Acute Fatty Liver With Pregnancy Dr. Mohammed Abdalla Egypt

1
Acute Fatty Liver With Pregnancy

• Dr. Mohammed Abdalla
• Egypt, Domiat General Hospital

2
Historical points

• (AFLP) was first identified by Sheehan in 1940
• The name AFLP has replaced earlier terminologies,
  acute yellow atrophy of pregnancy
• and acute obstetric fatty metamorphosis of
  liver

3
Incidence and Characteristics

• once in every 7,000 to 11,000 deliveries

4
Incidence and Characteristics

• Acute fatty liver of pregnancy most frequently
  complicates the third trimester and is commonly
  associated (or complicated ) with preeclampsia
  (50 to 100 percent).

Riely CA. Hepatic disease in pregnancy. Am J Med
199496(1A)18S-22S.   3. Samuels P, Cohen AW.
Pregnancies complicated by liver disease and
liver dysfunction. Obstet Gynecol Clin North Am
199219745-63
5
Incidence and Characteristics

• Incidence  1/7000 -11,000
• Age, (mean, range) 26 (16-39)
• Primiparous () 67
• Male baby () 60
• Onset week of pregnancy 33 (28-38)
• Mortality () ( Maternal )18 - ( Fetal) 47

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
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Liver Function Tests

• aspartate aminotransferase (AST)
• and alanine aminotransferase (ALT) evaluate Liver
  cell injury or necrosis

• Marked ALT elevation (viral hepatitis)
• Moderate ALT elevation (drug-induced
  hepatotoxicity, hyperemesis gravidarum,
  cholelithiasis, HELLP .AFLP.)

8
Liver Function Tests

• albumin level
• prothrombin time

• evaluate liver synthetic function (are depressed
  in cirrhosis or severe acute liver disease)

9
Liver function tests

• alkaline phosphatase,
• bilirubin,
• gamma glutamyl transpeptidase

evaluate Cholestasis and biliary obstruction
In normal pregnancies, alkaline phosphatase
levels may be elevated three- to fourfold,
secondary to placental alkaline phosphatase levels
10
Pathogenesis

• The etiology is not known precisely.

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Pathogenesis

• 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 ß oxidation enzyme.

• Matern D, Hart P, Murtha AP, Vockley J, Gregersen
  N, Millington DS, et al. Acute fatty liver of
  pregnancy associated with short-chain acyl-
  coenzyme A dehydrogenase deficiency. J Pediatr
  2001138585-8.   76. Brackett JC, Sims HF,
  Rinaldo P, et al. Two alpha subunit donor splice
  site mutations cause human trifunctional protein
  deficiency. J Clin Invest 1995952076-82.  

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CLINICAL PRESENTATION
Symptoms/Signs

• Vomiting
  80
• Abdominal pain
  52
• Jaundice
  93
• Encephalopathy 87
• Polydipsia
  80
• Pruritus
  60
• Ascitis
  47

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polydipsia,

• with or without polyuria, frequently is an early
  symptom in AFLP.

• Bourl iere M, Berman J, Ducrotte S, et al
  Polyuro-polydipsie et steatose hepatique aigue
  gravidique. Discussion a propos d'un cas. J
  Gynecol Obstet Biol Reprod 1879, 1989
•   Cammu H, Velkeniers B, Charels K, et al
  Idiopathic acute fatty liver of pregnancy
  associated with transient diabetes insipidus

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polydipsia,

• 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.

15
Lethargy and encephalopathy

• After hours or a few days, some patients become
  lethargic and may decline into hepatic coma, or
  milder degrees of mental impairment.

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ascitis

• Usually transient and rarely prominent.

17

• 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
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LABORATORY FEATURES

• Liver test abnormalities
• conjugated hyperbilirubinemia (usually between 5
  and 15 mg/dL)
• increased alkaline phosphatase (normal lt170)
• and modest increases in serum aminotransferases
  normal lt50 (usuallylt1000 IU/L)
• Leukocytosis occurs commonly
• thrombocytopenia
• decreased clotting factors
• Hypoglycemia and renal dysfunction

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Histopathology

• fatty metamorphosis by liver biopsy

• The hepatic architecture is intact and the
  lobules are swollen with compressed sinusoids
• Centrilobular microvesicular fatty infiltration
  of hepatocytes
• ballooning of hepatocytes

• Sherlock S. Acute fatty liver of pregnancy and
  the microvesicular fat diseases. Gut
  198324265-9.  

