Intrahepatic Cholestasis of Pregnancy (ICP)
Intrahepatic Cholestasis of Pregnancy (ICP), also called Obstetric Cholestasis, is a pregnancy-specific liver disorder characterized by:
- Pruritus (itching), especially palms and soles
- Elevated maternal serum bile acids
- Usually develops in the second or third trimester
- Resolves spontaneously after delivery
ICP is the most common pregnancy-specific liver disease and is associated with significant fetal morbidity and mortality, despite relatively benign maternal outcomes.
Etiology
ICP is multifactorial.
1. Hormonal Factors
Pregnancy hormones impair bile transport.
Estrogen
- Reduces bile acid excretion
- Inhibits hepatocyte transport pumps
Progesterone metabolites
- Direct cholestatic effects
- Impair canalicular bile flow
This explains:
- Third-trimester predominance
- Increased incidence in twins
- Resolution after delivery
2. Genetic Factors
Mutations affecting bile transporters:
|
Gene |
Protein |
|
ABCB4 |
MDR3 |
|
ABCB11 |
BSEP |
|
ATP8B1 |
FIC1 |
|
TJP2 |
Tight junction protein |
These mutations impair biliary secretion.
3. Environmental Factors
- Selenium deficiency
- Vitamin D deficiency
- Seasonal variation
- Geographic clustering
Pathophysiology
Normally:Hepatocyte → Canaliculus → Bile ducts → Intestine
In ICP:
- Estrogen + genetic predisposition
- Impaired bile acid transport
- Bile acids accumulate in blood
Result:
Maternal
- Pruritus
- Mild cholestasis
Fetal
Bile acids cross placenta causing:
- Placental vasoconstriction
- Umbilical vein constriction
- Fetal hypoxia
- Meconium passage
- Arrhythmias
- Sudden intrauterine death
Risk Factors
|
Risk Factor |
Association |
|
Previous ICP |
Strong |
|
Twin pregnancy |
Strong |
|
IVF pregnancy |
Increased |
|
Maternal age >35 years |
Increased |
|
Hepatitis C |
Increased |
|
Gallstones |
Increased |
|
Family history |
Increased |
|
Chronic liver disease |
Increased |
Clinical Features
Hallmark Symptom-Pruritus(Present in >80%)
Characteristics:
- Palms and soles first
- Worse at night
- Progressive
- No primary skin lesions
Excoriations occur due to scratching.
Associated Symptoms
|
Symptom |
Frequency |
|
Generalized itching |
Common |
|
Sleep disturbance |
Common |
|
Fatigue |
Common |
|
Dark urine |
Sometimes |
|
Pale stools |
Sometimes |
|
Mild RUQ discomfort |
Occasional |
|
Jaundice |
10–20% |
Physical Examination
Usually normal except:
- Scratch marks
- Excoriations
- Mild jaundice
Hepatomegaly absent.
Ascites absent.
Encephalopathy absent.
Diagnostic Criteria
Pruritus AND. Elevated bile acids. AND. Exclusion of other liver diseases
Laboratory Findings
|
Investigation |
Findings / Interpretation |
|
Serum Total Bile Acids (TBA) |
Most important test for diagnosis and risk stratification. |
|
Normal TBA |
<10 µmol/L |
|
Diagnostic TBA |
≥10–19 µmol/L (cutoff depends on laboratory) |
|
Severity Classification |
Fetal risk correlates directly with bile acid level. |
|
Mild ICP |
<40 µmol/L |
|
Moderate ICP |
40–99 µmol/L |
|
Severe ICP |
≥100 µmol/L |
|
ALT (Alanine Aminotransferase) |
Most sensitive liver enzyme. May be mildly elevated or rise to 2–30× the upper limit of normal. |
|
AST (Aspartate Aminotransferase) |
Usually elevated. |
|
ALP (Alkaline Phosphatase) |
Not useful diagnostically. Placenta produces ALP normally during pregnancy; therefore ALP can be markedly elevated even in healthy pregnant women. |
|
Bilirubin |
Usually normal. May rise mildly. Generally <5 mg/dL. |
|
GGT (Gamma-Glutamyl Transferase) |
Usually normal. Elevated GGT suggests an alternative diagnosis. |
|
Coagulation Profile (PT/INR) |
Usually normal. May become prolonged due to vitamin K deficiency in severe cholestasis. |
Ultrasound
Usually normal.
