What is the management approach for elevated Liver Function Tests (LFTs) in pregnant women?

Management of Elevated Liver Function Tests in Pregnancy

Elevated liver function tests in pregnancy require a systematic, trimester-based diagnostic approach that prioritizes pregnancy-specific liver disorders, followed by investigation of pre-existing or coincidental liver disease, with management tailored to the specific diagnosis and gestational age. 1

Initial Diagnostic Framework

Recognize Normal Physiological Changes

• Understand that normal pregnancy alters reference ranges: albumin decreases, alkaline phosphatase increases (up to 133-418 IU/L in third trimester), while AST, ALT, bilirubin, and GGT remain within non-pregnant ranges 2
• Hyperdynamic circulation, palmar erythema, and spider naevi are normal physiological findings that can mimic chronic liver disease 1

Essential Initial Laboratory Assessment

• Measure serum bile acids, transaminases, bilirubin, alkaline phosphatase, GGT, and platelets as the foundational workup 1
• Obtain coagulation profile and renal function tests, particularly in third trimester presentations 3
• Test for viral hepatitis markers (HBsAg, anti-HCV, IgM anti-HEV, IgM anti-HAV) to exclude viral etiologies 3

Critical Clinical History Elements

• Evaluate for pruritus, right upper quadrant pain, jaundice, and intractable vomiting as these symptoms guide diagnosis 1
• Obtain detailed medication history including prescribed, over-the-counter, and herbal products 2
• Screen for alcohol use and refer for management when appropriate 2

Trimester-Specific Differential Diagnosis

First Trimester (Most Common: Hyperemesis Gravidarum)

• Hyperemesis gravidarum causes elevated liver tests in 40-50% of severe cases 1
• Liver dysfunction occurs in approximately 50% of patients with intractable vomiting 4
• Treat with first-line anti-emetics: cyclizine, doxylamine/pyridoxine, prochlorperazine, or promethazine 1
• Liver tests typically normalize with symptom resolution 5

Second Trimester (Most Common: Viral Hepatitis)

• Viral hepatitis accounts for 47% of abnormal LFTs in this trimester 3
• Intrahepatic cholestasis of pregnancy (ICP) may begin presenting with pruritus and elevated bile acids 1
• Consider pre-existing liver disease or metabolic dysfunction-associated steatotic liver disease (MASLD), found in 16-18% of pregnant women 6

Third Trimester (Highest Risk Period)

• 59.2% of all abnormal LFTs occur in the third trimester, with the most serious conditions concentrated here 3
• HELLP syndrome (28.3%) and acute fatty liver of pregnancy (AFLP, 14.8%) are the most common causes 3
• Third trimester liver dysfunction carries 20.2% maternal mortality and 24.6% perinatal mortality 3

Management by Specific Diagnosis

Intrahepatic Cholestasis of Pregnancy (ICP)

• Diagnose with elevated serum bile acids (>10 μmol/L non-fasting in third trimester) 2
• Offer ursodeoxycholic acid (UDCA) for bile acids >40 μmol/L to treat maternal pruritus and reduce spontaneous preterm birth risk 1
• Continue UDCA throughout pregnancy as it is safe in pregnancy and breastfeeding 2
• Recommend delivery at 35 weeks' gestation for bile acids >100 μmol/L due to increased stillbirth risk 1
• For refractory pruritus, add rifampicin (300-600 mg daily) or anion exchange resins (cholestyramine 4-8 g/day or colestipol 5-10 g/day), given at least 4 hours after UDCA 2
• Correct vitamin K deficiency related to cholestasis 2

Preeclampsia and HELLP Syndrome

• Control severe hypertension with labetalol, nifedipine, or methyldopa; intravenous therapy may be required 1
• Administer magnesium sulfate to prevent eclamptic seizures in women with severe hypertension 1
• Deliver promptly once maternal coagulopathy and severe hypertension are corrected 1
• HELLP syndrome is associated with poor maternal and fetal outcomes, with DIC being the most common complication (20.2%) 3

Acute Fatty Liver of Pregnancy (AFLP)

• Consider intensive care admission for women with encephalopathy, elevated serum lactate, or high Swansea criteria score 1
• Microvesicular fat deposition can cause liver failure with coagulopathy and encephalopathy 4
• Expedite delivery once coagulopathy and metabolic derangements are treated 1
• Only immediate delivery can save mother and child in this life-threatening condition 4

Pre-existing Cholestatic Liver Disease (PBC/PSC)

• Continue UDCA during pregnancy in primary biliary cholangitis and primary sclerosing cholangitis as it is safe and associated with stable liver tests 2
• Approximately 50% will have worsening or de novo pruritus during pregnancy, but most maintain stable hepatic function 2
• Up to 70% have postnatal deterioration of serum liver tests, requiring close postpartum monitoring 2
• Perform repeated bile acid measurements when pruritus worsens, as higher levels correlate with reduced gestation length 2
• For PSC 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 used after first trimester if benefits outweigh risks 2

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

• Screen high-risk women with increased surveillance for gestational diabetes and hypertensive disease using appropriate national protocols 2
• Implement lifestyle modifications including dietary advice as for non-pregnant population 2
• Optimize treatment of metabolic comorbidities before conception and continue during pregnancy 2
• Encourage breastfeeding in women with MASLD 2

Diagnostic Imaging and Procedures

Safe Imaging Modalities

• Ultrasound and liver elastography are safe at any gestation 2
• Note that liver stiffness and controlled attenuation parameter may increase slightly in third trimester as normal physiology 2
• MRCP is safe at any gestation and should be used when cholestasis worsens in PSC 2
• ERCP can be performed when clinically necessary (fetal radiation <0.1-0.5 mGy, well below 50 mGy threshold), ideally in second/third trimester 2

Invasive Procedures

• Liver biopsy can be performed when clinical need/diagnostic uncertainty dictates and delay would be more dangerous, ensuring coagulopathy is corrected 2
• Endoscopy is safe in pregnancy, ideally performed in second trimester in left lateral position with judicious midazolam use 2

Post-Delivery Management

Immediate Postpartum Period

• Monitor liver function tests until normalization, which should occur within 3 months post-delivery 1
• Investigate for underlying liver disease if LFTs remain abnormal beyond 3 months 1
• Be vigilant for postpartum deterioration in women with pre-existing cholestatic disease (up to 70% experience worsening) 2

Long-term Considerations

• Consider genetic screening if there is family history of hepatobiliary disease, early onset, or severe disease 1
• Women with elevated GGT or ALT in early pregnancy have increased risk of subsequent complications, especially gestational diabetes 6

Critical Pitfalls to Avoid

• Do not dismiss elevated LFTs as physiological without proper workup, as 3-5% of pregnancies have abnormal liver tests requiring investigation 5, 7
• Do not delay delivery in AFLP or severe HELLP syndrome once stabilized, as maternal and fetal mortality remain high 3
• Do not stop immunosuppressive medications or disease-modifying treatments in women with pre-existing liver disease, as clinical deterioration poses greater risk 2
• Do not use obeticholic acid in pregnancy due to lack of safety data 2
• Do not overlook bile acid measurement in women with pruritus, as this is essential for ICP diagnosis and risk stratification 1