What is the significance and management of abnormal liver enzyme levels, such as elevated alanine transaminase (ALT) and aspartate transaminase (AST), in pregnant women with a history of liver disease?

Management of Elevated Liver Enzymes in Pregnancy

Abnormal liver enzymes in pregnant women with pre-existing liver disease require immediate systematic evaluation to distinguish pregnancy-specific disorders from exacerbations of underlying disease, with most chronic liver disease medications continued throughout pregnancy to prevent maternal deterioration. 1

Understanding Normal Physiological Changes

Before investigating abnormal liver enzymes, recognize that pregnancy alters reference ranges:

• Albumin decreases and alkaline phosphatase increases (up to 133-418 IU/L in third trimester) as normal physiological changes 2
• AST, ALT, bilirubin, and GGT should remain within non-pregnant ranges—elevations require investigation 2
• Physical findings like palmar erythema and spider naevi occur due to hyperdynamic circulation and hyperestrogenic state, mimicking chronic liver disease 1

Initial Diagnostic Workup

When encountering elevated liver enzymes, obtain:

• Serum bile acids, transaminases (AST/ALT), bilirubin, alkaline phosphatase, GGT, and platelet count 2
• Detailed medication history including prescribed, over-the-counter, and herbal products 2
• Screen for alcohol use with appropriate referral if positive 2
• Assess for symptoms: pruritus (suggests cholestasis), right upper quadrant pain, jaundice, nausea/vomiting 2

Trimester-Specific Differential Diagnosis

The timing of presentation is critical:

First Trimester

• Hyperemesis gravidarum causes elevated liver enzymes in 40-50% of severe cases; treat with cyclizine, doxylamine/pyridoxine, prochlorperazine, or promethazine 2, 3
• Consider pre-existing liver disease exacerbation 1

Second/Third Trimester

• Intrahepatic cholestasis of pregnancy (ICP): diagnose with serum bile acids >10 μmol/L (non-fasting in third trimester) 2
• Preeclampsia/HELLP syndrome: look for hypertension, hemolysis, thrombocytopenia 2, 3
• Acute fatty liver of pregnancy (AFLP): assess for encephalopathy, elevated lactate, high Swansea criteria score 2, 3

Management of Pre-Existing Liver Disease

The most critical principle: do NOT stop chronic liver disease medications during pregnancy—clinical deterioration poses greater risk than theoretical fetal harm. 2, 3

Medications to Continue

• Azathioprine, cyclosporine, tacrolimus, and prednisolone must not be stopped 3
• Ursodeoxycholic acid (UDCA) is safe throughout pregnancy and breastfeeding for primary biliary cholangitis and primary sclerosing cholangitis 2, 3
• Beta-blockers for variceal prophylaxis should continue unless contraindicated 3
• Wilson's disease therapy (zinc, D-penicillamine, trientine) continues with dose reduction of chelators in second/third trimesters 3

Monitoring Requirements

• Women on cyclosporine/tacrolimus require close monitoring for hypertension and preeclampsia 3
• Screen for gestational diabetes in women on glucocorticoids 3
• Women on >5 mg prednisolone daily for >3 weeks need increased glucocorticoid dose at delivery and with intercurrent illness 3

Expected Changes

• Approximately 50% of women with pre-existing cholestatic liver disease develop worsening or de novo pruritus, but most maintain stable hepatic function 2
• Up to 70% have postnatal deterioration of liver enzymes requiring close postpartum monitoring 2, 4

Management of Pregnancy-Specific Liver Disorders

Intrahepatic Cholestasis of Pregnancy (ICP)

Measure serum bile acids weekly from 32 weeks' gestation to identify concentrations >40 μmol/L, which indicate increased risk of adverse outcomes. 1

