Laboratory liver tests are broadly defined as tests useful in the evaluation and treatment of patients with hepatic dysfunction. The liver carries out metabolism of carbohydrate, protein and fats. Some of the enzymes and the end products of the metabolic pathway which are very sensitive for the abnormality occurred may be considered as biochemical marker of liver dysfunction. Some of the biochemical markers such as serum bilirubin, alanine amino transferase, aspartate amino transferase, ratio of aminotransferases, alkaline phosphatase, gamma glutamyl transferase, 5′ nucleotidase, ceruloplasmin, α-fetoprotein are considered in this article. An isolated or conjugated alteration of biochemical markers of liver damage in patients can challenge the clinicians during the diagnosis of disease related to liver directly or with some other organs. The term “liver chemistry tests” is a frequently used but poorly defined phrase that encompasses the numerous serum chemistries that can be assayed to assess hepatic function and/or injury.

World J Hepatol. 2021 Nov 27; 13(11): 1688–1698.

Liver biochemical tests are some of the most commonly ordered routine tests in the inpatient and outpatient setting, especially with the automatization of testing in this technological era. These tests include aminotransferases, alkaline phosphatase, gamma-glutamyl transferase, bilirubin, albumin, prothrombin time and international normalized ratio (INR). Abnormal liver biochemical tests can be categorized based on the pattern and the magnitude of aminotransferases elevation. Generally, abnormalities in aminotransferases can be classified into a hepatocellular pattern or cholestatic pattern and can be further sub-classified based on the magnitude of aminotransferase elevation to mild [< 5 × upper limit of normal (ULN)], moderate (> 5-< 15 × ULN) and severe (> 15 × ULN). Hepatocellular pattern causes include but are not limited to; non-alcoholic fatty liver disease/non-alcoholic steatohepatitis, alcohol use, chronic viral hepatitis, liver cirrhosis (variable), autoimmune hepatitis, hemochromatosis, Wilson’s disease, alpha-1 antitrypsin deficiency, celiac disease, medication-induced and ischemic hepatitis. Cholestatic pattern causes include but is not limited to; biliary pathology (obstruction, autoimmune), other conditions with hyperbilirubinemia (conjugated and unconjugated). It is crucial to interpret these commonly ordered tests accurately as appropriate further workup, treatment and referral can greatly benefit the patient due to prompt treatment which can improve the natural history of several of the diseases mentioned and possibly reduce the risk of progression to the liver cirrhosis.

Clin Biochem Rev. 2013 Nov; 34(3): 117–130. Tam metin için tıklayınız

De Ritis described the ratio between the serum levels of aspartate transaminase (AST) and alanine transaminase (ALT) almost 50 years ago. While initially described as a characteristic of acute viral hepatitis where ALT was usually higher than AST, other authors have subsequently found it useful in alcoholic hepatitis, where AST is usually higher than ALT. These interpretations are far too simplistic however as acute viral hepatitis can have AST greater than ALT, and this can be a sign of fulminant disease, while alcoholic hepatitis can have ALT greater than AST when several days have elapsed since alcohol exposure. The ratio therefore represents the time course and aggressiveness of disease that would be predicted from the relatively short half-life of AST (18 h) compared to ALT (36 h). In chronic viral illnesses such as chronic viral hepatitis and chronic alcoholism as well as non-alcoholic fatty liver disease, an elevated AST/ALT ratio is predictive of long terms complications including fibrosis and cirrhosis. There are methodological issues, particularly whether or not pyridoxal phosphate is used in the transaminase assays, and although this can have specific effects when patient samples are deficient in this vitamin, these method differences generally have mild effects on the usefulness of the assays or the ratio. Ideally laboratories should be using pyridoxal phosphate supplemented assays in alcoholic, elderly and cancer patients who may be pyridoxine deplete. Ideally all laboratories reporting abnormal ALT should also report AST and calculate the De Ritis ratio because it provides useful diagnostic and prognostic information.

Clinical Chemistry December 2000 vol. 46 no. 12 2027-2049

Purpose: To review information on performance characteristics for tests that are commonly used to identify acute and chronic hepatic injury.

Data Sources and Study Selection: A MEDLINE search was performed for key words related to hepatic tests, including quality specifications, aminotransferases, alkaline phosphatase, γ-glutamyltransferase, bilirubin, albumin, ammonia, and viral markers. Abstracts were reviewed, and articles discussing performance of laboratory tests were selected for review. Additional articles were selected from the references.

Guideline Preparation and Review: Drafts of the guidelines were posted on the Internet, presented at the AACC Annual Meeting in 1999, and reviewed by experts. Areas requiring further amplification or literature review were identified for further analysis. Specific recommendations were made based on analysis of published data and evaluated for strength of evidence and clinical impact. The drafts were also reviewed by the Practice Guidelines Committee of the American Association for the Study of Liver Diseases and approved by the committee and the Association’s Council.

