acute fatty liver versus help final.ppt

8/10/2019 Acute Fatty Liver Versus HELP Final.ppt

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Acute fatty liver versus HELLPsyndrome in obstetric ICU:

why and how todifferentiate?

BY

Bahaa-El-Din Ewees MD


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Physiological changes in liver tests during normalpregnancy

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


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Abnormal liver function tests occur in3 - 5%of pregnancies for different

reasons

Liver diseases in pregnancy

liver disorders that occur only inthe settingof pregnancy

liver disorders that occur coincidentallywithpregnancy


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Liver diseases in pregnancy

Only in the

setting of pregnancy

coincidental with pregnancy

Preeclampsia-

associated

Chronic liver diseases e.g.:

cholestatic liver disease,autoimmune hepatitis,

Wilson disease,

viral hepatitis, etc

not associated with

preeclampsia

The preeclampsia

itself

HELLP-syndrome

AFLP

Hyperemesisgravidarum

Intrahepatic cholestasis

of pregnancy


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HELLP syndrome


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Severe preeclampsia is complicated in 2-12% of cases (0.2-0.6% of allpregnancies) by hemolysis (H), elevatedliver tests (EL), and low platelet count(LP), the HELLP syndrome.

Etiology:microangiopathic hemolyticanemia +vascular endothelial injuryfibrin deposition in blood vessels +

platelet activation & consumption,small to diffuse areas of hemorrhage andnecrosis large hematomas +capsular tears +intraperitoneal bleeding.


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Clinical Features andDiagnosis


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Most patients: 27 - 36 weeks gestation,

but25% in postpartum period.

Can occur with any parity and age butcommoner in white, multiparous & olderpts.


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Clinical Picture:

Most patients

Less commonly

upper abd. pain& tenderness

Nauseavomiting

Malaiseheadache

Edemaweight gain

jaundiceuncommon (5%)

Hypertensionproteinuria

renal failure

+ uric acid

DI

Antiphospholipidsyndrome

some patients have no obviouspreeclampsia


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Aminotransferase: variable, from mild to 1020 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.


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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).


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Treatment


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Hospitalization & ICU carefor:

o antepartum stabilization of BP and DIC,

o seizure prophylaxis,o fetal monitoring.

pregnancy is > 34 wkgestational age

24-34 wk

immediate induction

corticosteroids for 48 h(fetal lung maturity)

delivery

The only definitive treatment is delivery

C ti t id hi h th l t


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Corticosteroids which cross the placenta(betamethasone or dexamethasone,)

for 24-48 hours

fetal lung maturity improves maternalplatelet count.

Tried treatment modalities for patients withongoing or newly developing symptoms

Antithrombotics(Heparin, aspirin)

plasmapheresis

plasma exchangewith FFPdialysis


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After delivery continue close monitoring of the mother

Up to 48 h

postpartum

worsening thrombocytopenia& increasing LDH levels

Most lab. values normalize

After 48 h

persistent or worseninglab. Abnormalities

by 4thpostpartum day

Postpartumcomplications

Maybe

normalization of platelets

5 days


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Fate & complications


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Reportedmaternal mortalityis1%

Perinatal mortalityrate ranges from

7%-22%and may be due to: premature detachment of placenta,

intrauterine asphyxia,

prematurity.


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Other complications:

No long-term effect on renal function

noted.

abruptio

placentaeDICARFARDS

pulmonary edemastrokeliver failurehepatic infarction


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Recurrence : Subsequent pregnanciescarry a high risk of complications

pre-eclampsia,

recurrence,

prematurity, IUGR,

abruptio placentae, perinatal mortality.


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Acute fatty liver

A t f tt li f (AFLP) i


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Acute fatty liver of pregnancy (AFLP) is ararebutseriousmaternal illness that occurs in thethird trimesterof pregnancy.

Incidence:1/10 000 to 1/15 000pregnancies.

Maternal mortality:18%

Fetal mortality:23%.

More common innulliparous womenand withmultiple gestation.


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Pathophysiology

Defects in intramitochondrial fatty acid beta-

oxidation (enzymatic mutations in fatty acidoxidation).

Heterozygous woman gets a homozygousfetus fetal fatty acids accumulate

return to the mothers circulation

extra load of long-chain fatty acids

triglyceride accumulationhepatic fat deposition & impaired maternalhepatic function.


