Evaluation of liver dysfunction

Liver blood tests are routinely used in diagnosis and management of hepatobiliary disease. Abnormal liver blood test results are often the first indicator of hepatobiliary disease and a common indication for abdominal imaging with ultrasound, computed tomography, or magnetic resonance imaging.[1]Metra BM, Guglielmo FF, Halegoua-DeMarzio DL, et al. Beyond the liver function tests: a radiologist's guide to the liver blood tests. Radiographics. 2022 Jan-Feb;42(1):125-42. https://pubs.rsna.org/doi/10.1148/rg.210137 http://www.ncbi.nlm.nih.gov/pubmed/34797734?tool=bestpractice.com ​ 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 red blood cells 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 transferase (gamma-GT)

• Lactate dehydrogenase.

Individual tests in these panels are not specific for liver disease. Therefore, pattern recognition is critical. Evaluation 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 symptoms, the nature of the liver test abnormality noted, and relevant scans and biopsies.[2]Royal Pharmaceutical Society. Liver function tests: indication and interpretation. Feb 2022 [internet publication]. https://pharmaceutical-journal.com/article/ld/liver-function-tests-indication-and-interpretation ​ 

Traditionally, liver test abnormalities have been grouped under the following patterns:[3]Kwo PY, Cohen SM, Lim JK. ACG clinical guideline: evaluation of abnormal liver chemistries. Am J Gastroenterol. 2017 Jan;112(1):18-35. http://www.ncbi.nlm.nih.gov/pubmed/27995906?tool=bestpractice.com

• Hepatocellular (predominantly ALT and AST elevations)

• Cholestatic (predominantly ALP elevation)

• Mixed/infiltrative (elevation of both ALT/AST and ALP).

Isolated elevation of liver tests is a less common occurrence in liver diseases, and a nonhepatic source should be considered in such instances. Bilirubin may be elevated in any category of liver disease.[4]Murali AR, Carey WD. Liver test interpretation - approach to the patient with liver disease: a guide to commonly used liver tests. April 2014 [internet publication]. https://teachmemedicine.org/cleveland-clinic-liver-test-interpretation 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.[5]Carey WD. How should a patient with an isolated GGT elevation be evaluated? Cleve Clin J Med. 2000 May;67(5):315-6. When other liver tests are abnormal, categorization according to pattern is helpful to determine the probable etiology.

Clinical correlation is essential when interpreting liver tests. Liver tests are abnormally elevated in 1% to 9% of the asymptomatic population.[6]Malakouti M, Kataria A, Ali SK, et al. Elevated liver enzymes in asymptomatic patients - what should I do? J Clin Transl Hepatol. 2017 Dec 28;5(4):394-403. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5719197 http://www.ncbi.nlm.nih.gov/pubmed/29226106?tool=bestpractice.com Further investigations with diagnostic serology and liver biopsy are normal in 6% of these patients.[7]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 Aug;35(2):195-9. http://www.ncbi.nlm.nih.gov/pubmed/11580141?tool=bestpractice.com Importantly, people with chronic liver disease or cirrhosis may have normal liver tests.[8]Ahmed Z, Ahmed U, Walayat S, et al. Liver function tests in identifying patients with liver disease. Clin Exp Gastroenterol. 2018 Aug 23;11:301-7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6112813 http://www.ncbi.nlm.nih.gov/pubmed/30197529?tool=bestpractice.com [9]Bacon BR. Treatment of patients with hepatitis C and normal serum aminotransferase levels. Hepatology. 2002 Nov;36(5 Suppl 1):S179-84. https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.1053/jhep.2002.36386 http://www.ncbi.nlm.nih.gov/pubmed/12407592?tool=bestpractice.com

Liver tests are markers of liver injury, not liver function.[3]Kwo PY, Cohen SM, Lim JK. ACG clinical guideline: evaluation of abnormal liver chemistries. Am J Gastroenterol. 2017 Jan;112(1):18-35. http://www.ncbi.nlm.nih.gov/pubmed/27995906?tool=bestpractice.com Functional assessment of the liver (evaluation of protein synthesis, metabolism, bile production, storage, and detoxification) can be determined by: 

• Conventional liver tests such as albumin and international normalized ratio

• Scoring systems such as Model for End-Stage Liver Disease and Child-Turcotte-Pugh score, based on laboratory test results and clinical features.