Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Alanine Aminotransferase (ALT) (SGPT) Alanine aminotransferase (ALT) is also known as serum glutamic pyruvic transaminase (SGPT). Alanine aminotransferase is an enzyme involved in the transfer of an amino group from the amino acid, alanine, to alpha-ketoglutaric acid to produce glutamate and pyruvate. ALT is located primarily in liver and kidney, with lesser amounts in heart and skeletal muscle. Increased ALT (SGPT) activity is more specific for liver damage than increased AST or SGOT activity as ALT is seldom increased in heart or muscle disease. Until 15 to 20 years of age plasma ALT activity is lower than AST. Thereafter, plasma ALT activity tends to be higher than AST activity until age 60. After that the activities become roughly equal. The half-life of ALT in the circulation is 47 +/- 10 hours. ALT activity in the liver is 3000 fold higher than in serum. Measurement of serum ALT activity is a good indicator of hepatocyte injury. Disease Peak ALT AST:ALT x ULN Ratio 10 - 40 <1 <15 <3 Alcoholic hepatitis 2-8 >2 <15 1-3 Toxic injury >40 >1 early <5 >5 transient Ischemic injury >40 >1 early <5 >5 transient Viral hepatitis Peak Bilirubin Protime Prolongation X ULN = times upper limit of normal, Protime prolongation is number of seconds above ULN ALT in viral hepatitis The best ALT discriminant value for recognizing acute hepatic injury is 300 U/L. ALT increases before appearance of jaundice & peak near onset of jaundice in viral hepatitis. Activity falls slowly, an average of 10% per day. ALT remains elevated for 27+/-16 days. ALT levels fluctuate between normal and abnormal in hepatitis C. 15 to 50% of patients with chronic hepatitis C have persistently normal ALT. In uncomplicated alcoholic hepatitis, ALT values are almost never >10 times the upper reference limit. Extremely elevated ALT levels are common in toxic hepatitis and hepatic ischemia secondary to circulatory collapse and heatstroke. 90% of cases with ALT >3000 U/L are due to toxic or ischemic injury. AST is usually higher than ALT and both enzymes peak in the first 24 hours after admission. After peaking, both levels fall rapidly; AST faster than ALT. Peak ALT levels bear no relationship to prognosis and may fall with worsening of the patient’s condition. In fulminant hepatic necrosis, decreasing ALT may signify a paucity of viable hepatocytes rather than recovery. 1 Slightly raised serum ALT levels Patients with cirrhosis, non-alcoholic steatohepatitis, cholestatic liver disease, fatty liver and hepatic neoplasm have slightly raised serum ALT levels (< 120 IU/L). Patients with cirrhosis seldom have ALT levels higher than two times normal. Cirrhotic patients without ongoing liver injury the values may have normal values. Other causes of elevated ALT include *hemochromatosis,*Wilson disease, *autoimmune hepatitis,* primary biliary cirrhosis, *sclerosing cholangitis and *alpha-1 antitrypsin deficiency. Medications cause abnormal aminotransferase levels Pain relief medications such as: aspirin, acetaminophen, ibuprofen, naproxen, Nadiclofenac, and phenylbutazone Anti-seizure medications such as: phenytoin, valproic acid , carbamazepine, and phenobarbital Antibiotics such as: tetracyclines, sulfonamides, isoniazid, sulfamethoxazole, nitrofurantoin, fluconazole and some other anti-fungals, etc. Cholesterol lowering drugs such as: the statins: lovastatin, pravastatin, atorvastatin,fluvastatin, rosuvastatin, simvastatin, and niacin Cardiovascular drugs such as:amiodarone, hydralazine, quinidine, etc. Other drugs Anti-depressant drugs of the tricyclic type With drug-induced liver enzyme abnormalities, the enzymes usually normalize weeks to months after stopping the medications. The medications most commonly associated with elevated ALT are *sulfonamides, *statins and *isoniazid. In most types of liver disease, AST activity is lower than ALT. Exceptions include alcoholic hepatitis and Reye syndrome. The ratio of AST to ALT in diagnosis of some liver diseases. In most patients with acute liver injury the ratio is 1 or less. In alcoholic hepatitis it is generally about 2. Deficiency of pyridoxal-5'-phosphate, a necessary coenzyme for both aminotransferases, is common in alcoholic liver disease. This deficiency decreases ALT to a greater extent than AST. In renal failure, AST and ALT are significantly lower than in healthy individuals, because of reduced availability of pyridoxal-5'-phosphate. In healthy individuals, ALT levels can vary 10 to 30% from one day to the next. ALT levels can fluctuate 45% during a single day, with highest levels occurring in the afternoon and lowest levels at night. A high body mass index