LIVER CIRRHOSIS (causes,pathophysiology,features,diagnosis,treatment)

Liver Cirrhosis is defined as the presence of fibrous bands that divide the liver into regenerative nodules. Liver Cirrhosis represents a late stage of progressive hepatic fibrosis Cirrhosis is a late stage of hepatic fibrosis that has resulted in widespread distortion of normal hepatic architecture. Cirrhosis is characterized by regenerative nodules surrounded by dense fibrotic tissue. Symptoms may not develop for years and are often nonspecific (eg, anorexia, fatigue, weight loss). Late manifestations include portal hypertension, ascites, and, when decompensation occurs, liver failure. Diagnosis often requires liver biopsy. Cirrhosis is usually considered irreversible. Treatment is supportive. Cirrhosis is a leading cause of death worldwide. The causes of cirrhosis are the same as those of fibrosis . In developed countries, most cases result from chronic alcohol abuse or chronic hepatitis Cirrhosis of unknown etiology (cryptogenic cirrhosis) is becoming less common as many specific causes (eg, chronic hepatitis C, steatohepatitis) are identified. Injury to the bile ducts also can result in cirrhosis, as occurs in mechanical bile duct obstruction, primary biliary cholangitis, and primary sclerosing cholangitis. Pathophysiology There are 2 primary ingredients: Hepatic fibrosis Regenerating liver cells In response to injury and loss, growth regulators induce hepatocellular hyperplasia (producing regenerating nodules) and arterial growth (angiogenesis). Among the growth regulators are cytokines and hepatic growth factors (eg, epithelial growth factor, hepatocyte growth factor, transforming growth factor-alpha, tumor necrosis factor). Insulin, glucagon, and patterns of intrahepatic blood flow determine how and where nodules develop Angiogenesis produces new vessels within the fibrous sheath that surrounds nodules. These vessels connect the hepatic artery and portal vein to hepatic venules, restoring the intrahepatic circulatory pathways. Such interconnecting vessels provide relatively low-volume, high-pressure venous drainage that cannot accommodate as much blood volume as normal. As a result, portal vein pressure increases. Such distortions in blood flow contribute to portal hypertension, which increases because the regenerating nodules compress hepatic venules. The progression rate from fibrosis to cirrhosis and the morphology of cirrhosis vary from person to person. Presumably, the reason for such variation is the extent of exposure to the injurious stimulus and the individual’s response. It is a histological diagnosis and can be classified into micro and macronodular by the size of mm. Risk of developing Hepatocellular Carcinoma Chronic Viral Infection - HBV HCV Wilson's disease α-1 antitrypsin deficiency Alcohol Haemochromatosis NASH Alcohol and liver Steatosis - is reversible with alcohol abstention Alcoholic hepatitis - Mallory body Alcoholic cirrhosis - hobnail appearance Causes Chronic Hepatitis C infection (Alcoholic liver disease (AST more than ALT Elevated GGT) Chronic Hepatitis B infection (HBsAg HBeAg/HBV-DNA) Autoimmune liver disease (Raised Ig and Autoantibodies) Primary Sclerosing cholangitis (pANCA MRCP/ERCP) Primary Biliary cirrhosis (Anti Mitochondrial Ab) Hereditary Haemochromatosis (Ferritin high Transferrin saturation high, Genetics) Wilson's disease (Young, low Ceruloplasmin raised Urine copper, KF rings) Budd-Chiari syndrome (USS caudate lobe) Drugs - amiodarone, methotrexate, methyldopa Cystic fibrosis (genetics + sweat Cl) Alpha-1 antitrypsin (Young emphysema low serum AAT) Idiopathic - unknown Drugs that should be avoided in Cirrhosis These would include NSAIDs with their effects on kidneys and gastric mucosa. ACE inhibitors may be involved in hepatorenal syndrome and are best stopped. Codeine, Narcotics, Benzodiazepines and anxiolytics can all precipitate or worsen hepatic encephalopathy Complications Portal hypertension Liver failure Portosystemic Encephalopathy - always look for flap and assess mental state Variceal Bleeding formed from left gastric and short gastric veins to the oesophagus Ascites Spontaneous bacterial peritonitis Hepatorenal syndrome Osteoporosis Hepatocellular carcinoma Investigations U&E LFT's (low Na common) Prothrombin time and Albumin reflect liver synthetic function