Autoimmune liver diseases & cirrhosis Flashcards
Autoimmune hepatitis pathogenesis
chronic disease of unknown cause
environmental agents trigger autoimmune response against liver antigens - can lead to cirrhosis if untreated
AI hepatitis clin features
Diagnosis of exclusion
May be asymptomatic/nonspecific
1/3 present with symptoms of acute hepatitis - fever, liver tenderness & jaundice
Extrahepatic: sicca, Raynaud’s, thyroiditis, Sjogren’s, arthralgias
Hypergammaglobulinemia: anti-SMA is most characteristic
also elevation in anti-LKM
can have false positive viral serology
Less specific: elevated ANA, RF
AI hepatitis labs
elevated serum aminotransferase
elevated serum immunoglobulin (mostly IgG)
positive antibodies: ANA, anti-SMA, or anti-LKM
Primary biliary cirrhosis pathogenesis
chronic and progressive cholestatic disease of the liver
etiology unknown, presumed to be autoimmune
destruction of the small-to-medium sized intrahepatic bile ducts leading to progressive cholestasis
Primary biliary clin features
fatigue, pruritis, RUQ discomfort mildly elevated ALT & AST significant elevation of ALP, GGT Raised immunoglobulin (mainly IgM) AMA hallmark (98% specificity)
Primary sclerosis cholangitis pathogenesis
cholestasis with inflammation and fibrosis of intrahepatic and extrahepatic bile ducts
may lead to cirrhosis and portal HTN
etiology unknown
75-90% patients also have IBD (Autoimmune cause?)
Primary sclerosis cholangitis clin features
increase in serum autoantibody levels: ANCA, ANA
increased ALP, mildly increased AST
often insidious with fatigue and pruritis
may present with signs of episodic bacterial cholangitis secondary to biliary obstruction
Hemochromatosis pathogenesis
Autosomal recessive
Most common genetic disease in European population
C282Y of HFE gene
Hemochromatosis clin features
chronic hepatitis HCC in 18.5% of cirrhotic patients with hemochromatosis Arthalgias of MCP joints Glucose intolerance, diabetes Skin pigmentation - bronze diabetes ED/testicular atrophy in late disease Transferrin sat > 50% serum ferritin > 400
Wilson’s disease pathogenesis
Uncommon autosomal recessive
defect of copper-transporting ATPase
excessive absorption from SI, decreased excretion
Deposition of copper in liver, brain, and other tissues
Wilson’s disease clin features
Liver disease during the first decade of life OR neuropsychiatric illness during third decade
Liver: cirrhosis, chronic active hepatitis, acute haptitis, fulminant liver failure, low risk of HCC
Eyes: Kayser-Fleischer rings
CNS: basal ganglia (wing flapping tremor, Parkinsonism), cerebellum (dysarthria, dyspgaia, incoordination, ataxia), cerebrum (psychosis, affective disorder)
Joints: arthritis, bone demineralization, calcification
Reduced serum ceruloplasmin, increased urinary copper excretion
NAFLD pathogenesis
insulin resistance implicated leading to hepatic steatosis
changes indistinguishable from alcoholic hepatitis
NAFLD clin features
often asymptomatic
fatigue, malaise, vague RUQ discomfort
elevated serum TG/cholesterol levels and insulin resistance
Elevated serum AST, ALT +/- ALP; AST/ALT < 1
NAFLD found in >80% of those who are obese
Alcoholic liver disease pathogenesis
acetaldehyde
Alcoholic liver disease clin features
Hepatic steatosis: typically asymptomatic, can have mild RUQ discomfort and hepatomegaly AST/ALT > 2, GGT elevation Active inflammation and hepatocyte damage Arterial bruit overl iver ascites, encephalopathy modest leukocytosis hyperbilirubinemia hgih INR hypoalbuminemia
Alpha-1 antitrypsin deficiency
Prevents release from hepatocytes
Low alveolar concentrations –> emphysema
Clinical liver disease due to accumulation in liver
Cirrhosis definition
chronic disease of the liver characterized by the replacement of normal tissue with fibrous tissue and the loss of functional liver cell
Morphologic characteristics of cirrhosis
- Bridging fibrous septa linking portal tracts to one another and portal tracts with terminal hepatic veins
- Parenchymal nodules containing hepatocytes encircled by fibrosis - nodularity due to cycles of regeneration & scarring
- Disruption of the architecture of the entire liver
Complications of hepatic cirrhosis/ portal HTN
hepatic encephalopathy hepato-cerebral degeneration esophageal varices ascites hepato-renal syndrome coagulopathy cirrhotic cardiomyopathy hepatopulmonary syndrome porto-pulmonary HTN
Hepatic encephalopathy tx
treat precipitant - infection, GI bleeding
lactulose - acidifies ammonia
Hepato-cerebral degeneration tx
liver transplant, effective?
Esophageal varice bleeding tx
ABCs pharmacologics to reduce portal pressure (somatostatin) endoscopy balloon tamponades emergency decompression shunt
Ascites treatment
salt restriction
Diuretics - spironolactone
large volume paracentesis - administer iv albumin
hepato-renal syndrome tx
reverse underlying splanchnic and sytemic vasodilation
- iv albumin, vasopressor therapy
evaluate for liver transplant
