From the Guidelines
The most common cause of idiopathic elevated liver enzymes is nonalcoholic fatty liver disease (NAFLD), which is often associated with metabolic syndrome and insulin resistance. When liver enzymes such as ALT, AST, ALP, or GGT are found to be elevated without an identifiable cause after a thorough medical evaluation, the condition is classified as idiopathic 1. Before accepting this diagnosis, patients should undergo comprehensive testing including viral hepatitis panels, autoimmune markers, metabolic screening, imaging studies, and medication reviews to rule out common causes like viral hepatitis, alcohol use, fatty liver disease, autoimmune hepatitis, medication effects, and biliary disorders.
Key Considerations
- The AST:ALT ratio is generally >2 in alcohol-induced fatty liver disease and <1 in metabolic disease-related fatty liver 1.
- NAFLD is a spectrum of fat deposition and hepatic inflammation followed by fibrosis due to metabolic insults, and it is the most common liver disease in first world countries, with a prevalence of 20% to 30% in the general population 1.
- Management typically involves monitoring liver enzymes every 3-6 months, avoiding hepatotoxic substances, maintaining a healthy weight, and following a liver-friendly diet low in processed foods and sugar.
- In many cases, idiopathic elevations are mild and may resolve spontaneously over time, but if elevations persist or worsen, referral to a hepatologist for possible liver biopsy may be warranted to rule out occult liver disease 1.
Screening and Diagnosis
- All individuals with steatosis should be screened for features of MetS, independent of liver enzymes, and all individuals with persistently abnormal liver enzymes should be screened for NAFLD 1.
- Noninvasive tests, such as elastography or fibrosis biomarkers, may be used to assess risk of fibrosis, but referral to a liver specialist and liver biopsy may be required for definitive diagnosis 1.
- Patients with type 2 diabetes or prediabetes and elevated liver enzymes (ALT) or fatty liver on ultrasound should be evaluated for presence of nonalcoholic steatohepatitis and liver fibrosis 1.
From the Research
Causes of Idiopathic Elevated Liver Enzymes
The causes of idiopathic elevated liver enzymes can be varied and complex. Some of the possible causes include:
- Non-alcoholic fatty liver disease (NAFLD) 2, 3
- Alcoholic liver disease 2
- Medication-associated liver injury 2
- Viral hepatitis (hepatitis B and C) 2, 3
- Hemochromatosis 2
- α(1)-antitrypsin deficiency 2
- Autoimmune hepatitis 2
- Wilson disease 2
- Extrahepatic conditions such as thyroid disorders, celiac disease, hemolysis, and muscle disorders 2
Evaluation of Elevated Liver Enzymes
The evaluation of elevated liver enzymes should be approached in a step-wise manner, taking into account the patient's history, physical examination, and laboratory test results 4, 2, 5. The initial evaluation should include a fasting lipid profile, measurement of glucose, serum iron, and ferritin, total iron-binding capacity, and hepatitis B surface antigen and hepatitis C virus antibody testing 2. Further testing may be necessary to rule out less common causes of elevated liver enzymes.
Testing Strategies
The choice of testing strategy for elevated liver enzymes depends on various factors, including the patient's pre-test probabilities and prior evaluations performed 6. A focused testing strategy may be more cost-effective in certain situations, while an extensive testing strategy may be necessary in other cases 6. The trade-offs between the two approaches involve the money spent on testing, the number of office visits needed, and the false positive results generated 6.
Liver Disease Progression
In some cases, elevated liver enzymes can be a sign of underlying liver disease, which can progress to cirrhosis if left untreated 3. The presence of hepatic steatosis in patients with hepatitis C infection can influence liver disease progression and response to antiviral therapy 3. Management of obesity and metabolic syndrome in patients with chronic hepatitis C may be important for reducing the risk of progression and improving the efficacy of antiviral therapy 3.