Acute Fatty Liver With Pregnancy

Dr. Mohammed Abdalla

Egypt, Domiat General Hospital

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”

Incidence and Characteristics

once in every 7,000 to 11,000

deliveries

• 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 1994;96(1A):18S-22S.  

3. Samuels P, Cohen AW. Pregnancies complicated by liver disease and liver dysfunction. Obstet Gynecol Clin North Am 1992;19:745-63

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%

Incidence and Characteristics

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

• 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.)

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

Liver Function Tests

albumin level

prothrombin time

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

Pathogenesis

The etiology is not known precisely.

•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.

•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 2001;138:585-8.   [76]. Brackett JC, Sims HF, Rinaldo P, et al. Two alpha subunit donor splice site mutations cause human trifunctional protein deficiency. J Clin Invest 1995;95:2076-82.  

Pathogenesis

CLINICAL PRESENTATION

Vomiting 80

Abdominal pain 52

Jaundice 93

Encephalopathy 87

Polydipsia 80

Pruritus 60

Ascitis 47

Symptoms/Signs

%

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 18:79, 1989

•  Cammu H, Velkeniers B, Charels K, et al: Idiopathic acute fatty liver of pregnancy associated with transient diabetes insipidus

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.

polydipsia,

• 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

ascitis

Usually transient and rarely prominent.

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

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

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 sinusoidsCentrilobular microvesicular fatty infiltration of hepatocytesballooning of hepatocytes

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

Complications

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

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  

renal involvement is less severe than with toxemia

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

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

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

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

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.

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

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

Liver biopsy is not Liver biopsy is not indicated for indicated for

diagnosisdiagnosisRiely CA, Latham PS, Romero R, Duffy TP. Acute fatty liver of pregnancy. A reassessment based on observations in nine patients. Ann Intern Med 1987;106:703-6.

• 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 41:839, 1996  

The mild jaundice.

and modest increase in serum aminotransferases are important signs

the diagnosis of. fulminant hepatitis (viral or toxic).

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.

No specific treatment

All patients should be

hospitalized as soon as the diagnosis of AFLP is suspected

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.

it seems convenient to

maintain glucose infusions . Because of the risk of a sudden hypoglycemia until a full metabolic recovery is obtained.

• 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.

Pregnancy terminationPregnancy termination

((yes yes OROR no no ))

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importance of interrupting pregnancy may seem questionable,

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

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But also that no patient has yet been reported with a recovery before delivery.

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•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 35:101, 1994  

•Hou SH, Levin S, Ahola S, et al: Acute fatty liver of pregnancy. Survival with early cesarean section. Dig Dis Sci 29:449,1984

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

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.

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

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

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

Thank YouDr. Mohammed Abdalla

EGYPT, Domiat general hospital