Why AST and ALT Rise in Heart Failure
AST and ALT elevate in heart failure primarily through two distinct mechanisms: hepatic congestion from elevated right atrial pressure causing passive liver injury, and hepatocellular necrosis from impaired hepatic perfusion (ischemic hepatitis or "shock liver"). 1, 2
Primary Pathophysiological Mechanisms
Hepatic Congestion (Most Common)
- Elevated central venous pressure (CVP) is the predominant driver of liver enzyme elevation in heart failure, with all liver function tests correlating with CVP in multivariable analysis 3
- Right ventricular dysfunction and systemic venous congestion lead to increased right atrial pressure, which transmits backward pressure to the hepatic veins, causing passive congestion of the liver 4, 1
- This congestion impairs hepatic blood flow and causes hepatocyte injury with subsequent enzyme leakage into the bloodstream 1
- Among liver enzymes, elevated bilirubin shows the strongest independent correlation with higher right atrial pressure (P <0.005), making it a particularly useful marker of venous congestion 2
Ischemic Hepatitis (Less Common but More Severe)
- Acute hepatocellular necrosis occurs when cardiac output drops sufficiently to impair hepatic perfusion, typically following hypotensive episodes 1
- This manifests as marked elevations in AST and ALT (often >8000 U/L in severe cases), though moderate elevations are more typical 5
- Only elevated AST, ALT, and total bilirubin are associated with both low cardiac index AND elevated CVP, indicating combined perfusion and congestion injury 3
- Ischemic hepatitis is usually self-limited and asymptomatic, with enzyme levels decreasing sharply as circulatory status improves 1, 5
Clinical Patterns and Severity
Prevalence in Acute Heart Failure
- Abnormal liver function tests are extremely common in acute heart failure: 46% have elevated AST, 31% have elevated ALT, 33% have elevated bilirubin, and 44% have low albumin 2
- Only 29% of acute heart failure patients have all liver function tests within normal ranges 2
Enzyme Pattern Characteristics
- Heart failure typically produces mild to moderate AST and ALT elevations (<5 times upper limit of normal in most cases) 1
- The AST:ALT ratio pattern differs from other liver diseases: while alcoholic liver disease shows AST:ALT >2:1 6, heart failure doesn't follow a consistent ratio pattern
- Markedly elevated transaminases (>3 times upper normal limit) in heart failure patients are associated with increased 180-day mortality 2
Independent Predictors of Enzyme Elevation
The following factors independently predict abnormal liver enzymes in heart failure patients:
For AST elevation: 2
- High hemoglobin levels
- Elevated NT-proBNP levels
For ALT elevation: 2
- High hemoglobin levels
- Elevated bilirubin
- Elevated NT-proBNP levels
For bilirubin elevation: 2
- High hemoglobin levels
- Low sodium levels
- Dilated right ventricle
Prognostic Implications
- Low albumin and markedly elevated AST/ALT (>3× upper normal limit) are associated with increased mortality during follow-up 2
- The prognostic value of abnormal liver tests relates to their interaction with cardiac index and CVP, essentially reflecting poor hemodynamic status 3
- Higher AST:ALT ratios (≥1.70) are independently associated with physical frailty and all-cause mortality in older heart failure patients 7
Clinical Caveats
- Prolonged recurrent congestive heart failure can lead to cardiac cirrhosis (fibrosis), representing chronic structural liver damage 1
- Acute liver failure may occur in patients with preexisting cirrhosis who develop severe heart failure or sustained hepatic ischemia 1
- The absence of prior shock or hypotensive episodes does not exclude significant AST/ALT elevation, as passive congestion alone can cause marked enzyme rises 5
- Enzyme elevations primarily indicate elevated CVP (congestion), while only AST, ALT, or total bilirubin elevations may indicate low cardiac index (poor perfusion) 3