4. • Acute fatty liver of pregnancy most
frequently complicates the third
trimester and is commonly associated
(or complicated ) with preeclampsia
(50 to 100 percent).
Incidence and Characteristics
6. Liver Function Tests
liver function tests” describes a
panel of laboratory tests profiling
discrete aspects of liver function
No single liver function
test is available to
quantify liver disease
7. • Pregnancy causes very few alterations in the
results of standard liver tests. The
aminotransferases (AST and ALT), γ-glutamyl
transpeptidase (GGTP), total bilirubin, and serum
bile acid level remain within the normal range.
• The alkaline phosphatase rises modestly in the
third trimester.
• The albumin level is lower than in nonpregnant
women, and the cholesterol level higher
Liver Function Tests
8. • aspartate aminotransferase (AST)
• and alanine aminotransferase (ALT)
evaluate Liver cell injury or necrosis
Liver Function Tests
•Marked ALT elevation (viral hepatitis)
•Moderate ALT elevation (drug-induced hepatotoxicity,
hyperemesis gravidarum, cholelithiasis, HELLP
.AFLP.)
9. evaluate liver synthetic function
(are depressed in cirrhosis or
severe acute liver disease)
Liver Function Tests
albumin level
prothrombin time
10. alkaline phosphatase,
bilirubin,
gamma glutamyl transpeptidase
Liver function tests
In normal pregnancies, alkaline phosphatase
levels may be elevated three- to fourfold,
secondary to placental alkaline phosphatase
levels
evaluate Cholestasis and biliary obstruction
12. •A genetic component has been suggested
•Recent research suggests that AFLP is
associated with a Glu474Gln mutation in the
long-chain 3-hydroxy acyl-coenzyme A
dehydrogenase (LCHAD), a fatty acid β oxidation
enzyme.
Pathogenesis
This gene mutation is recessive; therefore, outside
of pregnancy under normal physiological
conditions, women have normal fatty acid
oxidation.
13. • Recent studies document that infants born
of affected pregnancies can be deficient in
one of the enzymes of mitochondrial beta
oxidation of fatty acids, long chain 3-
hydroxyl-acyl CoA dehydrogenase
(LCHAD) . Affected infants are at risk for
developing nonketotic hypoglycemic
coma, often with death
Pathogenesis
16. with or without polyuria,
frequently is an early
symptom in AFLP.
polydipsia,
17. The patient may drink 2 or 3 liters
of liquids overnight. it often
exceeds the magnitude of
vomiting. It has been interpreted
as a transient diabetes insipidus.
polydipsia,
19. • After hours or a few days,
some patients become
lethargic and may decline
into hepatic coma, or milder
degrees of mental
impairment.
Lethargy and encephalopathy
21. After delivery, most patients
improve slowly, and a full
clinical and laboratory recovery
may take from 1 to 4 weeks.
But marked deterioration after
delivery has been observed
22. LABORATORY FEATURES
• Liver test abnormalities
conjugated hyperbilirubinemia (usually between
5 and 15 mg/dL)
increased alkaline phosphatase (normal <170)
and modest increases in serum
aminotransferases normal <50 (usually<1000
IU/L)
Leukocytosis occurs commonly
thrombocytopenia
decreased clotting factors
Hypoglycemia and renal dysfunction
23. Histopathology
fatty metamorphosis by liver biopsy:
•Sherlock S. Acute fatty liver of pregnancy and the
microvesicular fat diseases. Gut 1983;24:265-9.
The hepatic architecture is intact and the
lobules are swollen with compressed
sinusoids
Centrilobular microvesicular fatty infiltration
of hepatocytes
ballooning of hepatocytes
24. In contrast with viral hepatitis
and other common causes of
fulminant hepatic failure,
necrosis of hepatocytes is
always minor .
Vigil-De Gracia P, Lavergne JA. Acute fatty
liver of pregnancy. Int J Gynaecol Obstet
2001;72:193-5.
Histopathology
26. The upper gastrointestinal hemorrhage
may be caused by Mallory-Weiss
syndrome, acute gastric or
duodenal lesions (e.g., gastritis,
duodenitis, peptic ulcers), or it can
be a manifestation of a
coagulopathy.
