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Physiological changes in liver tests during normal pregnancy
Test
Bilirubin
Aminotransferases
Prothrombin time
Alkaline phosphatase
Fibrinogen
Normal Range
Unchanged or slightly decrease
Unchanged
Unchanged
Increases 2 to 4-fold
Increases 50%
Globulin
α -fetoprotein
WBC
Ceruloplasmin
Cholesterol
Triglycerides
Globulin
Hemoglobin
Increases in α and ß globulins
Moderate rise , esp. with twins
Increases
Increases
Increases 2-fold
Increases
Decreases in gamma-globulin
Decrease in later pregnancy

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


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 .

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.


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.

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


for: o antepartum stabilization of BP and DIC, o seizure prophylaxis, o 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) dialysis plasma exchange with FFP plasmapheresis

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



•
•
•


:
• pulmonary edema
• stroke
• liver failure
• hepatic infarction
• abruptio
• placentae
DIC
•
ARF
•
ARDS


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


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 .


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.

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





 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.

liver biopsy Imaging studies (US & CT) most definitive test often not done d. t. coagulopathy findings swollen, pale hepatocytes in the central zones
Inconsistent microvesicular fatty infiltration
(frozen section with oil red staining)

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 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.

Usually
Sometimes
Rarely
By 2 - 3 days postpartum laboratory abnormalities persist after delivery
& may initially worsen during first postpartum week liver enzymes
& encephalopathy improve 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.

HELLP
% Pregnancies 0.2%–0.6%
Onset/trimester 3 or postpartum
Family history No
Presence of preeclampsia
Yes
Typical clinical features
Aminotransferases
Hemolysis (anemia)
Thrombocytopenia
(50,000 often)
AFLP
0.005%–0.01%
3 or postpartum
Occasionally
50%
Liver failure with coagulopathy, encephalopathy hypoglycemia,
DIC
Mild , but may be up to 10-20-fold rise
300-500 typical but variable

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

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




Important to diff. AFLP from HELLP
Diff. mainly based on lab. + imaging (CT-
MRI)
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