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Liver Function Tests – StatPearls

Introduction

The liver, located in the right upper quadrant of the body and below the diaphragm is responsible for several functions including primary detoxification of various metabolites, synthesizing proteins, and producing digestive enzymes. The liver also has a significant role in metabolism, regulation of red blood cells (RBCs) and glucose synthesis and storage.

Typically when reviewing LFTs, the discussion includes alanine transaminase (ALT) and aspartate transaminase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), serum bilirubin, prothrombin time (PT), the international normalized ratio (INR) and albumin. These tests can be helpful in determining the area of hepatic injury, and the pattern of elevation can help organize a differential diagnosis.

The term “liver function tests“ is a misnomer as many of the tests do not comment on the function of the liver but rather pinpoint the source of the damage. Elevations in ALT and AST in out of proportion to ALP and bilirubin denotes a hepatocellular disease. Whereas, an elevation in ALP and bilirubin in disproportion to ALT and AST would denote a cholestatic pattern. The actual function of the liver can be graded based on its ability to produce albumin as well as vitamin K dependent clotting factors.[1][2][3]

Etiology and Epidemiology

Elevated LFTs are found in approximately 8% of the general population. These elevations may be transient in patients without symptoms with up to 30% elevations resolving after 3 weeks. Thus, care should be taken when interpreting these results to avoid unnecessary testing.[4][5]

Differential Diagnosis Based on Elevated LFTs

Hepatocellular pattern: Elevated aminotransferases out of proportion to alkaline phosphatase

  • ALT-predominant: Acute or chronic viral hepatitis, steatohepatitis, acute Budd-Chiari syndrome, ischemic hepatitis, autoimmune, hemochromatosis, medications/toxins, autoimmune, alpha1-antitrypsin deficiency, Wilson disease, Celiac disease

  • AST-predominant: Alcohol-related, steatohepatitis, cirrhosis, non-hepatic (hemolysis, myopathy, thyroid disease, exercise)

Cholestatic pattern: elevated alkaline phosphatase + GGT + bilirubin out of proportion to AST  and ALT

  • Hepatobiliary causes: Bile duct obstruction, primary biliary cirrhosis, primary sclerosing cholangitis, medication-induced, infiltrating diseases of the liver (sarcoidosis, amyloidosis, lymphoma, among others), cystic fibrosis, hepatic metastasis, cholestasis

  • Non-Hepatic causes of elevated alkaline phosphatase: Bone disease, pregnancy, chronic renal failure, lymphoma or other malignancies, congestive heart failure, childhood growth, infection or inflammation

Pathophysiology

Components of Liver Function Test


Hepatocellular Labs

Aminotransferase includes AST and ALT. They are markers of hepatocellular injury. They participate in gluconeogenesis by catalyzing the transfer of amino groups from aspartic acid or alanine to ketoglutaric acid to produce oxaloacetic acid and pyruvic acid respectively. AST is present in cytosolic and mitochondrial isoenzymes and is found in the liver, cardiac muscle skeletal muscle, kidneys, brain, pancreas, lungs, leucocytes, and red cells. It is not as sensitive or specific for the liver, and elevation in AST may be seen as secondary to nonhepatic causes as well. ALT is a cytosolic enzyme that is found in high concentrations in the liver. Hepatocellular injury and not necessarily cell death is the trigger for the release of these enzymes into the circulation. Both AST and ALT values are higher in normal males than females.[6] They also correlate with obesity with normal reference range higher in those with higher body mass index.[7]


Cholestasis Labs

Alkaline phosphatase is part of a family zinc metalloenzymes that are highly concentrated in the microvilli of the bile canaliculus as well as several other tissues (e. g., bone, intestines, placenta). During growth, due to increased osteoblastic activity, elevated levels of ALP are seen in children and adolescents.  The normal reference range levels also increase with age in females. Glycoprotein gamma-glutamyltransferase (GGT) is located on membranes of cells with high secretory or absorptive activities. Its main function is to catalyze the transfer of a gamma-glutamyl group from peptides to other amino acids. It is also abundant in many other sources of the body (kidney, pancreas, intestine, and prostate, testicles, spleen, heart, and brain) but is more specific for biliary disease when compared to alkaline phosphatase because it is not present in bone. The levels of GGT are higher in infants.[8]

Bilirubin is the end result of heme catabolism, with 80% being derived from hemoglobin. Unconjugated bilirubin is transported to the liver loosely bound to albumin. Bilirubin is water-insoluble and cannot be excreted in the urine. Bilirubin that is conjugated is water-soluble and appears in the urine. It is conjugated in the liver to bilirubin glucuronide and subsequently secreted into bile and the gut respectively.


Synthetic Function Tests

Albumin is synthesized in the liver, producing approximately 10 grams per day. With any liver disease, there is a fall in serum albumin, reflecting decreased synthesis. If liver function is normal and serum albumin is low, this may reflect on poor protein intake (malnutrition) or protein loss (nephrotic syndrome, malabsorption, or protein-losing enteropathy).

Prothrombin time (PT) measures the rate of conversion of prothrombin to thrombin. Except for factor VIII, all other coagulation factors are synthesized by the liver. Prothrombin time requires factors II, V, VII, and X and, as these are made in the liver, the liver’s function is crucial in coagulation. If the synthetic function of the liver is normal and prothrombin time is delayed this may indicate treatment with warfarin, consumptive coagulopathy (e.g., disseminated intravascular coagulopathy), or deficiency of vitamin K.

Results, Reporting, Critical Findings

Reference ranges for LFTs tend to vary depending on the laboratory.  Further, normal reference ranges vary between males and females and may be higher for those with higher body mass index.  

  • Alanine transaminase: 0 to 45 IU/L

  • Aspartate transaminase: 0 to 35 IU/L

  • Alkaline phosphatase: 30 to 120 IU/L

  • Gamma-glutamyltransferase: 0 to 30 IU/L

  • Bilirubin: 2 to 17 micromoles/L

  • Prothrombin time: 10.9 to 12.5 seconds

  • Albumin: 40 to 60 g/L

Clinical Significance

The levels of LFTs can point to the differentials. Many disease processes have very distinct abnormalities in the liver enzymes. Further investigation is warranted if repeated tests confirm abnormality.

Alcohol

In patients with alcoholism, AST to ALT ratio is generally at least 2:1, showing a high level of AST activity in alcoholic liver disease. Elevated GGT along with AST also suggests alcohol abuse.[9] GGT shall be used alone since it is not very specific for alcohol.[5]

Medications

Several medications are known to cause liver damage. Many of these are commonly used in daily practice including but not limited to NSAIDs, antibiotics, statins, anti-seizure drugs, and drugs for tuberculosis treatment.  Acute hepatocellular injury can be seen secondary to several drugs including but not limited to acetaminophen,[10]  allopurinol, NSAIDs, alcohol, anti-tuberculosis medications such as isoniazid, pyrazinamide, and rifampin, statins, antifungals such as ketoconazole, antibiotics such as tetracyclines, anti-seizure medications such as valproic acid and phenytoin, antidepressants such as fluoxetine, antipsychotics such as risperidone and antivirals such as valacyclovir and ritonavir. Acute cholestasis can be seen secondary to drugs including anabolic steroids, NSAIDs, tricyclic antidepressants, alcohol, antibiotics such as azithromycin, amoxicillin, nafcillin, rifampin, and trimethoprim-sulfamethoxazole.   Long-term use of these agents can also lead to chronic hepatocellular and/or cholestatic liver damage. Methotrexate, he commonly used medication for rheumatoid arthritis and other inflammatory arthritis can cause a mild transient elevation in LFTs, and can also cause permanent liver damage in liver fibrosis and cirrhosis, especially with higher cumulative doses.  Liver fibrosis can also be seen as secondary to chronic alcohol intake or methyldopa. Ergot alkaloids can result in ischemic necrosis. Oral contraceptives can result in hepatic venous outflow obstruction (Budd-Chiari syndrome). Herbal medications can also cause an elevation in LFTs.  

Viral Hepatitis

Viral illnesses are a common cause of hepatitis and elevation in LFTs.  Viral hepatitis B, C, and D can cause chronic hepatitis, while hepatitis A and E cause acute viral hepatitis. Several other viruses including HIV, Epstein-Barr (EBV) and Cytomegalovirus (CMV) can also cause hepatitis.[11]

Autoimmune Hepatitis

Autoimmune hepatitis is a chronic disease that is characterized by continuing hepatocellular inflammation and necrosis and a tendency to progress to cirrhosis. It is more common in young women than men with a 4:1 ratio. The patient usually presents with high LFTs without apparent cause. These patients can have positive autoantibodies including antinuclear antibody, anti-smooth muscle antibody, anti-liver/kidney microsomal antibodies, and antibodies to the liver antigen.

Hepatic Steatosis and Nonalcoholic Steatohepatitis

Fatty liver disease aka nonalcoholic steatohepatitis has gained more attention recently because of its ability to cause chronic hepatic disease as well as hepatocellular carcinoma (HCC). The typical patient with this disease is overweight, has type II diabetes, or has dyslipidemia and no evidence of clinically significant alcohol use. The AST and ALT are usually both elevated with a ratio of 1:1, with other liver function tests being normal.

Hemochromatosis

Hemochromatosis is the abnormal accumulation of iron in parenchymal organs, leading to organ toxicity. It is the most common autosomal recessive genetic disorder and the most common cause of severe iron overload. Clinical manifestations include diabetes, liver disease, and cutaneous hyperpigmentation. A raised serum ferritin level usually raises concerns for possible hemochromatosis, but a transferrin saturation greater than 45% is more reliable. HFE mutations (C282Y, H63D) is pivotal for the diagnosis of hereditary hemochromatosis. Secondary hemochromatosis can also be seen due to increased iron intake.

Wilson Disease

Wilson disease, a rare autosomal-recessive inherited disorder of copper metabolism, is characterized by excess copper deposition in the liver, brain, and other tissues. It is fatal if not recognized and treated early. A low serum ceruloplasmin level is seen in the majority (up to 85%) of the cases. Kayser-Fleischer rings can be a clinical clue but are not present all the time. The 24-hour urinary copper excretion test is usually abnormal with more than 100 micrograms of copper excretion in the urine indicating Wilson’s disease. A liver biopsy remains the confirmatory test. [11]

Alpha-1 Antitrypsin Deficiency

Alpha-1 antitrypsin deficiency (AATD) is a relatively common yet often undiagnosed genetic condition. Those with AATD are also predisposed to obstructive pulmonary disease and liver disease (e.g., cirrhosis and hepatocellular carcinoma in children and adults). AATD is one of the most common inherited disorders among Caucasians. Its primary manifestation is early-onset panacinar emphysema.

Enhancing Healthcare Team Outcomes

The liver function tests are one of the most commonly ordered laboratory tests. Mild isolated elevations in LFTs can be seen as normal fluctuations and shall not trigger expensive and extensive workup.  However, physicians shall be aware of various conditions that can lead to an elevation in LFTs.  Thorough history taking and physical examination can provide clues to the differential diagnosis.  Drug and medication history is of utmost importance.  The nursing team shall help with medication reconciliation.   Pharmacists can also assist in identifying potentially hepatotoxic agents.  Referral to specialists such as hepatologists may sometimes be indicated.  An interprofessional team approach can help identify the underlying etiology with appropriate management.[Level 5]

Special Considerations in Interpreting Liver Function Tests

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2. Kamath PS.
Clinical approach to the patient with abnormal liver function test results. Mayo Clin Proc.
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Raised liver enzymes in asymptomatic patients: investigation and outcome. Dig Dis.
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1997;5:58–77.

6. Healey CJ,
Chapman RW,
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Liver histology in hepatitis C infection: a comparison between patients with persistently normal or abnormal transaminases. Gut.
1995;37:274–8.

7. Haber MM,
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8. Helfgott SM,
Karlson E,
Beckman E.
Misinterpretation of serum transaminase elevation in “occult” myositis. Am J Med.
1993;95:447–9.

9. Sherman KE.
Alanine aminotransferase in clinical practice. Arch Intern Med.
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Alanine aminotransferase levels in Hispanics. Ethnic Dis.
1993;3:176–80.

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et al.
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1992;38:1853–9.

12. Salvaggio A,
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Body mass index and liver enzyme activity in serum. Clin Chem.
1991;37:720–3.

13. Palmer M,
Schaffner F.
Effect of weight reduction on hepatic abnormalities in overweight patients. Gastroenterology.
1990;99:1408–13.

14. Vajro P,
Lofrano MM,
Fontanella A,
Fortunato G.
Immunoglobulin complexed AST (“macro-AST”) in an asymptomatic child with persistent hyper-transaminasemia. J Pediatr Gastroenterol Nutr.
1992;15:458–60.

15. Yasuda K,
Okuda K,
Endo N,
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et al.
Hypoaminotransferasemia in patients undergoing long-term hemodialysis: clinical and biochemical appraisal. Gastroenterology.
1995;109:1295–300.

