From the Guidelines
Elevated liver function tests (LFTs) should be evaluated by first determining the pattern of abnormality (hepatocellular vs cholestatic) and severity, and then managing accordingly to prevent morbidity, mortality, and improve quality of life. The most recent and highest quality study, 1, provides guidance on the evaluation and management of abnormal LFTs.
Key Steps in Evaluation
- Obtain a detailed history focusing on medications, alcohol use, herbal supplements, and risk factors for viral hepatitis
- Order additional tests including complete blood count, coagulation studies, hepatitis serologies (A, B, C), autoimmune markers (ANA, anti-smooth muscle antibody), iron studies, and abdominal ultrasound
- Stop potential hepatotoxic medications when possible
Management Based on Severity
- For mild elevations (less than 3 times upper limit of normal), monitor LFTs every 2-4 weeks while investigating causes
- For moderate to severe elevations (greater than 3 times upper limit), consider gastroenterology referral
- Specific management depends on the underlying cause: viral hepatitis may require antiviral therapy, autoimmune hepatitis needs immunosuppression, alcoholic liver disease requires alcohol cessation, and non-alcoholic fatty liver disease benefits from weight loss and metabolic control
Urgent Referral
- Urgent referral is needed for signs of liver failure (jaundice, encephalopathy, coagulopathy) As noted in 1, liver function tests may reveal mild, moderate, or severe hepatocellular predominance and can be seen in alcoholic and nonalcoholic liver disease, acute hepatitis, and acute liver injury due to other causes. Additionally, 1 provides guidance on the workup and evaluation of hepatitis, including monitoring patient for abnormal liver blood tests and reviewing medications and supplements that may cause hepatotoxicity. However, the most recent and highest quality study, 1, takes precedence in guiding the evaluation and management of abnormal LFTs.
From the Research
Evaluation of Elevated LFTs
To evaluate a patient with elevated liver function tests (LFTs), it is essential to understand the biochemical basis of each LFT and correlate laboratory findings to the patient's clinical presentation 2. The key biochemical markers of hepatic function can be organized into the groupings of hepatocellular, cholestatic, or functioning liver, based on underlying enzymatic roles.
Causes of Elevated LFTs
The most common causes of elevated transaminase levels are:
- Nonalcoholic fatty liver disease
- Alcoholic liver disease
- Uncommon causes include:
- Drug-induced liver injury
- Hepatitis B and C
- Hereditary hemochromatosis
- Rare causes include:
- Alpha1-antitrypsin deficiency
- Autoimmune hepatitis
- Wilson disease
- Extrahepatic sources, such as:
- Thyroid disorders
- Celiac sprue
- Hemolysis
- Muscle disorders 3
Approach to Evaluation
An approach based on the prevalence of diseases that cause asymptomatic transaminase elevations can help clinicians efficiently identify common and serious liver disease 3. The initial evaluation should include:
- Assessment for metabolic syndrome and insulin resistance
- Complete blood count with platelets
- Measurement of serum albumin, iron, total iron-binding capacity, and ferritin
- Hepatitis C antibody and hepatitis B surface antigen testing
- The nonalcoholic fatty liver disease fibrosis score and the alcoholic liver disease/nonalcoholic fatty liver disease index can be helpful in the evaluation of mildly elevated transaminase levels 3
Further Testing
If testing for common causes is consistent with nonalcoholic fatty liver disease and is otherwise unremarkable, a trial of lifestyle modification is appropriate. If the elevation persists, hepatic ultrasonography and further testing for uncommon causes should be considered 3. A liver biopsy may be considered when serologic testing and imaging fails to elucidate a diagnosis, to stage a condition, or when multiple diagnoses are possible 4.
Prescribing in Patients with Abnormal LFTs
The prescribing of medicines to patients with abnormal LFTs requires careful consideration, and every effort must be made to establish the cause of the abnormal liver function 5. Idiosyncratic drug reactions are equally common in patients with normal or abnormal liver function. In advanced liver disease, drugs with predominant hepatic metabolism and/or excretion, particularly those with a narrow therapeutic index, should be used with caution 5.