Acute Fatty Liver Versus HELLP

7/25/2019 Acute Fatty Liver Versus HELLP

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Acute fatty liver versusAcute fatty liver versusHELLP syndrome inHELLP syndrome in

obstetric ICU:obstetric ICU:

why and how towhy and how todierentiate?dierentiate?

!!

ahaa"El"#in Ewees $#ahaa"El"#in Ewees $#


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Physiolo%ical chan%es in liver tests durin% normalPhysiolo%ical chan%es in liver tests durin% normal

&re%nancy&re%nancy

'est'est (ormal )an%e(ormal )an%e

BilirubinBilirubin Unchanged orUnchanged or slightly decreaseslightly decrease

AminotransferasesAminotransferases UnchangedUnchanged

Prothrombin timeProthrombin time UnchangedUnchanged

Alkaline phosphataseAlkaline phosphatase Increases 2 to 4-foldIncreases 2 to 4-fold

FibrinogenFibrinogen Increases 5!Increases 5!"lobulin"lobulin Increases in # and $ globulinsIncreases in # and $ globulins

# -fetoprotein# -fetoprotein %oderate rise%oderate rise& esp' (ith t(ins& esp' (ith t(ins

)B*)B* IncreasesIncreases

*eruloplasmin*eruloplasmin IncreasesIncreases

*holesterol*holesterol Increases 2-foldIncreases 2-fold

+riglycerides+riglycerides IncreasesIncreases

"lobulin"lobulin ,ecreases in gamma-globulin,ecreases in gamma-globulin

emoglobinemoglobin ,ecrease in later pregnancy,ecrease in later pregnancy


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Abnormal li.er function testsAbnormal li.er function tests

occur inoccur in * " +,* " +,of pregnancies forof pregnancies fordi/erent reasonsdi/erent reasons

0i.er diseases in pregnancy0i.er diseases in pregnancy

li.er disorders that occurli.er disorders that occur only inonly inthethe

setting ofsetting of pregnancypregnancy

li.er disorders that occurli.er disorders that occur coincidentallycoincidentally(ith pregnancy(ith pregnancy


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Liver diseases in pregnancy

Only in the

setting of pregnancy

coincidental with pregnancy

Preeclampsia-

associated

Chronic liver diseases e.g.:

cholestatic liver disease,autoimmune hepatitis,

Wilson disease,

viral hepatitis, etc

not associated with

preeclampsia

The preeclampsia

itself

HELLP-syndrome

AFLP

Hyperemesisgravidarum

Intrahepatic cholestasis

of pregnancy


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HELLP syndromeHELLP syndrome


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1e.ere preeclampsia is complicated in1e.ere preeclampsia is complicated in2-2! of cases 3'2-'! of all2-2! of cases 3'2-'! of allpregnancies by hemolysis 3pregnancies by hemolysis 3& ele.ated& ele.ated

li.er tests 3li.er tests 36060& and lo( platelet count& and lo( platelet count330P0P& the& the 600P syndrome600P syndrome''

Etiology:Etiology:microangiopathic hemolyticmicroangiopathic hemolyticanemiaanemia --.ascular endothelial in7ury.ascular endothelial in7ury8brin deposition in blood .essels8brin deposition in blood .essels --

platelet acti.ation 9 consumption&platelet acti.ation 9 consumption&

small to di/use areas of hemorrhagesmall to di/use areas of hemorrhageand necrosis large hematomasand necrosis large hematomas--capsular tearscapsular tears --intraperitonealintraperitoneal

bleeding'bleeding'


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Clinical Features andClinical Features and

DiagnosisDiagnosis


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%ost patients: 2; -


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Clinical Picture:Clinical Picture:

$ost &atients$ost &atients

0ess commonly0ess commonly

pper abd' painpper abd' pain

9 tenderness9 tenderness

>ausea>ausea

.omiting.omiting

%alaise%alaiseheadacheheadache

6dema6dema

(eight gain(eight gain

7aundice7aundice

uncommon 35!uncommon 35!

ypertensionypertension

proteinuriaproteinuria

renal failurerenal failure

? uric acid? uric acid

,I,I

AntiphospholipidAntiphospholipid

syndromesyndrome

ome patients ha.eome patients ha.e no obviousno obviouspreeclampsiapreeclampsia


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@,iagnosis,iagnosisreuires the presencereuires the presence ofof

all 3 laboratory criteria:all 3 laboratory criteria:

Based on platelet count, may be:severe Class ! "platelets #$,$$$%,

moderateClass & "#$ '((,$$$%,mildClass ) "!$$ '!#$,$$$%.

