Serina Farzin-Nasab, MD Emory University Family Medicine Residency Program

3 Categories: 1- Direct hepatocellular damage (transaminases) 2-Cholestasis ( bilirubin, alkaline phosphates) 3-Liver’s synthetic ability ( albumin, PT)

Transaminitis Hepatocyte necrosis leads to leakage of enzyme  Hepatitis  Toxic injury  Ischemic injury

 Hep C: liver cell death by apoptosis (programmed cell death) and by necrosis  1/3 pt’s with Hep C have persistently normal serum transaminases

 Levels of aminotransferases can rise in Severe muscular exertion or other muscle injuries, polymyositis  Hypothyroidism

AST and ALT levels do not follow a normal bell-shaped distribution AST and ALT are higher in obese pt’s, males and nonwhites ( blacks and Hispanics)

Causes of Elevated ALT or AST Values in Asymptomatic Patients A) Autoimmune hepatitis B) Hepatitis B C) Hepatitis C D) Drugs or toxins E) Ethanol F) Fatty liver

G) Growths (tumors) H) Hemodynamic disorder (congestive heart failure) I) Iron (hemochromatosis), copper (Wilson's disease) or alpha1-antitrypsin deficiency M) Muscle injury

Typical AST or ALT Values in Disease

 Cholestasis reflected in abnormal bilirubin and AP levels  In acute bile duct obstruction from a gallstone, AST and ALT levels often reach 500 U per L or more in the first hours, whereas AP and GGT levels can take several days to rise. MARKERS OF CHOLESTASIS

 Elevation of GGT alone results from enzyme induction by alcohol or aromatic medicatios  GGT is elevated in persons who drink 3 or more per day

Direct/conjugated hyperbilirubinemia  Conjugated bilirubin levels do not rise until the liver has lost approximately half of its excretory ability.  The presence of conjugated bilirubin in the urine ( urine dipstick), is always indicative of hepatobiliary disease.

Indirect/uncongealed Hyperbilirubinemia: Gilbert syndrome  Common benign inherited disorder  Levels between 2 and 3 mg/d  Patients develop detectable jaundice during acute illness or starvation

Hemolysis  Confirmed by an elevated retic count & increased haptoglobin levels.  In adults, no serious liver disease will cause elevation of indirect bili alone without a concurrent rise in direct bili levels.

AP  Elevated levels are found in adolescents, children (secondary to bone growth), and pregnant women  Women with persistently elevated AP levels primary biliary cirrhosis  Confirmed by a serum antimitochondrial antibody test

Hepatic Cause of elevated AP Hepatocellular disease (usually <3-fold increase) Alcoholic hepatitis Viral hepatitis Fatty infiltration of liver Cirrhosis

Hepatic Cause of elevated AP Obstructive processes (usually >3-fold increase)  Choledocholithiasis  Cancer of head of pancreas  Cholangiocarcinoma  Cholestatic hepatitis

Hepatic Cause of elevated AP Infiltrative, neoplastic, Primary or metastatic carcinomas (15- to 20-fold increase)  Primary biliary cirrhosis  Amyloidosis  Hepatic congestion caused by heart disease  Infectious mononucleosis

Hepatic Cause of elevated AP Medications: Captopril Erythromycin Gold salts Phenothiazines Trimethoprimand-sulfamethoxazole Anticonvulsants

 Increased synthesis of AP in Diabetes mellitus  44% of patients with DM have increased AP

Common Non hepatic Causes of Elevated GGT  Acetaminophen overdose  Acute myocardial infarction  Acute pancreatitis  Anticonvulsants (phenytoin, phenobarbital,  carbamazepine)

 Brain tumor  Diabetes mellitus  Hyperthyroidism  Infectious mononucleosis  Epilepsy

Albumin  An Index of liver synthetic capacity  Low albumin level and no other LFT abnormalities are likely to have a non hepatic cause

Albumin Non hepatic causes of low Albumin:  Inflammatory states such as burns, trauma, & sepsis  Active rheumatic disorders  Severe end-stage malnutrition  Pregnancy  Proteinuria

PT  Does not become abnormal until more than 80%of liver synthetic capacity is lost  Useful to be followed in acute hepatic failure (Factor 7 has very short half life)

PT  Vitamin K deficiency  Chronic cholestasis or fat malabsorption  A trial of vitamin K injections ( 5 mg /day SQ x 3 days) practical way to exclude vitamin K deficiency  PT should improve within a few days

Ammonia  Concentrations are much higher in the brain than in the blood and therefore do not correlate well  It is not unusual for the blood ammonia to be normal in a patient who is in a coma from hepatic encephalopathy.

QUIZ Other than hepatitis, causes of elevated serum GGT include all of the following except: A. Diabetes mellitus. B. Hypothyroidism. C. Brain tumor. D. Infectious mononucleosis. E. Acute myocardial infarction

Answer : B Hyperthyroidism is associated with elevated GTT

QUIZ The greatest increase in serum alkaline phosphatase is generally seen in a patient with which of the following conditions? A. Primary biliary cirrhosis. B. Alcoholic hepatitis. C. Viral hepatitis. D. Fatty infiltration of the liver. E. Cancer of the head of the pancreas

Answer: A Primary billiary cirrhosis

QUIZ In patients with viral hepatitis, the serum AST level is usually higher than the serum ALT level A. True. B. False

False

QUIZ Normally, most of the total bilirubin is conjugated. A. True B. False

False 70% of total Billi is non conjugated