What is the recommended diagnostic work‑up and management for a pregnant patient presenting with liver abnormalities, including hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, acute fatty liver of pregnancy, HELLP syndrome (hemolysis, elevated liver enzymes, low platelets), or decompensated chronic liver disease?

Liver Disorders in Pregnancy: Diagnostic Work-Up and Management

For any pregnant patient with liver abnormalities, immediately determine gestational age and pattern of liver enzyme elevation (hepatocellular vs. cholestatic), then systematically exclude pregnancy-specific conditions before investigating pre-existing or coincidental liver disease. 1

Initial Diagnostic Framework

Immediate Laboratory Assessment

• Obtain comprehensive liver panel: AST, ALT, alkaline phosphatase, GGT, total and direct bilirubin, albumin, and platelet count 1, 2
• Add pregnancy-specific markers: serum bile acids (non-fasting), coagulation studies (PT/INR, fibrinogen), complete blood count with peripheral smear, uric acid, creatinine, and lactate 1
• Assess for preeclampsia features: blood pressure measurement and urine protein quantification 1
• Screen for viral hepatitis: HAV IgM, HBsAg, HBc IgM, HCV antibody, HEV IgM, HSV DNA, CMV DNA, EBV antibodies 1, 3

Critical pitfall: Normal pregnancy increases alkaline phosphatase (up to 133-418 IU/L in third trimester) but AST, ALT, bilirubin, and GGT remain within non-pregnant ranges. 1, 2 Any elevation of aminotransferases or bilirubin is pathologic and requires investigation. 2

Medication and Exposure History

• Document all medications: prescribed, over-the-counter, herbal products, and supplements to identify potential drug-induced liver injury 1, 2
• Screen for alcohol use and refer for management when appropriate 1, 2

Trimester-Specific Differential Diagnosis

First Trimester (0-12 weeks)

Hyperemesis gravidarum is the primary pregnancy-specific cause:

• Liver enzyme elevations occur in 40-50% of severe cases and are typically mild (AST/ALT <300 IU/L) 1
• Management: First-line antiemetics include cyclizine, doxylamine/pyridoxine, prochlorperazine, or promethazine 2
• If liver tests are markedly elevated, screen for primary liver disease including viral hepatitis, autoimmune hepatitis, and Wilson disease 1

Second and Third Trimester (13-40 weeks)

Intrahepatic Cholestasis of Pregnancy (ICP)

Diagnosis:

• Serum bile acids >10 μmol/L in the setting of pruritus (typically after 30 weeks gestation) 1
• AST/ALT may be elevated 2-30 fold; bilirubin usually <6 mg/dL 1, 2
• Classic presentation: generalized pruritus without rash, most severe on palms and soles 2
• If initial bile acids are normal but pruritus persists, repeat testing as postprandial measurements detect higher levels than fasting samples 2

Management:

• Measure serum bile acids weekly from 32 weeks' gestation to identify concentrations >40 μmol/L, which indicate increased risk of adverse outcomes 1
• Initiate ursodeoxycholic acid (UDCA) 10-15 mg/kg/day in divided doses when bile acids exceed 40 μmol/L to treat maternal pruritus and reduce spontaneous preterm birth risk 1
• For refractory pruritus, consider rifampicin, cholestyramine, guar gum, or activated charcoal, though evidence is limited 1
• Monitor bile acids after starting UDCA, recognizing that UDCA itself is measured by enzymatic bile acid assays 1

Delivery timing based on bile acid concentration: 1, 2

• >100 μmol/L: Deliver at 36 weeks or at diagnosis if after 36 weeks (stillbirth risk increases after 35 weeks)
• 40-100 μmol/L: Deliver between 36-39 weeks
• <40 μmol/L: Aim for term delivery at 39 weeks

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

Diagnosis:

• Consider HELLP a manifestation of severe preeclampsia occurring after 20 weeks gestation 1
• Hemolysis (elevated LDH, decreased haptoglobin, schistocytes on smear), AST/ALT elevation (typically 2-10 fold), platelet count <100×10⁹/L 1
• Hypertension and proteinuria typically present but may be absent in up to 15% of cases 1
• Up to 30% of HELLP cases present postpartum 4

Management:

• Evaluate serum liver tests as abnormalities are associated with adverse maternal outcomes, but do not use in isolation to guide care 1
• Transfuse platelets if count <100×10⁹/L due to increased risk of abnormal coagulation and adverse outcomes 1
• For non-severe hypertension (SBP 140-159 or DBP 90-109 mmHg): initiate oral labetalol, nifedipine, or methyldopa 1
• For severe hypertension (SBP >160 or DBP >110 mmHg): treat urgently in monitored setting with oral or intravenous labetalol, nifedipine, or methyldopa 1
• Administer magnesium sulfate to prevent eclamptic seizures 2
• Deliver promptly once maternal coagulopathy and severe hypertension are corrected 1, 2

Prevention for future pregnancies:

• First-trimester screening to assess risk of early-onset preeclampsia 1
• Aspirin prophylaxis 150 mg nightly starting before 16 weeks' gestation until 36 weeks for high-risk women 1
• Calcium supplementation (1.5-2 g elemental calcium/day) for women with low calcium intake (<800 mg/day) 1

