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Intended use

In vitro test for the quantitative determination of alanine aminotransferase (ALT), with or without pyridoxal phosphate activation, in human serum and plasma on the cobas c 111 system.

", "Language": "en" }, { "Name": "TestPrinciple", "Value": "

Test principle

This assay follows the recommendations of the IFCC, but was optimized for performance and stability.

LREFSchumann G, Bonora R, Ceriotti F, et al. IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C. International Federation of Clinical Chemistry and Laboratory Medicine. Part 4. Reference procedure for the measurement of catalytic concentration of alanine aminotransferase. Clin Chem Lab Med 2022 Jul;40(7):718-724. doi: 10.1515/CCLM.2002.124.
,
LREFBergmeyer HU, Hørder M, Rej R. Approved recommendation (1985) on IFCC methods for the measurement of catalytic concentration of enzymes. Part 3. IFCC Method for alanine aminotransferase. J Clin Chem Clin Biochem 1986;24(7):481-495.
,
LREFECCLS. Determination of the catalytic activity concentration in serum of L-alanine aminotransferase (EC 2.6.1.2, ALAT). Klin Chem Mitt 1989;20:204-211.

ALT catalyzes the reaction between L-alanine and 2-oxoglutarate. The pyruvate formed is reduced by NADH in a reaction catalyzed by lactate dehydrogenase (LDH) to form L-lactate and NAD+.

Pyridoxal phosphate serves as a coenzyme in the amino transfer reaction. It ensures full enzyme activation.

ALT

L-alanine + 2-oxoglutarate

pyruvate + L-glutamate

LDH

Pyruvate + NADH + H+

L-lactate + NAD+

The rate of the NADH oxidation is directly proportional to the catalytic ALT activity. It is determined by measuring the decrease in absorbance.

", "Language": "en" }, { "Name": "MeasuringRange", "Value": "

Limits and ranges

Measuring range

2‑700 U/L (0.03‑11.7 µkat/L)

Determine samples having higher activities via the rerun function. Dilution of samples via the rerun function is a 1:10 dilution. Results from samples diluted using the rerun function are automatically multiplied by a factor of 10.

Lower limits of measurement

Lower detection limit of the test

2 U/L (0.03 µkat/L)

The lower detection limit represents the lowest measurable analyte level that can be distinguished from zero. It is calculated as the value lying 3 standard deviations above that of the lowest standard (standard 1 + 3 SD, repeatability, n = 21).

", "Language": "en" }, { "Name": "ExpectedValues", "Value": "

Expected values

Expected values
LREFThefeld W, Hoffmeister H, Busch EW, et al. Referenzwerte für die Bestimmungen der Transaminasen GOT und GPT sowie der alkalischen Phosphatase im Serum mit optimierten Standardmethoden. Dtsch Med Wschr 1974;99(8):343-351.

• Without PYP activation

Acc. to the optimized standard method (comparable to the IFCC method without pyridoxal phosphate activation

LREFKlein G, Lehmann P, Michel E, et al. Vergleich der IFCC-Methoden für ALAT, ASAT und GGT bei 37 °C mit den eingeführten Standardmethoden bei 25 °C und 37 °C. Lab Med 1994;18:403-404.
):

Males

up to 41 U/L

up to 0.685 µkat/L

Females

up to 33 U/L

up to 0.551 µkat/L

Calculated values: a factor of 1.85 is used for the conversion from 25 °C to 37 °C.

LREFZawta B, Klein G, Bablok W. Temperaturumrechnung in der klinischen Enzymologie? Klin Lab 1994;40:23-32.

• With PYP activation

acc. to IFCC/Standard Method 94 with pyridoxal phosphate activation:

LREFKlauke R, Schmidt E, Lorentz K. Recommendations for carrying out standard ECCLS procedures (1988) for the catalytic concentrations of creatine kinase, aspartate aminotransferase, alanine aminotransferase and γ-glutamyltransferase at 37 °C. Eur J Clin Chem Clin Biochem 1993;31:901-909.

Measured at 37 °C:

Males

10-50 U/L

(0.167-0.835 µkat/L)

Females

10-35 U/L

(0.167-0.585 µkat/L)

Consensus values with pyridoxal phosphate activation:

LREFThomas L, Müller M, Schumann G, et al. Consensus of DGKL and VDGH for interim reference intervals on enzymes in serum. J Lab Med 2005;29:301-308.

Males

up to 50 U/L

(up to 0.835 µkat/L)

Females

up to 35 U/L

(up to 0.585 µkat/L)

Each laboratory should investigate the transferability of the expected values to its own patient population and if necessary determine its own reference ranges.

", "Language": "en" }, { "Name": "LimitationInterference", "Value": "

Limitations - interference

• Without PYP activation
Criterion: Recovery within ± 10 % of initial value at an ALT activity of 30 U/L (0.501 µkat/L)

• With PYP activation
Criterion: Recovery within ± 10 % of initial value at an ALT activity of 35 U/L (0.585 µkat/L)

Icterus:

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an I index of 60 for conjugated and unconjugated bilirubin (approximate conjugated and unconjugated bilirubin concentration: 1026 µmol/L or 60 mg/dL ).

