Post on 18-Apr-2018
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