How should abnormal liver function tests be managed in a pregnant woman, taking into account severity, gestational age, and associated symptoms?

Management of Deranged Liver Function Tests in Pregnancy

Any elevation in aminotransferases, bilirubin, or bile acids during pregnancy is abnormal and requires immediate systematic investigation, with management determined by the specific diagnosis, gestational age, and severity of disease. 1

Initial Diagnostic Approach

Obtain a comprehensive liver panel immediately: AST, ALT, alkaline phosphatase, GGT, total and direct bilirubin, albumin, and platelet count. 1 Add pregnancy-specific markers including non-fasting serum bile acids, coagulation studies (PT/INR, fibrinogen), complete blood count with peripheral smear, uric acid, creatinine, and lactate. 2

Recognize Normal Pregnancy Changes

• Alkaline phosphatase increases physiologically to 133-418 IU/L in the third trimester due to placental production. 1
• Albumin decreases normally throughout pregnancy (28-37 g/L in first trimester). 1
• AST, ALT, bilirubin, GGT, and bile acids remain within non-pregnant ranges—any elevation is pathologic. 1

Determine Pattern and Timing

Classify the pattern as hepatocellular (elevated transaminases) versus cholestatic (elevated alkaline phosphatase, bile acids, bilirubin), then consider gestational age to narrow the differential diagnosis. 1, 2

Trimester-Specific Differential Diagnosis

First Trimester (0-12 weeks)

Hyperemesis gravidarum causes mild transaminase elevations (typically <300 IU/L) in 40-50% of severe cases. 1, 2 Measure liver tests but recognize these abnormalities are usually self-limiting. 1 Provide antiemetic treatment with cyclizine, doxylamine/pyridoxine, prochlorperazine, or promethazine. 2

Screen for coincidental viral hepatitis (HAV IgM, HBsAg, HBc IgM, HCV antibody, HEV IgM, HSV DNA, CMV DNA, EBV antibodies), autoimmune hepatitis (ANA, anti-smooth muscle antibody, quantitative IgG), and drug-induced liver injury through detailed medication history including over-the-counter and herbal products. 1, 2

Second and Third Trimester (13-40 weeks)

Intrahepatic Cholestasis of Pregnancy (ICP)

Diagnose ICP when serum bile acids exceed 10 μmol/L (non-fasting) accompanied by pruritus, typically after 30 weeks gestation. 1, 2 AST/ALT may be elevated 2-30 fold; bilirubin usually remains <6 mg/dL. 2, 3

Management algorithm:

• Measure serum bile acids weekly from 32 weeks gestation. 2
• Initiate ursodeoxycholic acid (UDCA) 10-15 mg/kg/day in divided doses when bile acids >40 μmol/L to treat maternal pruritus and reduce spontaneous preterm birth risk. 1, 2
• Continue UDCA throughout pregnancy and during breastfeeding—it is safe in both settings. 2
• For refractory pruritus despite UDCA, consider rifampicin, cholestyramine, guar gum, or activated charcoal (evidence limited). 2

Delivery timing based on bile acid concentration:

• >100 μmol/L: deliver at 36 weeks or at diagnosis if later due to markedly increased stillbirth risk. 1, 2
• 40-100 μmol/L: deliver between 36-39 weeks. 2
• <40 μmol/L: aim for term delivery at 39 weeks. 2

HELLP Syndrome (Hemolysis, Elevated Liver Enzymes, Low Platelets)

Diagnose HELLP when hemolysis (elevated LDH, low haptoglobin, schistocytes), AST/ALT 2-10× upper limit of normal, and platelet count <100×10⁹/L occur after 20 weeks gestation. 2 Note that hypertension and proteinuria may be absent in up to 15% of cases. 2

Management protocol:

• Control severe hypertension (SBP >160 mmHg or DBP >110 mmHg) urgently with oral or intravenous labetalol, nifedipine, or methyldopa in a monitored setting. 1, 2
• Treat non-severe hypertension (SBP 140-159 mmHg or DBP 90-109 mmHg) with oral labetalol, nifedipine, or methyldopa. 1, 2
• Administer magnesium sulfate to prevent eclamptic seizures in women with severe hypertension. 1, 2
• Transfuse platelets when count <100×10⁹/L to reduce coagulopathy-related complications. 2
• Deliver promptly once maternal coagulopathy and severe hypertension are corrected—delayed delivery increases maternal mortality. 1, 2, 4
• Perform abdominal ultrasound if severe epigastric or right upper quadrant pain develops to evaluate for hepatic hematoma or rupture. 1

