Interpretation of abnormal liver enzymes
Abdullah Alyouzbaki, MD University of Mosul, Faculty of MedicineLiver Enzymes Aminotransferases AST (SGOT) ALT (SGPT) Alkaline phosphatase Gamma glutamyl transpeptidase Synthetic function Albumin Prothrombin time Bilirubin
The use of or exposure to any chemical or medication (including prescription and over-the-counter medications as well as herbal therapies) The duration of LFT abnormalities The presence of any accompanying symptoms such as jaundice, arthralgias, myalgias, rash, anorexia, weight loss, abdominal pain, fever, pruritus, and changes in the urine and stool Parenteral exposures including transfusions, intravenous and intranasal drug use, tattoos, and sexual activity. Recent travel history, exposure to people with jaundice, exposure to possibly contaminated foods, occupational exposure to hepatotoxins, and alcohol consumption.
History
Temporal and proximal muscle wasting suggest longstanding diseases Stigmata of chronic liver disease include spider nevi, palmar erythema, gynecomastia, caput medusae Dupuytren's contractures, parotid gland enlargement, and testicular atrophy Enlarged left supraclavicular node (Virchow's node) or periumbilical nodule (Sister Mary Joseph's nodule) suggest an abdominal malignancy Jugular venous distension, a sign of right sided heart failure, suggests hepatic congestion
Physical Examination
Patterns predominantly reflecting hepatocellular injury Patterns predominantly reflecting cholestasis
Laboratory testing
Serum Proteins
The liver is the major site at which serum proteins are synthesized.These include albumin and the coagulation factors
Albumin
Average adult liver synthesizes approximately 15 g per day (200 mg/kg per day). The serum albumin reflects the Rate of synthesis Rate of degradation Volume of distribution. Albumin synthesis is regulated by a variety of influences including nutritional status Serum oncotic pressure Cytokines, and hormonesHypoalbuminemia Systemic inflammation Nephrotic syndrome Malnutrition
Coagulation factorsThe liver is the major site of synthesis of 11 blood coagulation proteins. Factor I (fibrinogen) Factor II (prothrombin) Factor V Factor VII Factor IX Factor X Factors XII Factor XIII
Coagulation factors
Prolonged Prothrombin time (PT) Congenital or Acquired Consumption of clotting factors (such as disseminated intravascular coagulation or severe gastrointestinal bleeding) Certain drugs ( Warfarin)Coagulation factors
Vitamin K deficiency Inadequate dietary intake, Prolonged obstructive jaundice, Malabsorption Administration of antibiotics that alter the gut flora.(PT typically returns to normal within 24 hours after a single parenteral injection of vitamin K). Poor utilization of vitamin K due to advanced parenchymal liver disease (Vitamin K supplementation is generally ineffective)
Serum Aminotransferases
Sensitive indicators of liver cell injury. ALT and AST < 30 - 40 IU/L ALT levels are normally higher in Men Vary directly with body mass index Serum lipid levels. Elderly Infants ? Race ALT levels are normally lower in Consumption of coffee and especially caffeine Renal Failure
Serum Aminotransferases
Correlate poorly with the magnitude of liver injury Elevated in most liver diseases. Extensive hepatocellular injury Acute viral hepatitis Shock liver (ischemic hepatitis) Acute drug- / toxin-induced liver injuryAlkaline Phosphatase
Found in many locations throughout the body Its precise function is not yet known Derived from three sources: liver, bone, and the intestinal tract.Retained bile acids appear to play a central role leading to increase synthesis in the liver followed by direct release into the circulation.
Alkaline Phosphatase
Level varies with age and gender Higher in men than in women Children elevated in both sexes, correlates well with the rate of bone growth Adolescent males may reach mean values three times greater than in normal adults Enzyme activity in serum may double late in normal pregnancy, primarily because of influx from the placentaGamma-Glutamyl TransPeptidase
Present in cell membranes in many tissues, including the kidneys, pancreas, liver, spleen, heart, brain, and seminal vesicles. Serum GGT and alkaline phosphatase correlate reasonably well. Elevation in GGT is not completely specific for hepatobiliary disease. High GGT values are found in people who take medicines such as barbiturates or phenytoin or ingest large quantities of alcoholPatterns predominantly reflecting hepatocellular injury Patterns predominantly reflecting cholestasis
Patterns predominantly reflecting hepatocellular injury Increase in AST and ALT
Patterns predominantly reflecting cholestasis Increase in Alkaline phosphatase and GGTP
Describes the appearance of distended and engorged umbilical veins which are seen radiating from the umbilicus across the abdomen to join systemic veins.Caput Medusae
Case 1
Abnormal liver enzymes for > 6 months AST 80 ALT 110 Alkaline phosphatase, GGTP and Bilirubin WNLMild chronic elevation of serum transaminases
Step 1 Viral Hepatitis Screen Medications and Herbs Alcohol abuse Steatosis and steatohepatitis
Step 1 Viral Hepatitis Screen Medications and Herbs Alcohol abuse Steatosis and steatohepatitis
Careful history and risk factors HBsAg HCV antibodies
Step 1 Viral Hepatitis Screen Medications and Herbs Alcohol abuse Steatosis and steatohepatitis
Predictable Acetaminophen Ethanol
Idiosyncratic Methyldopa Aspirin Phenytoin Halothane Isoniazid Chlordiazepoxide Methotrexate Nitrofurantoin Phenothiazines Phenylbutazone Sulindac Sulfonamides Valproic
Step 1 Viral Hepatitis Screen Medications and Herbs Alcohol abuse Steatosis and steatohepatitis
CAGE questionnaire Have you ever felt the need to cut down on drinking? Have you ever felt annoyed by criticism of your drinking? Have you ever had guilty feelings about your drinking? Have you ever taken a morning eye opener?
