Elevated Liver Enzymes in Preeclampsia: Pathophysiology
Elevated liver enzymes in preeclampsia result from hepatic ischemia and necrosis caused by widespread endothelial dysfunction, vasospasm, and reduced organ perfusion—a direct consequence of the systemic inflammatory response triggered by placental hypoperfusion and release of anti-angiogenic factors. 1
Primary Pathophysiologic Mechanism
The underlying cause follows a two-stage process that culminates in hepatic injury 2:
Stage 1: Placental Dysfunction
- Incomplete transformation of maternal spiral arteries due to shallow cytotrophoblast invasion creates high-resistance uteroplacental circulation 1, 3
- Placental hypoxia and ischemia trigger release of pathogenic factors into maternal circulation 2, 3
- The stressed placenta releases excessive soluble fms-like tyrosine kinase-1 (sFlt-1), which antagonizes vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) 2, 3
Stage 2: Systemic Endothelial Dysfunction and Hepatic Injury
- The angiogenic imbalance causes widespread endothelial dysfunction affecting multiple organ systems, including the liver 1, 2
- Vasospasm and reduced hepatic perfusion lead to hepatocyte necrosis and hemorrhage 2, 3
- Activation of the coagulation cascade further compromises hepatic microcirculation 1
Clinical Manifestations of Hepatic Involvement
Biochemical Abnormalities:
- Elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) reflect hepatocellular injury from ischemia 4, 5
- Mean ALT levels in preeclampsia are significantly elevated (55.81 ± 31.93 U/L) compared to normal pregnancy (15.22 ± 3.30 U/L, p<0.001) 5
- Mean AST levels similarly increase (41.34 ± 10.76 U/L vs 24 ± 2.54 U/L in controls, p<0.001) 5
- Elevated lactate dehydrogenase (LDH) indicates both hepatocellular damage and hemolysis 1
Clinical Symptoms:
- Right upper quadrant or epigastric pain results from liver capsule distension due to hepatic edema and subcapsular hemorrhage 1, 3
- These symptoms signal severe preeclampsia requiring urgent evaluation 1, 3
HELLP Syndrome: Severe Hepatic Manifestation
HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low Platelets) represents the severe end of the preeclampsia spectrum 1:
- This constellation of findings signifies more serious disease but remains part of preeclampsia, not a separate disorder 1
- Hemolysis occurs from microangiopathic injury as red blood cells traverse damaged endothelium 6
- Thrombocytopenia develops from platelet consumption and activation 7, 6
- The combination portends significant maternal morbidity and mortality risk 7, 8
Severity Correlation
The degree of liver enzyme elevation correlates with disease severity 1, 3:
- Mild preeclampsia may show minimal or no liver enzyme elevation 3
- Severe preeclampsia demonstrates more pronounced elevations with abnormal liver enzymes as a diagnostic criterion 1, 3
- Thrombocytopenia (<100,000/μL) combined with elevated liver enzymes indicates severe maternal organ dysfunction requiring delivery consideration 1
Critical Clinical Pitfall
Do not dismiss elevated liver enzymes as isolated findings—they represent systemic endothelial dysfunction and mandate comprehensive evaluation for other organ involvement including renal function, platelet count, and fetal well-being 1, 4. The presence of elevated liver enzymes, even without severe hypertension, warrants close monitoring as preeclampsia can progress rapidly to life-threatening complications including hepatic rupture 8.