Differential Diagnosis of Elevated Transaminases in Pregnancy

Initial Diagnostic Workup

The American College of Obstetricians and Gynecologists recommends obtaining total serum bile acids and a complete liver panel, including AST, ALT, bilirubin, GGT, alkaline phosphatase, and platelets, when transaminases are elevated at any gestational age 1, 2, 4, 5
Viral hepatitis serologies, including HBsAg, anti-HCV, HAV IgM, and HEV, should be obtained to rule out viral hepatitis 6
Autoimmune markers, such as AMA, ANA, and SMA, should be obtained to exclude autoimmune hepatitis or primary biliary cholangitis 4, 5
Coagulation studies, including PT and fibrinogen, should be obtained if third trimester presentation to assess for AFLP or HELLP 3

Early-onset intrahepatic cholestasis of pregnancy is suggested by bile acids >10 μmol/L with pruritus before third trimester, and requires genetic evaluation and multidisciplinary management 1, 4
Pre-existing chronic liver disease, such as PBC or autoimmune hepatitis, may be misdiagnosed as ICP, and requires continued ursodeoxycholic acid throughout pregnancy 5, 6

Preeclampsia with severe features and HELLP syndrome are obstetric emergencies that require urgent evaluation and management 3, 5
Acute fatty liver of pregnancy has high mortality if unrecognized, and requires intensive care admission and expedited delivery once coagulopathy and metabolic derangements are treated 3, 5
Intrahepatic cholestasis of pregnancy is the most common liver-specific disorder, and requires ursodeoxycholic acid and delivery at 36-39 weeks depending on bile acid levels 1, 2, 5

For elevated transaminases in first/second trimester without clear etiology, transaminases up to 3-4 times upper limit of normal can be safely observed with careful history and viral hepatitis testing, and repeat testing every 1-2 weeks if symptoms persist 7
For third trimester elevations, abnormal results are associated with shorter duration of pregnancy and require urgent evaluation, and delivery should not be delayed for laboratory confirmation in unstable patients 5
Imaging and procedures, such as ultrasound and liver elastography, can be safely performed at any gestation, and MRCP can be performed in second/third trimester when clinically necessary 5, 6

Do not assume normal alkaline phosphatase rules out liver disease, as alkaline phosphatase increases to 133-418 IU/L in normal third trimester 5
Do not diagnose ICP based on pruritus alone, as this leads to unnecessary preterm deliveries 7
Do not stop immunosuppressive medications in women with pre-existing liver disease, as clinical deterioration poses greater risk than medication continuation 5
Do not use obeticholic acid in pregnancy, as it lacks safety data 5, 6
Do not start ursodeoxycholic acid before obtaining baseline bile acids, as this prevents subsequent diagnosis 7

Verify complete resolution of transaminases and bile acids within 3 months of delivery, and refer to hepatology for evaluation of underlying chronic liver disease if abnormalities persist 4, 5, 7
Counsel about recurrence risk, as ICP recurs in up to 90% of subsequent pregnancies, and women with history of ICP have increased risk of later developing chronic hepatitis, liver fibrosis, hepatitis C, and cholangitis 4, 5