acute fatty liver versus hellp
TRANSCRIPT
-
7/25/2019 Acute Fatty Liver Versus HELLP
1/44
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 $#
-
7/25/2019 Acute Fatty Liver Versus HELLP
2/44
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
-
7/25/2019 Acute Fatty Liver Versus HELLP
3/44
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
-
7/25/2019 Acute Fatty Liver Versus HELLP
4/44
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
-
7/25/2019 Acute Fatty Liver Versus HELLP
5/44
HELLP syndromeHELLP syndrome
-
7/25/2019 Acute Fatty Liver Versus HELLP
6/44
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'
-
7/25/2019 Acute Fatty Liver Versus HELLP
7/44
Clinical Features andClinical Features and
DiagnosisDiagnosis
-
7/25/2019 Acute Fatty Liver Versus HELLP
8/44
%ost patients: 2; -
-
7/25/2019 Acute Fatty Liver Versus HELLP
9/44
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
-
7/25/2019 Acute Fatty Liver Versus HELLP
10/44
@,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&
-
7/25/2019 Acute Fatty Liver Versus HELLP
11/44
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'
-
7/25/2019 Acute Fatty Liver Versus HELLP
12/44
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&'
-
7/25/2019 Acute Fatty Liver Versus HELLP
13/44
TreatmentTreatment
-
7/25/2019 Acute Fatty Liver Versus HELLP
14/44
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
-
7/25/2019 Acute Fatty Liver Versus HELLP
15/44
*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
-
7/25/2019 Acute Fatty Liver Versus HELLP
16/44
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!
-
7/25/2019 Acute Fatty Liver Versus HELLP
17/44
Fate & complicationsFate & complications
-
7/25/2019 Acute Fatty Liver Versus HELLP
18/44
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.
-
7/25/2019 Acute Fatty Liver Versus HELLP
19/44
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
-
7/25/2019 Acute Fatty Liver Versus HELLP
20/44
#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'
-
7/25/2019 Acute Fatty Liver Versus HELLP
21/44
Acute fatty liverAcute fatty liver
f li f 3A f li f 3AF0P i i
-
7/25/2019 Acute Fatty Liver Versus HELLP
22/44
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''
-
7/25/2019 Acute Fatty Liver Versus HELLP
23/44
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'
-
7/25/2019 Acute Fatty Liver Versus HELLP
24/44
Clinical Features andClinical Features and
DiagnosisDiagnosis
-
7/25/2019 Acute Fatty Liver Versus HELLP
25/44
+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
-
7/25/2019 Acute Fatty Liver Versus HELLP
26/44
LaboratoryLaboratory
3ndin%s3ndin%s aminotransferase le.els 3from mildaminotransferase le.els 3from mildele.ation to IUD0& usuallyele.ation to IUD0& usually
-
7/25/2019 Acute Fatty Liver Versus HELLP
27/44
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%
-
7/25/2019 Acute Fatty Liver Versus HELLP
28/44
"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.
-
7/25/2019 Acute Fatty Liver Versus HELLP
29/44
TreatmentTreatment
-
7/25/2019 Acute Fatty Liver Versus HELLP
30/44
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-
-
7/25/2019 Acute Fatty Liver Versus HELLP
31/44
Fate & complicationsFate & complications
-
7/25/2019 Acute Fatty Liver Versus HELLP
32/44
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
-
7/25/2019 Acute Fatty Liver Versus HELLP
33/44
)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'
-
7/25/2019 Acute Fatty Liver Versus HELLP
34/44
H;< ';H;< ';
#I==E)E('IA'E#I==E)E('IA'E
HELLPHELLP A=LPA=LP
-
7/25/2019 Acute Fatty Liver Versus HELLP
35/44
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
-
7/25/2019 Acute Fatty Liver Versus HELLP
36/44
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
-
7/25/2019 Acute Fatty Liver Versus HELLP
37/44
-
7/25/2019 Acute Fatty Liver Versus HELLP
38/44
$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
-
7/25/2019 Acute Fatty Liver Versus HELLP
39/44
'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:
-
7/25/2019 Acute Fatty Liver Versus HELLP
40/44
=ollow"u& Precautions:=ollow"u& Precautions:
A de8ciency in long chain
-
7/25/2019 Acute Fatty Liver Versus HELLP
41/44
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
-
7/25/2019 Acute Fatty Liver Versus HELLP
42/44
*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
-
7/25/2019 Acute Fatty Liver Versus HELLP
43/44
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
-
7/25/2019 Acute Fatty Liver Versus HELLP
44/44