•Cano RI, Delman MR, Pitchumoni CS, et al: Acute fatty liver of pregnancy.
Complication by disseminated intravascular coagulation
•Killam AP, Dillard SH, Patton RC, et al: Pregnancy-induced hypertension
complicated by acute liver disease and disseminated intravascular
coagulation. Am J Obstet Gynecol 123:823, 1975
27. renal involvement is less severe
than with toxemia
(a mild proteinuria ,mild
edema and a mild increase
in blood urea nitrogen and
creatinine).
28. When renal failure is
aggravated, it usually is
impossible to distinguish
from toxemia.
29. A severe hypoglycemia often
appears at any stage of
the disease, or even
during clinical recovery.
31. Maternal mortality (18%) usually is
attributed to one of its
complications (gastrointestinal
hemorrhage, bleeding disorder,
renal failure, acute pancreatitis)
but not to liver failure alone.
32. It often is impossible to immediately
perform a liver biopsy in pregnant
patients with severe coagulation
abnormalities.
next
33. Therefore, in many cases, it is
necessary to rely on the clinical
and laboratory data and, in the
physician's and obstetrician's
experience,
next
36. • Ultrasound is most important in the
exclusion of biliary tract disorders, but its
value and the value of CT and MR imaging,
has been considered limited and not
helpful for the diagnosis and management of
patients with AFLP.
37. The mild jaundice.
and modest increase in serum
aminotransferases are important
signs
the diagnosis of. fulminant hepatitis
(viral or toxic).
38. Aspartate transaminase (AST)
and alanine transaminase (ALT)
• Aspartate transaminase (AST) and alanine transaminase
(ALT) are not elevated in normal pregnancies. These can
become elevated in many different conditions during
pregnancy. Some are unique to pregnancy, such as
preeclampsia/eclampsia, HELLP, and AFLP. High levels
of ALT can be seen in patients with viral hepatitis;
however, the highest levels are seen in patients with
acute toxic liver injury, as can be seen in
acetaminophen overdose . Both AST and ALT can be
elevated due to the hepatic injury.
39. the mild increase in blood pressure,
hyperuricemia, and the intense
thirst are
in fulminant hepatitis. and they favor the
diagnosis of acute fatty liver of pregnancy.
41. All patients should be
hospitalized as
soon as the diagnosis
of AFLP is suspected
42. Moderate or severely affected patients
(encephalopathic, deeply jaundiced,
with a prothrombin time less than
40% of the control), or with any
extrahepatic complications, should
be attended in intensive
care units.
43. it seems convenient to
maintain glucose
infusions . Because of the
risk of a sudden hypoglycemia
until a full metabolic recovery is
obtained.
44. • Two laboratory tests:
prothrombin time and blood
glucose, should be repeated at
least daily, Prothrombin time helps
to assess the prognosis of liver failure,
and blood glucose detects a severe
hypoglycemia.
47. As it noticed in some patients that the
disease does not immediately
improve after delivery
next
48. But also that no patient has
yet been reported with a
recovery before delivery.
next
49.
50. • Regional anesthesia may be obtained if a
coagulopathy is not evident. However, if a
coagulopathy is present, it should be corrected
prior to regional anesthesia as bleeding at the
puncture site is a concern. With general
anesthesia, the anesthesiologist should be careful
not to use agents that have potential
hepatotoxicity, such as halothane. Isoflurane has
no hepatotoxicity and may improve hepatic blood
flow.
51. AFLP should be suspected
when persistent vomiting,
malaise, encephalopathy or
jaundice appear in the final
weeks of pregnancy or in the
early puerperium.
52. Diagnosis is mainly based
on clinical and laboratory
grounds.
Liver biopsy is usually confirmatory,if done..
the emergency therapeutic decisions
usually are made without waiting for a
histologically proven diagnosis.
53. AFLP is a medical and obstetric
emergency because of the
metabolic alterations and
complications and because of
the impending need to interrupt
pregnancy.
54. close surveillance of future
pregnancies in patients affected
previously by this disease is
recommended.
55. an impaired fatty acid metabolism
during childhood. may affect
babies born of pregnancies with
AFLP.