New Guidelines Provide a Clearer Path Forward for Abnormal Liver Tests

William F. Balistreri, MD


February 01, 2018

In This Article

Approach to Persons With Abnormal Liver Chemistry Values

The authors discuss the risk factors, screening tests, and confirmatory tests for each of the commonly encountered liver diseases.[2] Their useful, specific recommendations take several forms.

Some are common sense. Before initiating an evaluation of abnormal liver chemistries, one should repeat the panel or perform a clarifying test to confirm that the liver chemistry value is actually abnormal.[2]

Some address common clinical scenarios.

  • Patients with elevated body mass index and other features of metabolic syndrome, including diabetes mellitus, obesity, hyperlipidemia, or hypertension, with mild elevations of ALT should undergo screening for NAFLD with ultrasound.

  • Celiac disease may be associated with modest elevations of aminotransferase levels; thus, screening should be considered in patients with persistently elevated liver chemistries.[2]

Some are clues to specific entities. For example, the magnitude of the liver chemistry abnormalities and the ratio of AST to ALT may help to guide evaluation of the patient.

  • For magnitude of rise <5X ULN, testing should assess for, among other disorders, hepatitis B and C, alcoholic liver disease, and NAFLD, and for >15X ULN or a massive elevation of ALT > 10,000 IU/L, testing should assess for acetaminophen toxicity and ischemic hepatopathy (shock liver).

  • A ratio of AST to ALT exceeding 3:1 further increases the likelihood of alcoholic liver disease. This ratio largely reflects the relatively lower serum activity of ALT compared with AST, driven by the pyridoxine deficiency observed in patients with alcoholic liver disease.[2]

Some are strong reminders.

  • If there are signs of acute liver failure, an elevated prothrombin time, or encephalopathy, prompt referral to a liver transplant center is required.

  • Ask patients with abnormal liver chemistry values about prescribed and over-the-counter medications, nonprescribed complementary or alternative medicines, and dietary or herbal supplements, which may be associated with drug-induced liver injury. These agents represent a common source for acute and chronic liver injury. Nearly all medications are associated with at least a small risk for elevation of ALT, AST, alkaline phosphatase, or bilirubin with or without hepatotoxicity.[2] Attributing liver injury to a specific substance may entail empirical drug discontinuation to observe recovery of liver chemistry values.

  • The guideline reminds us that the US National Library of Medicine offers the LiverTox website, as a helpful resource to ascertain whether a drug or supplement may be hepatotoxic.

The Bottom Line

The guidelines provide clinicians with useful information to inform their decision-making when encountering an individual with elevated values on liver chemistry tests. Although the report offers an algorithm for evaluation of AST or ALT levels, it is important to remember that when evaluating abnormal liver test levels, one size does not fit all.[4]

As stated in the guidelines, the evaluation of elevated AST and ALT levels should be guided by the degree of elevation, as well as the clinical presentation. Minimal elevations may be approached by a history and examination and discontinuation of hepatotoxic medicines and alcohol consumption.[2] An evaluation for autoimmune liver disease, Wilson disease, and alpha-1 antitrypsin deficiency is also warranted if the "common" causes are ruled out.[1] A liver biopsy may ultimately be required to obtain a diagnosis.

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