What are the common pitfalls in interpreting liver function tests. How do factors like gender, ethnicity, and body mass index affect liver enzyme levels. What are the special considerations for interpreting liver function tests in various medical conditions.

Understanding Liver Function Tests: Beyond the Numbers

Liver function tests (LFTs) are a crucial tool in assessing liver health, but their interpretation requires a nuanced understanding. Contrary to popular belief, these tests primarily assess liver injury rather than liver function. This distinction is vital for healthcare professionals and patients alike to grasp.

The commonly used LFTs include:

• Aspartate aminotransferase (AST)
• Alanine aminotransferase (ALT)
• Alkaline phosphatase (AP)
• Gamma-glutamyltransferase (GGT)
• Bilirubin
• Albumin
• Prothrombin time (PT)

While abnormal LFTs often indicate liver problems, it’s crucial to recognize that normal results don’t always guarantee a healthy liver. For instance, patients with cirrhosis and bleeding esophageal varices can have normal LFTs, highlighting the complexity of liver disease diagnosis.

The Nuances of Aminotransferase Levels: AST and ALT

Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are key markers of hepatocellular injury. However, their interpretation is not always straightforward. Why is this the case? Several factors can influence these enzyme levels, leading to potential misinterpretations.

Factors Affecting Normal Ranges

The normal range for aminotransferase levels can vary based on:

• Gender: Slightly higher in males
• Ethnicity: Slightly higher in non-whites
• Body Mass Index: Slightly higher in obese individuals

Understanding these variations is crucial for accurate interpretation. For example, a mildly elevated ALT level (less than 1.5 times normal) could be within the normal range for certain individuals based on these factors.

Chronic vs. Acute Liver Disease

In chronic liver diseases such as hepatitis C and cirrhosis, serum ALT levels may not accurately reflect the extent of liver inflammation. Why is this? In chronic conditions, liver cell death often occurs through apoptosis (programmed cell death) rather than necrosis. Apoptotic cells may produce fewer enzymes as they die, potentially leading to lower AST and ALT levels despite ongoing liver damage.

Alcoholic Hepatitis: A Diagnostic Challenge

Alcoholic hepatitis presents a unique challenge in LFT interpretation. How does it differ from other forms of hepatitis? Unlike typical hepatitis presentations, alcoholic hepatitis can mimic cholestatic conditions, making diagnosis tricky.

Key Characteristics of Alcoholic Hepatitis in LFTs

• Laboratory values may appear cholestatic
• Symptoms can mimic cholecystitis
• Minimal elevations of AST and ALT are common
• AST levels are typically higher than ALT levels

When encountering a patient with suspected alcoholic hepatitis, it’s crucial to consider the overall clinical picture alongside LFT results. An AST level greater than 500 U per L is unlikely to result from alcohol intake alone, and other causes, such as acetaminophen toxicity, should be considered in heavy drinkers.

Biliary Obstruction: When LFTs Mimic Acute Hepatitis

Biliary obstruction, particularly due to common bile duct stones, can present a diagnostic dilemma. How can it be distinguished from acute hepatitis? The key lies in understanding the temporal relationship between enzyme elevations.

Temporal Pattern of Enzyme Elevation in Biliary Obstruction

In cases of common bile duct stones:

• AST and ALT levels become elevated immediately
• Alkaline phosphatase (AP) and gamma-glutamyltransferase (GGT) elevations are delayed, often by several days

This pattern can lead to misdiagnosis of acute hepatitis in patients who present soon after passing common bile duct stones. Awareness of this temporal discrepancy is crucial for accurate diagnosis and appropriate management.

Isolated Enzyme Elevations: Decoding the Signals

Isolated elevations of specific liver enzymes can provide valuable diagnostic clues. How should these be interpreted? Let’s explore some common scenarios:

Isolated GGT Elevation

An isolated elevation of GGT may be induced by:

• Alcohol consumption
• Aromatic medications

Importantly, this elevation often occurs without actual liver disease. It’s a reminder that not all enzyme elevations indicate liver pathology.

Isolated Alkaline Phosphatase (AP) Elevation

In asymptomatic patients with normal GGT levels, an isolated AP elevation may suggest:

• Bone growth or injury
• Primary biliary cirrhosis
• Late pregnancy (AP levels naturally rise)

Isolated Unconjugated Bilirubin Elevation

When encountering an isolated elevation of unconjugated bilirubin, consider:

• Gilbert syndrome
• Hemolysis

These conditions often do not require extensive evaluation in asymptomatic patients.

Beyond Enzymes: Assessing Overall Liver Function

While enzyme levels provide valuable information about liver injury, assessing overall liver function requires a broader approach. Which parameters are most useful for this purpose? The key indicators of liver function are:

• Serum albumin
• Bilirubin
• Prothrombin time (PT)

These parameters can be applied in the modified Child-Turcotte grading system to assess overall hepatic function. This system provides a more comprehensive view of liver health beyond simple enzyme levels.

Interpreting Albumin Levels

Low albumin levels are not exclusive to liver disease. What other conditions can cause hypoalbuminemia? Consider the following causes:

• Acute or chronic inflammation
• Urinary loss
• Severe malnutrition
• Gastrointestinal loss (e.g., colitis or some uncommon small bowel diseases)

It’s also important to note that normal albumin values are lower during pregnancy.

