From the Guidelines
The initial workup for elevated liver enzymes should begin with a thorough history and physical examination, followed by laboratory testing to determine the pattern of elevation (hepatocellular vs cholestatic) and potential causes, as recommended by the most recent study 1. The workup should include a comprehensive metabolic panel, complete blood count, coagulation studies (PT/INR), and additional liver tests including alkaline phosphatase, GGT, bilirubin (total and direct), albumin, and hepatitis serologies (A, B, and C) 1. Some key points to consider in the workup include:
- Assessing for alcohol use, medication history (including over-the-counter drugs and supplements), and risk factors for fatty liver disease 1
- Ultrasound of the liver as the preferred initial imaging study, with CT or MRI considered for patients with moderate or severe aminotransferase increase or cholestatic predominance 1
- Management depends on the underlying cause, including discontinuing hepatotoxic medications, treating viral hepatitis if present, recommending alcohol cessation for alcoholic liver disease, and lifestyle modifications for non-alcoholic fatty liver disease (weight loss of 7-10%, Mediterranean diet, exercise) 1
- For autoimmune hepatitis, prednisone (starting at 40-60mg daily) with or without azathioprine (50-150mg daily) may be indicated 1
- Monitoring liver enzymes every 1-3 months initially, with frequency adjusted based on clinical response, and urgent hepatology referral and possible hospitalization for patients with signs of liver failure (encephalopathy, coagulopathy, ascites) or very high transaminases (>1000 IU/L) 1
From the Research
Initial Workup for Elevated Liver Enzymes
The initial workup for a patient with elevated liver enzymes involves a thorough drug history, a low threshold of suspicion, and the exclusion of other causes of liver disease 2. This is crucial because drug-induced liver injury (DILI) can present as a broad spectrum of adverse drug reactions, ranging from mild elevation in liver enzymes to fulminant liver failure 3.
Identification of DILI
The primary goal is to identify DILI early when the patient's liver enzymes are elevated and to discontinue the offending agent as soon as possible to prevent further injury 3. The American College of Gastroenterology (ACG) published guidelines to aid the clinician in diagnosing DILI, which includes variables such as temporal association, clinical-biochemical features, type of injury (hepatocellular and/or cholestatic), extrahepatic features, and the likelihood that a given agent is the culprit based on its known manifestations with prior cases 3.
Management of Elevated Liver Enzymes
Treatment consists of discontinuation of suspected drug(s), acetylcysteine in the course of paracetamol (acetaminophen) toxicity, and liver transplantation in selected cases of fulminant liver failure 2. Guidelines regarding the use of selected drugs such as methotrexate and halothane should be followed. Potentially hepatotoxic drugs should be used cautiously in alcoholic patients with or without liver involvement. Patients with uncompensated liver disease should receive a reduced dose of drugs adjusted to the degree of liver function impairment 2.
Key Considerations
- A thorough drug history is essential in the initial workup for elevated liver enzymes 2.
- The exclusion of other causes of liver disease is crucial in diagnosing DILI 3, 2.
- Discontinuation of the offending agent is the primary treatment for DILI 3, 2.
- Certain drugs, such as cyclosporine, may be used to induce biochemical remission in childhood autoimmune hepatitis 4.
- Autoantibodies, such as anti-SLA antibody, may be associated with drug-induced hepatitis 5.
Laboratory and Histologic Evaluation
Laboratory evaluation, including serum aspartate aminotransferase and gamma-globulin levels, is essential in monitoring disease activity 6. Liver tissue examination is the best method of evaluating completeness of response 6. Histologic evaluation may show chronic hepatitis and septal fibrosis, even after resolution of clinical and biochemical parameters 5.