Causes of ALT > AST
ALT elevation greater than AST is the characteristic pattern of most chronic liver diseases, particularly nonalcoholic fatty liver disease (NAFLD), viral hepatitis (especially hepatitis C), and medication-induced liver injury. 1, 2
Primary Causes by Clinical Context
Chronic Hepatitis C (Most Relevant to Your Patient)
Chronic HCV infection characteristically presents with ALT > AST in the early and active phases of disease, with persistent or fluctuating ALT elevations indicating active liver disease in 60-70% of chronically infected persons. 3, 2
ALT is typically higher than AST in early acute viral hepatitis because ALT is predominantly cytoplasmic and more liver-specific, making it a more sensitive marker of hepatocellular injury. 2
The AST/ALT ratio remains <1 throughout most of the course of chronic hepatitis C until cirrhosis develops, at which point the ratio reverses (AST becomes higher than ALT). 2, 4, 5, 6
In your patient with HCV, the ALT > AST pattern indicates active hepatocellular injury without advanced cirrhosis, as an AST/ALT ratio ≥1 has 95.9-100% specificity for distinguishing cirrhotic from non-cirrhotic patients. 5, 6
Nonalcoholic Fatty Liver Disease (NAFLD)
NAFLD is the most common cause of persistently elevated ALT with an AST:ALT ratio <1 in patients with metabolic risk factors including obesity, diabetes, and hypertension. 1
The ALT > AST pattern is characteristic of NAFLD until advanced fibrosis or cirrhosis develops, when the ratio reverses. 1
Medication-Induced Liver Injury
Medication-induced liver injury causes 8-11% of cases with mildly elevated liver enzymes and typically presents with ALT > AST in hepatocellular injury patterns. 1
All prescription medications, over-the-counter drugs, and herbal supplements should be checked against the LiverTox® database for hepatotoxic potential. 1
Acute Viral Hepatitis
- Acute viral hepatitis (hepatitis A, B, C, D, or E) typically shows ALT > AST with elevations >400 IU/mL, representing the highest ALT/LD ratio (mean 4.65) among liver diseases. 7
Why ALT is More Specific Than AST
ALT is highly specific for liver injury because it is primarily concentrated in liver tissue with minimal presence in cardiac muscle, skeletal muscle, or red blood cells. 1
ALT exists in low concentrations in skeletal muscle and kidney, whereas AST is present in cardiac muscle, skeletal muscle, kidneys, brain, and red blood cells, making AST less liver-specific. 1
Normal ALT ranges are sex-specific: 29-33 IU/L for men and 19-25 IU/L for women, significantly lower than commercial laboratory cutoffs. 1
Critical Pattern Recognition for Your HCV Patient
The ALT > AST pattern in chronic HCV infection indicates you are dealing with active hepatocellular injury without cirrhosis. 2, 4, 6
When HCV progresses to cirrhosis, the AST/ALT ratio reverses (AST becomes higher than ALT), serving as a marker of disease progression and fibrosis development. 2, 4
An AST/ALT ratio ≥1 in HCV patients has 100% specificity and positive predictive value for cirrhosis in some studies, though sensitivity is only 46.7-53.2%. 5, 6
Special Considerations for COPD Comorbidity
COPD itself does not directly cause the ALT > AST pattern, but medications used for COPD management should be reviewed for hepatotoxic potential. 1
Hypoxia from severe COPD can theoretically contribute to ischemic hepatitis, but this typically presents with AST > ALT and transaminases >1000 IU/L. 7
Important Pitfalls to Avoid
Do not assume normal ALT excludes significant liver disease - up to 30% of HCV patients have persistently normal ALT levels despite active disease, and 20-30% may have significant fibrosis progression. 8
Serial ALT and AST measurements over time are more informative than single values, as patients with chronic viral hepatitis may have fluctuating or intermittently normal ALT levels. 2
The AST may remain elevated in patients where ALT has returned to normal during and after treatment, suggesting that measuring both enzymes is useful. 4