Intrahepatic Cholestasis of Pregnancy

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Intrahepatic Cholestasis of Pregnancy

• Rare

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CholestasisWhat 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)

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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

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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

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Physiological ConsequencesThe 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)

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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 gt 10 x (Hay)
• Bilirubin lt 5mg/dL
• Total bile acids increase 100 fold

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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

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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

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IHCPTherapy

• 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

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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

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Case Study
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What is the Problem
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Case study(Hay)

• 32 year old Para 1 _at_ 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

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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

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Questions?
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Inherited and PediatricLiver Disease

• A Brief Overview

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Inherited and Pediatric Liver Diseases

• Wilson Disease
• Hereditary hemochromatosis
• Alpha 1 Antitrypsin Deficiency
• Inborn errors of metabolism
• Fibrocystic diseases
• Pediatric cholestatic diseases
• Porphyria

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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 130,000
• Carrier state 190
• Higher in Sardinians and Chinese, infrequent in
  Africa

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Wilson DiseaseVariable 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

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Wilson DiseaseVariable Presentation

• Neurological sequelae occur 2nd 3rd decade
• Increased or abnormal motor disorder w/
  tremor/dystonia
• Loss of movement w/ rigidity
• Psychiatric sequelae
• Depression
• Phobias
• Psychosis

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Wilson DiseaseOcular 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

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Wilson DiseaseInvolves 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

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Wilson DiseaseInvolves Other Organs

• Cardiomyopathy
• Muscles Rhabdomyolysis
• Pancreatitis
• Endocrine disorders

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Wilson DiseaseDiagnosis 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

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Wilson DiseaseTreatment

• 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

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Wilson Disease

• Prognosis is good on chelation therapy if
  diagnosed promptly
• Affected sibling diagnosed and treated prior to
  symptom onset has the best prognosis

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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

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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 170,000

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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

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Case Study