Flashcards in Functional Liver Tests and Treatment of Chronic Hepatitis Deck (23)
What is the common location and clinical implications of abnormal levels of Aspartate Aminotransferase (AST)?
Cytosol and mitochondria of hepatocytes
May result from non-hepatic injury as well
What is the common location and clinical implications of abnormal levels of Alanine Aminotransferase (ALT)?
Cytosol of all hepatocytes
What is the common location and clinical implications of abnormal levels of bilirubin?
Heme degradation product conjugated in ER of hepatocytes, excreted in bile
Cholestasis, impaired conjugation, biliary obstruction
Elevated indirect bilirubin = hemolysis
Elevated direct bilirubin = bile duct obstruction
What is the common location and clinical implications of abnormal levels of Alkaline Phosphatase?
Bile canaliculi microvilli
Serum Alk Phos is primarily from liver and bone
Cholestasis, infiltrative disease, biliary obstruction
What is the common location and clinical implications of abnormal levels of Albumin?
Synthesized in liver
What is the common location and clinical implications of abnormal levels of Prothrombin time?
Many blood coagulation factors are synthesized in the liver
What is the normal ratio of AST:ALT, what do common abnormalities indicate, and what levels signify a mild vs severe abnormality?
Normal ratio AST:ALT = 0.8
Ratio >1 is seen in cirrhosis
Ratio >2 suggests alcoholic liver disease
- Low ALT from B6 malabsorption
- High AST from alcohol preferentially damaging AST rich mitochondria
Normal levels of each ~50 Units/L
Mild elevation of AST or ALT = 15 times normal levels
Describe the etiology of jaundice
Jaundice is the result of elevated bilirubin. Bilirubin is a normal heme degradation product. It is normally taken up into hepatocytes and conjugated (glucoronidation) by the enzyme bilirubin-UGT in the ER to a water soluble form that is excreted into the bile canaliculi. Elevations in bilirubin may manifest as either conjugated (direct) hyperbilirubinemia or unconjugated (indirect) hyperbilirubinemia.
Name and describe three causes of unconjugated (indirect) hyperbilirubinemia
Gilbert's Syndrome: benign disease resulting from decreased expression of bilirubin-UGT. Patients have normal AST, ALT, and Alk Phos levels. Jaundice results from stress, and may be protective.
Crippler-Najjar syndrome: A more severe disease than Gilbert's resulting from mutation (Type II) or complete absence (Type I) of UGT. Type I = neurologic impairment
Hemolysis: Increased heme breakdown (i.e. Hemolytic anemia)
Name and describe four causes of conjugated (direct) hyperbilirubinemia
Extra hepatic obstruction of bile flow
Intrahepatic cholestasis: a functional impairment of bile formation within the hepatocyte
What are the four main patterns of disease that liver tests can detect?
Hepatocellular injury or necrosis
What are the hepatic and non-hepatic etiologies associated with mildly elevated AST or ALT?
Chronic HBV and HCV
Acute Viral hepatitis (including EBV and CMV)
Alcohol -related liver injury
What are the etiologies associated with severely elevated AST or ALT?
Acute viral hepatitis (Hep A-E, herpes)
Acute Budd-Chiari syndrome
Hepatic artery ligation or thrombosis
What are the etiologies associated with elevated alkaline phosphatase?
Bile duct obstruction
Primary biliary cirrhosis (PBC)
Primary Sclerosing Cholangitis (PSC)
Infiltrating Disease of liver
Chronic renal failure
Congestive heart failure
Infection and inflammation
What are some infiltrating diseases of the liver that cause elevated Alk Phos levels?
Other granulomatous diseases
What are all of the HBV serological markers and what do they indicate?
HBsAg = Hepatitis B surface antigen
Pos indicates active HBV infection
HBeAg = Hepatitis B envelope antigen
Pos indicates a high viral load
HBsAb = Hepatitis B surface antibody
Pos Indicates prior exposure, either infection or immunization
HBcAb = Hepatitis B core antibody
Pos Indicates prior infection only
HBeAb = Hepatitis B envelope antibody
Pos indicates low viral load
Pos indicates active viral replication
What is the goal of HBV treatment?
Loss of HBeAg and development of HBeAb associated with negative HBV DNA when treatment is stopped
Prevention of decompensated cirrhosis in those with advanced fibrosis
Note: loss of HBsAg rarely occurs (infection is still present, but not in high quantities
What are the treatment options for HBV?
Finite duration of therapy
What is the goal of HCV treatment?
Chronic HCV infection is defined as HCV RNA presence >6mo after infection
Goal of antiviral therapy is to clear HCV RNA such that patients remain HCV RNA clear 12 weeks after stopping therapy.
Sustained virological response = cure
What is the treatment for Hereditary Hemochromatosis?
HH - Inherited disorder resulting in increased iron absorption in duodenum, accumulating in liver
Therapeutic phlebotomy or chelation therapy with desfuroxamine
What is the treatment for autoimmune hepatitis?
AH - Chronic hepatitis characterized by immunologic and autoimmune features.
Treatment is based on immune suppression:
Relapse typically occurs if treatment is stopped after liver enzymes normalize
What is the treatment for Primary Biliary Cirrhosis?
PBC - Immune mediated disease causing damage to small intrahepatic bile ducts.
Treatment is ursodeoxycolic acid (UDCA):
A secondary bile acid produced by intestinal bacteria
Improves bile acid transport, detoxifies bile, provides cytoprotection