Step 1 Viral Hepatitis Screen Medications and Herbs Alcohol abuse Steatosis and steatohepatitis
Obese / Overweight Type 2 Diabetes Hyperlipidemia
Step 2 Autoimmune hepatitis Alpha-1-antitrypsin deficiency Wilson's disease
ANAASMAAnti LKMγ- Globulins A1AT level and phenotypeCeruloplasmin level 24 hour urine Cu collection
Step 3 Muscle disorders Thyroid disorders Celiac disease Adrenal insufficiency Anorexia nervosa
Step 4 Liver Biopsy
When transaminases more than double Negative ultrasound and other tests
The Origins of Liver Anatomy
The earliest representation of a LIVER Clay Model (Assyro-Babylonia civilization 3000-2000 B.C.) British Museum at LondonCase 2
Asymptomatic adult with intermittent jaundice and normal liver enzymes except for T. bilirubin 3.5 mg/dl (direct 2.5 mg/dl)Increased bilirubin production Extravascular hemolysis Extravasation of blood into tissues Intravascular hemolysis Dyserythropoiesis Impaired hepatic bilirubin uptake Congestive heart failure Portosystemic shunts Certain drugs - rifampin, probenecid flavaspadic acid, bunamiodyl Impaired bilirubin conjugation Crigler-Najjar syndrome type I and II Gilbert's syndrome Hyperthyroidism Liver diseases - chronic persistent hepatitis, advanced cirrhosis, Wilson's disease
Unconjugated hyperbilirubinemia
Case 2
Asymptomatic adult with intermittent jaundice and normal liver enzymes except for T. bilirubin 3.5 mg/dl (direct 2.5 mg/dl)Family history Drug history Hgh / Hct LDH Haptoglobulin TSH
Crigler Najjar
Crigler Najjar type I Exceptionally rare condition found in neonates Characterized by severe jaundice (bilirubin >20 mg/dL) Neurologic impairment due to kernicterus. Crigler-Najjar type II More common than Type I and can live into adulthood Bilirubin levels that range from 6 to 25 mg/dL. Bilirubin UDP glucuronosyl transferase activity is typically reduced. Bilirubin UDP glucuronosyl transferase activity can be induced by the administration of phenobarbital, which can reduce serum bilirubin levels in these patients.Gilbert's syndrome
Affects approximately 3 - 7 % of the population with Males > females (2 : 7) Reduced bilirubin UDP glucuronosyl transferase activity. Mild unconjugated hyperbilirubinemia with serum levels almost always less than 6 mg/dL. The serum levels may fluctuate and jaundice is often identified only during periods of illness or fasting.Suggested that jaundice is originated from obstruction of bile passage.
Rhazes (860-932 A.D.):Avicenna (980-1037 B.C.):
Differentiated obstructive jaundice from jaundice due to other causes. Noted meat intolerance of cirrhotic patientsCase 3
AST 1200 ALT 1450 Bilirubin 9.5 mg/dl (direct 6 mg/dl) Alkaline phosphatase 230 mg/dlPredominantly hepatocellular pattern with jaundice
Viral hepatitis Hepatitis A, B, C, D, and E Epstein-Barr virus Cytomegalovirus Drugs Predictable, dose-dependent (eg, acetaminophen) Unpredictable, idosyncratic (many drugs) Environmental toxins Vinyl chloride Jamaica bush tea - pyrrolizidine alkaloids Wild mushrooms - Amanita phalloides or verna Autoimmune hepatitis Wilson's disease
Case 4
Isolated elevation of the alkaline phosphatase and/ or GGTPPartial bile duct obstruction Primary biliary cirrhosis (PBC) Primary sclerosing cholangitis, Drugs such as androgenic steroids and phenytoin. Infiltrative diseases include sarcoidosis, other granulomatous diseases Unsuspected cancer metastatic to the liver.