Hemolysis:

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an H index of 130 (approximate hemoglobin concentration: 80 µmol/L or 130 mg/dL).

Lipemia (Intralipid):

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an L index of 150.
Lipemic samples interfere and may cause “High Abs” flagging.

Anticoagulants: Citrate and fluoride inhibit the enzyme activity.

Drugs: No interference was found at therapeutic concentrations using common drug panels.

LREFBreuer J. Report on the Symposium "Drug Effects in Clinical Chemistry Methods". Eur J Clin Chem Clin Biochem 1996;34:385-386.
,
LREFSonntag O, Scholer A. Drug interference in clinical chemistry: recommendation of drugs and their concentrations to be used in drug interference studies. Ann Clin Biochem 2001;38:376-385.

Exceptions:
Calcium dobesilate and Doxycycline HCl cause artificially low ALT values at the tested drug level.
Cyanokit (Hydroxocobalamin) may cause false-low results.
Physiological plasma concentrations of Sulfasalazine and Sulfapyridine may lead to false results.

In very rare cases, gammopathy, in particular type IgM (Waldenström’s macroglobulinemia), may cause unreliable results.

LREFBakker AJ, Mücke M. Gammopathy interference in clinical chemistry assays: mechanisms, detection and prevention. Clin Chem Lab Med 2007;45(9):1240-1243.

For diagnostic purposes, the results should always be assessed in conjunction with the patient’s medical history, clinical examination and other findings.

ACTION REQUIRED
Special Wash Programming: The use of special wash steps is mandatory when certain test combinations are run together on the cobas c 111 analyzer. For information about test combinations requiring special wash steps, please refer to the latest version of the carry over evasion list found with the CLEAN Method Sheet and the operator’s manual for further instructions.
Where required, special wash/carry-over evasion programming must be implemented prior to reporting results with this test.

", "Language": "en" }, { "Name": "OrderInformation", "Value": "

OrderInformation (CC Reagents - cobas + Integra)

Order information

Analyzer(s) on which kit(s) can be used

04718569190

Alanine aminotransferase acc. IFCC (4 × 100 tests)

cobas c 111

Materials required (but not provided):

04774221190

Pyridoxal Phosphate (4 × 200 tests)

Code 953

10759350190

Calibrator f.a.s. (12 × 3 mL)

Code 401

12149435122

Precinorm U plus (10 × 3 mL)

Code 300

12149443122

Precipath U plus (10 x 3 mL)

Code 301

05117003190

PreciControl ClinChem Multi 1 (20 × 5 mL)

Code 391

05947626190

PreciControl ClinChem Multi 1 (4 × 5 mL)

Code 391

05117216190

PreciControl ClinChem Multi 2 (20 × 5 mL)

Code 392

05947774190

PreciControl ClinChem Multi 2 (4 × 5 mL)

Code 392

", "Language": "en" }, { "Name": "SystemInformation", "Value": "

System information

ALTL: ACN 685

ALTPL: ACN 684

", "Language": "en" }, { "Name": "Handling", "Value": "

Reagent handling

Ready for use

", "Language": "en" }, { "Name": "TestDefinition", "Value": "

Application for serum and plasma

• Without PYP activation

cobas c 111 test definition

Measuring mode

Absorbance

Abs. calculation mode

Kinetic

Reaction direction

Decrease

Wavelength A/B

340/378 nm

Calc. first/last

20/35

Unit

U/L

Reaction mode

R1-S-SR

Pipetting parameters

Diluent (H2O)

R1

59 µL

10 µL

Sample

11 µL

26 µL

SR

17 µL

9 µL

Total volume

132 µL

• With PYP activation

cobas c 111 test definition

Measuring mode

Absorbance

Abs. calculation mode

Kinetic

Reaction direction

Decrease

Wavelength A/B

340/378 nm

Calc. first/last

20/35

Unit

U/L

Reaction mode

R1-DL-S-SR

Pipetting parameters

Diluent (H2O)

R1

59 µL

10 µL

Sample

11 µL

8 µL

Diluent (DL)

18 µL

SR

17 µL

9 µL

Total volume

132 µL

", "Language": "en" }, { "Name": "StorageStability", "Value": "

Storage and stability

Shelf life at 2-8 °C:

See expiration date on reagent

On-board in use and refrigerated on the analyzer:

weeks

", "Language": "en" }, { "Name": "Calibration", "Value": "

Calibration

Calibrator

Calibrator f.a.s.
Deionized water is used automatically by the instrument as the zero calibrator.

Calibration mode

Linear regression

Calibration interval

Each lot and as required following quality control procedures

Calibration interval may be extended based on acceptable verification of calibration by the laboratory.

