Serum liver chemistry tests, commonly called liver tests, or (mistakenly) liver function tests, are ordered for many reasons. Most laboratories offer these tests as a bundle, and this usually includes:
Bilirubin (breakdown product of the RBC after conjugation in the liver and secretion in biliary system excretion)
Alanine aminotransferase (ALT)
Alkaline phosphatase (ALP)
Serum albumin.
The following tests may also be included in this bundle:
Aspartate aminotransferase (AST)
Gamma-glutamyl transpeptidase (gamma-GT)
Lactate dehydrogenase (LDH).
Individual tests in these panels are not specific for liver disease. Therefore, pattern recognition is critical. Isolated elevation of liver tests is a less common occurrence in liver diseases, and a non-hepatic source should also be considered in such instances. Assessment of patients with abnormal liver tests should be guided by history, risk for liver disease, duration and severity of clinical findings, presence of comorbidities, and the nature of the liver test abnormality noted.
Traditionally, liver tests abnormalities have been grouped under the following patterns:
Hepatocellular (predominantly ALT and AST elevations)
Cholestatic (predominantly ALP elevation)[1]European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of cholestatic liver diseases. J Hepatol. 2009;51:237-267.
http://www.ncbi.nlm.nih.gov/pubmed/19501929?tool=bestpractice.com
Mixed/infiltrative.
Bilirubin may be elevated in any category of liver disease, and this does not aid in the classification.[2]Murali AR, Carey WD. Liver test interpretation - approach to the patient with liver disease: a guide to commonly used liver tests. April 2014. http:/www.clevelandclinicmeded.com (last accessed 4 July 2017).
http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/guide-to-common-liver-tests/
Isolated gamma-GT elevations are so common and so often unhelpful that many institutions have chosen to delete this test from their liver test panel.[3]Carey WD. How should a patient with an isolated GGT elevation be evaluated? Cleve Clin J Med. 2000;67:315-316.
http://www.ncbi.nlm.nih.gov/pubmed/10832186?tool=bestpractice.com
When other liver tests are abnormal, categorisation according to the pattern found is clinically valuable in the process of finding the possible aetiology of the liver disease. However, liver tests can be abnormally elevated in 1% to 4% of the asymptomatic population, and further investigations reveal that 6% of these patients have no obvious cause for liver disease (liver histology may be normal).[4]Poynard T, Imbert-Bismut F. Laboratory testing for liver disease. In: Boyer TD, Wright TL, Manns MP, et al, eds. Zakim and Boyer's hepatology: a textbook of liver disease, 5th ed. Philadelphia, PA: Saunders Elsevier; 2006:235-250.[5]Skelly MM, James PD, Ryder SD. Findings on liver biopsy to investigate abnormal liver function tests in the absence of diagnostic serology. J Hepatol. 2001;35:195-199.
http://www.ncbi.nlm.nih.gov/pubmed/11580141?tool=bestpractice.com
In addition, people with liver disease may have normal tests (16% of patients with hepatitis C and 13% of patients with varying histological damage due to non-alcoholic fatty liver diseases have persistently normal tests).[6]Giannini EG, Testa R, Savarino V. Liver enzyme alteration: a guide for clinicians. CMAJ. 2005;172:367-379.
http://www.cmaj.ca/cgi/content/full/172/3/367
http://www.ncbi.nlm.nih.gov/pubmed/15684121?tool=bestpractice.com
Liver tests may also be normal in people with hepatitis B who are in the immune-tolerant phase and in the inactive HBsAg carrier state.[7]Brook G, Soriano V, Bergin C; International Union against Sexually Transmitted Infections. 2010 European Guideline for the management of hepatitis B and C virus infections. Int J STD AIDS. 2010;21:669-678.
http://www.ncbi.nlm.nih.gov/pubmed/21139144?tool=bestpractice.com
Functional assessment of the liver (evaluating protein synthesis, metabolism, bile production, storage, and detoxification) can be determined by: [8]Bennink RJ, Tulchinsky M, de Graaf W, et al. Liver function testing with nuclear medicine techniques is coming of age. Semin Nucl Med. 2012;42:124-137.
http://www.ncbi.nlm.nih.gov/pubmed/22293167?tool=bestpractice.com
Conventional liver tests such as albumin and INR; these tests reflect the liver function
Scoring systems such as Model for End-Stage Liver Disease (MELD) and Child-Turcotte-Pugh (CTP) score, based on laboratory test results and clinical features.
More definitive assessment can be obtained by quantitative assays. However, these are relatively difficult to perform and are not easily available. Techniques include:[8]Bennink RJ, Tulchinsky M, de Graaf W, et al. Liver function testing with nuclear medicine techniques is coming of age. Semin Nucl Med. 2012;42:124-137.
http://www.ncbi.nlm.nih.gov/pubmed/22293167?tool=bestpractice.com
Non-isotope methodologies such as caffeine clearance, albumin synthesis, and antipyrine clearance
Isotope methodologies such as hepatocyte mass scintigraphy (99mTc-GSA) and aminopyrine breath test (13C or 14C-methyl).