The Role of Blood Ammonia Levels in Liver Assessment

Blood ammonia levels are often considered in liver function assessment, particularly in cases of suspected hepatic encephalopathy. However, their interpretation requires caution. Are elevated ammonia levels always indicative of hepatic encephalopathy?

Key Points About Blood Ammonia Levels

• Not necessarily elevated in patients with hepatic encephalopathy
• Most useful in patients with altered mental status of new onset or unknown origin
• Should be interpreted in conjunction with other clinical findings and laboratory tests

The relationship between blood ammonia levels and hepatic encephalopathy is complex. While elevated levels can support the diagnosis, normal levels do not rule it out. This underscores the importance of comprehensive clinical assessment in liver disease diagnosis.

Special Considerations in LFT Interpretation

Interpreting liver function tests requires consideration of various factors beyond the raw numbers. What special circumstances can affect LFT results? Let’s explore some key considerations:

Gender Differences

Males typically have slightly higher aminotransferase levels compared to females. This difference should be taken into account when interpreting borderline results.

Ethnicity

Non-white individuals may have slightly higher normal ranges for aminotransferase levels. This variation highlights the importance of using appropriate reference ranges for different populations.

Body Mass Index (BMI)

Obese individuals often have higher baseline aminotransferase levels. How does this affect interpretation? A mildly elevated ALT in an obese patient may not necessarily indicate liver disease and should be interpreted in the context of overall health status.

Pregnancy

Pregnancy can affect several liver function parameters:

• Alkaline phosphatase levels naturally rise in late pregnancy
• Normal albumin values are lower during pregnancy

These physiological changes must be considered when interpreting LFTs in pregnant women to avoid misdiagnosis.

Muscle Injury or Myopathy

Mild elevations in ALT levels can sometimes be attributed to muscle injury or myopathy rather than liver disease. How can this be distinguished? Considering the patient’s history of physical activity or muscle disorders is crucial in these cases.

Understanding these special considerations is essential for accurate interpretation of liver function tests. It underscores the importance of considering the whole patient, not just the numbers on a lab report.

Practical Approach to LFT Interpretation

Given the complexities involved in interpreting liver function tests, a systematic approach is crucial. How can healthcare professionals navigate these challenges effectively? Here’s a practical guide:

1. Consider the patient’s clinical context:
   • Age, gender, ethnicity, and BMI
   • Presence of symptoms
   • Medical history, including alcohol use and medications
2. Evaluate the pattern of abnormalities:
   • Hepatocellular (predominant AST/ALT elevation)
   • Cholestatic (predominant AP/GGT elevation)
   • Mixed pattern
3. Assess the degree of elevation:
   • Mild (less than 5 times upper limit of normal)
   • Moderate (5-10 times upper limit of normal)
   • Severe (more than 10 times upper limit of normal)
4. Consider special scenarios:
   • Isolated enzyme elevations
   • Discrepancies between clinical presentation and LFT results
5. Evaluate markers of liver function:
   • Albumin
   • Bilirubin
   • Prothrombin time
6. Determine the need for further testing:
   • Imaging studies
   • Viral hepatitis serologies
   • Autoimmune markers
   • Liver biopsy

By following this approach, clinicians can navigate the complexities of LFT interpretation more effectively, leading to more accurate diagnoses and appropriate management strategies.

The Future of Liver Function Assessment

As our understanding of liver physiology and pathology continues to evolve, so too do the methods for assessing liver function. What advancements are on the horizon for liver function testing?

Emerging Biomarkers

Research is ongoing into new biomarkers that may provide more specific and sensitive indicators of liver health. These include:

• MicroRNAs: Small, non-coding RNA molecules that may serve as early indicators of liver injury
• Cytokeratin-18 fragments: Markers of apoptosis that may help distinguish between different forms of liver disease
• Enhanced liver fibrosis (ELF) test: A panel of markers that assess liver fibrosis more accurately than traditional tests

Advanced Imaging Techniques

Imaging technologies are also advancing, offering new ways to assess liver function and structure:

• Elastography: Techniques like FibroScan that measure liver stiffness as an indicator of fibrosis
• Magnetic resonance elastography (MRE): Provides a more comprehensive assessment of liver fibrosis compared to ultrasound-based elastography
• Contrast-enhanced ultrasound: Offers detailed visualization of liver lesions and blood flow

Artificial Intelligence and Machine Learning

The integration of AI and machine learning algorithms with liver function data holds promise for more accurate interpretation and prediction of liver disease progression. These technologies could potentially:

• Identify subtle patterns in LFT results that human interpreters might miss
• Predict the likelihood of liver disease progression based on LFT trends over time
• Assist in differentiating between various liver conditions with similar LFT profiles

As these advancements continue to develop, they have the potential to revolutionize liver function assessment, leading to earlier detection of liver disease and more personalized treatment approaches. However, it’s important to note that while these technologies show promise, they will likely complement rather than replace traditional LFTs and clinical judgment in the foreseeable future.

The interpretation of liver function tests remains a complex but crucial aspect of clinical medicine. By understanding the nuances of these tests, considering special circumstances, and staying abreast of emerging technologies, healthcare professionals can more accurately assess liver health and provide optimal care for their patients.

