1. Acute fatty liver versus HELLP syndrome in obstetric ICU: why and how to differentiate? BY Bahaa-El-Din Ewees MD

2. Physiological changes in liver tests during normal pregnancy
Normal Range
Bilirubin
Unchanged or slightly decrease
Aminotransferases
Unchanged
Prothrombin time
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
Cholesterol
Increases 2-fold
Triglycerides
Decreases in gamma-globulin
Hemoglobin
Decrease in later pregnancy

3. 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

4. Liver diseases in pregnancy
coincidental with pregnancy
Only in the
setting of pregnancy
Chronic liver diseases e.g.:
cholestatic liver disease,
autoimmune hepatitis,
Wilson disease,
viral hepatitis, etc…
not associated with
preeclampsia
Preeclampsia-
associated
The preeclampsia
itself
Hyperemesis
gravidarum
HELLP-syndrome
Intrahepatic cholestasis
of pregnancy
AFLP

5. HELLP syndrome

6. Severe preeclampsia is complicated in 2-12% of cases (0. 2-0
Severe preeclampsia is complicated in 2-12% of cases ( % 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.

7. Clinical Features and Diagnosis

8. 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.

9. some patients have no obvious preeclampsia
Clinical Picture:
Most patients
Less commonly
upper abd. pain
& tenderness
jaundice
uncommon (5%)
renal failure
+ uric acid
Nausea
vomiting DI
Hypertension
proteinuria
Malaise
headache
Antiphospholipid
syndrome
Edema
weight gain
some patients have no obvious preeclampsia

10. Diagnosis requires the presence of all 3 laboratory criteria:
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.

11. 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.

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

13. Treatment

14. The only definitive treatment is delivery
Hospitalization & ICU care for:
antepartum stabilization of BP and DIC,
seizure prophylaxis,
fetal monitoring.
The only definitive treatment is delivery
gestational age
24-34 wk
pregnancy is > 34 wk
corticosteroids for 48 h
(fetal lung maturity)
immediate induction
delivery

15. Corticosteroids which cross the placenta
(betamethasone or dexamethasone,)
for hours
fetal lung maturity
improves maternal
platelet count.
Tried treatment modalities for patients with
ongoing or newly developing symptoms
plasmapheresis
Antithrombotics
(Heparin, aspirin)
plasma exchange
with FFP
dialysis

16. continue close monitoring of the mother
After delivery
continue close monitoring of the mother
Up to 48 h postpartum
RARELY
persistent or worsening
lab. Abnormalities
by 4th postpartum day
worsening thrombocytopenia
& increasing LDH levels
May be
After 48 h
Most lab. values normalize
Postpartum
complications
5 days
normalization of platelets

17. Fate & complications

18. Reported maternal mortality is 1%
Perinatal mortality rate ranges from 7%-22% and may be due to:
premature detachment of placenta,
intrauterine asphyxia,
prematurity.

19. Other complications: No long-term effect on renal function noted.
abruptio placentae
DIC
ARF
ARDS
pulmonary edema
stroke
liver failure
hepatic infarction

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

21. Acute fatty liver

22. Acute fatty liver of pregnancy (AFLP) is a rare but serious maternal illness that occurs in the third trimester of pregnancy.
Incidence: 1/ to 1/ pregnancies.
Maternal mortality: 18%
Fetal mortality: 23%.
More common in nulliparous women and with multiple gestation.

23. Pathophysiology
Defects in intramitochondrial fatty acid beta-oxidation (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.

24. Clinical Features and Diagnosis

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

26. Laboratory findings Bilirubin: frequently > 5mg/dL.
aminotransferase levels (from mild elevation to 1000 IU/L, usually ).
Bilirubin: frequently > 5mg/dL.
Commonly: leukocytosis, anemia.
With progress: thrombocytopenia (± DIC) & hypoalbuminemia.
May be: rising uric acid, renal impairment, metabolic acidosis, ammonia & biochemical pancreatitis.

27. Laboratory findings (Cont.)
liver biopsy
Imaging studies (US & CT)
most definitive test
Inconsistent
often not done
d. t. coagulopathy
swollen, pale hepatocytes
in the central zones
So, diagnosis is
usually based on
clinical & lab. findings
findings
microvesicular fatty infiltration
(frozen section with oil red staining)

28. 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.

29. Treatment

30. 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.

31. Fate & complications

32. Usually Sometimes Rarely
By days
postpartum
liver enzymes
& encephalopathy
improve
laboratory abnormalities
persist after delivery
& may initially worsen during
first postpartum week
Sometimes
patients progress to fulminant hepatic failure
with need for liver transplantation.
Rarely
Most patients improve in 1 to 4 weeks postpart

33. 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.

34. HOW TO DIFFERENTIATE

35. HELLP
AFLP
% Pregnancies
0.2%–0.6%
0.005%–0.01%
Onset/trimester
3 or postpartum
Family history No
Occasionally
Presence of preeclampsia
Yes
50%
Typical clinical features
Hemolysis (anemia)
Thrombocytopenia (50,000 often)
Liver failure with coagulopathy, encephalopathy
hypoglycemia, DIC
Aminotransfer-ases
Mild, but may be up to fold rise
typical but variable

36. <5 mg/dL unless massive necrosis
HELLP
AFLP
Bilirubin
<5 mg/dL unless massive necrosis
often >5 mg/dL, higher if severe
Hepatic imaging
Hepatic infarcts
Hematomas, rupture
Fatty infiltration
Histology
Patchy/extensive
necrosis, periportal hge, fibrin deposits
Microvesicular fat in zone 3
Maternal mortality
1%–25%
7%–18%
Fetal/perinatal mortality
11%
9%–23%
Recurrence in subsequent
Pregnancies
4%–19%
fatty acid oxidation defect %
No fatty acid oxidation defect rare

37. WHY TO DIFFERENTIATE

38. Major Risks AFLP HELLP DIC Infections & bleeding
(most life threatening).
DIC
ARF
Hypoglycemia
ARDS
pulmonary edema
Pancreatitis (develop after onset
of hepatic & renal dysfunction
need serial screening
of serum lipase and amylase
for several days after
hepatic dysfunction)
stroke & seizures
liver hges
(most life-threatening)

39. Therapeutic Options AFLP HELLP Late Early FFP Plasmapheresis
glucose
Antithrombotics:
(heparin, antithrombin,
low dose aspirin)
Liver transplant
(limited role)
Liver transplant
More definite role role
Steroids: rapid clinical &
lab. improvement
Blood transfusion

40. 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.

41. 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

42. 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.

43. In conclusion Important to diff. AFLP from HELLP
Diff. mainly based on lab. + imaging (CT-MRI)
Diff. because AFLP needs:
Maternal follow-up for recurrence
Baby follow-up for FAOD needing dietary control
Next pregnancies for presymptomatic diagnosis

44. THANK YOU