Acute fatty liver versus HELP final

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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 α and ß globulins
α -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
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
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 mother’s 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
often >5 mg/dL, higher if
severe
Fatty infiltration
1%–25%
7%–18%
11%
9%–23%
4%–19%
fatty acid oxidation defect
25%
No fatty acid oxidation defect
rare
Microvesicular fat in zone 3
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
o
Maternal follow-up for recurrence
Baby follow-up for FAOD needing dietary
control
Next pregnancies for presymptomatic
diagnosis
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