IN THE NAME OF GOD

LIVER DISEASE OCCURING DURING PREGNANCYDURING PREGNANCY

SOME LIVER DISEASES OR MULTI SYSTEM DISEASES WITH HEPATIC MANIFESTATIONSDISEASES WITH HEPATIC MANIFESTATIONS ARE SPECIFIC TO PREGNANCY1 INTRA HEPATIC CHOLESTASIS OF1_INTRA HEPATIC CHOLESTASIS OF PREGNANCY2 ACUTE FATTY LIVER2_ACUTE FATTY LIVER3_HEG4_PIH5 HELLP5_HELLP

PREGNANCY RELATED PHYSIOLOGIC CHANGES MAY WORSEN THE SEVSRITY CHANGES MAY WORSEN THE SEVSRITY OF HEPATOBILIARY DISEASES

CHOLELITHIASIS

THROMBOTIC DISEASES(BUDD CHIARI) THROMBOTIC DISEASES(BUDD CHIARI)

HEPATIT (E) INFECTION HEPATIT (E) INFECTION

NORMAL PHYSIOLOGIC AND ANATOMIC CHANGES

SPIDER ANGIOMA PALMAR ERYTHEMA PALMAR ERYTHEMA

HYPER ESTEROGENEMIA

SERUM ALBUMIN DECREASE TOTAL CHOLESTEROL AND TRIGLYCERIDE TOTAL CHOLESTEROL AND TRIGLYCERIDE INCREASE MARKEDLY DURING

PREGNANCYPREGNANCY ALKALIN PHOSPHATASE TWO OR FOUR TIMES GAMMA GLUTAMYL TRANSPEPTIDASE REDUCED ALT MILD INCRASE AST NO DIFFERENCE ALT MILD INCRASE AST NO DIFFERENCE BILIRUBIN IN ALL TRIMESTERS BILE ACID

Physiological changes in liver tests during normal pregnancy

TestTest Normal RangeNormal RangeTestTest Normal RangeNormal RangeBilirubinBilirubin Unchanged or Unchanged or slightly decreaseslightly decrease

AminotransferasesAminotransferases UnchangedUnchangedAminotransferasesAminotransferases UnchangedUnchanged

Prothrombin timeProthrombin time UnchangedUnchangedAlkaline phosphataseAlkaline phosphatase Increases 2 to 4Increases 2 to 4--foldfoldFibrinogenFibrinogen Increases 50%Increases 50%

GlobulinGlobulin Increases in α and ß globulinsIncreases in α and ß globulinsα α --fetoproteinfetoprotein Moderate riseModerate rise, esp. with twins, esp. with twinsWBCWBC IncreasesIncreasesCeruloplasminCeruloplasmin IncreasesIncreasesCeruloplasminCeruloplasmin IncreasesIncreasesCholesterolCholesterol Increases 2Increases 2--foldfoldTriglyceridesTriglycerides IncreasesIncreasesTriglyceridesTriglycerides IncreasesIncreasesGlobulinGlobulin Decreases in gammaDecreases in gamma--globulinglobulinHemoglobinHemoglobin Decrease in later pregnancyDecrease in later pregnancy

Abnormal liver function tests i 3 5% f i occur in 3 - 5% of pregnancies

for different reasons

Liver diseases in pregnancy

– liver disorders that occur only in the setting of y gpregnancy

– liver disorders that occur coincidentally withliver disorders that occur coincidentally with pregnancy

CARDINAL FEATURE: JAUNDICE JAUNDICE PRURITIS

ABDOMINAL PAIN ABDOMINAL PAIN NAUSEA VOMITING BIOCHEMICAL TEST ABNORMALITY BIOCHEMICAL TEST ABNORMALITY

Liver diseases in pregnancy

Only in thesetting of pregnancy

coincidental with pregnancy

High BP Chronic liver diseases e.g.:not associated withHigh BP-associated cholestatic liver disease,

autoimmune hepatitis,Wilson disease,

i l h i i

High BP

viral hepatitis, etc…The preeclampsia

itself Hyperemesis

HELLP-syndrome

gravidarum

AFLPIntrahepatic cholestasis

of pregnancy

29y G2 D1 (NVD) 35 W PRURITIS ON THE PALMS &THE SOLES WORSE AT NIGHT EXCORIATION DO TO SCRATCHING EXCORIATION DO TO SCRATCHING JAUNDICE BP=110/80 SS(_)(_)