Special Considerations in Interpreting Liver Function Tests

DAVID E. JOHNSTON, M.D.

A number of pitfalls can be encountered in the interpretation of common blood liver function tests. These tests can be normal in patients with chronic hepatitis or cirrhosis. The normal range for aminotransferase levels is slightly higher in males, nonwhites and obese persons. Severe alcoholic hepatitis is sometimes confused with cholecystitis or cholangitis. Conversely, patients who present soon after passing common bile duct stones can be misdiagnosed with acute hepatitis because aminotransferase levels often rise immediately, but alkaline phosphatase and γ-glutamyltransferase levels do not become elevated for several days. Asymptomatic patients with isolated, mild elevation of either the unconjugated bilirubin or the γ-glutamyltransferase value usually do not have liver disease and generally do not require extensive evaluation. Overall hepatic function can be assessed by applying the values for albumin, bilirubin and prothrombin time in the modified Child-Turcotte grading system.

The commonly used liver function tests (LFTs) primarily assess liver injury rather than hepatic function. Indeed, these blood tests may reflect problems arising outside the liver, such as hemolysis (elevated bilirubin level) or bone disease (elevated alkaline phosphatase [AP] level).

Abnormal LFTs often, but not always, indicate that something is wrong with the liver, and they can provide clues to the nature of the problem. However, normal LFTs do not always mean that the liver is normal. Patients with cirrhosis and bleeding esophageal varices can have normal LFTs. Of the routine LFTs, only serum albumin, bilirubin and prothrombin time (PT) provide useful information on how well the liver is functioning.

The general subject of LFTs^1,2 and the differential diagnosis of abnormal LFTs in asymptomatic patients^3–5 have been well reviewed. This article discusses some common pitfalls in the interpretation of LFTs. Hints for interpreting these tests are presented in Table 1.

Situation	Comments
Mildly elevated ALT level (less than 1.5 times normal)	ALT value could be normal for gender, ethnicity or body mass index.
	Consider muscle injury or myopathy.
Alcoholic hepatitis	Laboratory values can appear cholestatic, and symptoms can mimic cholecystitis.
	Minimal elevations of AST and ALT often occur.
AST level greater than 500 U per L	The AST elevation is unlikely to result from alcohol intake alone.
	In a heavy drinker, consider acetaminophen toxicity.
Common bile duct stone	Condition can simulate acute hepatitis
	AST and ALT become elevated immediately, but elevation of AP and GGT is delayed.
Isolated elevation of GGT level	This situation may be induced by alcohol and aromatic medications, usually with no actual liver disease.
Isolated elevation of AP level (asymptomatic patient with normal GGT level)	Consider bone growth or injury, or primary biliary cirrhosis.
	AP level rises in late pregnancy.
Isolated elevation of unconjugated bilirubin level	Consider Gilbert syndrome or hemolysis.
Low albumin level	Low albumin is most often caused by acute or chronic inflammation, urinary loss, severe malnutrition or liver disease; it is sometimes caused by gastrointestinal loss (e. g., colitis or some uncommon small bowel disease).
	Normal values are lower in pregnancy.
Blood ammonia level	Blood ammonia values are not necessarily elevated in patients with hepatic encephalopathy.
	Determination of blood ammonia levels is most useful in patients with altered mental status of new onset or unknown origin.

Markers of Hepatocellular Injury

The most commonly used markers of hepatocyte injury are aspartate aminotransferase (AST, formerly serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT, formerly serum glutamate-pyruvate transaminase [SGPT]). While ALT is cytosolic, AST has both cytosolic and mitochondrial forms.

Hepatocyte necrosis in acute hepatitis, toxic injury or ischemic injury results in the leakage of enzymes into the circulation. However, in chronic liver diseases such as hepatitis C and cirrhosis, the serum ALT level correlates only moderately well with liver inflammation. In hepatitis C, liver cell death occurs by apoptosis (programmed cell death) as well as by necrosis. Hepatocytes dying by apoptosis presumably synthesize less AST and ALT as they wither away. This probably explains why at least one third of patients infected with hepatitis C virus have persistently normal serum ALT levels despite the presence of inflammation on liver biopsy.^6,7 Patients with cirrhosis often have normal or only slightly elevated serum AST and ALT levels. Thus, AST and ALT lack some sensitivity in detecting chronic liver injury. Of course, AST and ALT levels tend to be higher in cirrhotic patients with continuing inflammation or necrosis than in those without continuing liver injury.

As markers of hepatocellular injury, AST and ALT also lack some specificity because they are found in skeletal muscle. Levels of these aminotransferases can rise to several times normal after severe muscular exertion or other muscle injury, as in polymyositis,⁸ or in the presence of hypothyroidism, which can cause mild muscle injury and the release of aminotransferases. In fact, AST and ALT were once used in the diagnosis of myocardial infarction.

