Intrahepatic Cholestasis of Pregnancy

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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 .

estrogen effect)  Pregnancy is associated w/ decreases in GI motility. bile acids)  Bilirubin excretion very mildly impaired during normal pregnancy  Biliary phospholipids secretion may be impaired (gene mutation. including gall bladder motility .Pathophysiology  Liver is an estrogen sensitive organ – Estrogen affects organic anion transport (bilirubin.

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) .

1% .1% of pregnancies  Recurrence in subsequent pregnancies  Pruritis develops in late 2nd and 3rd trimester  High transaminases .Intrahepatic Cholestasis of Pregnancy (IHCP)  Incidence 0.40% > 10 x (Hay)  Bilirubin < 5mg/dL  Total bile acids increase 100 fold .

Intrahepatic Cholestasis of Pregnancy (IHCP)  Pathogenesis: genetic. twins . 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.

progressive course to cirrhosis .ICHP Clinical Features  Pruritis is the defining characteristic  About 50% develop jaundice  Disappears rapidly after delivery  Severity is variable  Rarely see a familial.

 Reassurance and support  Consider early delivery in severe cases – Unbearable maternal pruritis or risk of fetal distress/death – Deliver at 38 weeks if mild.r.n. at 36 weeks for severe cases – if jaundice acid 10mg- .IHCP Therapy  Ursodeoxycholic 10mg/Kg/day  Cholestyramine  Vitamin K p.

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 .

and vomiting Ultrasound R/O Gallstones Family Hx Co-morbidities . pruritis.What is the Problem Abnormal LFTs Jaundice. abdominal pain.

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 .

i. D/C Urso  33 weeks .Case Study  Hepatitis reactive  Negative autoimmune markers  Urso 300 mg t. D/C Urso  2 weeks postpartum .delivery healthy baby.LFTs normal A.pruritis . C serologies non . is prescribed  32 weeks .resume Urso  37 weeks .feels well. B.d.

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. infrequent in Africa  .000  Carrier state 1:90  Higher in Sardinians and Chinese. other organs  World wide distribution  Incidence 1:30.

Wilson Disease Variable Presentation  Liver. 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 brain damage due to oxidative .

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 .

less frequent. a golden-brown deposit at the outer rim of the cornea  Sunflower cataract. Copper deposition in the lens .Wilson Disease Ocular Features  Classic finding: Kayser-Fleisher ring.

Wilson Disease Involves Other Organs  Hemolytic anemia 2/2 sporadic release of copper into the blood  Renal involvement w/ Fanconi syndrome. Vitamin D resistant rickets 2/2 renal damage . microscopic hematuria. stones  Arthritis 2/2 copper deposit in synovial joints  Osteoporosis.

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 .

nuts. shellfish. chocolate. decreasing absorption  Elimination of copper-rich foods from the diet: – Organ meats.Wilson Disease Treatment  Zinc interferes w/ copper binding. 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 .

investigate  Extrahepatic biliary atresia requires urgent surgical repair of abnormal hepatic or common bile ducts . usually due to immature glucouronosyl transferase or to breast feeding  If jaundice persists after 14 days.Pediatric Cholestatic Syndromes  Neonatal jaundice is common. transient.

congenital heart disease.e. TORCH: toxoplasmosis. cytomegalovirus.000 . Incidence: 1:70.. idiopathic  Intrauterine infections i. rubella.Pediatric Cholestatic Syndromes  Neonatal hepatitis 2/2 infection. herpes simplex  Alagille Syndrome – few bile ducts. skeletal abnormalities – Autosomal dominant.

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 .Pediatric Cholestatic Syndromes  Progressive Familial Intrahepatic Cholestasis.

Case Study .

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