Liver Pathology in Pregnancy

Introduction

• Liver disease complicates approximately 3% of all pregnancies, ranging from mild laboratory abnormalities to fulminant hepatic failure.^1,2
• Conditions are classified as pregnancy-specific (e.g., intrahepatic cholestasis, acute fatty liver of pregnancy, HELLP) or incidental to pregnancy (e.g., viral hepatitis, autoimmune hepatitis, Budd-Chiari).^1,2
• Pregnancy-specific disorders typically present in the late second or third trimester and may rapidly progress to maternal or fetal compromise.²
• The physiologic overlap between normal pregnancy and liver dysfunction (e.g., hyperdynamic circulation, hemodilution, reduced albumin, elevated alkaline phosphatase) can make diagnosis challenging.²
• Maternal morbidity and mortality are primarily driven by hepatic failure, coagulopathy, and obstetric complications such as preeclampsia and hemorrhage.²
• Fetal risks include preterm delivery, growth restriction, and stillbirth, depending on maternal disease severity.
• Obstetric indications determine the mode of delivery, but timely delivery is often lifesaving in acute maternal hepatic decompensation.²

Hepatic Physiology^1-4

• Normal pregnancy produces hormonal, hemodynamic, and metabolic adaptations that may mimic liver dysfunction.
• Estrogen and progesterone promote systemic vasodilation and increased cardiac output, resulting in a hyperdynamic circulation similar to that observed in chronic liver disease.
• Alkaline phosphatase increases two to fourfold from placental production; mild transaminase elevations can occur but are typically within the normal range for nonpregnant adults.
• Albumin concentration decreases due to hemodilution, which reduces oncotic pressure and alters drug-protein binding.
• Antithrombin III levels decline in normal pregnancy, producing a hypercoagulable state; in liver disease, this decrease may reflect impaired synthesis and contribute to unpredictable coagulation status.
• Portal pressures increase modestly in late pregnancy, and esophageal varices may develop even in women without preexisting liver disease.
• Spider hemangiomas and palmar erythema can appear physiologically in pregnancy but are also classic signs of chronic hepatic dysfunction.
• The physiologic overlap between pregnancy and hepatic pathology can delay recognition of liver disease and complicate anesthetic and obstetric management.

Liver Diseases in Pregnancy

Diseases Incidental to Pregnancy

• Incidental liver disease is that which may occur in any population but coincides with pregnancy.
• These include viral, autoimmune, vascular, metabolic, and gallbladder disease (Table 2).
• Disease manifestations and outcomes depend on the severity of hepatic dysfunction rather than etiology.
• Obstetric implications for incidental disease vary by disease type and can include fetal growth restriction, preterm delivery, neonatal respiratory distress syndrome, hypertensive complications, hemorrhage, and caesarean delivery.³
• Cirrhosis is an end-stage complication of chronic liver disease incidental to pregnancy. Although it is associated with anovulation, amenorrhea and infertility, the number of women becoming pregnant with cirrhosis is increasing.²
• Multidisciplinary care (obstetrics, hepatology, anesthesia) is essential, especially in women with cirrhosis or portal hypertension, who are at risk for variceal bleeding (up to 25%).⁴

Diseases Specific to Pregnancy

Anesthetic Considerations

General Considerations^1,3,5

• Management depends on the presence and severity of hepatic impairment, rather than solely on the disease type.
• Patients with liver disease without hepatic impairment can often be managed similarly to healthy parturients.
• Parturients with significant liver dysfunction should deliver at a Level II or III maternal care center with critical care, hepatology support, maternal-fetal medicine, and obstetric anesthesiology support.
• Goals should be to maintain intravascular volume and organ perfusion, correct coagulopathy, prevent hypoglycemia, and minimize hepatotoxic drug exposure.
• Multidisciplinary coordination (obstetric, anesthesia, hepatology, critical care, neonatology) is essential for optimal timing of delivery and anesthetic planning.
• Drug pharmacokinetics are altered: ↓ protein binding, ↑ volume of distribution, ↓ metabolism, and impaired excretion → require dose titration and cautious use of sedatives and opioids.
  • These changes place patients at high risk for local anesthetic toxicity, specifically bupivacaine toxicity, as it is highly protein-bound.¹
  • Patients with hemodynamic instability or encephalopathy may be particularly sensitive to anesthetics, opioids, and benzodiazepines, and judicious use is recommended.³
• Avoid hepatotoxins: acetaminophen ≤ 2 g/day in decompensated disease; avoid nonsteroidal anti-inflammatory drugs due to renal and bleeding risk and fetal closure of ductus arteriosus (depending on gestational age)
• Monitor for hypoglycemia and hemodynamic instability peridelivery; arterial line or central access may be appropriate for severe disease.

Neuraxial Anesthesia^1,5

• Preferred for obstetric anesthesia and analgesia when coagulation parameters permit.
• Neuraxial techniques are preferred in obstetric patients for analgesia and surgical anesthesia.1
• Contraindications: hypovolemia, thrombocytopenia (platelets < 70,000 × 106/L), and coagulopathy (INR > 1.5)¹
• Assess platelet trend and illness trajectory before block placement; re-check coagulation in evolving conditions (e.g., HELLP, AFLP).
• The potential for impaired clearance of local anesthetics and opioids should be considered.⁵
• Epidural test dose should be incremental; metabolism and clearance of local anesthetics may be reduced → ↑ risk of toxicity (especially bupivacaine).
• Systemic analgesia with inhaled nitrous oxide or opioid patient-controlled analgesia may be considered for labor in cases where neuraxial is contraindicated. Both alternatives require patient cooperation.
• Close monitoring for respiratory depression and sedation is needed for opioid-based techniques.
  • Remifentanil is an ideal agent as it does not rely on hepatic metabolism.³

General Anesthesia^3,5

• Indicated for obstetric emergencies, decompensated hepatic failure, or when neuraxial is contraindicated
• Aspiration risk is elevated → employ rapid sequence induction and video laryngoscopy.
• Use agents with minimal hepatic metabolism (propofol, sevoflurane, desflurane, isoflurane, nitrous oxide)
• Anticipate increased sensitivity to induction agents and opioids; titrate doses to effect.
• Maintain stable perfusion pressure and avoid hypotension to preserve hepatic and uteroplacental blood flow.
• Uterotonics (oxytocin, carboprost, methylergometrine) may be used at standard doses despite hepatic metabolism.
• Intraoperative bleeding is typically due to portal hypertension and mucosal friability rather than isolated coagulopathy.
• General anesthesia does not worsen maternal mortality, provided hemodynamics are well maintained.