What is the approach to abnormal Liver Function Tests (LFTs) in primary care?

From the Guidelines

When approaching abnormal liver function tests in primary care, I recommend a systematic evaluation beginning with a thorough history and physical examination to identify potential causes, as outlined in the most recent guidelines from 2023 1. This approach is crucial for identifying the underlying cause of abnormal liver function tests (LFTs) while avoiding unnecessary testing and ensuring appropriate management of potentially serious liver conditions.

Initial Evaluation

The initial evaluation should include repeating the LFTs to confirm abnormalities, as transient elevations are common, and categorizing the pattern as hepatocellular (predominant ALT/AST elevation), cholestatic (predominant alkaline phosphatase/GGT elevation), or mixed. For hepatocellular patterns, evaluate for common causes including medications (statins, antibiotics, NSAIDs), alcohol use, viral hepatitis (order HBsAg, anti-HCV), fatty liver disease, and hemochromatosis (check ferritin, transferrin saturation) 1. For cholestatic patterns, consider biliary obstruction, primary biliary cholangitis (check anti-mitochondrial antibodies), and medications.

Additional Testing

Additional testing should include complete blood count, albumin, PT/INR, and abdominal ultrasound to assess liver structure and rule out biliary obstruction. If initial workup is negative but LFTs remain abnormal, consider less common causes like autoimmune hepatitis (check ANA, ASMA), Wilson's disease (ceruloplasmin in younger patients), or alpha-1 antitrypsin deficiency.

Imaging Recommendations

According to the 2023 guidelines, for patients with abnormal liver functions tests with hepatocellular predominance, US abdomen and US duplex Doppler abdomen are usually appropriate as the initial imaging for mild aminotransferase increase, while US abdomen, US duplex Doppler abdomen, and CT abdomen and pelvis with IV contrast are usually appropriate for moderate or severe aminotransferase increase 1. For cholestatic patterns, US abdomen, MRI abdomen without and with IV contrast, and CT abdomen and pelvis with IV contrast are usually appropriate.

Management and Referral

Mild elevations (less than 2-3 times upper limit of normal) without symptoms can be monitored with repeat testing in 2-4 weeks while addressing modifiable factors like alcohol cessation, weight management, and medication adjustments. Refer to gastroenterology/hepatology if LFTs worsen, remain significantly elevated after 3-6 months, or if there are signs of advanced liver disease (jaundice, ascites, encephalopathy), as recommended by the guidelines from 2018 1. This systematic approach, based on the most recent and highest quality evidence, ensures that patients with abnormal liver function tests receive appropriate and timely care.

From the FDA Drug Label

Ask a doctor before use if you have liver disease. The approach to abnormal Liver Function Tests (LFTs) in primary care when considering the use of acetaminophen is to exercise caution and consult a doctor, especially if there is pre-existing liver disease 2.

• Key consideration: Presence of liver disease is a critical factor in deciding whether to use acetaminophen.
• Recommendation: Consult a doctor before using acetaminophen if abnormal LFTs or liver disease is suspected or known.

From the Research

Approach to Abnormal Liver Function Tests (LFTs) in Primary Care

• Abnormal liver function tests (LFTs) are a common situation encountered by physicians, and many of these patients do not have primary liver disease 3
• The evaluation of abnormal LFTs should include a review of previous laboratory test results, medical and family histories, substance use, and drugs, including over-the-counter drugs and herbal supplements 4
• A combination of a careful history and clinical examination along with interpretation of pattern of liver test abnormalities can often identify type and aetiology of liver disease, allowing for a targeted investigation approach 3
• The pattern and severity of liver injury may provide clues about the cause of disease and should guide diagnostic evaluation with serologic testing and liver imaging 5

Steps in Evaluating Abnormal LFTs

• Determine whether the abnormal LFTs are associated with the illness resulting in the admission to the hospital or preceded the present illness 6
• Determine the etiology of the underlying liver disease 6
• Evaluate the severity of the liver dysfunction and determine if acute liver failure (ALF) or acute decompensation of chronic liver failure is present 6
• Look for the presence of associated complications-either those of ALF or chronic liver failure as appropriate 6

Interpretation of Liver Test Results

• Liver biochemical tests can be categorized based on the pattern and the magnitude of aminotransferases elevation 7
• Abnormalities in aminotransferases can be classified into a hepatocellular pattern or cholestatic pattern 7
• Hepatocellular pattern causes include non-alcoholic fatty liver disease/non-alcoholic steatohepatitis, alcohol use, chronic viral hepatitis, liver cirrhosis, autoimmune hepatitis, and others 7
• Cholestatic pattern causes include biliary pathology, other conditions with hyperbilirubinemia, and others 7

Diagnostic Evaluation

• Tests should include a complete blood cell count; alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, and albumin levels; prothrombin time; hepatitis B surface antigen; hepatitis B core antibody; hepatitis C antibody; ferritin and iron levels and transferrin saturation; and right upper quadrant abdominal ultrasonography 4
• Additional tests and imaging should be based on patient-specific risk factors and the pattern of abnormal liver test results 4