Step 2 CK · Obstetrics & Gynecology

Liver Disease of Pregnancy: Cholestasis & Acute Fatty Liver

Name: Liver Disease of Pregnancy: Cholestasis & Acute Fatty Liver
Creator: Veli Bakalov, MD

One itches, one fails: sorting the liver diseases unique to late pregnancy

Obstetrics & Gynecology·Medical Disorders of Pregnancy·4 min read·9 high-yield points·Reviewed by Veli Bakalov, MD @HemeOncBuddy

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Intrahepatic cholestasis of pregnancy is late 2nd–3rd trimester pruritus of the palms and soles without a rash, confirmed by serum bile acids ≥10 µmol/L.
Ursodeoxycholic acid relieves cholestatic itching but does not clearly prevent stillbirth; give vitamin K if the PT is prolonged.
Deliver at 36 weeks when bile acids are ≥100 µmol/L; otherwise deliver between 36 and 39 weeks according to the level.
Cholestasis resolves after delivery but recurs in later pregnancies and with estrogen-containing contraceptives.
Acute fatty liver of pregnancy is third-trimester liver failure: vomiting, jaundice, hypoglycemia, prolonged INR, low fibrinogen, high ammonia and AKI.
AFLP is managed with ICU stabilization (dextrose, FFP, cryoprecipitate) and prompt delivery at any gestational age.
AFLP is linked to fetal LCHAD deficiency, so screen the newborn for a fatty acid oxidation disorder.
HELLP shows hemolysis, low platelets and hypertension with normal glucose; hypoglycemia and marked coagulopathy point to AFLP.
Hepatitis E can become fulminant in the third trimester; hyperemesis causes only a mild first-trimester transaminase rise.

Intrahepatic cholestasis of pregnancy

Presentation. Intense pruritus, worst on the palms and soles and at night, begins in the late second or third trimester. The skin shows only excoriations, with no primary rash, and jaundice is uncommon. Sex-steroid metabolites overload canalicular bile transport in genetically susceptible women (ABCB4 and ABCB11 variants), so the disorder clusters in families and is more common with twins.

Diagnosis. Pruritus plus serum total bile acids ≥10 µmol/L confirms it; transaminases rise mildly to moderately and bilirubin little. Atypical labs prompt a search for viral hepatitis, gallstones or preeclampsia, and a prolonged PT from fat malabsorption is corrected with vitamin K.

Treatment. Ursodeoxycholic acid (10 to 21 mg/kg/day, commonly 10 to 15) relieves itching and lowers bile acids and transaminases but has not been shown to prevent stillbirth. Antihistamines only aid sleep, and antenatal testing does not reliably predict the sudden fetal deaths.

≥10 µmol/Lserum bile acids: diagnostic with pruritus

≥100 µmol/Lbile acids: stillbirth risk rises sharply; deliver at 36 weeks

Delivery timing. Stillbirth, preterm birth, meconium-stained fluid and neonatal respiratory distress climb with the bile acid level. Bile acids ≥100 µmol/L call for delivery at 36 weeks; lower levels allow delivery between 36 and 39 weeks, depending on the level.

After delivery. Itching fades within days and labs normalize within weeks; persistent abnormalities suggest underlying liver disease such as primary biliary cholangitis or hepatitis C. Cholestasis commonly recurs in later pregnancies and can be provoked by estrogen-containing contraceptives.

Acute fatty liver of pregnancy

Mechanism. Failed mitochondrial fatty acid oxidation causes microvesicular fatty infiltration of hepatocytes. A fetus with long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency, an autosomal recessive defect, returns toxic long-chain metabolites to its heterozygous mother. Twins, a male fetus and low maternal BMI also raise risk; overall, AFLP complicates about 1 in 7,000–20,000 deliveries.

Presentation. Usually after 30 weeks or just postpartum: malaise, anorexia, nausea, vomiting and epigastric pain, then jaundice and encephalopathy. Polyuria and polydipsia from transient diabetes insipidus (the failing liver clears placental vasopressinase poorly) may come first, and about half of patients have hypertension.

Laboratory signature. Synthetic failure dominates: hypoglycemia, prolonged INR, low fibrinogen and antithrombin, high ammonia and bilirubin, acute kidney injury (rising creatinine and uric acid) and leukocytosis, with only moderately raised transaminases. The diagnosis is clinical, supported by ≥6 of the 14 Swansea criteria without another cause; biopsy showing microvesicular fat is rarely needed and risky with coagulopathy.

Stabilize in intensive careIV dextrose, FFP and cryoprecipitate for coagulopathy, blood pressure control
Deliver promptlyAt any gestational age; induction if progress will be quick, cesarean for usual indications after correcting coagulopathy
Support recoveryAnticipate postpartum hemorrhage; most women recover over weeks, and transplant is rarely needed
Test the newbornScreen for a fatty acid oxidation disorder and offer the parents genetic counseling

An infant with LCHAD deficiency risks hypoketotic hypoglycemia, cardiomyopathy and sudden death; if both parents are carriers, each pregnancy has a 25% chance of an affected fetus.

Distinguishing the mimics

Timing first. Hyperemesis gravidarum causes a mild first-trimester transaminase rise that resolves with rehydration; cholestasis appears in the late second or third trimester; preeclampsia, HELLP and AFLP belong to the third trimester and can present after delivery; viral hepatitis and gallstones occur at any time.

Cholestasis vs acute fatty liver vs HELLP

Feature	Intrahepatic cholestasis	Acute fatty liver	HELLP syndrome
Timing	Late 2nd–3rd trimester	3rd trimester or postpartum	3rd trimester or postpartum
Hallmark	Pruritus of palms and soles, no rash	Vomiting, abdominal pain, jaundice, encephalopathy	Hypertension, RUQ or epigastric pain
Key labs	Bile acids ≥10 µmol/L; mild transaminase rise	Hypoglycemia, ↑INR, ↓fibrinogen, ↑ammonia, AKI	Hemolysis, ↑LDH, platelets <100,000/μL; normal glucose
Maternal danger	Low	Liver failure, hemorrhage	Hemorrhage, eclampsia, hepatic rupture
Management	Ursodiol; deliver at 36–39 weeks by bile acid level	Stabilize and deliver at any gestation	Magnesium, BP control, delivery

HELLP versus AFLP. HELLP brings hemolysis (schistocytes, raised LDH), platelets <100,000/μL and hypertension with normal glucose and usually normal INR and fibrinogen; hypoglycemia, low fibrinogen and high ammonia point to AFLP. The two can overlap, and both are cured by delivery.

Viral hepatitis. Transaminases often exceed 1,000 with positive serology. Hepatitis E, spread fecal-orally in South Asia and Africa, can become fulminant in the third trimester with high maternal mortality. Herpes simplex hepatitis causes fever and very high transaminases, often without skin lesions or much jaundice, and needs empiric IV acyclovir.

Gallstones. Estrogen raises biliary cholesterol and progesterone slows gallbladder emptying, so biliary colic and cholecystitis are common in pregnancy; RUQ pain after meals, fever and a Murphy sign lead to ultrasound, while bile acids and glucose stay normal.