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7/28/2019 Group 4 Slides Pm After Break

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Intrahepatic

Cholestasis ofPregnancy

Rare


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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 organEstrogen affects organic anion transport

(bilirubin, bile acids)

Bilirubin excretion very mildlyimpaired during normal pregnancy

Biliary phospholipids secretion maybe impaired (gene mutation,

estrogen effect)Pregnancy is associated w/

decreases in GI motility, including

gall bladder motility


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Physiological Consequences:

The Liver in Pregnancy

Pregnant women more likely tobecome jaundiced if cholestatic orhepatocellular injury occur

Spider angiomata and palmarerythema develop in up to 2/3pregnancies due to effects ofestrogen and progesterone

Cholecystectomy generally safe

3rd Trimester see increased alk phos2/2 developing placenta (not liver)


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Intrahepatic Cholestasis of

Pregnancy (IHCP)

Incidence 0.1% - 1% of pregnancies

Recurrence in subsequentpregnancies

Pruritis develops in late 2nd and 3rdtrimester

High transaminases - 40% > 10 x

(Hay)

Bilirubin < 5mg/dL

Total bile acids increase 100 fold


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Intrahepatic Cholestasis of

Pregnancy (IHCP)

Pathogenesis: genetic, hormonal

Women who develop clinical cholestasisduring pregnancy or with oral

contraceptives likely have geneticpolymorphisms in the genes responsiblefor bile formation and flow

Familial - 10% occurrence in 1st

degreerelatives

Hormonal timing in pregnancy, twins


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ICHP Clinical Features

Pruritis is the defining characteristic

About 50% develop jaundice

Disappears rapidly after deliverySeverity is variable

Rarely see a familial, progressive

course to cirrhosis


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IHCP

Therapy

Ursodeoxycholic acid 10mg-10mg/Kg/day

Cholestyramine

Vitamin K p.r.n.Reassurance and support

Consider early delivery in severe

casesUnbearable 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 inliver physiology

Several unique diseases occur duringpregnancy and all resolve followingdelivery

Implications are disorder specific


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Case Study


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What is the Problem

Abnormal LFTs

Jaundice, pruritis,

abdominal pain,

and vomiting

Ultrasound

R/O GallstonesFamily Hx Co-morbidities


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Case study

(Hay)

32 year old Para 1 @ 24 weeks

two weeks of severe pruritis

Pruritis and abnormal LFTs in lastpregnancy

Known gallstones no biliary dilatationon 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 nonreactive

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 diseasesPorphyria


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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 1:30,000

Carrier state 1:90 Higher in Sardinians and Chinese,

infrequent in Africa


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Wilson Disease

Variable Presentation

Liver, brain damage due to oxidativestress

Age of onset between 6 to 45

May present as chronic liver diseaseor acute liver failure, progressiveneurological disorder without liverinvolvement or as a psychiatricillness


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Wilson Disease

Variable Presentation

Neurological sequelae occur 2nd 3rddecade: Increased or abnormal motor disorder

w/ tremor/dystoniaLoss of movement w/ rigidity

Psychiatric sequelaeDepression

Phobias

Psychosis


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Wilson Disease

Ocular Features

Classic finding: Kayser-Fleisher ring,a golden-brown deposit at the outerrim of the cornea

Sunflower cataract, less frequent.Copper deposition in the lens


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Wilson Disease

Involves Other Organs

Hemolytic anemia 2/2 sporadicrelease of copper into the blood

Renal involvement w/ Fanconisyndrome, microscopic hematuria,stones

Arthritis 2/2 copper deposit insynovial joints

Osteoporosis, Vitamin D resistantrickets 2/2 renal damage


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Wilson Disease

Involves Other Organs

Cardiomyopathy

Muscles: Rhabdomyolysis

PancreatitisEndocrine disorders


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Wilson Disease

Diagnosis and Treatment

Lab findings: Decreasedceruloplasmin and serum copper,excess urinary copper

24 hour urine x 3 to confirmdiagnosis

Histology: Hepatic copper deposition

Treatment is chelation:penicillamine, which increases urinary

copper excretion

ammonium tetrathiomolybdate


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Wilson Disease

Treatment

Zinc interferes w/ copper binding,decreasing absorption

Elimination of copper-rich foods fromthe 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 chelationtherapy if diagnosed promptly

Affected sibling diagnosed andtreated prior to symptom onset hasthe best prognosis


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Pediatric Cholestatic Syndromes

Neonatal jaundice is common,transient, usually due to immatureglucouronosyl transferase or to

breast feeding

If jaundice persists after 14 days,investigate

Extrahepatic biliary atresia requiresurgent surgical repair of abnormalhepatic or common bile ducts


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Neonatal hepatitis 2/2 infection,idiopathic

Intrauterine infections i.e., TORCH:

toxoplasmosis, rubella,cytomegalovirus, herpes simplex

Alagille Syndrome few bile ducts,

congenital heart disease, skeletalabnormalities

Autosomal dominant, Incidence:

1:70,000


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Progressive Familial IntrahepaticCholestasis, another group ofautosomal recessive disorders

involved w/ errors in bile acidsynthesis and bile acid transport

Byler Disease now called PFIC1

Byler Syndrome now called PFIC 2


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Case Study

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