What is the cause of abnormal Liver Function Tests (LFTs) with a normal Ultrasound (US)?

From the Guidelines

For deranged liver function tests (LFTs) with a normal ultrasound, the most likely cause is non-alcoholic fatty liver disease (NAFLD) or alcohol-induced liver disease, and I recommend a comprehensive evaluation to identify the underlying cause, starting with a detailed history and a complete hepatic panel, as suggested by the most recent study 1. When evaluating abnormal LFTs with a normal ultrasound, it is essential to consider the pattern of liver injury, as hepatocellular predominant liver chemistry is seen when aminotransferases are elevated much higher than ALP (cholestatic-pattern) 1.

• The increase in ALT is directly linked to hepatocyte injury, and common causes of mild increases in aminotransferases are NAFLD and alcohol-induced liver disease 1.
• The AST:ALT ratio can help differentiate between alcohol-induced fatty liver disease (generally >2) and metabolic disease-related fatty liver (generally <1) 1.
• A comprehensive evaluation should include:
  • A detailed history focusing on medication use, alcohol consumption, and risk factors for viral hepatitis
  • A complete hepatic panel including ALT, AST, alkaline phosphatase, GGT, bilirubin, albumin, and PT/INR to characterize the pattern of liver injury
  • Testing for viral hepatitis (HAV, HBV, HCV), autoimmune markers (ANA, ASMA, anti-LKM), iron studies, ceruloplasmin, and alpha-1 antitrypsin levels
  • Consideration of metabolic causes like NAFLD by checking lipid profile, HbA1c, and BMI assessment
• If these tests are inconclusive, consider referral to a hepatologist for possible liver biopsy, as suggested by 1. While waiting for results, advise the patient to avoid alcohol, review all medications for potential hepatotoxicity, and maintain a healthy diet, as the normal ultrasound rules out obvious structural abnormalities like masses, biliary obstruction, or cirrhosis, but cannot exclude microscopic liver disease processes that affect liver enzymes without changing liver appearance 1.

From the FDA Drug Label

Ursodiol therapy has not been associated with liver damage. Abnormalities in liver enzymes have not been associated with Ursodiol therapy and, in fact, Ursodiol has been shown to decrease liver enzyme levels in liver disease.

The cause of abnormal Liver Function Tests (LFTs) with a normal Ultrasound (US) is not directly addressed in the provided drug label for ursodeoxycholic acid 2.

• Key points:
  • Ursodiol therapy is not associated with liver damage.
  • Ursodiol decreases liver enzyme levels in liver disease. However, the label does not provide information on the cause of abnormal LFTs with a normal US.

From the Research

Causes of Abnormal Liver Function Tests (LFTs)

Abnormal LFTs can be caused by various factors, including:

• Idiosyncratic drug reactions, which are equally common in patients with normal or abnormal liver function 3
• Hepatotoxic drugs, which should be used with caution in patients with advanced liver disease 3
• Underlying liver disease, such as cirrhosis, which can have broad-reaching implications for prescribing medications 3
• Other medical conditions, such as heart failure, which can be associated with impaired clinical outcomes in patients with abnormal LFTs 4

Evaluation of Abnormal LFTs

The evaluation of abnormal LFTs typically involves:

• Determining whether the abnormal LFTs are associated with the patient's current illness or preceded it 5
• Assessing the severity of the liver dysfunction and determining if acute liver failure or acute decompensation of chronic liver failure is present 5
• Looking for the presence of associated complications, such as those of acute liver failure or chronic liver failure 5
• Using an algorithmic approach to narrow the spectrum of a differential diagnosis and ensure appropriate management and evaluation of the patient 6

Patterns of LFT Derangement

There are established patterns of LFT derangement, including:

• Cholestatic derangement
• Hepatocellular derangement
• Failure of synthetic function
• Indicators to the cause of the derangement can be assessed by evaluating the ratios of elevated assays in relation to one another 7

Normal Ultrasound (US) with Abnormal LFTs

There is no direct evidence in the provided studies to explain the cause of abnormal LFTs with a normal US. However, it is possible that the abnormal LFTs may be caused by factors other than structural liver disease, such as drug reactions or other medical conditions, which may not be visible on an ultrasound 3, 6, 5, 7, 4