Acute Fatty Liver of Pregnancy (AFLP)

Diagnose AFLP using the Swansea criteria: 6 or more of the following findings in a third-trimester or postpartum patient: vomiting, abdominal pain, polydipsia/polyuria, encephalopathy, elevated transaminases (>42 IU/L), elevated bilirubin (>0.8 mg/dL), hypoglycemia (<72 mg/dL), leukocytosis (>11×10⁶/L), elevated uric acid (>5.7 mg/dL), elevated ammonia (>42 IU/L), ascites or bright liver on ultrasound, renal impairment, and coagulopathy. 5

Critical distinguishing features from HELLP: prolonged PT, low fibrinogen, hypoglycemia, and encephalopathy strongly suggest AFLP over HELLP. 5

Management algorithm:

• Admit to intensive care if encephalopathy develops, serum lactate >2.8 mg/dL, MELD score >30, or Swansea criteria score >7. 1, 5
• Aggressively correct coagulopathy and metabolic derangements (hypoglycemia, hyperammonemia). 1, 2
• Expedite delivery once maternal stabilization permits—mode of delivery should be decided by multidisciplinary team. 1, 2
• Consider plasma exchange post-delivery for severe hepatic impairment (evidence limited to small case series). 1, 2
• Consider N-acetylcysteine for ICU-level disease (limited data but benefits demonstrated in other causes of acute liver failure). 1, 2
• Make early referral to a transplant center for women with severe hepatic failure or lack of improvement after delivery. 1, 2

Imaging Strategy

Use abdominal ultrasound without Doppler as first-line imaging—it is safe at any gestational age and evaluates the biliary tree, liver parenchyma, and vasculature. 1 Limited Doppler interrogation of hepatic vessels may be performed but minimize exposure time. 1

If further imaging is needed, MRI or MRCP without gadolinium is the preferred modality in all trimesters. 1 Gadolinium must be avoided throughout pregnancy because it crosses the placenta and accumulates in the fetal urinary tract. 1

ERCP can be performed when clinically necessary (fetal radiation <0.5 mGy, well below the 50 mGy safety threshold), ideally in the second or third trimester. 1, 2

Management of Pre-Existing Chronic Liver Disease

Continue most medications used for chronic liver disease management throughout pregnancy—stopping could cause clinical deterioration that poses greater risk than theoretical medication risks. 2 Women with pre-existing cholestatic diseases (primary biliary cholangitis, primary sclerosing cholangitis) should be counseled that approximately 50% will have worsening or de novo pruritus during pregnancy, but most maintain stable hepatic function. 1, 2

Continue UDCA during pregnancy in women with primary biliary cholangitis or primary sclerosing cholangitis—it is safe and associated with stable liver tests. 2 For primary sclerosing cholangitis with worsening cholestasis, perform ultrasound or MRCP to exclude obstruction or high-grade strictures accessible to endoscopic balloon dilatation. 2

Avoid obeticholic acid due to lack of safety data; fibrates may be considered after the first trimester if benefits are likely to exceed perceived risks. 2

Critical Pitfalls to Avoid

• Never assume elevated transaminases, bilirubin, or bile acids are normal in pregnancy—these always require investigation. 1, 2
• Do not delay delivery in preeclampsia, HELLP, or AFLP after maternal stabilization—postponement raises maternal mortality risk. 2, 4
• Recognize that bile acid levels >100 μmol/L in ICP markedly increase stillbirth risk after 35 weeks—timely delivery is essential. 2
• Do not stop immunosuppressive medications or disease-modifying treatments in women with pre-existing liver disease—clinical deterioration poses greater risk. 2
• Bilirubin levels, PT, GGT, and total bile acids remain normal throughout pregnancy in healthy women—any elevation warrants evaluation. 1

Multidisciplinary Care

All pregnant patients with liver disease at increased risk of maternal or fetal morbidity/mortality should be managed by a multidisciplinary team including hepatologist/gastroenterologist, maternal-fetal medicine specialist, obstetrician, and experienced midwife. 2 If such expertise is not locally available, refer to a center capable of providing multidisciplinary care. 2

Post-Partum Follow-Up

Monitor liver function tests until they return to normal, typically within 6 weeks after delivery for pregnancy-specific liver disorders. 2 If abnormalities persist beyond 6 weeks, evaluate for underlying chronic liver disease. 2 Women with a history of ICP have a 45-70% risk of recurrence in subsequent pregnancies. 2