Traceability: This method has been standardized against the original IFCC formulation using calibrated pipettes together with a manual photometer providing absolute values and the substrate-specific absorptivity, ε.

LREFSchumann G, Bonora R, Ceriotti F, et al. IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C. International Federation of Clinical Chemistry and Laboratory Medicine. Part 4. Reference procedure for the measurement of catalytic concentration of alanine aminotransferase. Clin Chem Lab Med 2022 Jul;40(7):718-724. doi: 10.1515/CCLM.2002.124.
,
LREFBergmeyer HU, Hørder M, Rej R. Approved recommendation (1985) on IFCC methods for the measurement of catalytic concentration of enzymes. Part 3. IFCC Method for alanine aminotransferase. J Clin Chem Clin Biochem 1986;24(7):481-495.

", "Language": "en" }, { "Name": "Limitations", "Value": "", "Language": "en" }, { "Name": "PerformanceData", "Value": "

Specific performance data

Representative performance data on the cobas c 111 analyzer are given below. Results obtained in individual laboratories may differ.

", "Language": "en" }, { "Name": "Precision", "Value": "

Precision

Precision was determined using human samples and controls in an internal protocol with repeatability (n = 21) and intermediate precision (3 aliquots per run, 1 run per day, 10 days). The following results were obtained:

• Without PYP activation

Repeatability

Mean

U/L (µkat/L)

SD

U/L (µkat/L)

CV

%

Precinorm U

39.6 (0.661)

0.5 (0.008)

1.1

Precipath U

127 (2.12)

1 (0.02)

0.5

Human serum 1

27.9 (0.466)

0.6 (0.010)

2.0

Human serum 2

99.4 (1.66)

0.5 (0.01)

0.5

Intermediate precision

Mean

U/L (µkat/L)

SD

U/L (µkat/L)

CV

%

Precinorm U

40.2 (0.671)

0.7 (0.012)

1.8

Precipath U

124 (2.07)

1 (0.02)

0.9

Human serum 3

22.0 (0.367)

0.6 (0.010)

2.9

Human serum 4

272 (4.54)

8 (0.14)

3.0

• With PYP activation

Repeatability

Mean

U/L (µkat/L)

SD

U/L (µkat/L)

CV

%

Precinorm U

41.5 (0.693)

0.6 (0.010)

1.5

Precipath U

132 (2.20)

1 (0.02)

0.4

Human serum 1

32.1 (0.536)

0.7 (0.012)

2.1

Human serum 2

337 (5.63)

2 (0.03)

0.5

Intermediate precision

Mean

U/L (µkat/L)

SD

U/L (µkat/L)

CV

%

Precinorm U

42.0 (0.701)

0.7 (0.012)

1.6

Precipath U

130 (2.17)

1 (0.02)

0.7

Human serum 3

32.7 (0.546)

0.9 (0.015)

2.7

Human serum 4

331 (5.53)

9 (0.15)

2.6

", "Language": "en" }, { "Name": "MethodComparison", "Value": "

Method comparison

ALT values for human serum and plasma samples obtained on the cobas c 111 analyzer (y) were compared with those determined using the same reagent on a COBAS INTEGRA 400 analyzer (x).

• Without PYP activation

Sample size (n) = 77

Passing/Bablok

LREFBablok W, Passing H, Bender R, et al. A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry, Part III. J Clin Chem Clin Biochem 1988 Nov;26(11):783-790.

Linear regression

y = 1.000x + 0.753 U/L

τ = 0.983

y = 0.999x + 0.924 U/L

r = 1.00

The sample activities were between 2.20 and 405 U/L (0.037 and 6.76 µkat/L).

• With PYP activation

Sample size(n) = 74

Passing/Bablok

LREFBablok W, Passing H, Bender R, et al. A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry, Part III. J Clin Chem Clin Biochem 1988 Nov;26(11):783-790.

Linear regression

y = 1.005x + 0.793 U/L

τ = 0.987

y = 1.011x + 0.672 U/L

r = 1.00

The sample activities were between 3.04 and 399 U/L (0.051 and 6.66 µkat/L).

", "Language": "en" }, { "Name": "Summary", "Value": "

Summary

Alanine aminotransferase (ALT) measurements, performed with this device, in human serum and plasma are used as an aid in diagnosis of hepatocellular injury and in monitoring chronic liver injury.

The enzyme alanine aminotransferase (ALT) is present in highest concentrations in the liver, in the cytosol of the hepatocytes, although it is also found in the kidney, and, in much smaller quantities, in heart and skeletal muscle cells.