Slight AST or ALT elevations (within 1.5 times the upper limits of normal) do not necessarily indicate liver disease. Part of this ambiguity has to do with the fact that unlike the values in many other biochemical tests, serum AST and ALT levels do not follow a normal bell-shaped distribution in the population.⁹ Instead, AST and ALT values have a skewed distribution characterized by a long “tail” at the high end of the scale (Figure 1).⁵ For example, the mean values for ALT are very similar from one population to another, but the degree to which the distribution is skewed varies by gender and ethnicity. The ALT distributions in males and nonwhites (i.e., blacks and Hispanics) tend to have a larger tail at the high end, so that more values fall above the upper limits of normal set for the average population.^10,11

AST and ALT values are higher in obese patients, probably because these persons commonly have fatty livers. ¹² ALT levels have been noted to decline with weight loss.¹³ Depending on the physician’s point of view, the upper limits of normal for AST and ALT levels could be set higher for more obese persons.

Rare individuals have chronically elevated AST levels because of a defect in clearance of the enzyme from the circulation.¹⁴ For both AST and ALT, the average values and upper limits of normal in patients undergoing renal dialysis are about one half of those found in the general population.¹⁵ Mild elevations of ALT or AST in asymptomatic patients can be evaluated efficiently by considering alcohol abuse, hepatitis B, hepatitis C and several other possible diagnoses (Table 2).⁵

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Various liver diseases are associated with typical ranges of AST and ALT levels (Figure 2). ALT levels often rise to several thousand units per liter in patients with acute viral hepatitis. The highest ALT levels—often more than 10,000 U per L—are usually found in patients with acute toxic injury subsequent to, for example, acetaminophen overdose or acute ischemic insult to the liver. AST and ALT levels usually fall rapidly after an acute insult.

Lactate dehydrogenase (LDH) is less specific than AST and ALT as a marker of hepatocyte injury. However, it is worth noting that LDH is disproportionately elevated after an ischemic liver injury.¹⁶

It is especially important to remember that in patients with acute alcoholic hepatitis, the serum AST level is almost never greater than 500 U per L and the serum ALT value is almost never greater than 300 U per L. The reasons for these limits on AST and ALT elevations are not well understood. In typical viral or toxic liver injury, the serum ALT level rises more than the AST value, reflecting the relative amounts of these enzymes in hepatocytes. However, in alcoholic hepatitis, the ratio of AST to ALT is greater than 1 in 90 percent of patients and is usually greater than 2.¹⁷ The higher the AST-to-ALT ratio, the greater the likelihood that alcohol is contributing to the abnormal LFTs. In the absence of alcohol intake, an increased AST-to-ALT ratio is often found in patients with cirrhosis.

The elevated AST-to-ALT ratio in alcoholic liver disease results in part from the depletion of vitamin B₆ (pyridoxine) in chronic alcoholics.¹⁸ ALT and AST both use pyridoxine as a coenzyme, but the synthesis of ALT is more strongly inhibited by pyridoxine deficiency than is the synthesis of AST. Alcohol also causes mitochondrial injury, which releases the mitochondrial isoenzyme of AST.

Patients with alcoholic hepatitis can present with jaundice, abdominal pain, fever and a minimally elevated AST value, thereby leading to a misdiagnosis of cholecystitis. This is a potentially fatal mistake given the high surgical mortality rate in patients with alcoholic hepatitis. ¹⁹

Markers of Cholestasis

Cholestasis (lack of bile flow) results from the blockage of bile ducts or from a disease that impairs bile formation in the liver itself. AP and γ-glutamyltransferase (GGT) levels typically rise to several times the normal level after several days of bile duct obstruction or intrahepatic cholestasis. The highest liver AP elevations—often greater than 1,000 U per L, or more than six times the normal value—are found in diffuse infiltrative diseases of the liver such as infiltrating tumors and fungal infections.

Diagnostic confusion can occur when a patient presents within a few hours after acute bile duct obstruction from a gallstone. In this situation, AST and ALT levels often reach 500 U per L or more in the first hours and then decline, whereas AP and GGT levels can take several days to rise.

Both AP and GGT levels are elevated in about 90 percent of patients with cholestasis.²⁰ The elevation of GGT alone, with no other LFT abnormalities, often results from enzyme induction by alcohol or aromatic medications in the absence of liver disease. The GGT level is often elevated in persons who take three or more alcoholic drinks (45 g of ethanol or more) per day.²¹ Thus, GGT is a useful marker for immoderate alcohol intake. Phenobarbital, phenytoin (Dilantin) and other aromatic drugs typically cause GGT elevations of about twice normal. A mildly elevated GGT level is a typical finding in patients taking anticonvulsants and by itself does not necessarily indicate liver disease.^22,23

Serum AP originates mostly from liver and bone, which produce slightly different forms of the enzyme. The serum AP level rises during the third trimester of pregnancy because of a form of the enzyme produced in the placenta. When serum AP originates from bone, clues to bone disease are often present, such as recent fracture, bone pain or Paget’s disease of the bone (often found in the elderly). Like the GGT value, the AP level can become mildly elevated in patients who are taking phenytoin.^22,23

If the origin of an elevated serum AP level is in doubt, the isoenzymes of AP can be separated by electrophoresis. However, this process is expensive and usually unnecessary because an elevated liver AP value is usually accompanied by an elevated GGT level, an elevated 5′-nucleotidase level and other LFT abnormalities.