16. Gitlin N,
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1992;87:831–6.

17. Cohen JA,
Kaplan MM.
The SGOT/SGPT ratio—an indicator of alcoholic liver disease. Dig Dis Sci.
1979;24:835–8.

18. Diehl AM,
Potter J,
Boitnott J,
Van Duyn MA,
Herlong HF,
Mezey E.
Relationship between pyridoxal 5′-phosphate deficiency and aminotransferase levels in alcoholic hepatitis. Gastroenterology.
1984;86:632–6.

19. Greenwood SM,
Leffler CT,
Minkowitz S.
The increased mortality rate of open liver biopsy in alcoholic hepatitis. Surg Gynecol Obstet.
1972;134:600–4.

20. Whitfield JB,
Pounder RE,
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Moss DW.
Serum γ-glutamyl transpeptidase activity in liver disease. Gut.
1972;13:702–8.

21. Whitehead TP,
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Whitfield AG.
Biochemical and hematological markers of alcohol intake. Lancet.
1978;1(8071):978–81.

22. Keeffe EB,
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Serum γ-glutamyl transpeptidase activity in patients receiving chronic phenytoin therapy. Dig Dis Sci.
1986;31:1056–61.

23. Mendis GP,
Gibberd FB,
Hunt HA.
Plasma activities of hepatic enzymes in patients on anticonvulsant therapy. Seizure.
1993;2:319–23.

24. Lieberman D,
Phillips D.
“Isolated” elevation of alkaline phosphatase: significance in hospitalized patients”. J Clin Gastroenterol.
1990;12:415–9.

25. Bosma PJ,
Chowdhury JR,
Bakker C,
Gantla S,
de Boer A,
Oostra BA,

et al.
The genetic basis of the reduced expression of bilirubin UDP-glucuronosyl-transferase 1 in Gilbert’s syndrome. N Engl J Med.
1995;333:1171–5.

26. Westwood A.
The analysis of bilirubin in serum. Ann Clin Biochem.
1991;28:119–30.

27. Rothschild MA,
Oratz M,
Schreiber SS.
Serum albumin. Hepatology.
1988;8:385–401.

28. Basile AS,
Jones EA.
Ammonia and GABA-ergic neurotransmission: interrelated factors in the pathogenesis of hepatic encephalopathy. Hepatology.
1997;25:1303–5.

29. Pugh RN,
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Transection of the oesophagus for bleeding oesophageal varices. Br J Surg.
1973;60:646–9.

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1986;6:928–31.

31. Garrison RN,
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1984;199:648–55.

32. Fattovich G,
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Mildly Elevated Liver Transaminase Levels in the Asymptomatic Patient

PAUL T. GIBONEY, M.D., Keck School of Medicine, University of Southern California, Los Angeles, California

Am Fam Physician. 2005 Mar 15;71(6):1105-1110.

Mild elevations in liver chemistry tests such as alanine transaminase and aspartate transaminase can reveal serious underlying conditions or have transient and benign etiologies. Potential causes of liver transaminase elevations include viral hepatitis, alcohol use, medication use, steatosis or steatohepatitis, and cirrhosis. The history should be thorough, with special attention given to the use of medications, vitamins, herbs, drugs, and alcohol; family history; and any history of blood-product transfusions. Other common health conditions, such as diabetes, heart disease, and thyroid disease, can cause or augment liver transaminase elevations. The recent American Gastroenterological Association guideline regarding the evaluation and management of abnormal liver chemistry tests proposes a practical, algorithmic approach when the history and physical examination do not reveal the cause. In addition to liver chemistries, an initial serologic evaluation includes a prothrombin time; albumin; complete blood count with platelets; hepatitis A, B, and C serologies; and iron studies. Depending on the etiology, management strategies may include cessation of alcohol use, attention to medications, control of diabetes, and modification of lifestyle factors such as obesity. If elevations persist after an appropriate period of observation, further testing may include ultra-sonography and other serum studies. In some cases, biopsy may be indicated.

Hepatic transaminase tests such as alanine transaminase (ALT) and aspartate transaminase (AST) often are part of standard laboratory panels in asymptomatic outpatients, similar to screening tests for blood donors and for life insurance applicants. The evaluation of an abnormal ALT or AST level in an asymptomatic patient therefore is a common challenge encountered by primary care physicians.

According to the American Gastroenterological Association (AGA), 1 to 4 percent of the asymptomatic population may have elevated serum liver chemistries.1 This is consistent with the usual definition of an elevated transaminase level of the top 2.5 percent of the population range. Although one study2 of 19,877 asymptomatic young Air Force trainees found that only 0.5 percent had elevated ALT levels, physicians who have more patients with obesity, diabetes, and hyperlipidemia will have to address this issue more often.

Given the frequency of this problem, physicians should develop an informed approach to the investigation of transaminase elevations. An audit of primary care practices found that these abnormalities are not always investigated appropriately and that opportunities to intervene in treatable cases sometimes are missed.3 No controlled clinical trials have compared approaches to the management of abnormal transaminase levels. However, the AGA recently published a technical review1 and a position statement4 on the evaluation of liver chemistry tests. This article reviews the interpretation of ALT and AST levels and summarizes the AGA recommendations on addressing reported elevations.

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Strength of Recommendations
Key clinical recommendation Label References

An algorithmic approach to evaluating mildly abnormal liver functions is recommended.

C

1

In the asymptomatic patient with negative serum testing and mild transaminase elevations, a period of lifestyle modification can be tried.

C

1

If abnormalities persist at the six-month follow-up visit, an ultrasonography of the liver is the recommended imaging modality.

C

1

ALT and AST are not useful screening tests in an otherwise healthy population.

C

1,10

The AST/ALT ratio is only somewhat helpful in diagnosis.

C

5,7

Strength of Recommendations
Key clinical recommendation Label References

An algorithmic approach to evaluating mildly abnormal liver functions is recommended.

C

1

In the asymptomatic patient with negative serum testing and mild transaminase elevations, a period of lifestyle modification can be tried.

C

1

If abnormalities persist at the six-month follow-up visit, an ultrasonography of the liver is the recommended imaging modality.

C

1

ALT and AST are not useful screening tests in an otherwise healthy population.

C

1,10

The AST/ALT ratio is only somewhat helpful in diagnosis.

C

5,7

Markers of Hepatic Injury and Necrosis

ALT and AST are two of the most reliable markers of hepatocellular injury or necrosis. Their levels can be elevated in a variety of hepatic disorders. Of the two, ALT is thought to be more specific for hepatic injury because it is present mainly in the cytosol of the liver and in low concentrations elsewhere. AST has cytosolic and mitochondrial forms and is present in tissues of the liver, heart, skeletal muscle, kidneys, brain, pancreas, and lungs, and in white and red blood cells. AST is less commonly referred to as serum glutamic oxaloacetic transaminase and ALT as serum glutamic pyruvic transaminase.

Although levels of ALT and AST can be extremely elevated (exceeding 2,000 U per L in cases of hepatocyte injury and necrosis related to drugs, toxins, ischemia, and hepatitis), elevations less than five times the upper limit of normal (i.e., about 250 U per L and below) are much more common in primary care medicine. The range of possible etiologies at this level of transaminase elevation is broader (Table 15,6) and the tests less specific. It also is important to recall that patients with normal ALT and AST levels can have significant liver disease in the setting of chronic hepatocyte injury (e.g., cirrhosis, hepatitis C).

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TABLE 1

Etiology of ALT or AST Elevations When Less Than Five Times Normal

Common hepatic causes

Alcohol

Cirrhosis

Hepatitis B (chronic)

Hepatitis C (chronic)

Steatosis/steatohepatitis

Medications/toxins

Acute viral hepatitis

Less common hepatic causes

Autoimmune hepatitis

Hemochromatosis

Alpha1-antitrypsin deficiency

Wilson’s disease

Nonhepatic causes

Celiac disease

Hemolysis

Myopathy

Hyperthyroidism

Strenuous exercise

Macro-AST

TABLE 1

Etiology of ALT or AST Elevations When Less Than Five Times Normal

Common hepatic causes

Alcohol

Cirrhosis

Hepatitis B (chronic)

Hepatitis C (chronic)

Steatosis/steatohepatitis

Medications/toxins

Acute viral hepatitis

Less common hepatic causes

Autoimmune hepatitis

Hemochromatosis

Alpha1-antitrypsin deficiency

Wilson’s disease

Nonhepatic causes

Celiac disease

Hemolysis

Myopathy

Hyperthyroidism

Strenuous exercise

Macro-AST

The ratio of AST to ALT has some clinical utility, but has important limitations. In many forms of acute and chronic liver injury or steatosis (fatty infiltration of the liver), the ratio is less than or equal to 1. This is particularly true in patients with hepatitis C. However, an AST/ALT ratio greater than 2 characteristically is present in alcoholic hepatitis. A recent study7 of 140 patients with nonalcoholic steatohepatitis (NASH; confirmed by liver biopsy) or alcoholic liver disease found a mean AST/ALT ratio of 0.9 in patients with NASH and 2.6 in patients with alcoholic liver disease. Within the population studied, 87 percent of patients with an AST/ALT ratio of 1.3 or less had NASH (87 percent sensitivity, 84 percent specificity). The severity of NASH as measured by the degree of fibrosis increased, as did the AST/ALT ratio. A mean ratio of 1.4 was found in patients with cirrhosis related to NASH. Wilson’s disease, a rare problem, can cause the AST/ALT ratio to exceed 4.5 While these ratios are suggestive of certain conditions, there is too much overlap between groups to rely on them exclusively when making a diagnosis.

Lactate dehydrogenase (LDH) is a less specific marker of hepatocellular necrosis and usually does not add diagnostic information to that obtained with ALT and AST testing. An exception to this is the transient but massive rise of LDH in cases of ischemic hepatitis and its sustained elevation that, along with elevated alkaline phosphatase levels, suggests malignant infiltration of the liver.5

Elevations of ALT and AST are not exclusive to liver pathology. Hyperthyroidism has been found in several studies to increase serum levels of liver enzymes including ALT and AST.8 Genetic influences on the level of ALT also are possible. A study9 of Danish twins showed that genetic factors accounted for 33 to 66 percent of the variation in ALT, gamma glutamyl transpeptidase, LDH, and bilirubin in patients 73 to 94 years of age. The AGA technical review states that serum ALT has diurnal variation, may vary day to day, and may be affected by exercise. It also notes that serum AST may be 15 percent higher in black men than white men. 1

Another cause of elevated liver transaminase levels is muscle injury. Strenuous exercise or myopathy can cause elevations (especially of AST) without causing any other symptoms. A creatine kinase or other muscle marker can be obtained to confirm or exclude such a process.

Annual screening of healthy, asymptomatic patients for liver disease using ALT and AST levels is not useful. A Japanese study10 assessed the accuracy of ALT and AST for detecting hepatitis C, excess alcohol use, and fatty liver disease in male bank employees and found the positive predictive value of the test to be low. Only 3.9 percent of the men with an abnormal ALT level had hepatitis C; 8 percent were excessive users of alcohol; and 35.7 percent had fatty liver.

Management

A thorough medical history and physical examination are the cornerstone of the evaluation of patients with mildly elevated liver transaminase levels.1  The history should attempt to identify risk factors for disease, with special attention directed toward family history, medications, vitamins, herbal supplements, drug use, alcohol use, abnormal liver testing, blood-product transfusions, and symptoms of liver disease. Table 26 lists selected medications and herbal supplements that may cause elevated transaminase levels. Physicians should ask patients directly about their use of illicit drugs, herbal supplements, and other alternative “supplements” because these sometimes are omitted from the patient’s initial response to questions.

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TABLE 2

Common Agents That Can Cause Liver Transaminase Elevations
Medications Herbal supplements/vitamins

Acetaminophen

Chaparral leaf

Amiodarone (Cordarone)

Ephedra

Amoxicillin-clavulanic acid

Gentian

Carbamazepine (Tegretol)

Germander

Fluconazole (Diflucan)

Jin bu huan

Glyburide (Micronase)

Kava

Heparin

Scutellaria (skullcap)

Isoniazid (INH)

Senna

Ketoconazole (Nizoral)

Shark cartilage

Labetalol (Normodyne)

Vitamin A

Nitrofurantoin (Furadantin)

Nonsteroidal anti-inflammatory drugs

Phenytoin (Dilantin)

Protease inhibitors

Sulfonamides

Trazodone (Desyrel)

TABLE 2

Common Agents That Can Cause Liver Transaminase Elevations
Medications Herbal supplements/vitamins

Acetaminophen

Chaparral leaf

Amiodarone (Cordarone)

Ephedra

Amoxicillin-clavulanic acid

Gentian

Carbamazepine (Tegretol)

Germander

Fluconazole (Diflucan)

Jin bu huan

Glyburide (Micronase)

Kava

Heparin

Scutellaria (skullcap)

Isoniazid (INH)

Senna

Ketoconazole (Nizoral)

Shark cartilage

Labetalol (Normodyne)

Vitamin A

Nitrofurantoin (Furadantin)

Nonsteroidal anti-inflammatory drugs

Phenytoin (Dilantin)

Protease inhibitors

Sulfonamides

Trazodone (Desyrel)

The presence of other significant health conditions that can cause or augment liver transaminase elevations also should be noted; examples are diabetes, heart disease (including congestive heart failure), thyroid disease, muscle disease, and cancer. Physical findings and sequelae of liver dysfunction are given in Table 3.

