Can celiac disease cause elevated liver enzymes, such as alanine transaminase (ALT) and aspartate transaminase (AST)?

Can Celiac Disease Cause Elevated Liver Enzymes?

Yes, celiac disease frequently causes elevated liver enzymes, with transaminase elevations occurring in 40% of adults and 54% of children at diagnosis, and these abnormalities typically normalize with a strict gluten-free diet in 75-100% of cases. 1

Prevalence and Pattern of Liver Enzyme Elevation

Celiac disease is present in approximately 9% of patients with chronic unexplained elevation of transaminases, making it an important consideration in the differential diagnosis of cryptogenic transaminitis. 1 The liver injury in celiac disease ranges from:

• Mildly elevated transaminases (most common presentation) 1
• Non-alcoholic fatty liver disease (NAFLD) 1
• Rarely, progression to cirrhosis 1

The prevalence of celiac disease in patients with elevated transaminase levels of unknown cause ranges from 1.5% to 9.0%, with higher rates in specific populations: 2.9% to 6.4% in autoimmune hepatitis patients and 0% to 6.0% in primary biliary cirrhosis. 1

Clinical Significance and Risk of Progression

Celiac disease patients have a 2.8-fold increased hazard ratio for developing NAFLD/NASH (95% CI 2.0-3.8), with an even higher risk in children (HR 4.6; 95% CI 2.3-10.1). 1 This represents a significant risk for progression to more severe liver disease if left untreated.

Celiac disease is twice as common in patients with cirrhosis than in the general population, underscoring the importance of early detection and treatment to prevent progression to end-stage liver disease. 1

Management: Gluten-Free Diet as Primary Treatment

Patients with celiac disease and elevated liver enzymes should follow a strict gluten-free diet to improve liver enzymes and histology, and to prevent progression to cirrhosis (Grade B recommendation, 96% consensus). 1

Expected Response to Treatment:

• Improvement or normalization of transaminases occurs in 75-100% of patients upon institution of a gluten-free diet 1
• Response typically occurs within 6-12 months of strict dietary adherence 2
• Case series demonstrate that even patients with serious liver disease referred for transplantation evaluation can have complete resolution of liver disease with dietary compliance 1

Evidence from Clinical Studies:

In five US patients with liver cirrhosis and celiac disease, ALT, AST, and bilirubin improved in four diet-compliant patients, with MELD scores improving in three of four patients (one patient with NASH cirrhosis worsened). 1 This demonstrates that even advanced liver disease can respond to gluten restriction.

When to Suspect Coexisting Liver Disease

Failure of liver enzymes to normalize after 12 months of strict gluten-free diet indicates coexisting liver disease and warrants further investigation. 3, 2 Common associations include:

• Autoimmune hepatitis (prevalence 2.9-6.4% in celiac patients) 1
• Primary biliary cholangitis 1
• Hepatitis C infection 3

In patients with celiac disease and autoimmune liver disease, simultaneous treatment for both conditions (gluten-free diet plus immunosuppression for autoimmune hepatitis) results in normalized aminotransferases. 2

Clinical Approach Algorithm

Initial Evaluation:

1. Test for celiac disease in any patient with unexplained transaminase elevation, particularly if AST/ALT are mildly elevated (<5× ULN) 4, 3
2. Check tissue transglutaminase antibody (tTGA) with total IgA level 1
3. Obtain duodenal biopsies if serologies are positive or clinical suspicion is high 1

Treatment and Monitoring:

1. Initiate strict gluten-free diet immediately upon diagnosis 1
2. Recheck liver enzymes at 6 and 12 months to assess response 2
3. If enzymes normalize: continue gluten-free diet and monitor annually 2
4. If enzymes remain elevated after 12 months of documented dietary compliance: investigate for coexisting liver disease including viral hepatitis, autoimmune hepatitis, hemochromatosis, and Wilson disease 3, 2

Critical Pitfalls to Avoid

• Do not assume normal liver enzymes exclude celiac disease - many patients have subclinical elevations or normal baseline values that still decrease significantly on a gluten-free diet 5
• Do not delay celiac testing in obese patients with presumed NAFLD - celiac disease can coexist with or cause NAFLD 4
• Do not attribute persistent transaminitis solely to dietary non-compliance without investigating for coexisting liver disease after 12 months 3, 2
• Be aware that tTGA may be falsely elevated in advanced liver disease, particularly with older guinea pig-based assays rather than human tissue transglutaminase 1

Mechanism and Additional Benefits

The literature suggests that increased intestinal permeability may be one mechanism by which liver damage occurs in celiac disease. 2 Beyond liver enzyme normalization, gluten restriction in patients with celiac disease and autoimmune liver disease reduces the risk of complications including malabsorption, osteoporosis, and malignancy. 1