In one study,²⁴ isolated AP elevations were evaluated in an unselected group of patients at a Veterans Affairs hospital. Most mild AP elevations (less than 1.5 times normal) resolved within six months, and almost all greater elevations had an evident cause that was found on routine clinical evaluation.

Persistently elevated liver AP values in asymptomatic patients, especially women, can be caused by primary biliary cirrhosis, which is a chronic inflammatory disorder of the small bile ducts. Serum antimitochondrial antibody is positive in almost all of these patients.

Indicators of How Well the Liver Functions

BILIRUBIN

Bilirubin results from the enzymatic breakdown of heme. Unconjugated bilirubin is conjugated with glucuronic acid in hepatocytes to increase its water solubility and is then rapidly transported into bile. The serum conjugated bilirubin level does not become elevated until the liver has lost at least one half of its excretory capacity. Thus, a patient could have obstruction of either the left or right hepatic duct without a rise in the bilirubin level.

Because the secretion of conjugated bilirubin into bile is very rapid in comparison with the conjugation step, healthy persons have almost no detectable conjugated bilirubin in their blood. Liver disease mainly impairs the secretion of conjugated bilirubin into bile. As a result, conjugated bilirubin is rapidly filtered into the urine, where it can be detected by a dipstick test. The finding of bilirubin in urine is a particularly sensitive indicator of the presence of an increased serum conjugated bilirubin level.

In many healthy persons, the serum unconjugated bilirubin is mildly elevated to a concentration of 2 to 3 mg per dL (34 to 51 μmol per L) or slightly higher, especially after a 24-hour fast. If this is the only LFT abnormality and the conjugated bilirubin level and complete blood count are normal, the diagnosis is usually assumed to be Gilbert syndrome, and no further evaluation is required. Gilbert syndrome was recently shown to be related to a variety of partial defects in uridine diphosphate-glucuronosyl transferase, the enzyme that conjugates bilirubin.²⁵

Mild hemolysis, such as that caused by hereditary spherocytosis and other disorders, can also result in elevated unconjugated bilirubin values, but hemolysis is not usually present if the hematocrit and blood smear are normal. The presence of hemolysis can be confirmed by testing other markers, such as haptoglobin, or by measuring the reticulocyte count.

Severe defects in bilirubin transport and conjugation can lead to markedly elevated unconjugated bilirubin levels, which can cause serious neurologic damage (kernicterus) in infants. However, no serious form of liver disease in adults causes elevation of unconjugated bilirubin levels in the blood without also causing elevation of conjugated bilirubin values.

When a patient has prolonged, severe biliary obstruction followed by the restoration of bile flow, the serum bilirubin level often declines rapidly for several days and then slowly returns to normal over a period of weeks. The slow phase of bilirubin clearance results from the presence of delta-bilirubin, a form of bilirubin chemically attached to serum albumin.²⁶ Because albumin has a half-life of three weeks, delta-bilirubin clears much more slowly than bilirubin-glucuronide. Clinical laboratories can measure delta-bilirubin concentrations, but such measurements are usually unnecessary if the physician is aware of the delta-bilirubin phenomenon.

ALBUMIN

Although the serum albumin level can serve as an index of liver synthetic capacity, several factors make albumin concentrations difficult to interpret.²⁷ The liver can synthesize albumin at twice the healthy basal rate and thus partially compensate for decreased synthetic capacity or increased albumin losses. Albumin has a plasma half-life of three weeks; therefore, serum albumin concentrations change slowly in response to alterations in synthesis. Furthermore, because two thirds of the amount of body albumin is located in the extravascular, extracellular space, changes in distribution can alter the serum concentration.

In practice, patients with low serum albumin concentrations and no other LFT abnormalities are likely to have a nonhepatic cause for low albumin, such as proteinuria or an acute or chronic inflammatory state. Albumin synthesis is immediately and severely depressed in inflammatory states such as burns, trauma and sepsis, and it is commonly depressed in patients with active rheumatic disorders or severe end-stage malnutrition. In addition, normal albumin values are lower in pregnancy.

PROTHROMBIN TIME

The liver synthesizes blood clotting factors II, V, VII, IX and X. The prothrombin time (PT) does not become abnormal until more than 80 percent of liver synthetic capacity is lost. This makes PT a relatively insensitive marker of liver dysfunction. However, abnormal PT prolongation may be a sign of serious liver dysfunction. Because factor VII has a short half-life of only about six hours, it is sensitive to rapid changes in liver synthetic function. Thus, PT is very useful for following liver function in patients with acute liver failure.

An elevated PT can result from a vitamin K deficiency. This deficiency usually occurs in patients with chronic cholestasis or fat malabsorption from disease of the pancreas or small bowel. A trial of vitamin K injections (e.g., 5 mg per day administered subcutaneously for three days) is the most practical way to exclude vitamin K deficiency in such patients. The PT should improve within a few days.

BLOOD AMMONIA

Measurement of the blood ammonia concentration is not always useful in patients with known or suspected hepatic encephalopathy. Ammonia contributes to hepatic encephalopathy; however, ammonia concentrations are much higher in the brain than in the blood and therefore do not correlate well.²⁸ Furthermore, ammonia is not the only waste product responsible for encephalopathy. Thus, blood ammonia concentrations show only a mediocre correlation with the level of mental status in patients with liver disease. It is not unusual for the blood ammonia concentration to be normal in a patient who is in a coma from hepatic encephalopathy.