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TABLE 3

Clues in the Evaluation of Mildly Elevated Liver Transaminase Levels
Clinical clue Suggested diagnosis

Longstanding alcohol abuse

Cirrhosis

Intravenous drug use, history of blood product transfusions, nonsterile needle exposure, AST/ALT ratio < 1.0

Hepatitis B or C

Obesity, diabetes, hyperlipidemia, AST/ALT ratio < 1.0

Steatosis/steatohepatitis

AST/ALT ratio > 2. 0

Alcoholic liver disease, Wilson’s disease

Increased iron levels

Hemochromatosis

Polypharmacy, illicit drug use, or certain herbal supplement use

Substance/medication-induced

Frequent, strenuous exercise

Exercise-induced

Intestinal bloating; oily, bulky stools

Celiac sprue

Hypergammaglobulinemia

Autoimmune hepatitis

Reduced ceruloplasmin levels, Kayser-Fleischer ring

Wilson’s disease

Depressed thyroid-stimulating hormone levels

Hyperthyroidism

TABLE 3

Clues in the Evaluation of Mildly Elevated Liver Transaminase Levels
Clinical clue Suggested diagnosis

Longstanding alcohol abuse

Cirrhosis

Intravenous drug use, history of blood product transfusions, nonsterile needle exposure, AST/ALT ratio < 1. 0

Hepatitis B or C

Obesity, diabetes, hyperlipidemia, AST/ALT ratio < 1.0

Steatosis/steatohepatitis

AST/ALT ratio > 2.0

Alcoholic liver disease, Wilson’s disease

Increased iron levels

Hemochromatosis

Polypharmacy, illicit drug use, or certain herbal supplement use

Substance/medication-induced

Frequent, strenuous exercise

Exercise-induced

Intestinal bloating; oily, bulky stools

Celiac sprue

Hypergammaglobulinemia

Autoimmune hepatitis

Reduced ceruloplasmin levels, Kayser-Fleischer ring

Wilson’s disease

Depressed thyroid-stimulating hormone levels

Hyperthyroidism

Once the history and physical examination are completed, additional testing can help discern the etiology of the transaminase elevation (Figure 1). 4

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Management of Mild ALT and AST Abnormalities

Figure 1.

Algorithm to manage mild ALT and AST abnormalities. (ALT = alanine transaminase; AST = aspartate transaminase.)

Adapted with permission from American Gastroenterological Association. Medical position statement: evaluation of liver chemistry tests. Gastroenterology 2002; 123:1365.

Management of Mild ALT and AST Abnormalities

Figure 1.

Algorithm to manage mild ALT and AST abnormalities. (ALT = alanine transaminase; AST = aspartate transaminase.)

Adapted with permission from American Gastroenterological Association. Medical position statement: evaluation of liver chemistry tests. Gastroenterology 2002; 123:1365.

INITIAL LABORATORY EVALUATION

Additional laboratory tests should be obtained when the history and physical examination show no obvious etiology for ALT and AST elevations. Ferritin, total iron-binding capacity, and serum iron can be used to look for hemochromatosis, while hepatitis A, B, and C serologies are used to rule out acute or chronic hepatitis.

Despite the emergence of widespread vaccination, hepatitis B remains a common cause of chronic liver disease in adults. Testing for hepatitis C is essential because its incidence has increased in the past decade, and new treatment strategies have been developed that can address this frequently missed problem.11

A prothrombin time (PT) and serum albumin should be ordered to identify patients with abnormalities of protein synthesis and liver function. Evaluation should be accelerated for patients with impaired hepatic synthetic function. A complete blood count with platelets also should be ordered. In addition to ruling out infection, neutropenia or thrombocytopenia can, along with an elevated PT, suggest advanced liver disease. An elevated mean red cell volume suggests heavy alcohol intake. Alkaline phosphatase and bilirubin are markers for hepatic cholestasis and should be ordered as part of the initial laboratory evaluation. While sometimes useful, they often are normal in the presence of hepatic injury.

LIFESTYLE MODIFICATION

If the patient is asymptomatic and the initial serum testing is negative, a period of lifestyle modification can be attempted. Effective lifestyle modification includes complete abstinence from alcohol, control of diabetes and hyperlipidemia, weight loss in overweight patients, and stopping or changing potentially hepatotoxic medications and supplements. Such lifestyle changes directly impact several of the causes of mild transaminase elevation (Table 1).5,6 These seemingly small modifications may be all that is needed to correct the abnormalities.

FOLLOW-UP AND IMAGING STUDIES

A repeat set of liver chemistries should be obtained after six months. If the patient’s presentation changes or the physician has concern for an evolving process, shorter intervals can be used. If abnormalities persist at the six-month follow-up visit, ultra-sonography of the liver is recommended. Computed tomography of the abdomen also is used in this setting, although clinical trials have not demonstrated an advantage of this more expensive modality.

Steatohepatitis (or nonalcoholic fatty liver disease) often is discovered by imaging. This condition may be the most frequent cause of mild liver chemistry elevations and is especially common in patients who are obese, and those who have diabetes or hyperlipidemia. One study12 of patients referred to a hospital-based gastroenterology practice found that in 83 percent of patients with elevated transaminase levels whose serum evaluation was otherwise negative, liver biopsy revealed steatosis or steatohepatitis. In 10 percent of the patients, however, liver biopsy was normal—a reminder that, at times, mildly elevated transaminase levels do not represent any underlying pathology. Excellent reviews of the management of nonalcoholic fatty liver disease have been published.13,14

If the diagnosis is not apparent from the ultrasound examination, further testing is suggested for alpha1-antitrypsin deficiency (alpha1-antitrypsin levels), Wilson’s disease (serum ceruloplasmin), celiac disease (antigliadin and anti-endomysial antibody), and autoimmune hepatitis (antinuclear antibody, anti–smooth-muscle antibody), as well as for nonhepatic causes of transaminase elevation. According to the AGA, the decision to perform a liver biopsy needs to be made on an individual basis, taking into consideration the patient’s age, lifestyle, liver chemistry abnormalities, desire for prognostic information, and associated comorbid conditions.1 Only with chronic mild transaminase elevations would an asymptomatic patient be considered a possible candidate for biopsy.

Changes in Reference Range for Chemistry Tests

Changes in Reference Range for Chemistry Tests

Changes in Reference Range for Chemistry Tests

Effective Tuesday, November 26, 2013, the University of Iowa Hospitals and Clinics core laboratory will change the adult reference ranges for five chemistry assays:







Test Epic # Previous Range New Range
ALANINE AMINOTRANSFERASE (ALT) LAB132 0 – 35 U/L Males

0 – 20 U/L Females
0 – 41 U/L Males

0 – 33 U/L Females
ASPARTATE AMINOTRANSFERASE (AST) LAB131 0 – 37 U/L Males

0 – 31 U/L Females
0 – 40 U/L Males

0 – 32 U/L Females
THYROXINE – FREE (FREE T4) LAB127 0. 92 – 1.57 ng/dL 0.90 – 1.70 ng/dL
CALCIUM-URINE 24 HR LAB580 15 – 150 mg/24 hr No range for normal / abnormal flagging
VITAMIN B12 LAB67 243 – 894 pg/mL 211 – 946 pg/mL

  • The changes in AST, Free T4, and vitamin B12 are to adjust to new methodology from switch to new chemistry analyzers in the core laboratory.  These ranges are from the package inserts of the FDA-approved assays.
  • The change in ALT reference range is a more significant shift.  The previous range, which is significantly narrower than the range used by many other institutions and commercial laboratories, was from a normal range study performed 20 years ago at Iowa.   Over the years, this tight range is flagging a high percentage of patients as abnormal.  Currently, 51% of adult females tested in the core laboratory are flagging abnormal for ALT.  While this tight range may help identify subclinical liver disease (e.g., early non-alcoholic steatohepatitis), it may also drive anxiety and downstream procedures.  However, to provide awareness of the “borderline” abnormal range of ALT that has increased risk of subclinical liver disease, the following comment will be appended to ALT results:

    “The upper limit of normal for alanine aminotransferase (ALT) reference ranges for adults is controversial with some authorities recommending limits as low as 30 U/L for males and 19 U/L for females.  There is increased incidence of subclinical liver disease (e.g., early steatohepatitis) in patients with ALT values in the range of 31-41 U/L for males and 20-33 U/L for females.  ALT values should always be interpreted in conjunction with clinical history, physical examination findings, and, if applicable, data from other diagnostic tests.

  • The change to 24 hr urine calcium is to turn off normal/abnormal flagging given that differences in diet and other factors influence calcium excretion and thus the expected range. The following comment will be appended to results:

    “24-Hour urinary calcium concentrations vary with amount of calcium in diet.

          Calcium-free diet: 5-40 mg Ca/day in urine

          Low to average calcium intake (up to 800 mg/day): 50-300 mg Ca/day in urine

          High calcium diet (800 mg/day or more): > 250 mg Ca/day in urine”

Questions should be directed to Matthew Krasowski, MD, PhD, medical director of the Clinical Chemistry (384-9380, [email protected]).

The AST and ALT levels on your blood test results – what do they mean?

AST and ALT are two common markers for diagnosing liver diseases. Patients with liver disorders often find their AST and ALT levels unsatisfactory, but what do the figures actually imply? And do patients of every kind of liver dysfunctions have the same levels?

 

AST:ALT ratio

Although the normal range of AST and ALT level varies among laboratories and countries, the ratio of AST:ALT is key when it comes to diagnosing liver diseases. The use of this ratio was first suggested by de Ritis in 1955. He found that the ratio decreased in patients with acute viral hepatitis and increased in patients with cirrhosis.

The AST:ALT ratio in a healthy individual would be around 1.15. If the ratio is more than 2.0 (up to 6.0), this denotes alcoholic liver disease. And if the ratio is between 1.4 and 2.0, it suggests cirrhosis. Interestingly enough, the severity of cirrhosis is measured by the level of the ratio, implying that patients of cirrhosis with a high AST:ALT ratio would probably have a more advanced case of cirrhosis. On the other hand, patients with acute viral hepatitis often have a very low AST:ALT ratio, ranging from 0.5 to 0.8.

Since AST level will increase significantly after one consumes alcohol, it could also be a marker for alcohol consumption. However, it should be noted that most patients with high alcohol consumption but without severe liver disease often do not have an AST/ALT ratio above 1, which means that a high ratio could probably be a result of advanced alcoholic liver disease.

Here’s an easy way to find out your AST:ALT ratio: divide your AST level as shown on your blood test results by your ALT level. For example, if your AST is 20 U/L and your ALT is 18 U/L, then your ALT ratio would be 1.05, which is within the normal range.

 

What is the magnitude of AST and ALT elevations for acute viral hepatitis?

Not only is the AST:ALT ratio useful when it comes to diagnosing liver diseases, the magnitude of AST and ALT elevations is also a crucial marker when it comes to differentiating the type of liver diseases patients have. One of the most obvious diseases that can be diagnosed through this method is acute viral hepatitis. In a research study of 15 laboratory tests, it was shown that all acute viral hepatitis patients showed an AST level greater than 200 U/L and an ALT level greater than 300 U/L, which both are 25 times the upper limit of normal levels.

 

Are AST and ALT elevations always related to liver diseases?

Since AST is found in various organs like liver, kidneys, heart, skeletal muscles, and brain, elevation of AST level could also be related to acute cardiac or skeletal muscle injury. A lesser degree of ALT elevation could also signal skeletal muscle injury or it is simply a bodily reaction after vigorous exercise. Therefore, AST and ALT elevations do not always suggest hepatic conditions, even though care should still be given when such situations occur.

 

Treatments

Despite the wide range of causes for AST and ALT elevations, it should never be ignored or viewed as a temporary issue. Since the increased levels of AST and ALT suggest the liver is inflamed, patients could try ways to lower the levels by first stopping any form of alcohol intake, followed by doing regular exercises and maintaining a balanced diet with sufficient portions of whole grains, leafy green vegetables, and dairy products. If necessary, patients could always try taking liver supplements that are safe and proven to help lower both the AST and ALT levels. Once both levels are controlled, it is a good indication that the liver is no longer inflamed or damaged.