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Histopathology

• 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
200172193-5.  
21
Complications

• cerebral edema,
• renal failure (60),
• hypoglycemia (53),
• infections (45)
• gastrointestinal hemorrhage (33),
• coagulopathy (30),
• fetal death
• severe postpartum hemorrhage

22

• 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
  123823, 1975  

23

• renal involvement is less severe than with toxemia

(a mild proteinuria ,mild edema and a mild
increase in blood urea nitrogen and creatinine).
24

• When renal failure is aggravated, it usually is
  impossible to distinguish from toxemia.

25

• A severe hypoglycemia often appears at any stage
  of the disease, or even during clinical recovery.

26

• Ascites, detected clinically or by ultrasound, is
  transient and rarely prominent.

27

• 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.

28
Diagnosis and managment

• It often is impossible to immediately perform a
  liver biopsy in pregnant patients with severe
  coagulation abnormalities.

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Diagnosis and managment

• Therefore, in many cases, it is necessary to rely
  on the clinical and laboratory data and, in the
  physician's and obstetrician's experience,

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Diagnosis and managment

• the emergency therapeutic decisions usually are
  made without waiting for a histologically proven
  diagnosis.

31
Diagnosis and managment

• Liver biopsy is not indicated for diagnosis

Riely CA, Latham PS, Romero R, Duffy TP. Acute
fatty liver of pregnancy. A reassessment based on
observations in nine patients. Ann Intern Med
1987106703-6.
32
Diagnosis and managment

• 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.

• Castro MA, Ouzounian JG, Colletti PM, et al
  Radiologic studies in acute fatty liver of
  pregnancy. A review of the literature and 19 new
  cases. J Reprod Med 41839, 1996  

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Diagnosis and managment

• The mild jaundice.
• and modest increase in serum aminotransferases
  are important signs

against
the diagnosis of. fulminant hepatitis (viral or
toxic).
34
Diagnosis and managment

• the mild increase in blood pressure,
  hyperuricemia, and the intense thirst are

uncommon
in fulminant hepatitis. and they favor the
diagnosis of acute fatty liver of pregnancy.
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TREATMENT

• No specific treatment

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TREATMENT

• All patients should be hospitalized as soon as
  the diagnosis of AFLP is suspected

37
TREATMENT

• 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.

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TREATMENT

• it seems convenient to maintain glucose infusions
  . Because of the risk of a sudden hypoglycemia
  until a full metabolic recovery is obtained.

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TREATMENT

• 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.

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TREATMENT

• Pregnancy termination
• (yes OR no )

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TREATMENT

• importance of interrupting pregnancy may seem
  questionable,

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TREATMENT

• As it noticed in some patients that the disease
  does not immediately improve after delivery

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TREATMENT
But also that no patient has yet been reported
with a recovery before delivery.
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TREATMENT
SO ,a prompt delivery is preferable.

• Vanjak D, Moreau R, Roche-Sicot J, et al
  Intrahepatic cholestasis of pregnancy and acute
  fatty liver of pregnancy. An unusual but
  favorable association? Gastroenterology 100
  1123, 1991
•   Riely CA Liver diseases of pregnancy. In
  Kaplowitz N (ed) Liver and biliary diseases, ed
  2. Baltimore, Williams Wilkins, 1996, p 483  
• Reyes H, Sandoval L, Wainstein A, et al Acute
  fatty liver of pregnancy A clinical study of 12
  episodes in 11 patients. Gut 35101, 1994  
• Hou SH, Levin S, Ahola S, et al Acute fatty
  liver of pregnancy. Survival with early cesarean
  section. Dig Dis Sci 29449,1984

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summary

• AFLP should be suspected when persistent
  vomiting, malaise, encephalopathy or jaundice
  appear in the final weeks of pregnancy or in the
  early puerperium.

46
summary

• 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.
47
summary

• AFLP is a medical and obstetric emergency because
  of the metabolic alterations and complications
  and because of the impending need to interrupt
  pregnancy.

48
summary

• close surveillance of future pregnancies in
  patients affected previously by this disease is
  recommended.

49
summary

• an impaired fatty acid metabolism during
  childhood. may affect babies born of pregnancies
  with AFLP.

50
Thank You

• Dr. Mohammed Abdalla
• EGYPT, Domiat general hospital