ALKALIN PHOSPHATAZ 800 BILIRUBIN TOTAL& DIRECT 3 9 &1 5 BILIRUBIN TOTAL& DIRECT 3.9 &1.5 HB=11 PLT=180.000

GGT ARE NORMAL GGT ARE NORMAL AST ELEVATED =600 ALT=410 PT =14 24 H URIN Pr =120 24 H URIN Pr 120 SONO=NORMAL

INTRA HEPATIC CHOLESTASIS OF PREGNANCY(ICP)

SECOND OR THIRD TRIMESTER

0 1 TO15 6 0.1 TO15.6 CAUSE IS UN KNOWN GENETIC(MDR3) HORMONAL TWIN HORMONAL TWIN THIRD TRIMESTER

ESTROGEN &PROGESTERON ESTROGEN &PROGESTERON Enviromental

PRURITUSABDOMINAL PAINABDOMINAL PAINJAUNDICE%10 EXCORIATIONEXCORIATIONLAB:BILE ACIDEAST &ALTAST &ALTBILIRUBINNL GTTNL GTTLIVER SONO NI

LIVER BIOPSY :

BILE PLUGS IN HEPATOCYTE AND CANALICULI

TREATMENT:

REDUCING SYMPTOMS& MATERNAL & FETAL MATERNAL & FETAL

COMPLICATION

URSODEOXYCHOLIC ACIDINCREASES BILE FLOWINCREASES BILE FLOW IMPROVE LFT &PRURITUSMETA ANALYSIS ON 454 PATIENTSMETA ANALYSIS ON 454 PATIENTSUDCA HAS BETTER OUT COMES THAN S _ADENOSYL _METHIONINECHOLESTYRAMIN (8gr/day)CHOLESTYRAMIN (8gr/day)Dexametazon (12 mg /day)

BILE ACID can cross the placenta lead fetal toxicityyUDCA DOSE15 Mg/kgDOSE15 Mg/kg500mg / bid300mg /tds

HYDROXYZIN25 -50 mg/day25 50 mg/day Can aggravate respiratory dificultis in PTLPTL CHOLESTYRAMIN 8TO 16 gr/d

steatorrhea &vit k deficiency SAM

RECURRENCE60 -70 PERCENT VARIABLE IN SEVSRITY VARIABLE IN SEVSRITY OCP (LD) AFTER NORMALIZATION

OF LFTOF LFT LFT 3 TO 6 MONTHS PROGESTIN BREST FEEDING

MATERNALMATERNAL OUT COMOUT COM

FETAL OUT COME

SIGNIFICANT RISK FOR FETUS 1 PTL(6 60%) 1_PTL(6_60%) 2_MECONIUM

3 IUFD 3_IUFD 4_RESPIRATORY DISTRESS

SYNDROM

IUFD”: SUDDEN DEVELOPMENT OF A SUDDEN DEVELOPMENT OF A

FETAL ARRHTHMIA OR VASOSPASM OF THE PLACENTALVASOSPASM OF THE PLACENTAL CHORIONIC SURFACE VESSELS

NST NST

TIME OF DELIVERY

37 WEEKS PRURITUS PRURITUS JAUNDICE PIROR HISTORY OF

IUFD+ICPIUFD+ICP 35 WEEKS

32YEARS G1 G1 TWINE/34W/BP=130/80 SS(-) 3 DAYS NAUSA &VOMITING MALASIA&JAUNDISE PR U/A= TRACE PR U/A= TRACE AST=250 BILL=6 DIRECT=3 ALT=500 WBC=15000 HGB=10.5 BS=60 PT=17, INR=1.7 FIB=150

ACUTE FATY LIVER

Acute fatty liver of pregnancy (AFLP) is a rarebut serious maternal illness that occurs in thethird trimester of pregnancy.