Aspartate Aminotransferase Blood Level – an overview

Transaminases

AST and ALT, formerly referred to as serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT), respectively, have been regarded as reliable and sensitive markers of liver injury. They are soluble enzymes present in the mitochondria and/or cytosol of hepatocytes; at times of hepatic injury, when cells are damaged or cell membranes become leaky, these enzymes are released into the circulation. However, the source of normally circulating aminotransferases is unclear. Interestingly, elevation of ALT in at least one animal model, the methionine-choline deficient diet–nonalcoholic steatohepatitis (MCD-NASH) animal, resulted from increased mRNA transcription.4 Although aminotransferases are considered sensitive markers of hepatocyte injury, transaminemia also occurs in nonhepatic diseases such as hemolysis, rhabdomyolysis (concurrent elevation in creatine phosphokinase), various muscular dystrophies, muscle exertion, anorexia nervosa, acute myocardial infarction, infarcted bowel, and celiac disease.

The range of normal values is calculated by each individual laboratory as the mean (±2 standard deviations [SD]) in a group of healthy people from the local geographic area.5 Frequently, these “healthy volunteers” may have unrecognized nonalcoholic fatty liver disease (NAFLD), resulting in elevated range of normal values. It has therefore been suggested recently that an ALT greater than 19 U/L for women and greater than 30 U/L for men should be considered abnormal. However, fluctuating levels are not uncommon in an individual. AST levels normally measure at approximately 0.8 of ALT levels; they vary slightly with age and gender, with men having higher levels than women.6

AST is also present in cardiac muscle, skeletal muscle, kidneys, brain, pancreas, lungs, leucocytes, and erythrocytes. Its half-life is 17 ± 5 hours, and serum levels show day-to-day variation of 5% to 10%.7 When stored, the activity of AST is stable at room temperature for 3 days, in the refrigerator for 3 weeks (<10% loss), and for years when frozen (<15% loss). 8 The organ-to-serum activity ratios suggest that AST activity in the liver is 9000 times higher than in serum. African Americans appear to have 15% higher levels, and strenuous exercise can lead to a threefold increase in serum levels.6 Rarely, isolated elevation in AST without concurrent elevation in other liver enzymes is noted, and this is a result of the presence of macro-AST enzyme. In this condition, AST forms complexes with other proteins, primarily immunoglobulin G (IgG), resulting in a chronically elevated AST level, which is of no clinical consequence.9

ALT, although generally believed to be more liver specific, is also present in muscle and kidney. Its half-life is 47 ± 10 hours, higher than that of AST. When stored, the activity of ALT in serum is stable at room temperature for 3 days and in the refrigerator for 3 weeks with less than 10% loss, but it is markedly decreased by freezing and thawing.8 The organ-to-serum activity ratio of ALT is 7600:1 in liver and 750:1 in muscle. Although day-to-day variation of serum ALT (10% to 30%) is comparable to that of serum AST, ALT also shows variability of approximately 45% during the day, with highest levels observed in the afternoon.7 Unlike AST, strenuous exercise results in 20% lower values of serum ALT.

In almost all liver diseases, ALT is higher than AST, except in alcoholic liver disease and advanced fibrosis.10 In alcoholic hepatitis, AST is greater than ALT, because alcohol increases mitochondrial release of AST while concurrently decreasing cytoplasmic production of ALT due to pyridoxine deficiency.11 In acute hepatocellular injury, the lower organ-to-serum activity and longer half-life of ALT in comparison with AST leads to a higher and immediate rise of AST followed by subsequent higher levels of ALT. Serum ALT has been shown to be a good indicator of overall health and mortality risk; in two recent studies, ALT levels correlated with mortality from all causes as well as death from cardiovascular disease. 12,13 AST and ALT are significantly lower in patients with renal failure.

Gender Differences in Healthy Ranges for Serum Alanine Aminotransferase Levels in Adolescence

Abstract

Background & Aims

There is a worldwide epidemic of obesity among adolescents who subsequently are at increased risk for the development of non alcoholic fatty liver disease (NAFLD). The serum alanine aminotransferase (ALT) is the most frequently used test for screening these individuals, but no age and gender-specific upper limits of normal (ULN) based on healthy population data in children are available. The objective of the present study was to define ULN for ALT in healthy children in order to use this as a tool for case finding.

Methods

A total of 975 school children (aged 7–18 years) were included in the study cohort. Highly significant correlations (all p<0.001) were noted between ALT values and measures of BMI, systolic and diastolic blood pressure, insulin levels, HOMA-IR, total cholesterol and triglyceride concentrations. In order to define the population with no risk factors, we excluded subjects having abnormal values for factors that correlated with ALT. This population comprised 186 boys and 185 girls.

Results

In boys, median serum ALT levels were 16 IU/L and 9, 11, 18, and 30 IU/L for the 5th, 25th, 75th, and 95th percentiles. In girls, median serum ALT was 13, and 7, 9, 16, and 21 IU/L for the 5th, 25th, 75th, and 95th percentiles, respectively. The ULNs for ALT were 30 IU/L and 21 IU/L for boys and girls respectively. We found a linear relationship between age and ALT in females (p<0.001) but not in males. By multiple logistic regression, independent predictors of an elevated ALT included the BMI, waist hip ratio and levels of serum total cholesterol. In females, age was an additional inverse predictor.

Conclusions

In children and adolescents, these normal limits for ALT should be applied. Those with persistent elevations should be investigated further.

Citation: Poustchi H, George J, Esmaili S, Esna-Ashari F, Ardalan G, Sepanlou SG, et al. (2011) Gender Differences in Healthy Ranges for Serum Alanine Aminotransferase Levels in Adolescence. PLoS ONE 6(6):
e21178.

https://doi.org/10.1371/journal.pone.0021178

Editor: Qamaruddin Nizami, Aga Khan University, Pakistan

Received: February 8, 2011; Accepted: May 22, 2011; Published: June 27, 2011

Copyright: © 2011 Poustchi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: The entire study was funded by The Ministry of Health and Medical Education in Iran, the deputy of health. There was no current external funding sources for this study. The funders has no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Introduction

There is a worldwide epidemic of obesity and diabetes, with an estimated 1 billion overweight adults [1]. Likewise, childhood obesity is increasing, with the development of end-organ damage in children and young adults [2], [3]. The spectrum of disorders related to adiposity is myriad, but includes insulin resistance, type 2 diabetes mellitus (T2DM), cardiovascular disease and fatty liver disease [4]–[9]. A central issue related to the management of obesity-related chronic diseases concerns laboratory screening and diagnosis. The serum alanine aminotransferase (ALT) activity correlates with obesity [10], reflects hepatocellular injury and is the most frequent test for screening and monitoring patients with non alcoholic fatty liver disease (NAFLD) [11]. Since NAFLD is a component of the metabolic syndrome and its consequences, it is not surprising that elevations in ALT activity are frequently present in persons with T2DM and cardiovascular disease and are associated with increased mortality [11]–[17].

Liver functions tests are the most frequently ordered tests in clinical practice, being relatively cheap and easy to measure. Of the panel, the ALT is the most specific screening test for hepatic necro-inflammation. Elevations in ALT activity usually reflect the presence of NAFLD, if other causes have been excluded. Data from pediatric studies indicate that NAFLD is an emergent problem, which in a proportion of cases, may progress to cirrhosis and liver-related morbidity and mortality [18]. Even in patients that do not develop advanced liver disease, an elevated ALT is an important surrogate for cardio-metabolic risk including dyslipidemia, hypertension and glucose intolerance. These patients are more likely to die of cardiovascular disease than from liver disease [19]–[25].

In screening for NAFLD, the quoted laboratory reference intervals for ALT serve as an important decision making tool [26], [27]. It has also been demonstrated that age and gender have significant effects on the levels of serum ALT and AST, with an inverted U pattern with respect to age [11], [28]–[30]. However, age and gender-specific upper limits of normal for the AST and ALT based on healthy population data in children are currently not available. Hence, the objective of the present study was to define upper limits of normal (ULN) for aminotransferases in healthy school age children in order to (1) define cut-offs for screening in primary and specialist health care settings and (2) to use this as a tool for early intervention in the management of fatty liver disease and as well, other complications of the metabolic syndrome.

Results

Of 1000 students who consented to participate, 74 were excluded as they were unable to fast overnight. Another student was excluded after testing positive for hepatitis B surface antigen (HBsAg). None of students were positive for hepatitis C antibody and all subjects denied cigarette smoking or alcohol consumption. Hence, the data presented is based on a cohort of 925 individuals. Table 1 presents baseline demographic data for the whole cohort including age, gender BMI, HOMA-IR, blood pressure, ALT and AST level, and fasting glucose, fasting lipid profile and fasting insulin. The age and gender distribution of the students who agreed to participate in the study were no different from those that declined.

We next determined whether any of the clinical and laboratory parameters measured correlated with the values for serum ALT. As noted (Table 2), highly significant and positive correlations (all p<0.001) were noted between the serum ALT and measures of BMI, systolic and diastolic blood pressure, insulin levels, calculated HOMA-IR, total cholesterol and triglyceride concentrations. In contrast, there was a weak but inverse correlation between ALT and age (spearman r −0.077; p<0.021).

In order to define the population with no risk factors for metabolic liver disease, we first excluded all subjects having abnormal values for factors correlated with ALT based on the definitions described earlier. This group, the healthy population, comprised of 186 boys and 185 girls and had values for fasting glucose, insulin levels, the total cholesterol and triglyceride within the normal range (80±7 mg/dl, 12±4 µU/ml, 141±17 mg/dl, 66±16 mg/dl, respectively. Table 1 lists the baseline characteristics of the total study cohort and of the healthy population.

We next defined the normal range and mean values for ALT and AST in these 371 normal subjects. Table 3 lists the median, mean and range for serum ALT and AST according to gender, and as well the percentiles for these values. In boys, serum ALT levels were 16 IU/L for the median, and 9, 11, 18, and 30 IU/L for the 5th, 25th, 75th, and 95th percentiles, respectively. Serum AST levels were 26 for the median, and 17, 23, 30, and 38 IU/L for the 5th, 25th, 75th, and 95th percentiles, respectively. In girls, serum ALT levels were 13 for the median, and 7, 8.6, 16, and 20.8 IU/L for the 5th, 25th, 75th, and 95th percentiles, respectively. Serum AST levels were 21 for the median, and 14, 18, 25, and 32.7 IU/L for the 5th, 25th, 75th, and 95th percentiles, respectively.

Values below the gender-specific 95th percentile were used to define the upper limit of normal value for the ALT and AST in boys and girls. Based on this definition, the ULNs for ALT were 30 IU/L and 21 IU/L for boys and girls respectively, while the ULNs for AST were 38 IU/L and 33 IU/L for boys and girls respectively. Gender-specific histograms of each of these values are presented in Figure 1.

In further analysis we found a linear relationship between age and ALT in females (p<0.001) but relationship for males was not significant (p = 0.41). Therefore, based on this finding we calculated 5th and 95th percentiles and predicted values for ALT by age in females (Figure 2).

Figure 2. 95th percentile, predicted and 5th percentile of ALT values by age for females.

The X axis represents current student age. The Y axis is the ALT level, and the top and bottom lines are the 95th and 5th percentile. The middle line represents the predicted values for ALT in female participants according to age.

https://doi.org/10.1371/journal.pone.0021178.g002

We next categorized females into three age groups: group a) 7–10 years (n = 41), group b) 11–14 (n = 57) and group c) 15–18 years (n = 76) and calculated a separate range of ALT for each group. The minimum and maximum values for these three groups were 8, 8, 7 and 24, 22, 20 respectively for girls aged 7–10 years, 11–14 and 15–18 years.

As shown in Table 2, ALT values were correlated with several anthropometric and laboratory variables. In order to determine which factors were independently associated with elevations in ALT (segregated by gender), we undertook multiple logistic regression analysis with input variables that included age, BMI, SBP, DBP, Total TG, total cholesterol, HOMA-IR and LDL cholesterol. As shown in Table 4, independent predictors of an elevated ALT as expected included the BMI, the waist hip ratio and levels of serum total cholesterol. In females, age was an additional inverse predictor. Again, as shown in the table, visceral obesity as measured by the waist hip ratio was a stronger predictor of elevations in ALT (OR 2.25 CI1.4–3.56 in boys and 1.8 CI 1.16–2.8 in girls) than the BMI.

In the final analysis, we compared the number of components of the metabolic syndrome in the group with normal and elevated ALT levels based on ULNs calculated in the current study. As shown in Table 5, ALT values were similar between those who had only one component of the metabolic syndrome and those who did not (p = 0.385). In contrast, those with 2 or more components of the metabolic syndrome had elevated ALT levels (p<0.001). The metabolic syndrome was present in 7% of those with a normal ALT, but in 21% of those with an elevated ALT.