*ately, +C, pulmonary edema, placental

abruption, and retinal detachment may be present.

emolysisemolysis

60606le.ated 0i.er +ests6le.ated 0i.er +ests

0P0P0o( Platelets0o( Platelets

0,C UD00,C UD0

EE indirect bilirubinindirect bilirubin

A1+C ;UD0A1+C ;UD0 5&5&


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AminotransferaseAminotransferase: .ariable& from mild to: .ariable& from mild to

G 2 fold& G 2 fold&

BilirubinBilirubin: usually 5 mgDd0': usually 5 mgDd0'

0i.er *+0i.er *+:: subcapsular hematomas&subcapsular hematomas&

intra-parenchymal hemorrhage& or infarctionintra-parenchymal hemorrhage& or infarction

hepatic rupture'hepatic rupture'

istologicallyistologically: focal hepatocyte necrosis&: focal hepatocyte necrosis&

periportal hemorrhage& and 8brin deposits'periportal hemorrhage& and 8brin deposits'


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C a!domen of a woman with severe HELLP syndrome "#$ wee%s&' A

large su!capsular hematoma e(tends over the Lt lo!e) *t lo!e has

heterogeneous+ hypodense appearance due to widespread necrosis+ with

,sparing of the areas of lt lo!e "compare perfusion with the normal

spleen&'


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TreatmentTreatment


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Hospitalization & ICU careHospitalization & ICU carefor:for:o antepartum stabiliHation of BP and ,I*&antepartum stabiliHation of BP and ,I*&

o seiHure prophylais&seiHure prophylais&o fetal monitoring'fetal monitoring'

&re%nancy is . */ w0%estational a%e

1/"*/ w0

immediate induction

corticosteroids for 4J h3fetal lung maturity

delivery

Te only de!niti"e treatment is deli"eryTe only de!niti"e treatment is deli"ery

* ti t id hi h th l t


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*orticosteroids (hich cross the placenta3betamethasone or deamethasone&

for 24-4J hours

fetal lung maturity impro.es maternalplatelet count'

+ried treatment modalities for patients (ithongoing or ne(ly de.eloping symptoms

Antithrombotics3eparin& aspirin

plasmapheresis

plasma echange(ith FFPdialysis


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After deliveryAfter delivery continue close monitoring of the mothecontinue close monitoring of the mothe

U& to /2 h

&ost&artum

(orsening thrombocytopeni(orsening thrombocytopeni

9 increasing 0, le.els9 increasing 0, le.els

%ost lab' .alues normaliH%ost lab' .alues normaliH

After /2h

persistent or (orseningpersistent or (orsening

lab' Abnormalitieslab' Abnormalities

by 4by 4ththpostpartum daypostpartum day

PostpartumPostpartum

complicationscomplications

$aybe

normaliHation of plateletsnormaliHation of platelets

++

daysdays

)A)E

L!


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Fate & complicationsFate & complications


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KeportedKeportedmaternal mortalitymaternal mortalityisis

!!

Perinatal mortalityPerinatal mortalityrate rangesrate rangesfromfrom;!-22!;!-22!and may be due to:and may be due to:@premature detachment of placenta,premature detachment of placenta,

@ intrauterine asphyxia,intrauterine asphyxia,

@prematurity.prematurity.


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Lther complicationsLther complications::

>o long-term e/ect on renal>o long-term e/ect on renal

function noted'function noted'

@abruptioabruptio

placentaeplacentae@,I*,I*@AKFAKF@AK,1AK,1

@pulmonarypulmonary

edemaedema@[email protected] failureli.er failure@hepatichepatic

infarctioninfarction


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#ecurrence#ecurrence :: 1ubseuent1ubseuent

pregnancies carry a high risk ofpregnancies carry a high risk of

complicationscomplications

@ pre-eclampsia&pre-eclampsia&

@ recurrence&recurrence&@ prematurity&prematurity&

@ IU"K&IU"K&

@ abruptio placentae&abruptio placentae&

@ perinatal mortality'perinatal mortality'


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Acute fatty liverAcute fatty liver

f li f 3A f li f 3AF0P i i


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Acute fatty li.er of pregnancy 3Acute fatty li.er of pregnancy 3AF0PAF0P is a is ararerarebutbutseriousseriousmaternal illness thatmaternal illness that

occurs in theoccurs in thethird trimesterthird trimesterof pregnancy'of pregnancy'

Incidence:Incidence:D to D5 D to D5 pregnancies'pregnancies'

%aternal mortality:%aternal mortality:J!J!

