Download Cholestasis of Pregnancy

Intrahepatic
Cholestasis of
Pregnancy
Rare
Cholestasis:
What Does it Mean?
 Pathology:
Histological
demonstration of bile in liver tissue
 Physiology: Measurable reduction in
hepatic secretion of solutes and
water
 Biochemical: Demonstrable
accumulation in blood of substances
normally excreted in bile (bilirubin,
cholesterol, bile acids)
Liver Diseases in Pregnancy

High estrogen state:
– Intrahepatic cholestasis of pregnancy
– Gallstones and sludge occur more frequently

Altered fatty acid metabolism:
– Acute fatty liver of pregnancy

Vascular diseases affect the liver:
– Pre-eclampsia
– HELLP Syndrome

Viral hepatitis:
– Vertical transmission of hepatitis B and C
Pathophysiology
 Liver
is an estrogen sensitive organ
– Estrogen affects organic anion transport
(bilirubin, bile acids)
 Bilirubin
excretion very mildly
impaired during normal pregnancy
 Biliary phospholipids secretion may
be impaired (gene mutation,
estrogen effect)
 Pregnancy is associated w/
decreases in GI motility, including
gall bladder motility
Physiological Consequences:
The Liver in Pregnancy
 Pregnant
women more likely to
become jaundiced if cholestatic or
hepatocellular injury occur
 Spider angiomata and palmar
erythema develop in up to 2/3
pregnancies due to effects of
estrogen and progesterone
 Cholecystectomy generally safe
 3rd Trimester see increased alk phos
2/2 developing placenta (not liver)
Intrahepatic Cholestasis of
Pregnancy (IHCP)
 Incidence
0.1% - 1% of pregnancies
 Recurrence in subsequent
pregnancies
 Pruritis develops in late 2nd and 3rd
trimester
 High transaminases - 40% > 10 x
(Hay)
 Bilirubin < 5mg/dL
 Total bile acids increase 100 fold
Intrahepatic Cholestasis of
Pregnancy (IHCP)
 Pathogenesis:
genetic, hormonal
– Women who develop clinical cholestasis
during pregnancy or with oral
contraceptives likely have genetic
polymorphisms in the genes responsible
for bile formation and flow
– Familial - 10% occurrence in 1st degree
relatives
– Hormonal – timing in pregnancy, twins
ICHP Clinical Features
 Pruritis
is the defining characteristic
 About 50% develop jaundice
 Disappears rapidly after delivery
 Severity is variable
 Rarely see a familial, progressive
course to cirrhosis
IHCP
Therapy
 Ursodeoxycholic
acid 10mg-
10mg/Kg/day
 Cholestyramine
 Vitamin K p.r.n.
 Reassurance and support
 Consider early delivery in severe
cases
– Unbearable maternal pruritis or risk of
fetal distress/death
– Deliver at 38 weeks if mild, at 36 weeks
for severe cases – if jaundice
Summary
 Normal
pregnancy is associated w/
characteristic, benign changes in
liver physiology
 Several unique diseases occur during
pregnancy and all resolve following
delivery
 Implications are disorder specific
Case Study
What is the Problem
Abnormal LFTs
Jaundice, pruritis,
abdominal pain,
and vomiting
Ultrasound
R/O Gallstones
Family Hx
Co-morbidities
Case study
(Hay)
 32
year old Para 1 @ 24 weeks
– two weeks of severe pruritis
– Pruritis and abnormal LFTs in last
pregnancy
– Known gallstones – no biliary dilatation
on ultrasound
– No abdominal pain, fever, rash
– Exam normal apart from pregnancy
– AST 277 ALT 655 Bili 2.1 Alk Phos 286
Case Study
 Hepatitis
A, B, C serologies non
reactive
 Negative autoimmune markers
 Urso 300 mg t.i.d. is prescribed
 32 weeks - feels well; D/C Urso
 33 weeks - pruritis - resume Urso
 37 weeks - delivery healthy baby;
D/C Urso
 2 weeks postpartum - LFTs normal
Questions?
Inherited and Pediatric
Liver Disease
A Brief Overview
Inherited and Pediatric Liver
Diseases
 Wilson
Disease
 Hereditary hemochromatosis
 Alpha 1 Antitrypsin Deficiency
 Inborn errors of metabolism
 Fibrocystic diseases
 Pediatric cholestatic diseases
 Porphyria
Wilson Disease
Autosomal recessive pattern of inheritance
 Defective gene: ATP7B on chromosome 13
 Leads to copper overload in liver, other
organs
 World wide distribution
 Incidence 1:30,000
 Carrier state 1:90
 Higher in Sardinians and Chinese,
infrequent in Africa

Wilson Disease
Variable Presentation
 Liver,
brain damage due to oxidative
stress
 Age of onset between 6 to 45
 May present as chronic liver disease
or acute liver failure, progressive
neurological disorder without liver
involvement or as a psychiatric
illness
Wilson Disease
Variable Presentation
 Neurological
decade:
sequelae occur 2nd – 3rd
– Increased or abnormal motor disorder
w/ tremor/dystonia
– Loss of movement w/ rigidity
 Psychiatric
sequelae
– Depression
– Phobias
– Psychosis
Wilson Disease
Ocular Features
 Classic
finding: Kayser-Fleisher ring,
a golden-brown deposit at the outer
rim of the cornea
 Sunflower cataract, less frequent.
Copper deposition in the lens
Wilson Disease
Involves Other Organs
 Hemolytic
anemia 2/2 sporadic
release of copper into the blood
 Renal involvement w/ Fanconi
syndrome, microscopic hematuria,
stones
 Arthritis 2/2 copper deposit in
synovial joints
 Osteoporosis, Vitamin D resistant
rickets 2/2 renal damage
Wilson Disease
Involves Other Organs
 Cardiomyopathy
 Muscles:
Rhabdomyolysis
 Pancreatitis
 Endocrine disorders
Wilson Disease
Diagnosis and Treatment
 Lab
findings: Decreased
ceruloplasmin and serum copper,
excess urinary copper
 24 hour urine x 3 to confirm
diagnosis
 Histology: Hepatic copper deposition
 Treatment is chelation:
– penicillamine, which increases urinary
copper excretion
– ammonium tetrathiomolybdate
Wilson Disease
Treatment
 Zinc
interferes w/ copper binding,
decreasing absorption
 Elimination of copper-rich foods from
the diet:
– Organ meats, shellfish, nuts, chocolate,
mushrooms
– Check drinking water supply
 Liver
transplantation if ALF
Wilson Disease
 Prognosis
is good on chelation
therapy if diagnosed promptly
 Affected sibling diagnosed and
treated prior to symptom onset has
the best prognosis
Pediatric Cholestatic Syndromes
 Neonatal
jaundice is common,
transient, usually due to immature
glucouronosyl transferase or to
breast feeding
 If jaundice persists after 14 days,
investigate
 Extrahepatic biliary atresia requires
urgent surgical repair of abnormal
hepatic or common bile ducts
Pediatric Cholestatic Syndromes
 Neonatal
hepatitis 2/2 infection,
idiopathic
 Intrauterine infections i.e., TORCH:
toxoplasmosis, rubella,
cytomegalovirus, herpes simplex
 Alagille Syndrome – few bile ducts,
congenital heart disease, skeletal
abnormalities
– Autosomal dominant, Incidence:
1:70,000
Pediatric Cholestatic Syndromes
 Progressive
Familial Intrahepatic
Cholestasis, another group of
autosomal recessive disorders
involved w/ errors in bile acid
synthesis and bile acid transport
– Byler Disease now called PFIC1
– Byler Syndrome now called PFIC 2
Case Study