Discussion

In this study we undertook an age- and gender-based approach to define upper limits of normal for ALT and AST in school aged children and adolescents. In boys, ULNs for ALT and AST were 30 and 38 IU/L respectively. In girls the ULN for ALT and AST were 21 and 33 IU/L, respectively, and in this group ULNs for ALT (but not for AST) was inversely associated with age. In girls therefore, the ULN for ALT was 24 IU/L (age 7–10 years), 22 IU/L (11–14 years), and 20 IU/L (15–18 years). In multiple logistic regression analysis, serum total cholesterol, BMI and waist to hip ratio were independent predictors of an elevated ALT.

In defining reference intervals, identifying a group of healthy individuals is of paramount importance. For determining ULNs for ALT and AST therefore, subjects should be free of risk factors for liver diseases. In affluent nations, the most common liver disease in children and adolescents is NAFLD with a rate between 2.6% to 9.8% [31], [32]. The prevalence of NAFLD in the aforementioned age group in Iran is comparable, with a rate between 2.3% to 7.1% [33], [34]. Since Iran is located in an intermediate zone for HBV, we checked for hepatitis B surface antigen and to exclude HCV infection, anti-HCV antibody was assessed.

To determine ranges of ALT and AST in healthy children and adolescents, we next assessed for factors associated with serum ALT in univariate analysis. BMI, systolic and diastolic blood pressure, insulin levels, calculated HOMA-IR, the total cholesterol and triglyceride concentrations correlated with the serum ALT. Therefore, participants who had abnormal results for these components based on age-specific published values were excluded. In addition, those with elevated blood pressure or blood glucose were excluded and as discussed earlier, none of the subjects consumed alcohol or smoked cigarettes. Thus, the ULN values quoted for healthy children and adolescents in this study are likely to reflect true normative values at this age and are in accordance with studies published from elsewhere [35], [36]. Our sample size, we believe, is adequate for this purpose based on a consensus document produced by the Clinical and Laboratory Standards Institute (CLSI), formally known as the NCCLS [37]. They suggest that 120 is the minimum number of samples needed to establish a reference range to have a 90% confidence interval for the 97.5th percentile. Moreover if 198 samples are used then the confidence interval for the 97.5th percentile becomes 99%.

The upper limit of normal for ALT and AST in boys was higher than in girls. The reason for this is not known, but could relate to differences in muscle mass and sex hormones between genders. In this regard, it is well established that serum concentrations of estradiol are low in preadolescent girls and increase at menarche, while after menopause, serum concentrations decline to the levels below or similar to that in men [38]. These age-related hormonal changes could in part account for the reductions in the ULN of ALT that we observed in girls.

Considering the association between abnormal ALT values, cardiovascular disease, type 2 diabetes and NAFLD, our gender-specific reference ranges could help preventive health care systems in case ascertainment of children at higher risk of future morbidity. Consistent with this, we have shown that ALT levels were elevated in those with two or more components of the metabolic syndrome. Therefore, encountering elevated ALT values should prompt a thorough assessment of cardio-metabolic risk and the institution of preventive measures including lifestyle change and pharmacotherapy [32].

Our study has limitations in that we stratified normative ALT values in girls according to age, but had less than the 120 persons in each category as recommended by the Expert Panel on reference values [39]. However, studies such as the present one are difficult to undertake in children. Finally, segregation according to pubertal stages would have been ideal, but this was not ethically feasible.

In conclusion, we have used rigorous criteria to define normal values for serum aminotransferases in children. These limits should be routinely used when assessing children and adolescents. Further, we suggest that those with persistent elevations should be assessed for the metabolic syndrome and its components (if viral hepatitis has been excluded), and managed aggressively to improve long term health outcomes and quality of life.

Methods

The study protocol was approved by the Ethics Council of the Iran Ministry of Health and Medical Education. The study population was selected using a stratified multistage random sampling design according to the age, gender and geographic location of children from the city of Tehran, Iran. For this study, Tehran was divided into 5 geographic regions. Written invitations were sent to 11,000 randomly selected students from public school registries in the 5 regions. A stratified cluster random sampling design was conducted on those students who responded. Ultimately, 1,000 students aged 7–18 were enrolled in the study. Written informed consent was obtained from parents and oral consent from students after full explanation of the procedures. For blood sampling, students were invited to the Children’s Medical Centre and one of the parents accompanied his/her child. Each student was initially assessed by a trained nurse who administered a questionnaire to obtain information on demographic variables, the medical history, dietary habits, alcohol consumption and cigarette smoking. Ten ml of venous blood was taken from an ante-cubital vein in clotted tubes, placed in ice and transported to the reference laboratory. All laboratory assessments were performed on the same day. All subjects subsequently underwent a liver ultrasound by an expert radiologist.

Body weight was measured in all students in the upright position to the nearest 0.1 kg while wearing light clothing without shoes. Height was measured to the nearest millimeter with a portable stadiometer. Waist circumference was measured at the end of normal expiration to the nearest millimeter, at the narrowest point between the lower borders of the rib cage and the iliac crest. Hip circumference was obtained at the widest point between hip and buttock.

Blood pressure was measured using a mercury sphygmomanometer after confirming that subjects did not consume caffeine or smoke cigarettes 30 min prior to the measurement. All subjects were seated for at least 5 minutes. The first and fifth Korotkoff sounds were recorded as the systolic blood pressure (SBP) and the diastolic blood pressure (DBP), respectively. This was measured twice and the mean used in the analysis.

Plasma concentrations of glucose, total cholesterol, triglyceride, high density lipoprotein (HDL) cholesterol, AST, ALT and insulin were measured using an auto analyzer (Hitachi 912 auto-analyzer, Tokyo, Japan). All subjects were checked for hepatitis B surface antigen (HBsAg) and anti-HCV antibody (HCVAb).

The body mass index (BMI) was calculated as weight divided by the height in meters squared (kg/m2). Gender-specific BMI cut-off values based on 6 nationally representative data sets were used to define overweight and obesity in children [40].

Normotensive systolic and diastolic blood pressure was defined as the National High Blood Pressure Education Program (NHBPEP) recommended cut-point of the 90th percentile for age, gender, and height [41]. A triglyceride (TG) concentration ≥100 mg/dl was considered elevated based on the criteria used to define the metabolic syndrome in adolescents [42]. High density lipoprotein-cholesterol (HDL-C) <50 mg/dl was used to define a low HDL cholesterol, except in boys aged 15–18 years, in whom <45 mg/dl was used as the definition for low HDL cholesterol [42]. Fasting glucose ≥100 mg/dl was classified as elevated based on the recommendations of the American Diabetes Association (2003) and the WHO (2006) [43], [44]. The cut-offs for total cholesterol (T-C <170 mg/dl) and low density lipoprotein-cholesterol (LDL-C <110 mg/dl) were accepted as normal [45]. Insulin resistance was calculated using the homeostasis model assessment of insulin resistance (HOMA-IR) [46]and insulin resistance was defined as HOMA-IR >2 [23]. We used NCEP-ATP III criteria to define the metabolic syndrome [47].

Fatty liver was diagnosed on an abdominal ultrasound performed in all subjects using an ALOKA SSD 1700 machine by an experienced radiologist, unaware of the laboratory and other results. The presence of fatty liver was determined using accepted criteria that included a diffuse increase in echo texture (bright liver), increased liver echo texture compared with the kidneys, vascular blurring and deep attenuation [48].

All data were analyzed using SPSS for Windows Version 15 (SPSS Inc, Chicago, USA). The Student’s t test and one-way ANOVA were used for continuous variables. Non-parametric tests were used when parametric assumptions were not met. Independent predictors of ALT were identified by multiple logistic regression analysis, with backward stepwise variable selection. A p-value of ≤0.05 denoted significance.

The Medical Ethics Committee in Digestive Disease Research Center approved the conduct of the current study. Study was conducted in accord with principles of Declaration of Helsinki. Informed consent was signed by guardians of all participating adolescents. Data were de-identified and the personnel were blind to the identity of subjects.

Author Contributions

Conceived and designed the experiments: HP JG. Performed the experiments: SE FE GA. Analyzed the data: HP SE SGS. Contributed reagents/materials/analysis tools: HP JG SMA. Wrote the paper: HP JG SE SGS SMA.

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    Sattar N, Scherbakova O, Ford I, O’Reilly DS, Stanley A, et al. (2004) Elevated alanine aminotransferase predicts new-onset type 2 diabetes independently of classical risk factors, metabolic syndrome, and C-reactive protein in the west of Scotland coronary prevention study. Diabetes 53: 2855–2860.
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    HH AK, Henderson J, Vanhoesen K, Ghishan F, Bhattacharyya A (2008) Nonalcoholic fatty liver disease in children: a single center experience. Clin Gastroenterol Hepatol 6: 799–802.
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    Suzuki A, Angulo P, Lymp J, St Sauver J, Muto A, et al. (2005) Chronological development of elevated aminotransferases in a nonalcoholic population. Hepatology 41: 64–71.
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    Clark JM, Brancati FL, Diehl AM (2002) Nonalcoholic fatty liver disease. Gastroenterology 122: 1649–1657.
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    Adams LA, Waters OR, Knuiman MW, Elliott RR, Olynyk JK (2009) NAFLD as a risk factor for the development of diabetes and the metabolic syndrome: an eleven-year follow-up study. Am J Gastroenterol 104: 861–867.
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    Schwimmer JB, Behling C, Newbury R, Deutsch R, Nievergelt C, et al. (2005) Histopathology of pediatric nonalcoholic fatty liver disease. Hepatology 42: 641–649.
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    Jorgensen LG, Brandslund I, Hyltoft Petersen P (2004) Should we maintain the 95 percent reference intervals in the era of wellness testing? A concept paper. Clin Chem Lab Med 42: 747–751.
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    Alavian SM, Mohammad-Alizadeh AH, Esna-Ashari F, Ardalan G, Hajarizadeh B (2009) Non-alcoholic fatty liver disease prevalence among school-aged children and adolescents in Iran and its association with biochemical and anthropometric measures. Liver Int 29: 159–163.
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    Cole TJ, Bellizzi MC, Flegal KM, Dietz WH (2000) Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ 320: 1240–1243.
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    (2004) Pediatrics 114: 555–576. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. (2004).
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    de Ferranti SD, Gauvreau K, Ludwig DS, Neufeld EJ, Newburger JW, et al. (2004) Prevalence of the metabolic syndrome in American adolescents: findings from the Third National Health and Nutrition Examination Survey. Circulation 110: 2494–2497.
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    (2005) Diabetes Care 28: S4–S36. Standards of medical care in diabetes. (2005).
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    (1998) Pediatrics 101: 141–147. American Academy of Pediatrics. Committee on Nutrition. Cholesterol in childhood. (2004).
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    Uwaifo GI, Fallon EM, Chin J, Elberg J, Parikh SJ, et al. (2002) Indices of insulin action, disposal, and secretion derived from fasting samples and clamps in normal glucose-tolerant black and white children. Diabetes Care 25: 2081–2087.
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    (2001) JAMA 285: 2486–2497. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). (2001).
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    Farrell GC, Chitturi S, Lau GK, Sollano JD (2007) Guidelines for the assessment and management of non-alcoholic fatty liver disease in the Asia-Pacific region: executive summary. J Gastroenterol Hepatol 22: 775–777.

90,000 “Why are ALT and AST elevated in the blood, what does this mean?” – Yandex.Qu

What is a thyroid nodule?

Node is the collective name for any delimited formation in the thyroid gland. This is not a diagnosis, but a designation that some kind of formation was found – either the doctor probed it when examining the patient, or saw it during an ultrasound (less often, another type) examination. Most often, nodules are not tumors, but represent a change in the structure of the gland, especially characteristic of adult residents of regions of iodine deficiency, which include most of the regions of Russia.This is the so-called colloid goiter, which makes up about 80-90% of all nodules in the thyroid gland and does not always require treatment. The other 10-20% are tumors, which can be both benign and malignant. It is most often impossible to reliably distinguish between tumor and colloidal nodes only with the help of ultrasound, therefore, when a nodular formation (one or more) is detected, a preliminary diagnosis of a nodular goiter is established, and then indications for clarifying examinations are determined.

Nodular goiter is a very common pathology, around which there are many unfounded fears, unnecessary actions, and sometimes even unnecessary operations. Everything is based on international and national guidelines for the diagnosis and treatment of nodular goiter, namely on these very detailed and well-grounded American guidelines http://thyca.org/download/document/409/DTCguidelines.pdf

And here are less detailed and more questionable Russian recommendations https: // endojournals.ru / index.php / serg / article / view / 7960/5760

So is finding thyroid nodules always a cause for concern?

Fortunately, not always. With the widespread use of ultrasound, it is often necessary to deal with the identification of clinically insignificant nodes. The detection of formations with a diameter of up to 1 cm in the composition of the gland is rather rarely of clinical significance. Further examination of nodules less than 1 cm in size in the vast majority of cases is not required for adults.Such a finding is most often not able to influence the further prognosis for life and health, therefore, subject to the normal functioning of the thyroid gland, further action when such changes are detected on ultrasound is usually not required. It is important that the ultrasound examination is carried out by a competent doctor who knows what and how to describe – and even better, is familiar with the modern ultrasound classification of nodes according to the TI-RADS system (modification from 2017).

