Acute fatty liver versus

HELLP syndrome in
obstetric ICU:

why and how to

differentiate?
BY

Bahaa-El-Din Ewees MD

Physiological changes in liver tests during normal

pregnancy
Test
Bilirubin

Normal Range
Unchanged or slightly decrease

Aminotransferases

Unchanged

Prothrombin time
Alkaline phosphatase

Unchanged
Increases 2 to 4-fold

Fibrinogen

Increases 50%

Globulin
-fetoprotein

Increases in and globulins

Moderate rise, esp. with twins

WBC
Ceruloplasmin

Increases
Increases

Cholesterol
Triglycerides

Increases 2-fold
Increases

Globulin
Hemoglobin

Decreases in gamma-globulin
Decrease in later pregnancy

Abnormal liver function tests

occur in 3 - 5% of pregnancies for
different reasons

Liver diseases in pregnancy

liver disorders that occur only in the
setting of pregnancy
liver disorders that occur coincidentally
with pregnancy

Liver diseases in pregnancy

coincidental with pregnancy

Only in the
setting of pregnancy

Preeclampsiaassociated

The preeclampsia
itself

not associated with

preeclampsia

Chronic liver diseases e.g.:

cholestatic liver disease,
autoimmune hepatitis,
Wilson disease,
viral hepatitis, etc

Hyperemesis
gravidarum

HELLP-syndrome
AFLP

Intrahepatic cholestasis
of pregnancy

HELLP syndrome

Severe preeclampsia is complicated in

2-12% of cases (0.2-0.6% of all
pregnancies) by hemolysis (H), elevated
liver tests (EL), and low platelet count
(LP), the HELLP syndrome.

Etiology: microangiopathic hemolytic

anemia + vascular endothelial injury
fibrin deposition in blood vessels +
platelet activation & consumption,
small to diffuse areas of hemorrhage
and necrosis
large hematomas
+ capsular tears + intraperitoneal
bleeding.

Clinical Features and

Diagnosis

Most patients: 27 - 36 weeks

gestation,
but 25% in postpartum period.

Can occur with any parity and age

but commoner in white, multiparous
& older pts.

Clinical Picture:
Most patients

upper abd. pain

& tenderness

Nausea
vomiting
Malaise
headache

Less commonly

jaundice
uncommon (5%)

Hypertension
proteinuria
Edema
weight gain

some patients have no obvious preeclampsia

renal failure
+ uric acid

DI

Antiphospholipid
syndrome

Diagnosis requires the presence of

all 3 laboratory criteria:
H
Hemolysis
LDH>600 U/L
indirect bilirubin

EL
Elevated Liver Tests
AST> 70U/L

LP
Low Platelets
<150,000

Based on platelet count, may be:

severe/ Class 1 (platelets 50,000),
moderate/Class 2 (50 99,000),
mild/Class 3 (100 150,000).
Lately, DIC, pulmonary edema, placental
abruption, and retinal detachment may be present.

Aminotransferase: variable, from mild to

10 20 fold,

Bilirubin: usually < 5 mg/dL.

Liver CT:

subcapsular hematomas,
intra-parenchymal hemorrhage, or infarction
hepatic rupture.

Histologically: focal hepatocyte necrosis,

periportal hemorrhage, and fibrin deposits.

CT abdomen of a woman with severe HELLP syndrome (39 weeks). A

large subcapsular hematoma extends over the Lt lobe; Rt lobe has
heterogeneous, hypodense appearance due to widespread necrosis, with
sparing of the areas of lt lobe (compare perfusion with the normal
spleen).

Treatment

Hospitalization & ICU care for:

o
o
o

antepartum stabilization of BP and DIC,

seizure prophylaxis,
fetal monitoring.
The only definitive treatment is delivery

pregnancy is > 34 wk

gestational age
24-34 wk
corticosteroids for 48 h
(fetal lung maturity)

immediate induction

delivery

Corticosteroids which cross the placenta

(betamethasone or dexamethasone,)
for 24-48 hours

fetal lung maturity

improves maternal
platelet count.

Tried treatment modalities for patients with

ongoing or newly developing symptoms
Antithrombotics
(Heparin, aspirin)

plasmapheresis

dialysis

plasma exchange
with FFP

After delivery

continue close monitoring of the mother

persistent or worsening
lab. Abnormalities
by 4th postpartum day
May
be

Postpartum
complications

LY
E
AR

Up to 48 h
postpartu
m

worsening thrombocytopenia
& increasing LDH levels
After 48
h

Most lab. values normalize

5
days

normalization of platelets

Fate & complications

 Reported maternal mortality is

1%

Perinatal

mortality rate ranges

from 7%-22% and may be due to:
premature detachment of placenta,
intrauterine asphyxia,
prematurity.

 Other

complications:

pulmonary

edema
stroke
liver failure
hepatic
infarction

abruptio

placentae
DIC
ARF
ARDS

No long-term effect on renal

function noted.

Recurrence : Subsequent
pregnancies carry a high risk of
complications
pre-eclampsia,
recurrence,
prematurity,
IUGR,
abruptio placentae,
perinatal mortality.

Acute fatty liver

Acute fatty liver of pregnancy (AFLP) is a

rare but serious maternal illness that
occurs in the third trimester of pregnancy.

Incidence: 1/10 000 to 1/15 000

pregnancies.

Maternal mortality: 18%

Fetal mortality: 23%.

More common in nulliparous women and

with multiple gestation.