Fetal mortality:Fetal mortality:2

%ore common in%ore common innulliparous (omennulliparous (omenandand

(ith(ithmultiple gestationmultiple gestation''


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Patho&hysiolo%yPatho&hysiolo%y

,efects in intramitochondrial fatty acid beta-,efects in intramitochondrial fatty acid beta-

oidation 3enHymatic mutations in fatty acidoidation 3enHymatic mutations in fatty acidoidation'oidation'

eteroHygous (oman gets a homoHygouseteroHygous (oman gets a homoHygous

fetus fetal fatty acids accumulatefetus fetal fatty acids accumulate return to the mother=s circulationreturn to the mother=s circulation

etra load of long-chain fatty acidsetra load of long-chain fatty acids

triglyceride accumulationtriglyceride accumulationhepatic fat deposition 9 impaired maternalhepatic fat deposition 9 impaired maternalhepatic function'hepatic function'


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Clinical Features andClinical Features and

DiagnosisDiagnosis


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+ypical presentation:+ypical presentation:

a - 2 (k history of nausea&a - 2 (k history of nausea&

.omiting& abdominal pain 9 fatigue&.omiting& abdominal pain 9 fatigue&

Maundice 3freuent&Maundice 3freuent& moderate to se.ere hypoglycemia&moderate to se.ere hypoglycemia&

hepatic encephalopathy&hepatic encephalopathy&

coagulopathy'coagulopathy'

L b


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LaboratoryLaboratory

3ndin%s3ndin%s aminotransferase le.els 3from mildaminotransferase le.els 3from mildele.ation to IUD0& usuallyele.ation to IUD0& usually


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Laboratory 3ndin%s 5Cont67Laboratory 3ndin%s 5Cont67

liver bio&sy

most de8niti.e test

often not doned' t' coagulopathy

s(ollen& pale hepatocytes

in the central Hones

micro.esicular fatty in8ltration3froHen section (ith oil red staining

3ndin%s

Ima%in% studies 5U8 9 C'7

Inconsistent

8o:dia

%nosis

is

usually

based

on

clinical9

lab63n

din%


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"B% ematoylin-eosin

stain "high po/er% sho/s

hepatocytes stuffed /ithmicrovesicular fat "free

fatty acids% and centrally

located nuclei.

istological appearance of the liver in 01*2istological appearance of the liver in 01*2.

"0% 3udan stain "lo/

po/er% sho/s diffuse fatty

infiltration "red staining%involving predominantly

4one ), /ith relative

sparing of periportal

areas.


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TreatmentTreatment


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If no obstetric indication& normal deli.ery isIf no obstetric indication& normal deli.ery ispreferred to *1 3 ! of ma7or intra-preferred to *1 3 ! of ma7or intra-abdominal bleedingabdominal bleeding

*areful attention to the infant: risk of*areful attention to the infant: risk ofcardiomyopathycardiomyopathy&& neuropathyneuropathy&& myopathymyopathy&&nonketotic hypoglycemianonketotic hypoglycemia&& hepatic failurehepatic failure&&

andand death'death'

'reatment involves

early recognition 9 diagnosis immediate terminationof pregnancy-


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Fate & complicationsFate & complications


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Usually By 2 - < dayspostpartum

li.er enHymes9 encephalopath

impro.e

8ometimeslaboratory abnormalities

persist after deli.ery9 may initially (orsen during

8rst postpartum (eek

)arelypatients progress to fulminant hepatic failure

(ith need for li.er transplantation'

$ost patients impro"e in % to 'ee(s postpart


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)ith ad.ances in supporti.e)ith ad.ances in supporti.emanagement& the maternal mortalitymanagement& the maternal mortality

is no( ;!-J! and fetal mortalityis no( ;!-J! and fetal mortalityN!-2

*omplications:*omplications:@ Infectious and bleeding remain theInfectious and bleeding remain themost life threatening'most life threatening'

0i.er transplantation has a .ery0i.er transplantation has a .erylimited role because of the greatlimited role because of the greatpotential for reco.ery (ith deli.ery'potential for reco.ery (ith deli.ery'


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H;< ';H;< ';

#I==E)E('IA'E#I==E)E('IA'E

HELLPHELLP A=LPA=LP


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HELLPHELLP A=LPA=LP

!!

PregnanciesPregnancies'2!G'!'2!G'! '5!G'!'5!G'!

