Abnormalities of standard liver biochemical tests are common – about 14% of adults have Alanine Aminotransferase (ALT) levels above the upper end of reference range while over 20% have elevated Gamma-Glutamyl Transferase (GGT) levels. So, what is the relevance to health outcomes?
Elevated levels of both are associated with significantly elevated risks (up to 20-fold) of mortality from liver disease. Elevated GGT levels are also a marker of increased cardiovascular disease mortality, largely due to its reflection of the metabolic syndrome and non-alcoholic fatty liver disease (the liver component of the metabolic syndrome).
Furthermore, many serious conditions ranging from gallstones or malignancy through to hepatic drug reaction can manifest as jaundice, ‘cholestatic patterns’ (elevated alkaline phosphatase, GGT and/or bilirubin) or various combinations of abnormal liver biochemistry results. Cirrhosis of the liver is the 11th commonest cause of mortality world-wide, being higher in men than women.
Mortality from chronic liver disease is largely due to the development of cirrhosis, portal hypertension and its clinical sequelae (ascites, variceal bleeding, encephalopathy, and renal failure) ultimately resulting in liver failure, and hepatocellular carcinoma (the second commonest global cause of cancer death after primary lung cancer).
Significant liver disease can be completely asymptomatic thus clinicians are required to evaluate the cause and requirement for further investigation and treatment of patients presenting with this problem.
Navigating the pathway by which abnormal liver biochemistry is evaluated can be challenging. The free resource, Abnormal Liver Function Test pathway at HealthPathway WA, helps clinicians in the evaluation and decision for referral of patients with abnormal liver biochemistry. For login details email healthpathways@wapha.org.au.
The key issues when considering a liver problem are
- What is the cause and is it treatable?
- How severe is the condition?
- What should the follow-up be?
The most important clinical sequelae of liver disease are red flagged in the pathway to enable rapid identification of those requiring urgent referral (ascites, jaundice, encephalopathy, acute gastrointestinal bleeding, or acute severe hepatitis).
The commonest causes of liver disease in our community are non-alcoholic fatty liver disease (now renamed as metabolic associated fatty liver disease to better align with the metabolic syndrome), alcohol-related liver disease (still the commonest cause for emergency department presentation with decompensated liver disease), chronic viral hepatitis (B and C), and drug induced liver injury (from many prescribed and non-prescribed medications or supplements). Collectively these causes account for up to 80% of all liver disease in our community with fatty liver diseases (alcohol or non-alcoholic/metabolic) accounting for half the cases.
Less common, but important, conditions also cause liver disease. Hereditary haemochromatosis is common enough (one in every 190 individuals of northern European descent) to warrant consideration and even has its own HealthPathway for assistance. The Abnormal Liver Function Test pathway will guide the clinician through common causes, how to investigate, what to do, how to treat, when to refer and provides links for patients to access information.
Finally, a word of caution. There has been considerable advancement in the availability of non-invasive biochemical or radiological tests for the determination of advanced hepatic fibrosis (very advanced fibrosis or cirrhosis). Whilst these are useful, many of the cut-off values for these parameters vary for the different aetiologies of liver disease or in some cases the tests have not been validated in a particular liver disease.
By and large, most of the non-invasive tests, AST to platelet ratio index (APRI), Fibrosis-4 (Fib-4) and Hepascore, have been validated in chronic viral hepatitis and alcohol-related liver disease. The APRI or Fib4 can be calculated from rebatable simple blood tests (ALT, AST, platelet count and patient age only required). Hepascore is not currently rebated by Medicare. Non-alcoholic fatty liver disease is more complex and has its own biomarker panel.
The biomarker scores and their interpretation can be found at https://www.hepatitisc.uw.edu/page/clinical-calculators/apri and https://nafldscore.com
Elastography is useful for detecting fibrosis or cirrhosis but is confounded by liver inflammation (which can provide false positive elevations suggesting fibrosis or cirrhosis is present) and can be technically difficult in obese individuals.
Fibroscan is used primarily in major teaching hospitals, requires a dedicated machine, and is not rebated by Medicare. Radiology providers can also provide elastography when performing hepatic ultrasound at little or no additional cost to the ultrasound in most instances.
If in doubt, refer the patient for a clinical review by your favourite gastroenterologist or hepatologist.
Key messages
- Adopt a logical approach when considering management
- Free resources are available to assist
- Not all new assessments have been clinically validated.
– References available on request
Author competing interests – nil