ALT Predominance in Early Viral Hepatitis
In the initial phase of viral hepatitis, ALT is more elevated than AST primarily due to ALT's greater hepatocyte specificity and longer half-life (36 hours vs 18 hours for AST), while later AST elevation reflects progression to more severe liver injury with mitochondrial damage and cirrhosis. 1
Biochemical Pattern in Acute Viral Hepatitis
Initial Phase: ALT > AST
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 ALT/AST ratio in acute viral hepatitis averages 4.65, reflecting marked ALT predominance during the initial inflammatory phase. 3
Both aminotransferases are markedly elevated (often >1000 IU/L) in acute viral hepatitis, but ALT rises more dramatically due to its exclusive cytoplasmic location and release with even mild hepatocyte membrane disruption. 4
Later Phase: AST May Rise or Predominate
When viral hepatitis progresses to cirrhosis, the AST/ALT ratio reverses (AST becomes higher than ALT), serving as a marker of disease progression and fibrosis development. 2
This reversal occurs because AST has both cytoplasmic and mitochondrial isoforms; severe hepatocyte injury with mitochondrial damage releases mitochondrial AST, increasing total AST levels disproportionately. 1
The shorter half-life of AST (18 hours) compared to ALT (36 hours) means that sustained AST elevation despite its faster clearance indicates ongoing severe injury. 1
Clinical Significance of the Ratio
Diagnostic Value
An ALT/AST ratio >1 is characteristic of acute viral hepatitis in the early phase, helping differentiate it from other causes of acute liver injury. 3, 1
The ratio provides information about both the time course and aggressiveness of disease, with ratio changes reflecting disease evolution. 1
Prognostic Implications
AST elevation exceeding ALT in acute viral hepatitis can indicate fulminant disease and represents a warning sign requiring urgent evaluation. 1
In chronic viral hepatitis, an elevated AST/ALT ratio (AST > ALT) predicts long-term complications including progressive fibrosis and cirrhosis. 1
Progressive decline in serum albumin, prolongation of prothrombin time, and declining platelet counts accompany the AST/ALT ratio reversal as cirrhosis develops. 2
Monitoring Considerations
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 same laboratory assay should be used for serial monitoring to ensure consistency, as methodological differences (particularly pyridoxal phosphate supplementation) can affect results. 1
Laboratories reporting abnormal ALT should routinely report AST and calculate the AST/ALT ratio because it provides essential diagnostic and prognostic information about disease stage and severity. 1