LREFKim WR, Flamm SL, Di Bisceglie AM, et al. Public Policy Committee of the American Association for the Study of Liver Disease. Serum activity of alanine aminotransferase (ALT) as an indicator of health and disease. Hepatology 2008 Apr;47(4):1363-1370. doi: 10.1002/hep.22109.
ALT catalyzes the transfer of amino groups from L‑alanine to α‑ketoglutarate, resulting in the converted products L‑glutamate and pyruvate. This is a critical process of the tricarboxylic acid cycle, in which the coenzyme pyridoxal phosphate (also known as pyridoxal‑5‑phosphate or active vitamin B6) is required. When liver injury occurs, ALT is released from injured liver cells and causes a significant serum elevation.
LREFKim WR, Flamm SL, Di Bisceglie AM, et al. Public Policy Committee of the American Association for the Study of Liver Disease. Serum activity of alanine aminotransferase (ALT) as an indicator of health and disease. Hepatology 2008 Apr;47(4):1363-1370. doi: 10.1002/hep.22109.
Measurement of ALT activity is therefore used for the diagnosis of hepatic diseases such as acute and chronic viral hepatitis, nonalcoholic fatty liver disease (NAFLD), alcohol‑related liver disease, ischemic hepatopathy, autoimmune hepatitis, biliary injury, suspected malignant infiltration, cholestasis.
LREFKim WR, Flamm SL, Di Bisceglie AM, et al. Public Policy Committee of the American Association for the Study of Liver Disease. Serum activity of alanine aminotransferase (ALT) as an indicator of health and disease. Hepatology 2008 Apr;47(4):1363-1370. doi: 10.1002/hep.22109.
Serum elevations of ALT activity are rarely observed in conditions other than parenchymal liver disease.
LREFPanteghini M, Bais R. Amino Transferases. In: Burtis CA, Ashwood ER, Bruns DE. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 5th ed. 2012;573-576.
In addition, ALT testing is recommended for monitoring chronic hepatitis status and progression.
LREFGuidelines for the Prevention, Care and Treatment of Persons with Chronic Hepatitis B Infection. Geneva: World Health Organization; 2015 Mar.

Although both serum aspartate aminotransferase (AST) and ALT become elevated whenever disease processes affect liver cell integrity, evidence suggests that ALT is a more specific marker of hepatic injury than AST. Moreover, elevations of ALT activity persist longer than elevations of AST activity.

LREFKim WR, Flamm SL, Di Bisceglie AM, et al. Public Policy Committee of the American Association for the Study of Liver Disease. Serum activity of alanine aminotransferase (ALT) as an indicator of health and disease. Hepatology 2008 Apr;47(4):1363-1370. doi: 10.1002/hep.22109.
,
LREFKwo PY, Cohen SM, Lim JK. ACG Clinical Guideline: Evaluation of Abnormal Liver Chemistries. Am J Gastroenterol 2017 Jan;112(1):18-35. doi: 10.1038/ajg.2016.517.

In patients with vitamin B6 deficiency (insufficient endogenous pyridoxal phosphate), serum aminotransferase activity may be decreased. The addition of pyridoxal phosphate to this assay causes an increase in aminotransferase activity (activation higher for AST than for ALT). Pyridoxal phosphate activation prevents falsely low aminotransferase activity in patient samples with insufficient endogenous pyridoxal phosphate (vitamin B6 deficiency).

LREFSchumann G, Bonora R, Ceriotti F, et al. IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C. International Federation of Clinical Chemistry and Laboratory Medicine. Part 4. Reference procedure for the measurement of catalytic concentration of alanine aminotransferase. Clin Chem Lab Med 2022 Jul;40(7):718-724. doi: 10.1515/CCLM.2002.124.

", "Language": "en" }, { "Name": "Reagents", "Value": "

Reagents - working solutions

R1

TRIS buffer: 224 mmol/L, pH 7.3 (37 °C); L-alanine: 1120 mmol/L; albumin (bovine): 0.25 %; LDH (microorganisms): ≥ 45 µkat/L; stabilizers; preservative

PYP

Pyridoxal phosphate (DL): 730 µmol/L; preservative

SR

NADH (yeast): ≥ 1.7 mmol/L; 2-oxoglutarate: 94 mmol/L; preservative; additives

", "Language": "en" }, { "Name": "PrecautionsWarnings", "Value": "

Precautions and warnings

For in vitro diagnostic use for health care professionals. Exercise the normal precautions required for handling all laboratory reagents.

Infectious or microbial waste:
Warning: handle waste as potentially biohazardous material. Dispose of waste according to accepted laboratory instructions and procedures.

Environmental hazards:
Apply all relevant local disposal regulations to determine the safe disposal.

Safety data sheet available for professional user on request.

", "Language": "en" }, { "Name": "Caution", "Value": "", "Language": "en" }, { "Name": "QualityControl", "Value": "

Quality control

For quality control, use control materials as listed in the “Order information” section. In addition, other suitable control material can be used.

The control intervals and limits should be adapted to each laboratory’s individual requirements. Values obtained should fall within the defined limits. Each laboratory should establish corrective measures to be taken if values fall outside the defined limits.

Follow the applicable government regulations and local guidelines for quality control.