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Clinical Features and

Diagnosis


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Typical presentation:

a 1 - 2 wk history of nausea, vomiting,abdominal pain & fatigue,

Jaundice (frequent), moderate to severe hypoglycemia,

hepatic encephalopathy,

coagulopathy.

L b fi di


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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.


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Laboratory findings (Cont.)

liver biopsy

most definitive test

often not doned. t. coagulopathy

swollen, pale hepatocytes

in the central zones

microvesicular fatty infiltration(frozen section with oil red staining)

findings

Imaging studies (US & CT)

Inconsistent


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(B) Hematoxylin-eosin

stain (high power) shows

hepatocytes stuffed withmicrovesicular fat (free

fatty acids) and centrally

located nuclei.

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.


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Treatment


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If no obstetric indication, normal delivery ispreferred to CS ( % of major intra-abdominalbleeding)

Careful attention to the infant: risk ofcardiomyopathy, neuropathy, myopathy,nonketotic hypoglycemia, hepatic failure, and

death.

Treatment involves

early recognition & diagnosis immediate terminationof pregnancy+


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Fate & complications


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With advances in supportive management,the maternal mortality is now 7%-18%

and fetal mortality 9%-23%.

Complications:

Infectious and bleeding remain the most lifethreatening.

Liver transplantation has a very limited

role because of the great potential forrecovery with delivery.


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HOW TO

DIFFERENTIATE

HELLP AFLP


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HELLP AFLP

% Pregnancies 0.2%0.6% 0.005%0.01%

Onset/trimester 3 or postpartum 3 or postpartum

Family history No Occasionally

Presence ofpreeclampsia

Yes 50%

Typical clinicalfeatures

Hemolysis (anemia)

Thrombocytopenia(50,000 often)

Liver failure withcoagulopathy,encephalopathy

hypoglycemia,DIC

Aminotransfer-

ases

Mild, but may be up

to 10-20-fold rise

300-500 typical

but variable

HELLP AFLP


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HELLP AFLP

Bilirubin 5mg/dL, higher ifsevere

Hepaticimaging

Hepatic infarcts

Hematomas,rupture

Fatty infiltration

Histology Patchy/extensive

necrosis, periportalhge, fibrin deposits

Microvesicular fat in zone 3

Maternalmortality

1%25% 7%18%

Fetal/perinatalmortality 11% 9%23%

Recurrence insubsequent

Pregnancies

4%19% fatty acid oxidation defect25%

No fatty acid oxidation defect

rare


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WHY TO DIFFERENTIATE


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Major Risks

Infections & bleeding

(most life threatening).

Hypoglycemia

AFLP HELLP

Pancreatitis (develop after onsetof hepatic & renal dysfunction

need serial screeningof serum lipase and amylase

for several days afterhepatic dysfunction)

DIC

ARF

ARDS

pulmonary edema

stroke & seizures

liver hges

(most life-threatening)

Th ti O ti


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Therapeutic Options

AFLP HELLP

FFP

glucose

Liver transplant(limited role)

Antithrombotics:(heparin, antithrombin,

low dose aspirin)

Steroids: rapid clinical &lab. improvement

Blood transfusion

Early Late

Plasmapheresis

Liver transplantMore definite role role

Follow up Precautions:


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Follow-up Precautions:

A deficiency in long chain 3-hydroxyacyl-CoAdehydrogenase (LCHAD) is thought to beassociated with the development of AFLP.

Under normal circumstances, an individual thatis heterozygous for enzymatic mutations infatty acid oxidation will not have abnormalfatty oxidation.

Affected patients should be screened for


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Affected patients should be screened fordefects in fatty acid oxidation as

recurrence in subsequent children is 25%,and recurrence of AFLP in mothers is alsopossible.

Presymptomatic diagnosis of FAOD withThe application of tandem mass

spectrometry to newborn screening is aneffective way to identify most FAODpatients presymptomatically

reduce morbidity and avoid mortality

Current management of pts with FAOD


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Current management of pts with FAODincludes 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 thelong-term outcome.

l i


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In conclusion

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

MRI)

Diff. because AFLP needs:

o Maternal follow-up for recurrence

o Baby follow-up for FAOD needing dietarycontrol

o Next pregnancies for presymptomatic

diagnosis


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acute fatty liver versus help final.ppt

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