May show:Gallstones/Sludge
Purpose:Mainly to exclude other pathology.
Fetal Complications
|
Fetal Complication |
Details |
|
Preterm Birth |
Can be spontaneous or iatrogenic (medically indicated early delivery). Most common fetal complication of ICP. |
|
Meconium-Stained Liquor |
Elevated maternal bile acids stimulate the fetal colon, resulting in passage of meconium into the amniotic fluid. |
|
Fetal Distress |
Occurs due to placental dysfunction, umbilical vessel vasoconstriction, and fetal hypoxia. |
|
Neonatal Respiratory Distress |
Can occur even in near-term infants. |
|
Stillbirth |
Most feared complication. Often sudden, unpredictable, and may occur without preceding warning abnormalities on fetal surveillance. Risk rises sharply when serum bile acids ≥100 µmol/L. |
Differential Diagnosis of Pruritus in Pregnancy
|
Condition |
Distinguishing Feature |
|
ICP |
Elevated bile acids |
|
PUPPP |
Rash present |
|
Atopic eruption |
Eczema-like lesions |
|
Pemphigoid gestationis |
Bullae |
|
Drug reaction |
Exposure history |
|
Scabies |
Burrows, contacts affected |
Differential Diagnosis of Deranged LFTs in Pregnancy
|
Condition |
Key Features |
|
ICP |
Itching + ↑ bile acids |
|
Hyperemesis gravidarum |
Early pregnancy |
|
Preeclampsia |
HTN + proteinuria |
|
HELLP syndrome |
Hemolysis + thrombocytopenia |
|
Acute fatty liver of pregnancy |
Liver failure features |
|
Viral hepatitis |
Very high transaminases |
|
Gallstones |
Biliary pain |
|
Autoimmune hepatitis |
Autoantibodies |
Management
Ursodeoxycholic Acid (UDCA)
First-line treatment.
Mechanism
- Improves bile flow
- Replaces toxic bile acids
- Protects hepatocytes
Dose-10–15 mg/kg/day
Typical:-300 mg twice daily or 300 mg three times daily
May increase up to:21 mg/kg/day
Symptomatic Treatment of Pruritus
Antihistamines
Examples:Chlorpheniramine/Hydroxyzine
Limited effect on cholestatic itching but improve sleep.
Topical Measures
- Emollients
- Cooling lotions
- Oatmeal baths
Provide temporary relief.
Vitamin K
Consider when:
- Prolonged PT/INR
- Steatorrhea
- Severe cholestasis
Dose:10 mg orally daily.
Fetal Surveillance
Important but imperfect.
Methods
|
Test |
Use |
|
Daily fetal movement count |
Common |
|
NST |
Weekly/Biweekly |
|
CTG |
Surveillance |
|
BPP |
Adjunct |
|
Growth ultrasound |
Serial monitoring |
Important Point
Normal fetal surveillance does NOT eliminate stillbirth risk.
Stillbirth may occur suddenly.
Timing of Delivery
|
ICP Severity (Based on Total Bile Acids) |
Recommended Timing of Delivery |
|
Mild ICP (<40 µmol/L) |
38–39 weeks |
|
Moderate ICP (40–99 µmol/L) |
36–38 weeks |
|
Severe ICP (≥100 µmol/L) |
35–36 weeks |
|
Important Guideline Point |
Many guidelines recommend delivery at 36 weeks for severe ICP because the risk of stillbirth rises substantially thereafter. |
Postpartum Course
|
Parameter |
Resolution |
|
Itching |
24–72 hr |
|
Bile acids |
Days–weeks |
|
ALT/AST |
Weeks |
|
Jaundice |
Weeks |
Postpartum Follow-Up
Repeat:
- LFTs
- Bile acids
At: 4–12 weeks postpartum
Persistent abnormalities require evaluation for:
- Chronic liver disease
- Primary biliary cholangitis
- Primary sclerosing cholangitis
- Viral hepatitis
- Genetic cholestatic disorders