What if large node (s) are found?

Mandatory action upon detection of nodular formations with a diameter of more than 1 cm is to determine the function of the thyroid gland (i.e.That is, we check how the hardware works). This is done by measuring the serum TSH level. Russian recommendations also contain a clause on determining the level of blood calcitonin (a marker of one of the rare but dangerous types of thyroid cancer) – we look at it with nodes 1 cm or more once. That is, a normal calcitonin count means that you no longer need to monitor calcitonin.

With normal TSH levels, no medication is needed. You cannot cure a knot with pills, we need to decide whether we can live with it in peace, or we need to do something with it.Further, the question arises of conducting a fine-needle puncture biopsy of the node to establish a cytological diagnosis – in this way we can find out what cells the node consists of. Who needs a puncture? According to Russian recommendations, all patients with nodular formations 1 cm or more in size. The only exceptions are “clean cysts”, which do not need to be punctured. A cyst is a bubble of fluid, and the words “cystic degeneration”, which so excite many, do not mean anything bad.

American and European guidelines suggest a more flexible approach when deciding on a puncture of nodes.First, we must evaluate the ultrasound characteristics of the node according to the TI-RADS system, and then act on the basis not only of the size, but also of the “degree of suspicion” of the node.

It is important that the preparations after puncture are evaluated by a competent cytologist. We must get a conclusion according to the international cytological classification, or at least formulated in such a way that it is understandable for an endocrinologist and an endocrine surgeon. Next, we act depending on what is written in the conclusion.

If the puncture turned out to be uninformative (few cells got into the preparation), then it is redone.

If a colloidal goiter is found, observe. Most colloidal (non-neoplastic) nodes do not require referral to an endocrine surgeon and do not prevent the patient from staying healthy throughout life. Treatment is required only if the thyroid gland is malfunctioning (increased function of the nodules), or with symptoms of compression of the neck organs by very large nodes. I note that the method of choice for nodular toxic goiter (hyperfunctioning nodes) is not an operation, but treatment with radioactive iodine.

Tumor nodes are almost always the basis for surgical intervention, the volume of which depends on the specific cytological diagnosis.

Can a knot (s) affect well-being and cause painful symptoms?

This is only possible in two cases:

1) In the presence of a so-called “hyperfunctioning” node that is out of control of the endocrine system and releases too many hormones. In this case, the patient will have symptoms of thyrotoxicosis (palpitations, tremors in the hands, weight loss, etc.)and the doctor will detect an excess of thyroid hormones in the blood and prescribe appropriate treatment. It should be noted that when thyrotoxicosis is detected, thyroid scintigraphy is performed first, and a puncture biopsy may not be required.

2) The nodule is so large that it causes symptoms of compression of the surrounding organs (usually in such patients we are talking about a multinodular goiter) – there is shortness of breath and swallowing disorders, as well as a feeling of constant discomfort and compression in the neck.

Very rarely, usually with a hemorrhage in a node, the patient may feel pain in the neck. In most cases, the nodule does not cause any sensations and does not affect well-being, therefore, it is erroneous to explain any symptoms (for example, an increase in blood pressure, change in body weight) by the presence of a node in the thyroid gland with a normal level of TSH. However, tumor nodes usually do not cause any symptoms, but it is they that require surgical intervention and careful medical supervision after surgery.Actually, the main goal of a puncture biopsy of nodules is to find out if the nodule is the focus of thyroid cancer. Fortunately, the overwhelming majority of malignant neoplasms of the thyroid gland, with appropriate treatment, have an excellent prognosis for a full and long life, as well as the patient’s work capacity, so it is important not to miss the moment for timely intervention.

90,000 ALT, take a blood test for ALT (ALT, alanine aminotransferase)

Method of determination
Kinetic UV method (optimized DGKC method), 37 ° C.

Study material
Blood serum

Home visit available

Online check-in

Alanine aminotransferase is an intracellular enzyme involved in the metabolism of amino acids.The test is used to diagnose lesions of the liver, heart and skeletal muscles.

Synonyms: Glutamate pyruvate transaminase; Serum glutamate pyruvate transaminase; SGPT.

Alanine aminotransferase; Serum glutamic-pyruvic transaminase; SGPT; Alanine transaminase.

Brief characteristics of the analyte AlAT

Alanine aminotransferase belongs to a group of enzymes that catalyze the reversible conversion of a-keto acids into amino acids by transferring amino groups.The highest activity of ALT is detected in the liver and kidneys, the lowest – in the heart, skeletal muscles, pancreas, spleen, lungs, erythrocytes. ALT is a cytoplasmic enzyme. When cells are damaged or destroyed, the enzyme is released, which leads to an increase in its activity in the blood.

Under what conditions can the serum ALT level increase

Elevated serum ALT activity is generally regarded as an indicator of liver parenchymal damage.

Despite the combined increase in the level of transaminases (ALT and AST) with damage to liver cells, in most types of liver pathology, the increase in serum ALT activity is more significant, this enzyme is a more specific marker of liver disease than AST (see test No. 9).

ALT activity values ​​exceeding 50 times the upper limit of normal values ​​are mainly caused by viral hepatitis, acute hepatic perfusion disorders or acute liver necrosis caused by exotoxins.In viral hepatitis, an increase in enzyme activity occurs at a very early date, before the appearance of clinical signs and symptoms of the disease in the prodromal period. In dynamics, with a favorable course of the process, the ALT activity slowly decreases to its initial values ​​over several weeks. The persistence of elevated alanine aminotransferase activity for more than 6 months after an episode of acute hepatitis is used to diagnose chronic hepatitis. In most patients with chronic hepatitis, the maximum ALT activity is seven times higher than the norm by no more than 7 times.In chronic hepatitis C, the ALT level in a significant number of patients may be normal for a long time or only borderline elevated.

Toxic hepatitis gives a picture similar to infectious hepatitis, with very high ALT and AST values ​​in severe cases. A more moderate increase in ALT activity is observed in alcoholic hepatitis.

The levels of ALT and AST in liver cirrhosis vary, depending on the stage of the cirrhotic process, more often within the range from the upper limit of the norm to a 4-5-fold increase (the level of AST may become higher than ALT, which is associated with a decrease in the production of ALT by liver).In myocardial infarction, serum ALT increases to a lesser extent than AST, since the activity of alanine aminotransferase in cardiomyocytes is 15 times lower than that of AST. In uncomplicated myocardial infarction, ALT levels may be only slightly increased or remain within the reference range. In clinical practice, the AST / ALT ratio (de Ritis coefficient) is used for diagnosis. With hepatic enzymatic disease (acute viral and toxic hepatitis), the de Ritis coefficient can decrease to 0.2-0.5, with myocardial infarction and skeletal muscle damage – it is more than 1.5.

For what purpose is the level of ALT in blood serum determined?

Determination of the level of ALT in blood serum is used mainly in the diagnosis and control of the course of liver diseases, as well as in complex panels of screening biochemical studies.

What can affect the result of the study of ALT in serum

A slight or moderate increase in the activity of AST and ALT was observed after taking various drugs, such as non-steroidal anti-inflammatory drugs, antibiotics, antiepileptic drugs.There is evidence that an increase in the concentration of alanine aminotransferase can be with an adverse reaction to statin therapy. With a significant increase in the activity of aminotransaminases in the blood, a discussion and change in therapy is required.

90,000 Pass a blood test for GGT (Gamma Glutamyl Transpeptidase) at the KDL

laboratory

GGT (gamma-glutamyltransferase or gamma-glutamyltranspeptidase) is an enzyme involved in the metabolism of amino acids.It is found in the highest concentration in the kidneys, liver, pancreas, in smaller amounts in other tissues of the body. The highest level of GGT is found in the kidney tissue, the enzyme present in the serum comes mainly from the hepatobiliary system. An increased concentration of GGT in the blood serum is most often a marker of a violation of the outflow of bile (cholestasis), as well as intoxication caused by alcohol or drugs.

In what cases is the study usually prescribed?

A blood test for GGT is important for the diagnosis of liver pathology, for this purpose it is usually prescribed together with the following studies: AST, ALT, bilirubin, alkaline phosphatase.GGT is highly informative in detecting obstructive jaundice, cholangitis and cholecystitis; an increase in the level of this indicator begins earlier than in other hepatic markers, and lasts longer.

In viral hepatitis, GGT does not increase much, and in this case, the determination of transaminases (ALT, AST) is more useful. High levels of GGT are observed in violation of the outflow of bile, obstructive processes in the liver (ten times higher than normal), in the presence of primary or secondary (metastases) neoplasms, with cirrhosis.

What do the test results mean?

Norms of gamma-glutamyltransferase concentration in blood differ depending on gender and age.

An increase in the activity of gamma-glutamyl transpeptidase (GGT) is observed in various hepatic pathologies. The highest scores indicate biliary obstruction, which may be hepatic or extrahepatic, alcoholic liver disease, and cirrhosis. In combination with an increase in alkaline phosphatase, it is characteristic of hepatobiliary diseases.Increased values ​​are also seen in patients taking drugs such as phenytoin and phenobarbital.

Simultaneous increase in GGT and alkaline phosphatase suggests cholestasis. With prolonged use of alcohol, GGT increases in isolation from alkaline phosphatase. An increase in alkaline phosphatase at normal GGT values ​​indicates the presence of bone diseases. With muscle diseases, renal failure and pregnancy with an increase in alkaline phosphatase, normal GGT values ​​are noted.

Timing of the test.

Usually, the result of the GGT analysis can be obtained the next day.

How to prepare for the analysis?

The general rules of preparation for taking blood from a vein should be followed. Detailed information can be found in the corresponding section.

Description of the analysis of Alanine aminotransferase (ALT) in Donetsk

Code: 02-407

Price: 140 rub

Description

Alanine aminotransferase (ALT) is an enzyme that is present primarily in liver and kidney cells and to a lesser extent in heart and muscle cells.

When ALT-rich cells are damaged or destroyed, the enzyme is released into the bloodstream, which leads to an increase in its activity in the blood.

Alanine aminotransferase is released into the bloodstream in liver diseases (viral hepatitis, tumors, cirrhosis, toxic lesions, and others). Therefore, enzyme activity is used as an indicator of liver damage. Along with other studies that perform the same tasks, the ALT test is included in the so-called “liver tests”.Alanine aminotransferase and AST (aspartate aminotransferase) are the most informative indicators of liver damage.

In viral hepatitis, the increase in ALT activity is usually proportional to the severity of the disease. Alanine aminotransferase is a more specific marker of liver disease than AST. In acute cases, the activity of the enzyme in the blood serum can exceed normal values ​​by 50-100 times or more. In viral hepatitis, an increase in ALT activity occurs in the early stages – before the onset of jaundice.The enzyme activity is also increased in patients with anicteric form of the disease. In dynamics, with a favorable course of the process, the activity of Alanine aminotransferase slowly decreases to the initial values ​​for several weeks.

A 5-10-fold increase in the activity of transaminases (ALT and AST) is observed in patients with primary or metastatic liver carcinomas (AST is higher than ALT). But in the early stages of the oncological process, the levels of transaminases may be within normal limits.

In obstructive jaundice, the increase in values ​​can be small and late, a rapid and noticeable increase followed by a sudden decrease within 12-72 hours is considered characteristic of acute obstruction of the bile ducts.

Toxic hepatitis gives a picture similar to infectious hepatitis, with very high ALT and AST values ​​in severe cases.

A more moderate increase in ALT activity is observed in alcoholic hepatitis.

The levels of transaminases in liver cirrhosis vary depending on the stage of the process, ranging from the upper limit of the norm to a 4-5-fold increase.

In uncomplicated myocardial infarction, ALT levels are usually slightly increased or remain within reference values.An increase in serum ALT in myocardial infarction may indicate the development of congestion in the liver.

An important indicator in clinical practice is the ratio of AST / ALT activity (de Ritis coefficient). It is advisable to calculate its values ​​only with increased activity of one or both enzymes. An increase in the coefficient of more than 1.4 is noted in cirrhosis, severe alcoholic and toxic liver damage, which is evidence of deep necrosis of hepatocytes.In uncomplicated viral hepatitis or non-alcoholic liver damage, the coefficient value is less than 1.0. With myocardial infarction, ALT activity increases slightly, so the de Ritis coefficient increases sharply

Preparation for analysis

Blood for research is donated in the morning on an empty stomach after an 8-12 hour night fasting period (you can drink water).On the eve of donating blood, fatty foods should be excluded from the diet.

Requirements

Interpretation of results

Interpretation of test results contains information for the attending physician and is not a diagnosis.