Blood ammonia levels are best measured in arterial blood because venous concentrations can be elevated as a result of muscle metabolism of amino acids. Blood ammonia concentrations are most useful in evaluating patients with stupor or coma of unknown origin. It is not necessary to evaluate blood ammonia levels routinely in patients with known chronic liver disease who are responding to therapy as expected.

Grading Liver Function by Child-Turcotte Class

In communicating among themselves, many physicians use the Child-Turcotte class as modified by Pugh, often termed the “Child class,” to convey information about overall liver function and prognosis (Table 3).²⁹ This grading system can be used to predict overall life expectancy and surgical mortality in patients with cirrhosis and other liver diseases.³⁰

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For elective general abdominal surgery, perioperative mortality is in the neighborhood of several percent for patients who fall into the Child class A, 10 to 20 percent for those in class B and approximately 50 percent for those in class C.³¹ These percentages must be balanced by prognostic considerations when transplantation becomes an option. The presence of cirrhosis by itself is not an indication for liver transplantation, and transplantation is rarely performed in patients who fall into Child class A. For example, the 10-year survival rate is as high as 80 percent in patients with hepatitis C and cirrhosis who have Child class A liver function and no variceal bleeding.³² However, once patients with any type of liver disease fall into the Child-Turcotte class B or class C category, survival is significantly reduced and transplantation should be considered.

What To Do About Fluctuating Liver Enzyme Levels

Liver enzymes are proteins the liver produces. The amount of these proteins in your blood is a good indication of your liver’s overall health. But elevated liver enzyme levels do not always mean serious liver damage or disease.

Sometimes, factors such as hormonal changes or reactions to medications can cause temporarily elevated liver enzyme levels. Elevated levels caused by these factors will generally return to normal in about 2 to 4 weeks without treatment.

Your liver makes proteins called liver enzymes that help your body perform necessary functions. For instance, liver enzymes help your body:

• fight infections
• make coagulation proteins that are necessary for blood clotting
• break down the food you eat
• break down toxins

Your liver makes several liver enzymes, including:

• Aspartate transaminase (AST)
• Alkaline phosphatase (ALP)
• Alanine transaminase (ALT)
• Gamma-glutamyl transferase (GGT)

These liver enzyme levels are a good indicator of how well your liver is functioning. A liver panel test checks liver enzyme levels in your blood.

A healthcare professional might order this test as part of routine blood work, as a way to monitor you if you’re at risk for liver disease, or as a diagnostic test if you have symptoms of liver disease or liver damage.

There are many reasons liver enzyme levels can change. Some causes are temporary and will resolve on their own. Other causes are more serious and will require medical treatment.

Temporary causes of changes in liver enzyme levels include:

• Hormones: Fluctuations in your liver levels can occur during your menstrual cycle and pregnancy.
• Certain medications: Some medications, including acetaminophen, antibiotics, and some cholesterol-lowering medications, can elevate your liver enzyme levels.
• Herbal supplements: Supplements such as iron, vitamin A, comfrey, and chaparral can elevate liver enzyme levels.
• Alcohol: Heavy drinking can raise your liver enzyme levels.

Causes of elevated liver enzyme levels that are more likely to be chronic include:

• Fatty liver disease: Heavy alcohol use, obesity, and a range of other factors can cause fatty liver disease. No matter the cause, fatty liver disease raises your liver enzyme levels.
• Hemochromatosis: Hemochromatosis is a rare condition that occurs when your body builds up too much iron. Elevated liver enzyme levels can be a symptom of the condition.
• All types of hepatitis: Any type of hepatitis, including hepatitis A, hepatitis B, hepatitis C, autoimmune hepatitis, and alcoholic hepatitis, causes liver inflammation and elevated liver enzymes.
• Cirrhosis: Cirrhosis is chronic liver damage. This damage causes elevated levels of liver enzymes.
• Liver cancer: Cancer that impacts your liver will also affect your liver enzyme levels.
• Hemolysis: Hemolysis is a type of anemia that occurs when your red blood cells are destroyed. It’s sometimes seen with alcohol-related liver diseases, and it can cause changes to liver enzyme levels.
• Thyroid disease: Hyperthyroidism can sometimes cause high levels of liver enzymes.
• Metabolic syndrome: Metabolic syndrome is a term that refers to a group of conditions that raise your risk of diabetes, heart disease, and stroke. These conditions include high blood pressure, high cholesterol, high blood sugar, and carrying excess weight around your midsection. People with metabolic syndrome may also have elevated liver levels.

The exact threshold for what is considered an elevated level or a typical level depends on your age, gender, health goals, and the values used by the specific lab. You can see some standard thresholds below.

• AST: under 36 U/L
• ALP: between 20 and 140 U/L
• ALT: under 25 U/L for women or under 33 U/L for men
• GGT: between 5 and 40 U/L

A liver function test might also measure:

• Albumin: between 35 and 50 U/L
• Bilirubin: between 0. 1 and 1.2 mg/dl

These values are not enzymes, but they’re also important chemicals made by your liver.

