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Intrahepatic 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

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Intrahepatic Cholestasis of Pregnancy

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  1. Intrahepatic Cholestasis of Pregnancy Rare

  2. 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)

  3. 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

  4. 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

  5. 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)

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. Case Study

  12. What is the Problem

  13. 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

  14. 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

  15. Questions?

  16. Inherited and PediatricLiver Disease A Brief Overview

  17. Inherited and Pediatric Liver Diseases • Wilson Disease • Hereditary hemochromatosis • Alpha 1 Antitrypsin Deficiency • Inborn errors of metabolism • Fibrocystic diseases • Pediatric cholestatic diseases • Porphyria

  18. 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

  19. 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

  20. 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

  21. 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

  22. 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

  23. Wilson DiseaseInvolves Other Organs • Cardiomyopathy • Muscles: Rhabdomyolysis • Pancreatitis • Endocrine disorders

  24. 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

  25. 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

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

  27. 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

  28. 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

  29. 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

  30. Case Study

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