can increase ALT levels by 40 to 50%. Specimen Required Container/Tube: Plain, red-top tube(s) or serum gel tube(s) Reject Due To Specimens other than Serum Hemolysis Mild OK; Gross reject 2 Reference range is 20 - 60 IU/L Specimen requirement is one SST tube of blood. ALT is stable at room temperature for 3 days and refrigerated for 3 weeks. Hemolysis causes moderate increases in ALT levels. Investigations in asymptomatic patients with increased liver enzyme level Level I Test Abnormality Interpretation Full blood count Macrocytosis Suggests alcohol excess if GGT also raised Thrombocytopenia Possible hypersplenism (portal hypertension) AMA positive, IgM Probable primary biliary cirrhosis ASM/ANA positive, IgG Strongly suggestive of autoimmune hepatitis Ferritin Elevated Possible haemochromatosis, investigate further Hepatitis B surface antigen Positive Implies chronic infection Hepatitis C antibody Positive Suggests chronic infection Autoantibodies Level II Test Abnormality Interpretation Liver ultrasound Mass/dilated ducts Tumour/stones Anti‐endomysial antibodies Positive Suggests coeliac disease α1‐Antitrypsin level Low Suggests deficiency. Phenotype required (PiZZ or PiM implicated) Others: for example, caeruloplasmin, urine copper as dictated by clinical context Low Wilson's disease Adapted from the American Gastroenterology Association. Level 1 suggested first investigation set; Level 2, if no diagnosis obtained after Level 1. 3 AMA, antimitochondrial antibody; ANA, antinuclear antibody; ASM, anti‐smooth muscle actin monoclonal antibody; IgM, immunoglobulin M.J Clin Pathol. 2006 December; 59(12): 1229–1237. Factors affecting AST and ALT activity, other than liver injury. Factor AST(SGOT) Time of day 45% variation during day; highest in afternoon, lowest at night 5–10% variation from one 10–30% variation from one day to next day to next Day-to-day ALT(SGPT) Comments Similar in liver disease and health, and in elderly and young Race/gender 15% higher in AfricanNo significant difference American men between African-American, other women BMI 40–50% higher with high 40–50% higher with high BMI , Direct relationship between BMI weight and AST, ALT Meals No effect No effect Exercise Threefold increase with 20% lower in those who Effect of exercise seen strenuous exercise exercise at usual levels than in predominantly in men; those who do not exercise or minimal difference in women exercise more strenuously (<10%). Enzymes increase than usual more with strength training Specimen Stable at room temp for 3 Stable at room temperature Stability based on serum storage days, in refrigerator for 3 for 3 days, in refrigerator for 3 separated from cells; stable weeks (<10% decrease); weeks (10–15% decrease); for 24 h in whole blood, stable for years frozen marked decrease with marked increase after 24 h (10–15% decrease) freezing/thawing Hemolysis, Significant increase Moderate increase Dependent on degree of hemolytic attributable to release from hemolysis; usually anemia red cell severalfold lower than increases in LDH Muscle injury Significant increase Moderate increase Related to amount of increase in CK Diagnosis and Monitoring of Hepatic Injury. I.Performance Characteristics of Laboratory Tests D. Robert Dufour,John A. Lott,Frederick S. Nolte,David R. Gretch,Raymond S. Koff,and Leonard B. Seeff Clinical Chemistry 46: 2027-2049, 2000; 4 References W S A Smellie, J Forth, S Ryder, M J Galloway, A C Wood, and I D Watson Best practice in primary care pathology: review 5 J Clin Pathol. 2006 December; 59(12): 1229–1237. DAVID E. JOHNSTON, M.D. Special Considerations in Interpreting Liver Function Tests AAFP April 15 1999 2223-2233 D. Robert Dufour,John A. Lott, Frederick S. Nolte,David R. Gretch,Raymond S. Koff,and Leonard B. Seeff Diagnosis and Monitoring of Hepatic Injury. I. Performance Characteristics of Laboratory Tests Clinical Chemistry 46:12 2027–2049 (2000) American Gastroenterological Association Medical position statement: evaluation of liver chemistry tests. Gastroenterology 2002. 1231364–1366 Richard M. Green Steven Flamm AGA technical review on the evaluation of liver chemistry tests Gastroenterology Volume 123, Issue 4 , Pages 1367-1384 Giannini E G, Testa R, Savarino V. Liver enzyme alteration: a guide for clinicians. CMAJ 2005.172367–379.379. Take home message Elevated ALT values are seen in liver diseases characterized by a destruction of hepatocytes. Twenty to fifty-fold elevations are most frequently encountered. In infectious hepatitis the ALT/AST ratio, which normally and in other condition is <1, becomes greater than unity. ALT levels are usually elevated before clinical signs and symptoms of disease appear. 5