Pathophysiology

Defects in intramitochondrial fatty acid betaoxidation (enzymatic mutations in fatty acid

oxidation).

Heterozygous woman gets a homozygous

fetus
fetal fatty acids accumulate
return to the mothers circulation
extra load of long-chain fatty acids
triglyceride accumulation
hepatic fat deposition & impaired maternal
hepatic function.

Clinical Features and

Diagnosis

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

Laboratory
findings

aminotransferase levels (from mild

elevation to 1000 IU/L, usually 300 500).

Bilirubin: frequently > 5mg/dL.
Commonly: leukocytosis, anemia.
With progress: thrombocytopenia (
DIC) & hypoalbuminemia.
May be: rising uric acid, renal
impairment, metabolic acidosis,
ammonia & biochemical pancreatitis.

Laboratory findings (Cont.)

liver biopsy

Imaging studies (US & CT)

most definitive test

often not done

d. t. coagulopathy
findings swollen, pale hepatocytes
in the central zones

microvesicular fatty infiltration

(frozen section with oil red staining)

Inconsistent

is
s n s
i
s
o g
o
d in
n
e
ag as find
i
b .
d
,
y b
l
o
l
S ua
la
us al &
c
i
in
l
c

Histological appearance of the liver in AFLP.

AFLP
(A) Sudan stain (low
power) shows diffuse fatty
infiltration (red staining)
involving predominantly
zone 3, with relative
sparing of periportal
areas.

(B) Hematoxylin-eosin
stain (high power) shows
hepatocytes stuffed with
microvesicular fat (free
fatty acids) and centrally
located nuclei.

Treatment

Treatment involves

early recognition & diagnosis

immediate termination
of pregnancy

If no obstetric indication, normal delivery is

preferred to CS ( % of major intraabdominal bleeding)
Careful attention to the infant: risk of
cardiomyopathy, neuropathy, myopathy,
nonketotic hypoglycemia, hepatic failure,
and death.

Fate & complications

Usually

Sometimes

Rarely

By 2 - 3 days
postpartum

liver enzymes
& encephalopathy
improve

laboratory abnormalities
persist after delivery
& may initially worsen during
first postpartum week

patients progress to fulminant hepatic failure

with need for liver transplantation.

Most patients improve in 1 to 4 weeks postpart

With advances in supportive

management, the maternal mortality
is now 7%-18% and fetal mortality
9%-23%.

Complications:

Infectious and bleeding remain the

most life threatening.

Liver transplantation has a very

limited role because of the great
potential for recovery with delivery.

HOW TO
DIFFERENTIATE

%
Pregnancies
Onset/trimest
er
Family history
Presence of
preeclampsia
Typical
clinical
features

HELLP
0.2%0.6%

AFLP
0.005%0.01%

3 or postpartum

3 or
postpartum
Occasionally
50%

No
Yes
Hemolysis
(anemia)
Thrombocytopeni
a (50,000 often)

Liver failure
with
coagulopathy,
encephalopathy
hypoglycemia,
DIC

Bilirubin
Hepatic
imaging

HELLP
AFLP
<5 mg/dL unless often >5 mg/dL, higher
massive necrosis if severe
Hepatic infarcts Fatty infiltration
Hematomas,
rupture

Histology

Patchy/extensive Microvesicular fat in

zone 3
necrosis,
periportal hge,
fibrin deposits

Maternal
mortality
Fetal/perinata
l mortality
Recurrence in
subsequent

1%25%

7%18%

11%

9%23%

4%19%

fatty acid oxidation defect

25%
No fatty acid oxidation defect

WHY TO
DIFFERENTIATE

Major Risks
AFLP
Infections & bleeding
(most life threatening).

Hypoglycemia

Pancreatitis (develop after onset

of hepatic & renal dysfunction
need serial screening
of serum lipase and amylase
for several days after
hepatic dysfunction)

HELLP
DIC
ARF
ARDS
pulmonary edema
stroke & seizures
liver hges
(most life-threatening)

Therapeutic Options
AFLP
FFP
glucose

HELLP
Early

Late

Antithrombotics:
(heparin, antithrombin,
low dose aspirin)

Plasmapheresis

Liver transplant
(limited role)

Steroids: rapid clinical &

lab. improvement

Blood transfusion

Liver transplant
More definite role role

Follow-up Precautions:
A deficiency in long chain 3-hydroxyacylCoA dehydrogenase (LCHAD) is thought
to be associated with the development
of AFLP.

Under normal circumstances, an

individual that is heterozygous for
enzymatic mutations in fatty acid
oxidation will not have abnormal fatty
oxidation.

Affected patients should be screened

for defects in fatty acid oxidation as
recurrence in subsequent children is
25%, and recurrence of AFLP in
mothers is also possible.

Presymptomatic diagnosis of FAOD

with The application of tandem mass
spectrometry to newborn screening
is an effective way to identify most
FAOD patients presymptomatically
reduce morbidity and avoid mortality

Current management of pts with

FAOD includes long-term dietary
therapy of:
fasting

avoidance,
low-fat/high-carbohydrate diet
restriction of long-chain fatty acid
intake and substitution with mediumchain fatty acids.

These dietary approaches appear

promising in the short-term, but not
the long-term outcome.

In conclusion
Important to diff. AFLP from HELLP
Diff. mainly based on lab. + imaging
(CT-MRI)
Diff. because AFLP needs:

o
o

Maternal follow-up for recurrence

Baby follow-up for FAOD needing
dietary control
Next pregnancies for presymptomatic
diagnosis