A liver function test is a standard blood draw. It can be done during a regular office visit. You don’t generally need any special preparation before a liver function test, although a doctor might ask you to fast for 12 to 24 hours before the blood draw. You can read more about liver function tests here.

The treatment for elevated liver enzymes depends on the cause. In many cases, liver enzyme levels return to normal on their own within about a month. You might need to switch medications, stop taking a supplement, or cut back on drinking if you drink, but you will not need a treatment plan.

In other cases, your doctor might need to treat the condition that’s raising your liver enzyme levels. They might order more tests, such as imaging tests, to get a better look at your liver or blood tests. They might also order a liver biopsy. Depending on your results, you might be referred to a specialist. Treatment will depend on your final diagnosis.

If you’re concerned your liver enzyme levels might be elevated, you might consider making some lifestyle changes at home, such as:

• reducing or eliminating alcohol from your diet
• being cautious about the medications and supplements you take
• staying active, including exercising regularly
• trying to add liver-friendly foods to your diet
• maintaining a moderate weight

Liver enzyme levels are an important indication of your liver’s health. When your enzyme levels are too high, it can be a symptom of liver damage or disease.

Some causes of elevated liver levels, such as hormonal changes or certain medications, are temporary and might resolve without treatment. Other causes are more serious and can include conditions such as cirrhosis, hepatitis C, and liver cancer.

Treatment for high liver enzyme levels depends on the cause.

Liver diagnostics – ALT blood test

Alanine aminotransferase (ALT) is an enzyme found in cells. Its main amount is concentrated in the liver, so the test is used as an indicator of the presence of liver diseases. It is used to diagnose cirrhosis and hepatitis in combination with other tests. The main function of the enzyme in the body is the release of energy from food. Normally, the concentration of the enzyme should not exceed 45 U / l. This rate is set for adults over 18 years of age. In children, normal values ​​vary with age.

Indications for examination

An examination of the liver condition is performed if the patient has the following symptoms:

• fatigue;
• pain in the right hypochondrium;
• jaundice of the sclera and skin;
• enlargement of the abdomen;
• dark urine;
• vomiting and nausea;
• pruritus.

Indicators may increase in the following cases: with the abuse of alcohol, hereditary predisposition to liver disease, viral hepatitis, taking a number of medications. The test is often included in a preventive examination program.

General

Normally, only a small amount of the enzyme can be present in the bloodstream. The release of a large amount of ALT occurs with large-scale cell damage. This organ is located in the abdominal cavity (top right), takes part in many vital processes. The liver is involved in the processing of nutrients, the synthesis of many proteins, the production of bile, and it breaks down toxic substances that are potentially harmful to the body.

An ALT blood test is necessary to check the condition of the liver in patients who are taking drugs that are potentially harmful to this organ and in patients with hepatitis. It should be borne in mind that an increase in the level of this enzyme is not always associated with liver pathologies. It is also found in other organs, so an increase in performance may indicate their pathology.

ALT and AST are the most important liver indications . In many cases, tests for the amount of these enzymes are done at the same time. In the diagnosis, both indicators and their ratio are used (it can be used to determine the cause of liver damage). During treatment, tests are carried out several times at regular intervals to monitor the dynamics of the patient’s condition.

Interpretation of results

Reference values ​​are determined according to the age and sex of the patient. In men, normal values ​​may be higher than in women. As a rule, the results of the study are ready the next day after donating blood. For their interpretation, you must consult a doctor. Self-medication is unacceptable, as it can cause irreparable harm to health.

Reasons for the increase in ALT:

• mononucleosis;
• alcoholism;
• cirrhosis of the liver;
• malignant neoplasm;
• hepatitis;
• heart failure;
• muscle injury;
• kidney damage;
• sunstroke.

Taking certain medications (if the drugs are taken for a long time) can also lead to an increase in indicators. This test, as a rule, is not prescribed independently, but in combination with other studies. This makes it possible to obtain the most complete picture of the patient’s health, make an accurate diagnosis and select the most effective treatment regimen. Sometimes, in the presence of diseases, laboratory parameters of the state of the liver remain within the normal range. In such cases, additional examination is required.

ALT (ALT, Alanine aminotransferase, alanine transaminase, SGPT, Alanine aminotransferase)

Alanine aminotransferase (AlAT, ALT) is an intracellular enzyme, the content of which in the blood of healthy people is low. It is mainly found in the cells of the liver, myocardium, skeletal muscles, pancreas. When cells containing ALT are damaged or destroyed, the enzyme is released into the bloodstream, and its concentration in the blood increases.

Determination of the level of alanine aminotransferase is carried out for the diagnosis of liver diseases and dynamic monitoring of their treatment. The analysis is performed for suspected acute or chronic hepatitis of viral or toxic etiology, cirrhosis of the liver, primary tumors, or metastatic liver disease.

The growth of alanine aminotransferase in the blood in hepatitis is noted much earlier than the onset of the icteric stage, which makes it possible to identify the pathology at the initial stage.

As part of a screening examination (preventive examination of persons who do not have complaints) to assess the state of the liver, before planned hospitalization and surgical treatment, an analysis for ALT is prescribed together with another enzyme – AsAT (aspartate aminotransferase).