Recommendations: Although many specific recommendations are made in the guidelines, some summary recommendations are discussed here. Alanine aminotransferase is the most important test for recognition of acute and chronic hepatic injury. Performance goals should aim for total error of <10% at the upper reference limit to meet clinical needs in monitoring patients with chronic hepatic injury. Laboratories should have age-adjusted reference limits for enzymes in children, and gender-adjusted reference limits for aminotransferases, γ-glutamyltransferase, and total bilirubin in adults. The international normalized ratio should not be the sole method for reporting results of prothrombin time in liver disease; additional research is needed to determine the reporting mechanism that best correlates with functional impairment. Harmonization is needed for alanine aminotransferase activity, and improved standardization for hepatitis C viral RNA measurements.

Zealand Family Physician Journal, 29, 117-120. Volume 34 Number 3, June 2007

This guide (updated from an earlier version published in the NZFP in 20021) is intended to provide easily accessible information on appropriate investigation and likely diagnoses. First view Figure 1, then look at notes as indicated.
• For single enzyme elevations see Note 1. • If multiple enzyme abnormalities refer to Question 1.

Ulster Med J 2012;81(1):30-36

Abstract
Liver enzymes are commonly used in the evaluation of patients with a range of diseases. Classically they are used
to give information on whether a patient’s primary disorder is hepatitic or cholestatic in origin. However, knowledge of enzyme ratios and pattern recognition allow much more information to be derived from these simple tests. This paper offers an insight to generalists on how to extract greater information from these tests in order to improve the investigation and management of liver disease.

[Indian J Pediatr 2007; 74 (7) : 663-671]

ABSTRACT
Liver function tests (LFT) are a helpful screening tool, which are an effective modality to detect hepatic dysfunction. Since the liver performs a variety of functions so no single test is sufficient to provide complete estimate of function of liver. Often clinicians are faced with reports that do not tally with the clinical condition of the patient and they face difficulty in interpreting the LFT. An attempt is being made to study and understand the LFT and simplify their interpretation with algorithms.

Postgrad Med J. 2003 Jun;79(932):307-12

Abstract
Interpretation of abnormalities in liver function tests is a common problem faced by clinicians. This has become more common with the introduction of automated routine laboratory testing. Not all persons with one or more abnormalities in these tests actually have liver disease. The various biochemical tests, their pathophysiology, and an approach to the interpretation of abnormal liver function tests are discussed in this review.

CMAJ • February 1, 2005; 172 (3):367-379

ISOLATED ALTERATIONS OF BIOCHEMICAL MARKERS OF LIVER DAMAGE in a seemingly healthy patient can present a challenge for the clinician. In this review we provide a guide to interpreting alterations to liver enzyme levels. The functional anatomy of the liver and pathophysiology of liver enzyme alteration are briefly reviewed. Using a schematic approach that classifies enzyme alterations as predominantly hepatocellular or predominantly cholestatic, we review abnormal enzymatic activity within the 2 subgroups, the most common causes of enzyme alteration and suggested initial investigations.

Guideline için Tıklayınız

This guideline provides recommendations for the interpretation and evaluation of abnormal liver test results in adults. It should be used in conjunction with other guidelines, such as Clinical Management of Chronic Hepatitis B, Clinical Management of Chronic Hepatitis C, Investigation and Management of Iron Overload and Viral Hepatitis Testing.

Background
Abnormal liver tests may indicate an abnormality of the liver and provide clues as to the nature of the problem. However, in an asymptomatic patient, mild abnormalities may not be clinically significant. A systematic approach to evaluating the patient and ordering further tests will help to efficiently identify any underlying disease.7
Further testing and referrals may not be necessary in many circumstances.
The term ‘liver function test’ should not be used when referring to serum enzyme levels because they correlate poorly with metabolic activities of the liver.
There are two broad categories of liver enzyme abnormalities.7,9 (see Table 2) Usually the most marked abnormality points to the underlying category of disorder.
1. Hepatocellular injury (e.g. hepatitis) – damaged liver cells develop leaky membranes, allowing for escape of intracellular enzymes into the bloodstream.1,3,10 The major intracellular enzymes are aspartate aminotransferase (AST) and alanine aminotransferase (ALT).
2. Cholestasis (e.g. biliary obstruction or hepatic infiltration) – obstructed/damaged intra- or extrahepatic bile ducts cause the induction of synthesis of alkaline phosphatase (ALP) and gammaglutamyl transpeptidase (GGT). In acute biliary obstruction, elevation of these enzyme levels often lags symptoms by approximately 24 hours. An isolated elevation of GGT is a relatively common finding and does not necessarily indicate significant liver disease.7
NOTE: Bilirubin is not a useful test for distinguishing between cholestasis and hepatocellular injury
because it may be elevated in both situations.1,3