Reference values ​​(norm):

9016 9016

Alanine aminotransferase, U / L

13.0 – 45.0

Children: newborns

9016 9016 9016 <

<35.0

Women

Increase in ALT value:

  • Hepatotoxic drugs and drugs causing cholestasis
  • Necrosis of hepatocytes of any etiology
  • 98

    Cardiac trauma

  • liver
  • Obstructive jaundice
  • Liver tumors
  • Extensive myocardial infarction
  • Myositis muscular dystrophy
  • Sometimes with hemolytic diseases, preeclampsia, chronic alcoholism, severe burns, severe pancreatitis Add
  • Analyzes

    To confirm the diagnosis of hepatitis C it is necessary: ​​

    1.Biochemical blood test:
    Alanine aminotransferase (ALT, ALT, ALT)
    Aspartate aminotransferase (AST, AsAT, AST)
    Bilirubin
    Glucose
    Gamma-glutamyl transpeptidase (GGT, GGTP)
    Protein total
    Ferritin
    Albumin
    Protein fractions
    Creatinine

    2. PCR analysis of hepatitis C (qualitative / quantitative analysis)
    3.Elastography (fiber scan)

    4. Carrying out genotyping of hepatitis C virus (HCV)

    For a complete diagnosis of hepatitis C and making a clinical decision on treatment, it is necessary to pass the following tests:


    1. Biochemical blood test : a study that allows for the analysis of various trace elements in the blood to assess the functional state of organs and systems of the human body.

    Components of a biochemical blood test used in the diagnosis of viral hepatitis:

    Alanine aminotransferase (ALT, ALT, ALT) is an enzyme contained in tissues in the liver and released into the blood when it is damaged. Elevated ALT levels can be caused by viral, toxic, or other liver damage. In chronic viral hepatitis, the ALT level can fluctuate over time from normal values ​​to several norms, so this enzyme must be monitored every 3-6 months.It is generally accepted that the ALT level reflects the degree of activity of hepatitis, however, in about 20% of patients with chronic viral hepatitis with a stable normal level of ALT, serious liver damage is found. It can be added that ALT is a sensitive and accurate test for the early diagnosis of acute hepatitis.
    Aspartate aminotransferase (AST, AST, AST) is an enzyme found in the tissues of the heart, liver, skeletal muscles, nervous tissue and kidneys and other organs. An increase in AST in a blood test together with ALT in patients with viral hepatitis may indicate liver cell necrosis.When diagnosing hepatitis, special attention should be paid to the AST / ALT ratio, called the de Ritis coefficient. An excess of AST in the blood test over ALT in patients with hepatitis may indicate severe liver fibrosis or toxic (drug or alcoholic) liver damage. If AST in the analysis is significantly increased, then this indicates necrosis of hepatocytes, accompanied by the disintegration of cellular organelles.
    Alkaline phosphatase (ALP, AR, Alkaline phosphatase, ALP, ALKP) is used to diagnose liver diseases accompanied by cholestasis.A joint increase in alkaline phosphatase and GGT may indicate a pathology of the biliary tract, cholelithiasis, a violation of the outflow of bile. This enzyme is located in the epithelium of the bile ducts, therefore, an increase in its activity indicates cholestasis of any genesis (intra- and extrahepatic). An isolated increase in the level of alkaline phosphatase is an unfavorable prognostic sign and may indicate the development of hepatocellular carcinoma.
    Bilirubin is one of the main components of bile.It is formed as a result of the breakdown of hemoglobin, myoglobin and cytochromes in the cells of the reticuloendothelial system, spleen and liver. Total bilirubin includes direct (conjugated, bound) and indirect (unconjugated, free) bilirubin. It is believed that the increase in bilirubin in the blood (hyperbilirubinemia) due to the direct fraction (more than 80% of the total bilirubin is direct bilirubin) is of hepatic origin. This situation is typical for chronic viral hepatitis. It may also be associated with impaired excretion of direct bilirubin due to cytolysis of hepatocytes.An increase in concentration due to free bilirubin in the blood may indicate a volumetric lesion of the liver parenchyma. Another reason may be congenital pathology – Gilbert’s syndrome. Also, the concentration of bilirubin (bilirubinemia) in the blood can increase if the outflow of bile is obstructed (blockage of the bile ducts). During antiviral therapy for hepatitis, an increase in bilirubin can be caused by an increase in the intensity of erythrocyte hemolysis. With hyperbilirubinemia over 30 μmol / l, jaundice appears, which is manifested by yellowing of the skin and sclera of the eyes, as well as darkening of urine (urine becomes dark beer color).
    Glucose (Glucose) – used in the diagnosis of diabetes mellitus, endocrine diseases, and diseases of the pancreas.
    Gamma glutamyl transpeptidase (GGT, GGTP) is an enzyme whose activity increases in diseases of the hepatobiliary system (a marker of cholestasis). It is used in the diagnosis of obstructive jaundice, cholangitis and cholecystitis. GGT is also used as an indicator of toxic liver damage caused by alcohol and hepatotoxic drugs.GGT is assessed in conjunction with ALT and alkaline phosphatase. This enzyme is found in the liver, pancreas, kidneys. It is more sensitive to abnormalities in liver tissue than ALT, ASAT, alkaline phosphatase, etc. It is especially sensitive to prolonged alcohol abuse. At least five processes in the liver increase its activity: cytolysis, cholestasis, alcohol intoxication, tumor growth, and drug damage. In chronic viral hepatitis, a persistent increase in GGTP indicates either a severe process in the liver (cirrhosis) or toxic effects.
    Total protein (Protein total) – the total concentration of proteins (albumin and globulins) in the blood serum. A strong decrease in total protein in the analysis may indicate a lack of liver function.
    Ferritin (Ferritin) – the main indicator of iron stores in the body. An increase in ferritin in chronic viral hepatitis may indicate hepatic pathology. An increase in ferritin levels can be a factor that reduces the effectiveness of antiviral therapy.
    Albumin (Albumin) – the main protein of blood plasma, synthesized in the liver A decrease in its level may indicate liver pathology caused by acute and chronic diseases. A decrease in the amount of albumin indicates severe liver damage with a decrease in its protein-synthetic function, which occurs already in the stage of liver cirrhosis.
    Protein fractions – protein components contained in the blood. There are quite a large number of protein fractions, however, for people with chronic viral hepatitis, special attention should be paid to five main ones: albumin, alpha1-globulins, alpha2-globulins, beta-globulins and gamma-globulins.A decrease in albumin may indicate liver and kidney pathology. An increase in each of the globulins can indicate various disorders in the liver.
    Creatinine is the result of the metabolism of proteins in the liver. Creatinine is excreted by the kidneys in the urine. An increase in the level of creatitine in the blood may indicate a violation of the normal functioning of the kidneys. The analysis is done before antiviral therapy to assess its safety.

    2. PCR analysis of hepatitis C (hepatitis C RNA, HCV RNA) – qualitative and quantitative research.
    A qualitative test indicates the presence of a virus in the blood. This test is necessary for all patients with antibodies to hepatitis C. Its result may be “detected” or “not detected”. Reference values ​​(value that should be normal) – “not found”. A “detected” result may indicate that the virus is multiplying and infecting all new liver cells. A qualitative PCR test has a certain sensitivity (10-500 IU / ml.). This means that if the virus is present in the blood at a very low concentration (below the detection threshold of the method), a “not detected” result can be obtained.Therefore, when conducting high-quality PCR in patients with low viremia (virus concentration), for example, undergoing antiviral therapy, it is important to know the sensitivity of the diagnostic system. To control the virological response during antiviral therapy, it is desirable to use a diagnostic system with a sensitivity of at least 50 IU / ml. These criteria are met, for example, by analyzers COBAS AMPLICOR HCV-TEST (analytical sensitivity 50 IU / ml or 100 copies / ml), RealBest HCV RNA (analytical sensitivity 15 IU / ml or 38 copies / ml) and others.

    Quantitative PCR (viral load) analysis is a test for the concentration of the virus in the blood. Viral load is the number of units of genetic material (viral RNA) that is present in a given volume of blood (usually 1 ml, which corresponds to 1 cubic centimeter). This amount is expressed in numbers, units of measure IU / ml (international units per milliliter). The amount of virus can be displayed in different ways. For example, 1.5 million IU / ml, which corresponds to 1.500.000 IU / ml or 1.5 * 106 IU / ml. Some laboratories use other units of measurement – copies / ml. The conversion factor from copies to international units is different for different test systems. The approximate value can be recalculated according to the formula 1 IU / ml = 4 copies / ml, for example, 5.5 * 105 IU / ml = 2.2 * 106 copies / ml.

    It is important to remember that there is no direct relationship between the concentration of the virus in the blood and the severity of hepatitis C.

    What does viral load affect?

    The higher the concentration of the virus, the higher the risk of transmitting the virus, for example through sexual intercourse or through vertical transmission.And also the concentration of the virus affects the effectiveness of treatment (if the treatment is carried out on the basis of interferon). Thus, a low viral load is a favorable factor during therapy, and a very high viral load is an unfavorable factor. Also, quantitative PCR is of great importance when conducting interferon therapy to assess its success and plan the duration of the course. So, with a quick response to treatment and low viremia before therapy, treatment times can be shortened. Conversely, with a slow decrease in the concentration of the virus, AVT can be prolonged.

    3.Elastography (Fiber Scan)
    It is necessary to exclude food intake 4 hours before the study. Excess weight affects the accuracy of the result, therefore, the medical specialist reserves the right to decide on the possibility of conducting a study.

    Elastography is a study of liver tissue, which is performed using the FibroScan apparatus. It is used as an alternative to biopsy. Allows to determine the degree of liver fibrosis in patients with chronic liver diseases, primarily with chronic viral hepatitis.The procedure is similar to an ultrasound scan, it takes no more than 10-15 minutes. This method is simple, painless and harmless.
    The principle of elastography is based on the relationship between tissue elasticity and the degree of fibrosis: the lower the elasticity (that is, the denser the liver tissue), the more pronounced the fibrosis. The sensor is installed in the intercostal spaces on the right, where the liver is located. A jolt is felt with each measurement. To obtain an accurate result, at least 10 measurements are taken, on the basis of which the device calculates the average result.This figure reflects the density of the liver tissue, according to which the doctor-researcher judges the severity of fibrosis and makes a conclusion. Depending on the indicators, the degree of fibrosis is determined according to the Metavir scale.

    Legend:

    F 0-3 – stages of fibrosis on the METAVIR scale in chronic hepatitis.

    F 4 liver cirrhosis.

    F 4 + EVP – cirrhosis of the liver with the presence of varicose veins of the esophagus.

    F 4 + EVP * – liver cirrhosis, portal hypertension complicated by bleeding from varicose veins of the esophagus.

    HCC – hepatocellular carcinoma.

    * in some cases, a puncture biopsy of the liver may be indicated.

    4. Carrying out genotyping of the hepatitis C virus (HCV)

    An important analysis that influences the choice of treatment regimen, as well as determining the duration. The presence of a virus of a particular genotype does not give any estimate of the severity of the course of the disease.Different genotypes have different drug resistance (resistance), therefore, a different treatment regimen is selected for each type. There is also evidence that patients with genotype 3 are more likely to have a concomitant liver disease – steatosis. Genotypes 1 and 3 of hepatitis C are the most common in Russia, Belarus and Ukraine.

    There are 6 main genotypes of the hepatitis C virus and about 500 subtypes. Genotype 1 is the most widespread in the world (40-80%). Type 1a is often found in the United States; type 1b is typical for Western Europe and South Asia.Genotype 2 occurs with a frequency of 10-40%. Genotype 3 is common in Scotland, Australia, India and Pakistan. HCV type 4 is typical for Central Asia and North Africa, genotype 5 – for South Africa, 6 – for some Asian countries. In Russia, genotype 1b prevails, then with a decreasing frequency – 3, 1a, 2, in the USA – 1a / 1b, 2b, and 3a.

    Having all the above results, a medical specialist will be able to make a complete diagnosis, determine the level of development of the viral process in the body, assess the state of the liver and the degree of its damage, and give recommendations on an effective treatment regimen.

    It is also recommended to be tested for antibodies to hepatitis B virus and, in the case of hepatitis B, for antibodies to hepatitis D. Timely detection of these forms of viral hepatitis can help stop or slow down the process of liver destruction by these viruses.

    Biochemical blood test for alanine aminotransferase (ALT)

    Diagnostic direction

    Functional state of the body

    General characteristics

    Catalyzes the transfer of the amino group from alanine to alpha-ketoglutaric acid, is found in the heart, liver, skeletal muscles, etc.ALT is an intracellular enzyme; its content in the blood serum of healthy people is low. But when cells rich in ALT (liver, heart muscle, skeletal muscles, kidneys) are damaged or destroyed, these enzymes are released into the bloodstream, which leads to an increase in their activity in the blood. In viral hepatitis, the degree of increase in ALT activity is proportional to the severity of the disease. In acute cases, the activity of the enzyme in the blood serum may exceed normal values ​​by 5-10 times or more.In viral hepatitis, an increase in enzyme activity occurs very early – even before the onset of jaundice. The enzyme activity is also increased in patients with anicteric form of the disease. In dynamics, with a favorable course of the process, the ALT activity slowly decreases to its initial values ​​over several weeks. A rapid decrease in enzyme activity in combination with increasing hyperbilirubinemia indicates a poor prognosis.

