Cholestasis of pregnancy

Question 1

How common is ICP?

Answer 1

0.3-15.%

Question 2

What is ICP?

Answer 2

Hepatic disorder characterized by pruritis and an elevation in serum bile acid levels

Question 3

What is the pathophysiology of ICP?

Answer 3

fetal arrhythmia or vasospasm of placental chorionic surface vessels induced by high levels of bile acids; also activate myometrial oxytocin receptors

Question 4

What causes ICP?

Answer 4

unknown-genetic, hormonal and environmental

Genetic ABCB4(adenosine triphosphate binding cassette, subfamily B, member 4) gene encoding MDR3(multidrug resistance 3) protein involved in PFIC3(progressive familial intrahepatic cholestasis) 

Estrogen/Progesterone-common in twins, sulfated progesterone metabolites may result in saturation of hepatic transport system 

IVF 

Environmental-Chile, colder months in Chile and Scandivania, Bolivia

Question 5

What are ICP risk factors?

Answer 5

Preexisting hepatobiliary dx – cirrhosis, gallstones, cholecystitis, nonalc pancreatitis, mult gestation, AMA, genetic

Question 6

List ddx for 2T/3T pruritis with a rash

Answer 6

atopic eruption of pregnany (AEP_, polymorphic eruption of pregnancy (PEP), pemphigoid gestationis (PG) and ICP.

Question 7

List ddx for 2T/3T pruritis without a rash

Answer 7

chronic renal failure, hypo/hyperThyroidism, liver dx, malabsorption, parsitosis/helminthosis, HIV, Hodgkin dx, Leukemia, NH-Lymphoma, Polycythemia rubra vera, Tumors (paraneoplastic), Drugs (HCTZ, opioids), multiple sclerosis, psychiatric dx – anxiety/depression/OCD

Question 8

List causes of bile acid elevation

Answer 8

primary biliary cholangitis, obstructive bile duct lesion, primary sclerosing cholangitis, drugs (TMP-SMX, phenothazines, amp), liver tumor, EBV/CMV, hematic amyloidosis, lymphoma/solid organ malignancies, hepatic sarcoidosis, AI hepatitis, idiopathic adulthood ductopenia, TPN, familial ICP. Cirrhosis, sickle cell ICP, hepatic congestion from HF, crohn disease

Question 9

What conditions is ICP associated with?

Answer 9

PreE and AFLP, Hepatobiliary cancer, immune mediated disease, CVD

Question 10

What are s/s of ICP?

Answer 10

pruritus on palms and soles of feet, worse at night, jaundice and excoriations due to scratching

Question 11

How do you diagnose ICP?

Answer 11

total and fractionated (cholic, chenodeoxycholic and deoxycholic) bile acid levels – 4 to 14 days for results with mass spectrometry and liquid chromatography
Vs enzymatic assay 4 hr-4 days

Follow-up labs yes, but not weekly, and repeat 4-6 weeks ppm

increased bile acids 
elevated cholic/chenodeoxycholic acid ratio 
decreased glycine/taurine ratio 
increased alk phos, tbili (usually max of 6 mg/dL) and dbili 
GGT nml (differentiates from other cholestatic markers) 
AST/ALT >1000U/L 
PT usually nml (reflects Vitamin K def if abnml often caused by cholestyramine) 

Ultrasound-biliary ducts not dilated, hepatic parenchyma nml

Dx - pruritis with elevated total serum bile acids (>10 umol/L) +/- ALT/AST

+/- liver biopsy: bile plugs in hepatocytes and canaliculi in zone 3

Question 12

Ppm considerations

Answer 12

Refer to liver specialist, if not normalized

Breastfeeding NOT contraindicated

Question 13

When do you deliver ICP?

Answer 13

36 0/7-39 0/7 wks or upon diagnosis after 37 wks; no FLM

TBA >/= 100 umol/L delivery at 36 weeks

Lancet 2019 BA<100 not associated with adverse perinatal outcome

Question 14

Who would you delivery earlier than 37-39 weeks?

Answer 14

excruciating and unremitting pruritis not relieved with pharmacotherapy,

  prior h/o fetal demise before 36 wks due to ICP with ICP recurring in current pregnancy 

  Preexisting or acute hepatic disease w/ clinical or lab evidence of worsening hepatic function

Question 15

What is the treatment for ICP?

Answer 15

Ursodeoxycholic acid - 300 mg TID (10-15 mg/kg/day-max 21mg/kg/day) until delivery

increases bile flow. Relieves pruritis, improves liver biochemical tests 

concern that bile acids cross placenta and may lead to fetal toxicity 

Hydroxyzine 25 - 50 mg/day. Antihistamine. May aggravate respiratory difficulties in preterm babies.

Cholestyramine 8-16 g/day

Decreases ileal absorption of bile salts, increasing fecal excretion by binding to bile acids in the gut 

May increase steatorrhea/GI side effects and exacerbate Vitamin K deficiency (treat hypoprothrombinemia before delivery to prevent hemorrhage) 

SAMe(S adenosyl methionine) - 800 mg/day IV (not used, but studied)

Other uncertain-dexamethasone, charcoal, UV light, topical emollients, phenobarbital

Rifampin –add to UDCA

Diphenhydramine (Benadryl)

Calamine lotion, menthol creams

Question 16

Maternal complications of ICP

Answer 16

PTD, meconium-stained amniotic fluid, reeclampsia and stillbirth.

Question 17

Fetal complications of ICP

Answer 17

Prematurity, meconium stained amniotic fluid, IUFD, increased RDS (bile acids entering lungs), Stillbirth incidence after 37 wks is 1.2 % and fetal arrhythmia

Question 18

What causes fetal arrhythmia in ICP?

Answer 18

taurocholate, principal bile acid (crosses placenta) raised in fetal comptmt causes abnml cardiomyocyte contractions, rhythm and desynchronication of calcium dynamics.

vasospasm of placental chorionic surf vessels from high bile acids.

Question 19

Bile acids and associated morbidity/mortality rate

Answer 19

<10 28% (complication rates)
10-40 29%
40-100 19%
>100 60%

Question 20

Recurrence rate of ICP

Answer 20

60-70% up to 90%

Question 21

ICP prognosis

Answer 21

may develop hepatobiliary dx – chronic hepatitis, liver fibrosis, cirrhosis, hep C