LnsetDtrimestLnsetDtrimesterer

< or postpartum< or postpartum < or< orpostpartumpostpartum

Family historyFamily history >o>o LccasionallyLccasionally

Presence ofPresence ofpreeclampsiapreeclampsia

OesOes 5!5!

+ypical+ypical

clinicalclinicalfeaturesfeatures

emolysisemolysis

3anemia3anemia

+hrombocytopeni+hrombocytopeni

a 35& oftena 35& often

0i.er failure0i.er failure

(ith(ithcoagulopathy&coagulopathy&

encephalopathyencephalopathy

hypoglycemia&hypoglycemia&

,I*,I*

HELLPHELLP A=LPA=LP


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HELLPHELLP A=LPA=LP

BilirubinBilirubin 55mgDd0 unlessmgDd0 unless

massi.e necrosismassi.e necrosisoftenoften C5C5mgDd0& highermgDd0& higher

if se.ereif se.ere

epaticepatic

imagingimagingepatic infarctsepatic infarcts

ematomas&ematomas&rupturerupture

Fatty in8ltrationFatty in8ltration

istologyistology PatchyDetensi.ePatchyDetensi.e

necrosis&necrosis&periportal hge&periportal hge&8brin deposits8brin deposits

%icro.esicular fat in%icro.esicular fat in

Hone Kecurrence inKecurrence in

subseuentsubseuent

4!GN!4!GN! fatty acid oidation defectfatty acid oidation defect25!25!

>o fatty acid oidation defect>o fatty acid oidation defect


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$a>or )is0s

Infections 9 bleeding

3most life threatening'

ypoglycemia

AF0P 600P

ancreatitis 3de.elop after onsetof hepatic 9 renal dysfunction

need serial screeningof serum lipase and amylase

for se.eral days afterhepatic dysfunction

,I*

AKF

AK,1

pulmonary edema

stroke 9 seiHures

li.er hges

3most life-threatening

'h ti ; ti


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'hera&eutic ;&tions

AF0P 600P

FFP

glucose

i.er transplant3limited role

Antithrombotics:3heparin& antithrombin&

lo( dose aspirin

1teroids: rapid clinical 9lab' impro.ement

Blood transfusion

6arly 0ate

Plasmapheresis

0i.er transplant%ore de8nite role rol

=ollow u& Precautions:=ollow u& Precautions:


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=ollow"u& Precautions:=ollow"u& Precautions:

A de8ciency in long chain


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A/ected patients should be screenedA/ected patients should be screened

for defects in fatty acid oidation asfor defects in fatty acid oidation as

recurrence in subseuent children isrecurrence in subseuent children is25!& and recurrence of AF0P in25!& and recurrence of AF0P in

mothers is also possible'mothers is also possible'

Presymptomatic diagnosis of FAL,Presymptomatic diagnosis of FAL,

(ith(ith+he application of tandem mass+he application of tandem mass

spectrometry to ne(born screeningspectrometry to ne(born screeningis an e/ecti.e (ay to identify mostis an e/ecti.e (ay to identify most

FAL, patients presymptomaticallyFAL, patients presymptomatically

reduce morbidity and a.oid mortalityreduce morbidity and a.oid mortality

*urrent management of pts (ith*urrent management of pts (ith


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*urrent management of pts (ith*urrent management of pts (ith

FAL, includes long-term dietaryFAL, includes long-term dietary

therapy of:therapy of: fasting a.oidance&fasting a.oidance& lo(-fatDhigh-carbohydrate dietlo(-fatDhigh-carbohydrate diet

restriction of long-chain fatty acidrestriction of long-chain fatty acidintake and substitution (ith medium-intake and substitution (ith medium-

chain fatty acids'chain fatty acids'

+hese dietary approaches appear+hese dietary approaches appear

promising in the short-term& but notpromising in the short-term& but not

the long-term outcome'the long-term outcome'

I l i


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In conclusionIn conclusion

Important to di/' AF0P from 600PImportant to di/' AF0P from 600P ,i/' mainly based on lab' ? imaging,i/' mainly based on lab' ? imaging

3*+-%KI3*+-%KI

,i/' because AF0P needs:,i/' because AF0P needs:o %aternal follo(-up for recurrence%aternal follo(-up for recurrence

o Baby follo(-up for FAL, needingBaby follo(-up for FAL, needingdietary controldietary control

o >et pregnancies for presymptomatic>et pregnancies for presymptomatic

diagnosisdiagnosis


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Acute Fatty Liver Versus HELLP

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