Incidence: 1/10 000 to 1/15 000 pregnancies.

Maternal mortality: 18%

Fetal mortality: 23%.

More common in nulliparous women and withmultiple gestation.

Pathophysiology Defects in intramitochondrial fatty acid beta-

oxidation (enzymatic mutations in fatty acid oxidation).

Heterozygous woman gets a homozygous Heterozygous woman gets a homozygous fetus fetal fatty acids accumulate

t t th th ’ i l tireturn to the mother’s circulationextra load of long-chain fatty acids

triglyceride accumulation hepatic fat deposition & impaired maternal hepatic function.

Typical presentation: Jaundice (frequent),moderate to severe hypoglycemiamoderate to severe hypoglycemia, hepatic encephalopathy, coagulopathy. a 1 2 wk history of nausea vomiting a 1 - 2 wk history of nausea, vomiting,

abdominal pain & fatigue,

yfindings

aminotransferase levels (from mild elevation to 1000 IU/L, usually 300 - 500).e e a o o 000 U/ , usua y 300 500)

Bilirubin: frequently > 5mg/dL.CCommonly: leukocytosis, anemia.

With progress: thrombocytopenia (± DIC)With progress: thrombocytopenia ( DIC) & hypoalbuminemia.Ma be rising ric acid renal impairmentMay be: rising uric acid, renal impairment, metabolic acidosis, ammonia & biochemical pancreatitis.

(B) H t li i

Histological appearance of the liver in AFLPHistological appearance of the liver in AFLP.

(A) S d i (l (B) Hematoxylin-eosin stain (high power) shows hepatocytes stuffed with

(A) Sudan stain (low power) shows diffuse fatty infiltration (red staining) hepatocytes stuffed with

microvesicular fat (free fatty acids) and centrally

infiltration (red staining) involving predominantly zone 3, with relative y ) y

located nuclei.o e 3, t e at e

sparing of periportal areas.

Treatment involves

early recognition & diagnosis immediate termination+early recognition & diagnosis

of pregnancy+

If no obstetric indication, normal delivery is preferred to CS ( % of major intra-abdominal bleeding)

Careful attention to the infant: risk ofcardiomyopathy, neuropathy, myopathy, nonketotic hypoglycemia, hepatic failure, and death.

Usually By 2 - 3 dayspostpartum

liver enzymes & encephalopathpostpartum & encephalopathy

improve

Sometimeslaboratory abnormalities

persist after delivery& may initially worsen during

first postpartum week

Rarelypatients progress to fulminant hepatic failure

with need for liver transplantation.

Most patients improve in 1 to 4 weeks postpart

HELLPHELLP AFLPAFLPBilirubinBilirubin <5<5 mg/dL unless mg/dL unless

massive necrosismassive necrosisoften often >5>5 mg/dL, higher if mg/dL, higher if severeseveremassive necrosismassive necrosis severesevere

Hepatic Hepatic imagingimaging

Hepatic infarctsHepatic infarctsHematomas,Hematomas,

Fatty infiltrationFatty infiltrationg gg g Hematomas, Hematomas,

ruptureruptureHistologyHistology Patchy/extensivePatchy/extensive Microvesicular fat in zone 3Microvesicular fat in zone 3

necrosissnecrosiss

MaternalMaternal 1%1% 25%25% 7%7% 18%18%Maternal Maternal mortalitymortality

1%1%––25%25% 7%7%––18%18%

Fetal/perinatalFetal/perinatal 11%11% 9%9%––23%23%Fetal/perinatal Fetal/perinatal mortalitymortality

11%11% 9%9% 23%23%

Recurrence in Recurrence in b tb t

4%4%––19%19% fatty acid oxidation defect fatty acid oxidation defect 25%25%subsequentsubsequent

PregnanciesPregnancies

25%25%No fatty acid oxidation defect No fatty acid oxidation defect rarerare