• Offer UDCA for bile acids >40 μmol/L to treat maternal pruritus and reduce spontaneous preterm birth risk 1, 2
• Plan elective delivery at 35 weeks' gestation for bile acids >100 μmol/L due to increased stillbirth risk after this gestational age 1, 2
• Consider additional therapies for pruritus (rifampicin, cholestyramine, guar gum, activated charcoal) though evidence is limited 1
• Perform repeated bile acid measurements when pruritus worsens, as higher levels correlate with reduced gestation length 2
• Monitor bile acids after starting UDCA, recognizing that UDCA itself is measured by enzymatic bile acid assays 1

Preeclampsia/HELLP Syndrome

• Control severe hypertension with labetalol, nifedipine, or methyldopa; intravenous therapy may be required 2, 3
• Administer magnesium sulfate to prevent eclamptic seizures in women with severe hypertension 2, 3
• Deliver promptly once maternal coagulopathy and severe hypertension are corrected 2, 3

Acute Fatty Liver of Pregnancy (AFLP)

• Consider intensive care admission for women with encephalopathy, elevated serum lactate, or high Swansea criteria score 2, 3
• Expedite delivery once coagulopathy and metabolic derangements are treated 2, 3
• Recovery is typically rapid after delivery with supportive care 4

Special Considerations for Specific Conditions

Autoimmune Hepatitis (AIH)

• Continue prednis(ol)one, budesonide, and thiopurines throughout pregnancy, including for de novo AIH diagnosed during pregnancy 3
• Consider increasing immunosuppression postpartum due to high flare risk 3, 4
• Women have increased rates of gestational diabetes, hypertensive disorders, preterm birth, and fetal growth restriction requiring close obstetric surveillance 3

Primary Sclerosing Cholangitis (PSC)

• Perform ultrasound or MRCP when cholestasis worsens to exclude obstruction or high-grade strictures accessible to endoscopic balloon dilatation 2
• MRCP is safe at any gestation 2

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

• Screen high-risk women with increased surveillance for gestational diabetes and hypertensive disease 2
• Implement lifestyle modifications including dietary advice 2
• Optimize treatment of metabolic comorbidities before conception and continue during pregnancy 2
• Encourage breastfeeding in women with MASLD 2, 4

Cirrhosis and Portal Hypertension

• Women must undergo screening endoscopy within 1 year prior to conception to assess for varices and institute primary prophylaxis 3
• Perform endoscopic band ligation for high-risk varices during pregnancy 3
• Delivery should be performed for obstetric indications, considering severity and distribution of portal hypertension 3

Diagnostic Imaging Safety

• 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
• Liver biopsy may be performed when benefits outweigh risks 1, 3

Postpartum Management

• Monitor liver function tests until complete normalization, which should occur within 3 months post-delivery 2, 4
• If liver enzymes remain abnormal beyond 3 months, investigate for underlying liver disease 2, 4
• Consider genetic screening if there is family history of hepatobiliary disease, early onset, or severe disease (particularly ABCB11, ABCB4, or ATP8B1 variants) 4
• ICP symptoms typically resolve within days to weeks after delivery 4

Critical Pitfalls to Avoid

• Never stop azathioprine, cyclosporine, tacrolimus, or prednisolone during pregnancy—disease flare risk outweighs theoretical fetal risks 2, 3
• Do not use obeticholic acid in pregnancy due to lack of safety data 2
• Do not assume all elevated liver enzymes will resolve spontaneously—ensure active monitoring until normalization 4
• Do not discontinue immunosuppressive medications in women with autoimmune hepatitis postpartum, as flares are common 3, 4
• Do not delay investigation beyond 3 months if liver function tests remain abnormal postpartum 4

Multidisciplinary Approach

Women with liver diseases of pregnancy associated with increased risk of maternal or fetal morbidity or mortality should be managed by a multidisciplinary team including a physician, obstetrician, and midwife with expertise in the field. 1 If not available locally, refer to a center where this approach can be implemented 1

All women with chronic liver disease or history of gestational liver disease should be offered pre-pregnancy counseling from a team with expertise in managing these disorders. 1, 3