", "Language": "en" }, { "Name": "SpecimenPreparation", "Value": "

Specimen collection and preparation

For specimen collection and preparation only use suitable tubes or collection containers.

Only the specimens listed below were tested and found acceptable.
Serum
Plasma: Li-heparin, K3-EDTA

The sample types listed were tested with a selection of sample collection tubes that were commercially available at the time of testing, i.e. not all available tubes of all manufacturers were tested. Sample collection systems from various manufacturers may contain differing materials which could affect the test results in some cases. When processing samples in primary tubes (sample collection systems), follow the instructions of the tube manufacturer.

Separate the serum or plasma from the clot or cells promptly.

Centrifuge samples containing precipitates before performing the assay.

See the limitations and interferences section for details about possible sample interferences.

Stability:

LREFWHO Publication: Use of anticoagulants in diagnostic laboratory investigations, WHO/DIL/LAB/99.1 Rev.2:Jan 2002.

3 days at 20‑25 °C

7 days at 4‑8 °C

7 days at -20 °C (± 5 °C )

Freeze only once.

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Intended use

In vitro test for the quantitative determination of alanine aminotransferase (ALT), with or without pyridoxal phosphate activation, in human serum and plasma on the cobas c 111 system.

", "Language": "en" }, { "Name": "TestPrinciple", "Value": "

Test principle

This assay follows the recommendations of the IFCC, but was optimized for performance and stability.

LREFBergmeyer HU, Hørder M, Rej R. Approved recommendation (1985) on IFCC methods for the measurement of catalytic concentration of enzymes. Part 3. IFCC Method for alanine aminotransferase. J Clin Chem Clin Biochem 1986;24(7):481-495.
,
LREFECCLS. Determination of the catalytic activity concentration in serum of L-alanine aminotransferase (EC 2.6.1.2, ALAT). Klin Chem Mitt 1989;20:204-211.
,
LREFSchumann G, Bonora R, Ceriotti F, et al. IFCC Primary Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes at 37 °C – Part 4. Reference Procedure for the Measurement of Catalytic Activity Concentration of Alanine Aminotransferase. Clin Chem Lab Med 2002;40(7):718-724.

ALT catalyzes the reaction between L-alanine and 2-oxoglutarate. The pyruvate formed is reduced by NADH in a reaction catalyzed by lactate dehydrogenase (LDH) to form L-lactate and NAD+.

Pyridoxal phosphate serves as a coenzyme in the amino transfer reaction. It ensures full enzyme activation.

ALT

L-alanine + 2-oxoglutarate

pyruvate + L-glutamate

LDH

Pyruvate + NADH + H+

L-lactate + NAD+

The rate of the NADH oxidation is directly proportional to the catalytic ALT activity. It is determined by measuring the decrease in absorbance.

", "Language": "en" }, { "Name": "MeasuringRange", "Value": "

Limits and ranges

Measuring range

2‑700 U/L (0.03‑11.7 µkat/L)

Determine samples having higher activities via the rerun function. Dilution of samples via the rerun function is a 1:10 dilution. Results from samples diluted using the rerun function are automatically multiplied by a factor of 10.

Lower limits of measurement

Lower detection limit of the test

2 U/L (0.03 µkat/L)

The lower detection limit represents the lowest measurable analyte level that can be distinguished from zero. It is calculated as the value lying 3 standard deviations above that of the lowest standard (standard 1 + 3 SD, repeatability, n = 21).

", "Language": "en" }, { "Name": "ExpectedValues", "Value": "

Expected values

Expected values
LREFThefeld W, Hoffmeister H, Busch EW, et al. Referenzwerte für die Bestimmungen der Transaminasen GOT und GPT sowie der alkalischen Phosphatase im Serum mit optimierten Standardmethoden. Dtsch Med Wschr 1974;99(8):343-351.

• Without PYP activation

Acc. to the optimized standard method (comparable to the IFCC method without pyridoxal phosphate activation

LREFKlein G, Lehmann P, Michel E, et al. Vergleich der IFCC-Methoden für ALAT, ASAT und GGT bei 37 °C mit den eingeführten Standardmethoden bei 25 °C und 37 °C. Lab Med 1994;18:403-404.
):

Males

up to 41 U/L

up to 0.685 µkat/L

Females

up to 33 U/L

up to 0.551 µkat/L

Calculated values: a factor of 1.85 is used for the conversion from 25 °C to 37 °C.

LREFZawta B, Klein G, Bablok W. Temperaturumrechnung in der klinischen Enzymologie? Klin Lab 1994;40:23-32.

• With PYP activation

acc. to IFCC/Standard Method 94 with pyridoxal phosphate activation:

LREFKlauke R, Schmidt E, Lorentz K. Recommendations for carrying out standard ECCLS procedures (1988) for the catalytic concentrations of creatine kinase, aspartate aminotransferase, alanine aminotransferase and γ-glutamyltransferase at 37 °C. Eur J Clin Chem Clin Biochem 1993;31:901-909.

