What are the implications of elevated liver enzyme levels, such as Alanine Transaminase (ALT) and Aspartate Transaminase (AST), during pregnancy?

Elevated Liver Enzymes in Pregnancy

Elevated liver enzymes in pregnancy represent either normal physiologic changes (alkaline phosphatase only) or pathologic conditions requiring urgent evaluation, with the specific pattern, timing, and associated symptoms determining whether immediate delivery is needed to prevent maternal and fetal mortality.

Normal Physiologic Changes vs. Pathologic Elevations

Expected Normal Changes

• Alkaline phosphatase (ALP) physiologically increases 2-fold above normal beginning in the second trimester due to placental production, not liver disease 1, 2
• Albumin decreases during the second half of pregnancy due to hemodilution, which is normal 1, 2
• ALT, AST, bilirubin, bile acids, and GGT should remain normal throughout pregnancy—any elevation is pathologic and requires investigation 1, 2

Critical Distinction

• If ALP is elevated with normal GGT, bilirubin, and aminotransferases, this represents normal pregnancy physiology 2
• If GGT is elevated alongside ALP, this indicates hepatic origin and requires workup 2, 3

Pregnancy-Specific Liver Diseases by Trimester

First Trimester (0-12 weeks)

Hyperemesis Gravidarum 1

• Occurs in 0.35-2.0% of pregnancies 1
• Abnormal liver enzymes in ~50% of cases, rarely >1,000 IU/L 1
• ALT typically greater than AST 1
• Treatment is supportive: rehydration, electrolyte correction, thiamine supplementation to prevent Wernicke's encephalopathy, and antiemetics 1
• Biochemical abnormalities resolve with hydration and resolution of vomiting 1

Second/Third Trimester (13-40 weeks)

Intrahepatic Cholestasis of Pregnancy (ICP) 1

• Prevalence 0.4-10% of pregnancies 1
• Diagnosis requires bile acids >10 μmol/L plus generalized pruritus (especially palms/soles) without rash 1, 3
• AST and ALT elevated 2-30 times upper limit of normal 1
• Maternal mortality 0%, but fetal/perinatal mortality 0.4-1.4% 1
• Treatment: UDCA improves pruritus and liver tests in 67-80% of patients 1
• Delivery at 36-38 weeks appears to prevent stillbirth, though not evidence-based 1
• Recurrence rate 45-70% in subsequent pregnancies 1

HELLP Syndrome 1

• Prevalence 0.2-0.6% of pregnancies 1
• Typically third trimester or postpartum 1
• Triad: Hemolysis, Elevated liver enzymes (mild to 10-20-fold), Low platelets (<50,000-150,000/μL) 1
• Commonly associated with preeclampsia 1
• Maternal mortality 1-25%, fetal/perinatal mortality 11% 1
• Bilirubin typically <5 mg/dL 1
• Can present with hepatic infarcts, hematomas, or hepatic rupture 1

Acute Fatty Liver of Pregnancy (AFLP) 1

• Prevalence 0.005-0.010% of pregnancies 1
• Third trimester or postpartum 1
• Presents with liver failure: jaundice, coagulopathy, encephalopathy, hypoglycemia, DIC 1
• AST and ALT 300-1,000 U/L (5-15-fold elevation) 1
• Low antithrombin III, elevated PT, low fibrinogen 1
• Maternal mortality 7-18%, fetal mortality 9-23% 1
• Imaging shows fatty infiltration 1

Diagnostic Algorithm

Step 1: Determine Pattern

• Hepatocellular pattern: Elevated ALT/AST with normal or mildly elevated ALP 1
• Cholestatic pattern: Elevated ALP and/or GGT with normal or mildly elevated aminotransferases 1
• Mixed pattern: Both elevated 1

Step 2: Severity Classification

• Mild: <5 times upper reference limit 1
• Moderate: 5-10 times upper reference limit 1
• Severe: >10 times upper reference limit 1

Step 3: Trimester-Specific Workup 3

First/Second Trimester:

• Obtain total serum bile acids, complete liver panel (AST, ALT, bilirubin, GGT, ALP, platelets) 3
• Viral hepatitis serologies (HBsAg, anti-HCV, HAV IgM, HEV) 3
• Autoimmune markers (AMA, ANA, SMA) 3
• If transaminases <3-4 times upper limit without clear etiology, can observe with repeat testing every 1-2 weeks 3

Third Trimester:

• Same workup as above PLUS coagulation studies (PT, fibrinogen) to assess for AFLP or HELLP 3
• Do not delay delivery for laboratory confirmation in unstable patients 3
• Assess for preeclampsia (blood pressure, proteinuria) 1

Critical Pitfalls to Avoid

• Do not assume elevated ALP indicates liver disease—it is normal in pregnancy if other tests are normal 2, 3
• Do not diagnose ICP based on pruritus alone without bile acids >10 μmol/L 3
• Do not start UDCA before obtaining baseline bile acids, as this prevents subsequent diagnosis 3
• Do not use obeticholic acid in pregnancy—it lacks safety data 3
• Minor aminotransferase elevations may herald life-threatening AFLP or HELLP syndrome 4

Postpartum Management

• All liver enzyme abnormalities should resolve within 3 months postpartum 3, 5
• If ALP remains elevated at 3 months, investigate for chronic liver disease (autoimmune hepatitis, primary biliary cholangitis) 5
• Verify complete resolution of transaminases and bile acids 3, 5
• ICP recurs in up to 90% of subsequent pregnancies 3
• Women with ICP history have increased risk of chronic hepatitis, liver fibrosis, and cholangitis later in life 3

Long-Term Implications

• Elevated GGT or ALT in early pregnancy increases risk of gestational diabetes 6, 7
• High-normal liver enzymes (at 80th percentile or above) in early pregnancy associated with 31.4% population attributable fraction for gestational hypertension and 23.2% for preeclampsia 7
• Non-alcoholic fatty liver disease found in 16-18% of pregnant women, associated with increased pregnancy complications and abnormal fetal growth 6