Acute Fatty Liver of Pregnancy (AFLP)

Diagnosis:

• Classic triad: coagulopathy, hypoglycemia, and encephalopathy in third trimester 2, 3
• AST/ALT typically 300-500 IU/L (may be higher); bilirubin <5 mg/dL; marked coagulopathy (prolonged PT/INR, low fibrinogen) 1, 2
• Elevated serum lactate and elevated Swansea criteria score indicate severity 1

Management:

• Admit to intensive care if encephalopathy develops, serum lactate is elevated, MELD score >30, or Swansea criteria >7 1, 3
• Aggressively correct coagulopathy and metabolic derangements (hypoglycemia, hyperammonemia) 1, 2, 3
• Expedite delivery once coagulopathy and remediable metabolic derangements are treated; decisions about mode of delivery should be made jointly by obstetricians, hepatologists, and multidisciplinary team 1, 3
• Consider plasma exchange post-delivery to improve maternal disease severity and decrease time to recovery in women with severe hepatic impairment (limited data from small case series) 1
• Consider N-acetylcysteine for women requiring ICU admission, though data are limited 1
• Early referral to transplant center for severe hepatic impairment that may require transplantation 1, 3

Critical pitfall: AFLP carries 7-18% maternal mortality and 9-23% fetal mortality. 2 Do not delay delivery after maternal stabilization.

Diagnostic Imaging Strategy

Imaging Modality Selection

• First-line: Abdominal ultrasound without contrast is the preferred imaging modality throughout pregnancy 1, 2
• Limited Doppler study of hepatic vasculature can be used, but exposure time should be minimized 1
• Liver elastography is safe at any gestation, though liver stiffness and controlled attenuation parameter may increase slightly in third trimester as normal physiology 2

Advanced Imaging When Needed

• MRI/MRCP without gadolinium is preferred over CT imaging and safe at any gestation 1, 2
• Gadolinium is contraindicated in pregnancy because it crosses the placenta and accumulates in fetal urinary tract 1
• Abdominal CT without contrast is generally safe, but cumulative ionizing radiation exposure should be as low as possible and less than 50 mGy 1
• Use of iodinated contrast is recommended only if essential for diagnosis 1
• ERCP can be performed when clinically necessary (fetal radiation <0.1-0.5 mGy, well below 50 mGy threshold), ideally in second or third trimester 1, 2

Management of Pre-Existing Chronic Liver Disease

General Principles

• Continue most medications used for chronic liver disease management as stopping could cause clinical deterioration 2
• Do not stop immunosuppressive medications or disease-modifying treatments in women with pre-existing liver disease, as clinical deterioration poses greater risk 2

Specific Conditions

Chronic Hepatitis B

• Screen for HBsAg in first trimester to recognize and reduce risk of mother-to-child transmission 1
• Start tenofovir disoproxil fumarate at week 24-28 for pregnant women with HBV DNA >200,000 IU/ml or HBeAg-positive status; continue up to 12 weeks after delivery 1
• For women with advanced fibrosis or cirrhosis, continue tenofovir throughout pregnancy 1
• Breastfeeding is safe for infants born to mothers treated with tenofovir 1
• Immunoglobulin is not recommended as it is not effective at reducing mother-to-child transmission regardless of maternal HBV DNA titre 1

Chronic Hepatitis C

• Screen and counsel women of reproductive age to undergo antiviral treatment before pregnancy or after delivery and breastfeeding 1
• If necessary, directly acting agents can be considered during pregnancy after thorough discussion about potential risks and benefits with multidisciplinary team 1

Primary Biliary Cholangitis and Primary Sclerosing Cholangitis

• Continue UDCA during pregnancy 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
• 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 2

Autoimmune Hepatitis

• Continue immunosuppressive therapy throughout pregnancy to prevent flares 4
• Consider increasing dose postpartum due to risk of flares 4
• Azathioprine (at low doses), prednisone, and UDCA are compatible with breastfeeding 4

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

• Screen high-risk women with increased surveillance for gestational diabetes (17% vs 7% in non-CLD pregnancies) and hypertensive complications (16% vs 3.8-3.9%) 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, 4

Multidisciplinary Management

All women with liver diseases of pregnancy associated with increased risk of maternal or fetal morbidity or mortality should be managed by a multidisciplinary team that includes, at minimum, 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

Postpartum Follow-Up

• Monitor liver function tests until complete normalization, typically within 6 weeks for pregnancy-specific liver disorders 2, 4
• If liver tests remain abnormal beyond 3 months postpartum, investigate for underlying chronic liver disease 2, 4
• For women with history of ICP, consider genetic screening if there is family history of hepatobiliary disease, early onset, or severe disease (variants in ABCB11, ABCB4, or ATP8B1 genes) 4
• Recurrence risk for ICP in subsequent pregnancies is 45-70% 2
• Most HELLP cases resolve within 48-72 hours postpartum; continue antihypertensive therapy and monitor blood pressure closely 4
• Recovery from AFLP is typically rapid after delivery with supportive care 4