Measured at 37 °C:

Males

10-50 U/L

(0.167-0.835 µkat/L)

Females

10-35 U/L

(0.167-0.585 µkat/L)

Consensus values with pyridoxal phosphate activation:

LREFThomas L, Müller M, Schumann G, et al. Consensus of DGKL and VDGH for interim reference intervals on enzymes in serum. J Lab Med 2005;29:301-308.

Males

up to 50 U/L

(up to 0.835 µkat/L)

Females

up to 35 U/L

(up to 0.585 µkat/L)

Each laboratory should investigate the transferability of the expected values to its own patient population and if necessary determine its own reference ranges.

", "Language": "en" }, { "Name": "LimitationInterference", "Value": "

Limitations - interference

• Without PYP activation
Criterion: Recovery within ± 10 % of initial value at an ALT activity of 30 U/L (0.501 µkat/L)

• With PYP activation
Criterion: Recovery within ± 10 % of initial value at an ALT activity of 35 U/L (0.585 µkat/L)

Icterus:

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an I index of 60 for conjugated and unconjugated bilirubin (approximate conjugated and unconjugated bilirubin concentration: 1026 µmol/L or 60 mg/dL ).

Hemolysis:

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an H index of 130 (approximate hemoglobin concentration: 80 µmol/L or 130 mg/dL).

Lipemia (Intralipid):

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an L index of 150.
Lipemic samples interfere and may cause “High Abs” flagging.

Anticoagulants: Citrate and fluoride inhibit the enzyme activity.

Drugs: No interference was found at therapeutic concentrations using common drug panels.

LREFBreuer J. Report on the Symposium "Drug Effects in Clinical Chemistry Methods". Eur J Clin Chem Clin Biochem 1996;34:385-386.
,
LREFSonntag O, Scholer A. Drug interference in clinical chemistry: recommendation of drugs and their concentrations to be used in drug interference studies. Ann Clin Biochem 2001;38:376-385.

Exceptions:
Calcium dobesilate and Doxycycline HCl cause artificially low ALT values at the tested drug level.
Cyanokit (Hydroxocobalamin) may cause false-low results.
Physiological plasma concentrations of Sulfasalazine and Sulfapyridine may lead to false results.

In very rare cases, gammopathy, in particular type IgM (Waldenström’s macroglobulinemia), may cause unreliable results.

LREFBakker AJ, Mücke M. Gammopathy interference in clinical chemistry assays: mechanisms, detection and prevention. Clin Chem Lab Med 2007;45(9):1240-1243.

For diagnostic purposes, the results should always be assessed in conjunction with the patient’s medical history, clinical examination and other findings.

ACTION REQUIRED
Special Wash Programming: The use of special wash steps is mandatory when certain test combinations are run together on the cobas c 111 analyzer. For information about test combinations requiring special wash steps, please refer to the latest version of the carry-over evasion list found with the CLEAN Method Sheet and the operator’s manual for further instructions.
Where required, special wash/carry-over evasion programming must be implemented prior to reporting results with this test.

", "Language": "en" }, { "Name": "OrderInformation", "Value": "

OrderInformation (CC Reagents - cobas + Integra)

Order information

Analyzer(s) on which kit(s) can be used

04718569190

Alanine aminotransferase acc. IFCC (4 × 100 tests)

cobas c 111

Materials required (but not provided):

04774221190

Pyridoxal Phosphate (4 × 200 tests)

Code 953

10759350360

Calibrator f.a.s. (12 × 3 mL)

Code 401

12149435160

Precinorm U plus (10 × 3 mL)

Code 300

12149443160

Precipath U plus (10 x 3 mL)

Code 301

05947626160

PreciControl ClinChem Multi 1 (4 × 5 mL)

Code 391

05947774160

PreciControl ClinChem Multi 2 (4 × 5 mL)

Code 392

", "Language": "en" }, { "Name": "SystemInformation", "Value": "

System information

ALTL: ACN 685

ALTPL: ACN 684

", "Language": "en" }, { "Name": "Handling", "Value": "

Reagent handling

Ready for use

", "Language": "en" }, { "Name": "TestDefinition", "Value": "

Application for serum and plasma

• Without PYP activation

cobas c 111 test definition

Measuring mode

Absorbance

Abs. calculation mode

Kinetic

Reaction direction

Decrease

Wavelength A/B

340/378 nm

Calc. first/last

20/35

Unit

U/L

Reaction mode

R1-S-SR

Pipetting parameters

Diluent (H2O)

R1

59 µL

10 µL

Sample

11 µL

26 µL

SR

17 µL

9 µL

Total volume

132 µL

• With PYP activation

cobas c 111 test definition

Measuring mode

Absorbance

Abs. calculation mode

Kinetic

Reaction direction

Decrease

Wavelength A/B

340/378 nm

Calc. first/last

20/35

Unit

U/L

Reaction mode

R1-DL-S-SR

Pipetting parameters

Diluent (H2O)

