY 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Begin End Time to plete____________________ Number Connection Test (NCT) Sample handwriting Draw a star NUMBER CONNECTION TEST 70 Electroencephalogram in Hepatic Encephalopathy EL