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

Serina Farzin-Nasab, MDEmory UniversityFamily 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:CaptoprilErythromycinGold salts PhenothiazinesTrimethoprimand-sulfamethoxazoleAnticonvulsants

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 elevatedserum 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 alkalinephosphatase is generally seen in a

patientwith 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