R1

59 µL

10 µL

Sample

11 µL

8 µL

Diluent (DL)

18 µL

SR

17 µL

9 µL

Total volume

132 µL

", "Language": "en" }, { "Name": "StorageStability", "Value": "

Storage and stability

ALTL

Shelf life at 2-8 °C:

See expiration date on reagent

On-board in use and refrigerated on the analyzer:

4 weeks

PYP

Shelf life at 2-8 °C:

See expiration date on reagent

On-board in use and refrigerated on the analyzer:

4 weeks

", "Language": "en" }, { "Name": "Calibration", "Value": "

Calibration

Calibrator

Calibrator f.a.s.
Deionized water is used automatically by the instrument as the zero calibrator.

Calibration mode

Linear regression

Calibration interval

Each lot and as required following quality control procedures

Calibration interval may be extended based on acceptable verification of calibration by the laboratory.

Traceability: This method has been standardized against the original IFCC formulation using calibrated pipettes together with a manual photometer providing absolute values and the substrate-specific absorptivity, ε.

LREFBergmeyer HU, Hørder M, Rej R. Approved recommendation (1985) on IFCC methods for the measurement of catalytic concentration of enzymes. Part 3. IFCC Method for alanine aminotransferase. J Clin Chem Clin Biochem 1986;24(7):481-495.
,
LREFSchumann G, Bonora R, Ceriotti F, et al. IFCC Primary Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes at 37 °C – Part 4. Reference Procedure for the Measurement of Catalytic Activity Concentration of Alanine Aminotransferase. Clin Chem Lab Med 2002;40(7):718-724.

", "Language": "en" }, { "Name": "Limitations", "Value": "", "Language": "en" }, { "Name": "PerformanceData", "Value": "

Specific performance data

Representative performance data on the cobas c 111 analyzer are given below. Results obtained in individual laboratories may differ.

", "Language": "en" }, { "Name": "Precision", "Value": "

Precision

Precision was determined using human samples and controls in an internal protocol with repeatability (n = 21) and intermediate precision (3 aliquots per run, 1 run per day, 10 days). The following results were obtained:

• Without PYP activation

Repeatability

Mean

U/L (µkat/L)

SD

U/L (µkat/L)

CV

%

Precinorm U

39.6 (0.661)

0.5 (0.008)

1.1

Precipath U

127 (2.12)

1 (0.02)

0.5

Human serum 1

27.9 (0.466)

0.6 (0.010)

2.0

Human serum 2

99.4 (1.66)

0.5 (0.01)

0.5

Intermediate precision

Mean

U/L (µkat/L)

SD

U/L (µkat/L)

CV

%

Precinorm U

40.2 (0.671)

0.7 (0.012)

1.8

Precipath U

124 (2.07)

1 (0.02)

0.9

Human serum 3

22.0 (0.367)

0.6 (0.010)

2.9

Human serum 4

272 (4.54)

8 (0.14)

3.0

• With PYP activation

Repeatability

Mean

U/L (µkat/L)

SD

U/L (µkat/L)

CV

%

Precinorm U

41.5 (0.693)

0.6 (0.010)

1.5

Precipath U

132 (2.20)

1 (0.02)

0.4

Human serum 1

32.1 (0.536)

0.7 (0.012)

2.1

Human serum 2

337 (5.63)

2 (0.03)

0.5

Intermediate precision

Mean

U/L (µkat/L)

SD

U/L (µkat/L)

CV

%

Precinorm U

42.0 (0.701)

0.7 (0.012)

1.6

Precipath U

130 (2.17)

1 (0.02)

0.7

Human serum 3

32.7 (0.546)

0.9 (0.015)

2.7

Human serum 4

331 (5.53)

9 (0.15)

2.6

", "Language": "en" }, { "Name": "MethodComparison", "Value": "

Method comparison

ALT values for human serum and plasma samples obtained on the cobas c 111 analyzer (y) were compared with those determined using the same reagent on a COBAS INTEGRA 400 analyzer (x).

• Without PYP activation

Sample size (n) = 77

Passing/Bablok

LREFBablok W, Passing H, Bender R, et al. A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry, Part III. J Clin Chem Clin Biochem 1988 Nov;26(11):783-790.

Linear regression

y = 1.000x + 0.753 U/L

τ = 0.983

y = 0.999x + 0.924 U/L

r = 1.00

The sample activities were between 2.20 and 405 U/L (0.037 and 6.76 µkat/L).

• With PYP activation

Sample size(n) = 74

Passing/Bablok

LREFBablok W, Passing H, Bender R, et al. A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry, Part III. J Clin Chem Clin Biochem 1988 Nov;26(11):783-790.

Linear regression

y = 1.005x + 0.793 U/L

τ = 0.987

y = 1.011x + 0.672 U/L

r = 1.00

The sample activities were between 3.04 and 399 U/L (0.051 and 6.66 µkat/L).