The level of ALT together with other enzymes is evaluated in diseases of the pancreas and gallbladder – pancreatitis, cholecystitis, cholelithiasis; if there are complaints of unexplained general weakness, fatigue, yellowness of the skin and sclera, abdominal pain, including a feeling of heaviness in the right hypochondrium, nausea, vomiting.

In addition, the ALT level is taken into account in myocardial infarction and myocarditis, although in cases of heart damage it is only of secondary importance. The study is prescribed for suspected myositis, myodystrophy, when complaints of muscle pain cannot be explained by injuries or excessive physical activity.

Donation is a mandatory reason for testing for ALT.

ALT values ​​are assessed in any chronic disease, before prescribing drug therapy, for example, antitumor, anti-tuberculosis drugs, to assess the initial state of the liver and over time to assess drug tolerance.

Preparation for the procedure

It is better to take the test in the morning on an empty stomach (after an 8-14 hour break after the last meal).

Drinking water is allowed.

If necessary, it is permissible to donate blood 4-6 hours after a light meal.

On the eve it is desirable to avoid physical and emotional overload, overeating.

Avoid alcohol intake 5-6 days before the test.

Avoid smoking 30 minutes before blood sampling.

Deadline

The survey is completed within one business day.

What can affect the results

Intense physical activity the day before and even a few days before the test can lead to damage to muscle tissue (the so-called tear of muscle fibers) and, accordingly, an increase in the level of ALT. For the same reason, the analysis given after the injury is not informative.

Taking alcohol, certain drugs (antibiotics, non-steroidal anti-inflammatory drugs, anticancer drugs, oral contraceptives, etc.) often distort the result of the study. The list of medications taken should be discussed with the doctor who ordered the analysis, cancel those that are possible – without risk to health.

ALT (ALT, Alanine aminotransferase, alanine transaminase)

For research, blood is taken from a vein. Usually, ASAT (AST, Aspartate aminotransferase) is determined simultaneously and the ratio of ASAT / AlAT (de Ritis coefficient) is estimated.

You can take a blood test for ALT (ALT, Alanine aminotransferase, alanine transaminase) at the nearest INVITRO medical office. The list of offices where biomaterial is accepted for laboratory testing is presented in the “Addresses” section.

Interpretation of test results contains information for the attending physician and is not a diagnosis. The information in this section should not be used for self-diagnosis or self-treatment. An accurate diagnosis is made by the doctor, using both the results of this examination and the necessary information from other sources: history, results of other examinations, etc.

Normal

Units of measure: U/l.

Reference values ​​

Explanation of indicators

The level of ALT depends on the age and sex of the patient. Minor deviations from the norm, as a rule, do not require drug therapy, and the recommendations associated with them, such as rational nutrition, avoidance of alcohol, etc. should be discussed with your doctor.

The AST/ALAT ratio (de Ritis ratio) is normally between 0.91 and 1.75.

What do low readings mean

A significant decrease in the level of ALT can be detected in severe liver damage, for example, in the terminal stage of liver cirrhosis, when the number of liver cells is significantly reduced.

What do high rates mean

First of all, with an increase in ALT, liver problems should be suspected: fatty hepatosis, hepatitis of viral or toxic etiology, cirrhosis of the liver, liver cancer – primary or metastatic.

The degree of increase in ALT is usually associated with the extent or severity of liver damage, but cannot be considered as a determining factor for the prognosis of the disease. The maximum levels of ALT (and AST) – more than a hundred times higher than the norm, are observed in patients with acute viral and drug-induced hepatitis.

A significant increase in alanine aminotransferase can be observed in acute cholecystitis, cholelithiasis, and acute destructive pancreatitis. Another reason may be the use of hepatotoxic drugs that damage liver cells.

An increase in the level of ALT is detected with extensive injuries of the skeletal muscles, severe myositis and myodystrophy, frequent intramuscular injections.

A less significant increase in ALT is recorded in acute myocardial infarction and myocarditis.

Additional examination in case of deviation of the indicator from the norm

If a change (often an increase) in the level of ALT is detected, patients are consulted

general practitioners

,

gastroenterologists

, hepatologists, infectious disease specialists.

To clarify the diagnosis, in addition to ALT, other liver enzymes (AST, gamma-HT, alkaline phosphatase, bilirubin), clinical blood counts, and markers of viral hepatitis, primarily hepatitis B and hepatitis C, are usually examined.

An ultrasound examination of the abdominal organs is performed, according to indications – computed tomography (CT) with contrast.

If damage to the skeletal muscles is suspected, the CPK enzyme is additionally examined and a rheumatologist is consulted.

If there is a suspicion of damage to the heart muscle, a consultation with a cardiologist is required. Usually, the doctor prescribes additional electrocardiography (ECG), echocardiography, blood test for CF-CPK, troponin I.

O.P. The role of new reference values ​​of alanine aminotransferase in the diagnosis of various forms of non-alcoholic fatty liver disease in patients with metabolic syndrome. Journal of Biomedical Technologies № 1. 2015. P. 9-15.

Clinical guidelines “Liver cancer (hepatocellular)”. Developed by: Association of Oncologists of Russia, Russian Society of Clinical Oncology, Russian Society of Radiologists and Radiologists.