Does hepatic steatosis (fatty liver disease) cause elevated liver function tests (LFTs) in adults?

Does Hepatic Steatosis Cause Elevated LFTs?

Yes, hepatic steatosis commonly causes elevated liver function tests, particularly mild elevations in aminotransferases (ALT and AST), though importantly, normal LFTs do not exclude the presence of steatosis or even advanced liver disease.

Pattern of LFT Abnormalities in Hepatic Steatosis

Aminotransferase Elevation:

• Patients with nonalcoholic fatty liver disease (NAFLD) most commonly present with mildly elevated AST and/or ALT, typically with an AST:ALT ratio <1 1
• The AST:ALT ratio may reverse to >1 in later stages of disease, but this does not exclude NAFLD 1
• NAFLD and alcohol-induced liver disease are the most common causes of mild aminotransferase increases 1
• In metabolic disease-related fatty liver, the AST:ALT ratio is generally <1, whereas alcohol-induced fatty liver disease typically shows AST:ALT >2 1

Other LFT Abnormalities:

• Alkaline phosphatase and/or gamma-glutamyltransferase may be mildly elevated 1
• Bilirubin typically remains normal unless advanced disease is present 1
• Elevated INR, hypoalbuminemia, or thrombocytopenia suggest cirrhosis or portal hypertension and may be the primary findings in advanced fibrosis 1

Critical Caveat: Normal LFTs Do Not Exclude Disease

This is a major clinical pitfall that can lead to missed diagnoses:

• Although 50% of patients with NAFLD have normal liver chemistries, up to 80% of patients with NASH may be identified based on elevated transaminases 1
• A normal or near-normal ALT level does not exclude nonalcoholic steatohepatitis (NASH) 1
• Normal liver enzymes do not exclude advanced fibrosis—ALT has only 50% sensitivity for NASH and 40% sensitivity for advanced fibrosis 2
• ALT typically falls as fibrosis progresses, creating a false sense of improvement 2
• Clinicians overly rely on abnormal liver enzymes to identify patients with NAFLD, potentially missing patients with significant liver disease 3

Clinical Spectrum and Implications

Disease Progression:

• Simple hepatic steatosis occurs in 70-75% of NAFLD cases without cellular injury 1
• Nonalcoholic steatohepatitis (NASH) occurs in 25-30% of cases with hepatocyte injury and inflammation, which can progress to fibrosis, cirrhosis, and hepatocellular carcinoma 1
• The presence and progression of liver fibrosis is the main predictor of liver-related death, not the degree of steatosis or LFT elevation 4

Approach to Patients with Steatosis and Elevated LFTs

Initial Evaluation:

• Exclude other causes of liver disease including viral hepatitis, alcohol-related liver disease (>21 drinks/week in men, >14 drinks/week in women), medications, hemochromatosis, autoimmune hepatitis, and Wilson disease 1, 2
• Obtain comprehensive metabolic panel, complete blood count with platelets, and assess for metabolic risk factors 1, 2

Risk Stratification for Fibrosis:

• Calculate FIB-4 score (using AST, ALT, age, and platelet count) as first-tier assessment: <1.3 indicates low risk, 1.3-2.67 indicates indeterminate risk, and >2.67 indicates high risk of advanced fibrosis 1, 2
• For indeterminate FIB-4 scores, perform second-tier testing with transient elastography (VCTE thresholds: <8.0 kPa low risk, 8.0-12.0 kPa indeterminate, >12.0 kPa high risk) or Enhanced Liver Fibrosis test (ELF thresholds: <7.7 low risk, 7.7-9.8 indeterminate, >9.8 high risk) 2
• Refer high-risk patients (FIB-4 >2.67, VCTE >12.0 kPa, or ELF >9.8) to hepatology for consideration of liver biopsy and surveillance 2

Key Point on Imaging:

• Patients with incidentally discovered hepatic steatosis on imaging, especially those with elevated aminotransferases, have significantly higher risk of progression to cirrhosis or hepatocellular carcinoma and should undergo fibrosis risk stratification 1
• Ultrasound has 84.8% sensitivity and 93.6% specificity for moderate-to-severe steatosis (>30% fat content), but sensitivity drops to 53.3-65% for mild steatosis 1