", "Language": "en" }, { "Name": "Summary", "Value": "

Summary

Summary
LREFSherwin JE. Liver function. In: Kaplan LA, Pesce AJ, eds. Clinical Chemistry, theory, analysis, and correlation. St. Louis: Mosby 1984;420-438.
,
LREFMoss DW, Henderson AR, Kachmar JF. Enzymes. In: Tietz NW, ed. Fundamentals of Clinical Chemistry, 3rd ed. Philadelphia, PA: WB Saunders 1987;346-421.

The enzyme alanine aminotransferase (ALT) has been widely reported as present in a variety of tissues. The major source of ALT is the liver, which has led to the measurement of ALT activity for the diagnosis of hepatic diseases. Elevated serum ALT is found in hepatitis, cirrhosis, obstructive jaundice, carcinoma of the liver, and chronic alcohol abuse. ALT is only slightly elevated in patients who have an uncomplicated myocardial infarction.

Although both serum aspartate aminotransferase (AST) and ALT become elevated whenever disease processes affect liver cell integrity, ALT is the more liver-specific enzyme. Moreover, elevations of ALT activity persist longer than elevations of AST activity.

In patients with vitamin B6 deficiency, serum aminotransferase activity may be decreased. The apparent reduction in aminotransferase activity may be related to decreased pyridoxal phosphate, the prosthetic group for aminotransferases, resulting in an increase in the ratio of apoenzyme to holoenzyme.

The addition of pyridoxal phosphate to the assay causes an increase in aminotransferase activity. The activation is higher for AST than for ALT. Pyridoxal phosphate activation prevents falsely low aminotranferase activity in patient samples with insufficient endogenous pyridoxal phosphate (vitamin B6 deficiency).

", "Language": "en" }, { "Name": "Reagents", "Value": "

Reagents - working solutions

R1

TRIS buffer: 224 mmol/L, pH 7.3 (37 °C); L-alanine: 1120 mmol/L; albumin (bovine): 0.25 %; LDH (microorganisms): ≥ 45 µkat/L; stabilizers; preservative

PYP

Pyridoxal phosphate (DL): 730 µmol/L; preservative

SR

NADH (yeast): ≥ 1.7 mmol/L; 2-oxoglutarate: 94 mmol/L; preservative; additives

", "Language": "en" }, { "Name": "PrecautionsWarnings", "Value": "

Precautions and warnings

PCW-ALL11

For in vitro diagnostic use for health care professionals. Exercise the normal precautions required for handling all laboratory reagents.

Infectious or microbial waste:
Warning: handle waste as potentially biohazardous material. Dispose of waste according to accepted laboratory instructions and procedures.

Environmental hazards:
Apply all relevant local disposal regulations to determine the safe disposal.

Safety data sheet available for professional user on request.

For USA: Caution: Federal law restricts this device to sale by or on the order of a physician.

", "Language": "en" }, { "Name": "Caution", "Value": "", "Language": "en" }, { "Name": "QualityControl", "Value": "

Quality control

For quality control, use control materials as listed in the \"Order information\" section.

In addition, other suitable control material can be used.

The control intervals and limits should be adapted to each laboratory’s individual requirements. Values obtained should fall within the defined limits. Each laboratory should establish corrective measures to be taken if values fall outside the defined limits.

Follow the applicable government regulations and local guidelines for quality control.

", "Language": "en" }, { "Name": "SpecimenPreparation", "Value": "

Specimen collection and preparation

For specimen collection and preparation only use suitable tubes or collection containers.

Only the specimens listed below were tested and found acceptable.
Serum
Plasma: Li-heparin, K3-EDTA

The sample types listed were tested with a selection of sample collection tubes that were commercially available at the time of testing, i.e. not all available tubes of all manufacturers were tested. Sample collection systems from various manufacturers may contain differing materials which could affect the test results in some cases. When processing samples in primary tubes (sample collection systems), follow the instructions of the tube manufacturer.

Separate the serum or plasma from the clot or cells promptly.

Centrifuge samples containing precipitates before performing the assay.

See the limitations and interferences section for details about possible sample interferences.

Stability:

LREFWHO Publication: Use of anticoagulants in diagnostic laboratory investigations, WHO/DIL/LAB/99.1 Rev.2:Jan 2002.

3 days at 20‑25 °C

7 days at 4‑8 °C

7 days at −20 °C

Freeze only once.

Sample stability claims were established by experimental data by the manufacturer or based on reference literature and only for the temperatures/time frames as stated in the method sheet. It is the responsibility of the individual laboratory to use all available references and/or its own studies to determine specific stability criteria for its laboratory.

", "Language": "en" } ] } } ] }

ALTL

Alanine aminotransferase acc. IFCC with or without pyridoxal phosphate activation

IVD For in vitro diagnostic use.
ALTL

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