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

Normal Range

Bilirubin

Unchanged or slightly decrease

Aminotransferases

Unchanged

Prothrombin time

Unchanged

Alkaline phosphatase

Increases 2 to 4-fold

Fibrinogen

Increases 50%

Globulin

Increases in and globulins

-fetoprotein

Moderate rise, esp. with twins

WBC

Increases

Ceruloplasmin

Increases

Cholesterol

Increases 2-fold

Triglycerides

Increases

Globulin

Decreases in gamma-globulin

Hemoglobin

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 212% 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
renal failure

jaundice
uncommon (5%)

Hypertension
proteinuria
Edema
weight gain

some patients have no obvious preeclampsia

+ uric acid

DI

Antiphospholipid
syndrome

Diagnosis requires the presence of all 3

laboratory criteria:
H
Hemolysis

EL
Elevated Liver Tests

LP
Low Platelets

LDH>600 U/L
indirect bilirubin

AST> 70U/L

<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

improves maternal
platelet count.

fetal lung maturity

Tried treatment modalities for patients with

ongoing or newly developing symptoms
Antithrombotics
(Heparin, aspirin)

plasmapheresis

dialysis

plasma exchange
with FFP

continue close monitoring of the mother

After delivery

Up to 48 h
postpartum

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

Postpartum
complications

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
stroke

liver

edema

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

Histological appearance of the liver in 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 intra-abdominal
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

HELLP

AFLP

% Pregnancies 0.2%0.6%

0.005%0.01%

Onset/trimester 3 or postpartum

3 or postpartum

Family history

No

Occasionally

Presence of
preeclampsia

Yes

50%

Typical clinical
features

Hemolysis (anemia) Liver failure with

Thrombocytopenia coagulopathy,
encephalopathy
(50,000 often)
hypoglycemia,
DIC

Aminotransfer- Mild, but may be up 300-500 typical

ases
to 10-20-fold rise
but variable

HELLP

Bilirubin
Hepatic
imaging
Histology

Maternal
mortality

Fetal/perinatal
mortality
Recurrence in
subsequent
Pregnancies

AFLP

<5 mg/dL unless

massive necrosis
Hepatic infarcts
Hematomas,
rupture
Patchy/extensive
necrosis, periportal
hge, fibrin deposits
1%25%

often >5 mg/dL, higher if

severe
Fatty infiltration

11%

9%23%

4%19%

fatty acid oxidation defect

25%
No fatty acid oxidation defect
rare

Microvesicular fat in zone 3

7%18%

WHY TO DIFFERENTIATE

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

HELLP
DIC

ARF
Hypoglycemia
Pancreatitis (develop after onset
of hepatic & renal dysfunction
need serial screening
of serum lipase and amylase
for several days after
hepatic dysfunction)

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-hydroxyacyl-CoA
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 medium-chain 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 (CTMRI)
Diff. because AFLP needs:

o
o

Maternal follow-up for recurrence

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