    Indications for appointment

    1.Diagnosis of liver diseases. 2. Diagnostics and differential diagnostics of myocardial infarction and other diseases of the heart muscle, pathology of skeletal muscles. 3. Monitoring the dynamics and treatment of viral hepatitis.

    Marker

    Marker of liver dysfunctions.

    Clinical significance

    Required for the diagnosis and monitoring of liver diseases associated with liver damage (necrosis).

    Composition of indicators:

    Alanine aminotransferase

    Method :
    Spectrophotometric

    Measuring range :
    3-500

    Unit of measure for :
    Units per liter

    Reference values:

    Age

    Comments

    Execution possible on biomaterials:

    Biological material

    Delivery terms

    Container

    Volume

    Serum

    Delivery terms:

    24 Hours.at a temperature from 2 to 25 degrees Celsius

    Container:

    Vacutainer with release gel

    Volume:

    8.5 Milliliters

    Capillary blood

    Delivery terms:

    24 Hours.at a temperature from 2 to 25 degrees Celsius

    Container:

    Microvet with activator of blood coagulation

    Volume:

    500 Microliter

    Rules for the preparation of the patient

    Standard conditions: In the morning until 11.00, strictly on an empty stomach, after 8-12 hours of the fasting period. Possibly: During the working day of ML “DILA”, if there are special instructions from the doctor. Break at least 6 hours after eating (fatty foods should be excluded).

    You can add this study to the cart on this page

    Interference:

    • Hepatotoxic medicines and drugs that cause cholestasis.
    • Aspirin, cyclosporin, phenothiazines, interferon.

    Interpretation:

    • Hepatocyte necrosis of any etiology, heart failure, acute anoxia, extensive trauma.
      Liver cirrhosis, obstructive jaundice, liver tumors, extensive myocardial infarction, myocarditis, myositis, muscular dystrophy; sometimes with hemolytic diseases, preeclampsia, chronic alcoholism, severe burns, severe pancreatitis.

    From the series … – Dok Lana Mornatural Health & Beauty Solutions

    From the series Headings “Confused, scattered” from Monatural. This is when you either didn’t understand, didn’t understand the Info, or the conflicting opinions of Insta_Nutri completely confused you.

    After the publication of this Rubric, with a joking / ironic beginning, and consideration of the IS “problem-madness” about “low blood protein” and what this indicator depends on, and how to “fight” this without a struggle, but with understanding, I understood that there is the following “problem”:

    in the comments of the post about the “protein in the blood”, and more than once, questions have been asked about the AST / ALT ratio or, in other words, the De Ritis coefficient.In the comments, I explained, no, fears and misunderstandings remain, there are still alarming messages in a personal message.

    Guys, girls, I ask you, if you liked the post, then please, study other posts, do not ask questions “from the bulldozer”, “for luck.” And with us (Mornatural) remain those who love detailed information, well, not counting those who are used to cheating and “writing” quick “their” posts from ready-made material (

    I will answer this question (about the ratio-retio AST / ALT) ONE sentence.But to begin with, I would like to note that with a sad smile, sometimes with a very wide (sorry (!), I can’t help it) it is read when girls create a problem for themselves out of the blue. Yes, it would be fine for myself, so they are still beginning to diligently look for her from their children.

    REMEMBER! I quote this from official sources in English and Russian, I do not even write with my proposal))

    “The calculation of the de Ritis coefficient is advisable ONLY when the AST and / or ALT go beyond the reference values.”

    “ONLY” when, once again, ALT OR / AND AST, by themselves, ALREADY, ABOVE normal reference values!

    A NOT when they are within the normal range, and you are trying to calculate their ratio (retio).

    Please do yourself a favor and stop escalating where you want to enjoy life! ) If you read something similar from Nutri, then I think that you probably did not understand the info.
    And if you took this from a source, the cat claims to be educational, and even professional info and consider the ratio at normal values ​​of AST and ALT, then they are not Nutri, but “inside”.

    That’s it! This is the meaning of this post. Details below.

    I suggest a little “walk” on the lab tests “liver panel” (let’s call it so):

    AST, ALT – enzymes in liver cells, when liver cells were destroyed, the levels of these enzymes increased in the blood. I would like to draw your attention to the fact that the cells “collapsed” are an anatomical / structural disorder of the organ / tissues, these are not functional values, we cannot judge the functions of the liver by AST and ALT.

    (THIS IS IMPORTANT, I explain this more than once during consultations, there are other tests on liver functionality.I think there will be more of them over time.

    Ultrasound – also will not show functional disorders, more structural, anatomical. Liver enlargement, calcification, uneven edges, etc. Will not show how the liver copes with ammonia, or the lag of phase 1 of detoxification from the second, or how glutathione conjugation works. Based on this:

    The classic liver lab panel may be excellent, but this does not mean that the liver is functioning at its full 100!).

    ALT – MORE specific for liver cells, but! REMEMBER, it can increase after intense exercise (in a small amount of ALT is present in muscles, kidneys),

    while AST LESS is specific for the liver (this enzyme is found in other tissues: heart and muscle, erythrocytes, kidneys).

    We can divide the panel results on the liver: AST, ALT, GGT, alkaline phosphatase (ALP), bilirubin fractions into 3 categories of problems:

    -Hepatocellular, as I said, liver cells-hepatocytes have collapsed

    -Cholestatic-stagnant bile – the problem occurs in the bile ducts of the liver and / or bile ducts outside the liver.

    -Infiltrative, liver tissue was replaced by something not specific for it, like some kind of formation, infiltration, cyst, etc. We will not analyze these.

    AST, ALT, GGT and ALP are most useful to differentiate hepatocellular disorders from cholestatic ones.

    ALT norms vary in different laboratories, on average, about 40 U / L, but recent studies show that its upper / normal limit should be reduced in lab norms, that is, in terms of ALT, we can build on even its high gr norm, how worth taking into account, in contrast to the AST.

    The boundaries of the norm for wives and the husband are also different, for women, a high gr of the norm will be lower than for a husband.And now they propose to make it somewhere around 21-23 U / L for wives and 29-30 for husbands.

    Abnormal values ​​of AST, ALT can be divided into: “soft” increases, medium (5 or more times) and high (more than 10 times).

    Abnormal values ​​may vary depending on age, gender, ethnicity, and certain medications.

    The ratio of AST to ALT has a LITTLE value in order to find the CAUSE of damage to hepatocytes, with the exception of acute alcoholic hepatitis, in which AST will be 2 times higher than ALT (in 75% of cases), and AST and ALT themselves will be increased quite significantly ( for example, AST may be 100-200, and ALT may even be normal).

    If the ratio (ratio) AST / ALT = 3, then it is strictly associated with acute alcoholic liver damage (toxic liver damage)

    Increased GGT in the case of an increase in AST / ALT more than 2 will support the diagnosis of alcoholic hepatosis. Mothers, sisters, wives, GGT in this case can be used as a marker of abstinence from alcohol.

    In severe alcoholic liver damage, bilirubin and prothrombin time also increase – these are serious markers (additional).Why prothrombin time? The liver produces Vit K, which plays an important role in blood coagulation factors.

    If AST is above 400, and ALT is above 200, then something else is taking place (while I say so, we will not disassemble, hands-on-feet and to a specialist).

    Moderately elevated AST, ALT and their retio (ratio) equal to 1 and LESS will occur in non-alcoholic fatty hepatosis, which, by the way, is a marker of what? Diabetes, metabolic syndrome, insulin resistance. In some, 13% of people with non-alcoholic fatty hepatosis may have normal AST, ALT – subclinical liver disease.We do an ultrasound scan.

    With non-alcoholic fatty hepatosis, GGT may also increase.

    With viral hepatitis, AST and ALT can be significantly increased. Although 16% of patients with Hepatitis C may have normal AST values.

    Despite the fact that in hepatitis ALT activity grows faster and higher than AST, and their ratio becomes less than 0.6, HOWEVER, in case of a poor prognosis, the AST / ALT ratio will, ON THE contrary, increase.

    AST / ALT retio more than 1, in 61% of patients with viral hepatitis and with fibrosis, and in 24% without fibrosis – an unfavorable indicator.

    ONCE AGAIN, Ritis’s rate in this case, we count with VIR Hepatitis – once, and with ABNORMAL indicators of AST, ALT.

    I give a link to a scientific article, a fairly detailed description of the lab tests for the liver, because I know that your info-Russian-language Internet contradicts this one. Rather, it is presented in a simplified way, in general.

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC545762/

    In terms of AST, we are starting not just from high limits of the norm, but from clearly overestimated values.

    For example, AST can be 3 times higher than the norm, and the alkaline phosphatase will be only slightly higher than the norm, say 135 at a rate of 120 U / ml, and this will be typical for hepatocellular lesions (at the level of liver cells).

    In case of obstruction of the biliary tract, cholangitis (inflammation of the bile ducts), the ALP value will be higher than AST and ALT. Once again, with problems with bile outflow, AST and ALT may also be increased, but ALP will be increased to a greater extent. An increase in GGT in the event of an increase in ALP will only support information on cholestasis.

    If the AST is slightly overestimated, it is worth repeating the test in a couple of weeks. That is, we remember, we take into account the height / norms of the ALT gr, but the AST is looking at a clear overestimation – above the norms.

    A slight increase in AST, and even ALT, as high as 5%, can occur with intense sports. That is, in healthy people.

    AST grows at the same time as AST / ALT retio, the Ritis coefficient of more than 2, in this case, may indicate damage to the heart muscle, but there are other tests to confirm or deny damage to heart cells.So? I would not even consider it here, so as not to confuse you.

    Bilirubin in conjunction with ALT, AST:

    In liver diseases, direct and indirect bilirubin may be increased, plus an increase in AST and ALT may also occur.

    With hemolysis, indirect bilirubin is elevated and anemia occurs, and LDH will also be elevated.

    With Gilbert INDIRECT bilirubin is increased. AST and ALT can be increased too, but in the “classic” will be the norm.

    And fasting increases morning bilirubin.

    Blood albumin (such a protein) is also a marker of the LIVER, not just a diet. And we have already discussed this.

    Lowered AST and ALT are usually not considered a problem, but they may indicate a deficiency of vit B6 (see below), but low albumin, yes, an abnormal result.

    If AST and ALT are enzymes, then they catalyze something (speed up certain reactions) and affect the Krebs cycle, by the way, and those who listened to our webinar and read the IG message “base”, remember that almost all enzymes have their own cofactors (coenzymes-copilots), and so I give you this “Tip” (useful secret) – they are p-5-p (vit B6 in active form) are dependent! Especially ALT.

    Consequently, a B6 deficiency (especially in those who love to drink) can lead to increased ratio AST / ALT. Children may have an increase or decrease in retio, not the fact that they drink and they have developed metabolic syndrome, maybe this is again about nutritional deficiencies?

    Moderately and “mildly” elevated AST and ALT, what’s next? We stop drinking alcohol altogether for three weeks and retake the analysis. Possible farming? We stop and retake the analysis. If they still exceed the norm, we take into account ferritin (high) and transferrin saturation (high), autoimmune diseases in young and middle-aged women, exclude hepatitis, celiac disease, check the status of copper and the level of ceruloplasmin (copper toxicity).

    I am not talking about supplementation yet.

    All that I have given here is a “general”, but not bad, with details all the same, cheat sheet, but not an “alphabet” from “a” to “z”. There are many nuances, and the MOST IMPORTANT, symptomatology, anamnesis and the doctor ALL of this takes into account. No need to wipe your brains out to “bald spots”, guessing your analyzes on IG info. And in the IG, not all analyzes can be interpreted, because there are many questions about the anamnesis and an endless correspondence will begin, “what did you take”, “what other diseases”, “and did exercise”, “and lay in the hospital”, “and a diet” , and “which company did you host”, “how do you celebrate and how often?” and so on. And whoever “blurs” something to you in the answers, it is possible only “blurt out”.

    And pozh-that, once again, the entire “panel on the liver” is considered in aggregate, and with abnormal indicators, and not with normal ones.

    Yes, in children, alkaline phosphatase can be increased, their bones are growing.

    As always, I was going to write shortly. Well, that’s why “smart” synopses of “biochemists” are made from us, which are then “even” quoted by doctors)))))

    All my time and my efforts (2:30 am and my adrenal glands have already lost hope and faith in me) I dedicate to my clients and “ordinary” – UNUSUAL for us (Monatural)) OUR subscribers and, of course, beloved Forum users.