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Acute fatty liver of pregnancy

Acute fatty liver of pregnancy
Richard H Lee, MD
Nancy Reau, MD
Section Editors:
Keith D Lindor, MD
Charles J Lockwood, MD, MHCM
Deputy Editors:
Kristen M Robson, MD, MBA, FACG
Vanessa A Barss, MD, FACOG
Literature review current through: Mar 2023. | This topic last updated: Mar 29, 2023.

INTRODUCTION — Acute fatty liver of pregnancy (AFLP) is an obstetric emergency characterized by maternal liver dysfunction and/or failure that can lead to maternal and fetal complications, including death. Prompt delivery and supportive maternal care are important for achieving a full recovery for the mother.

The clinical features, diagnosis, and management of AFLP will be reviewed here. A general approach to the patient who develops liver disease during pregnancy is presented separately and has also been addressed in a guideline issued by the American College of Gastroenterology [1]. (See "Approach to evaluating pregnant patients with elevated liver biochemical and function tests".)

EPIDEMIOLOGY AND RISK FACTORS — Acute fatty liver of pregnancy (AFLP) is rare, with an approximate incidence of 1 in 7000 to 20,000 pregnancies [2-6]. Given the association with inherited defects, the incidence may vary based on ethnicity, but epidemiology studies are lacking. (See 'Pathogenesis' below.)

Potential risk factors for AFLP include [1,3,4,7,8]:

Fetal long-chain 3-hydroxyacyl CoA dehydrogenase deficiency

Prior episode of AFLP

Multiple gestation

Preeclampsia or hemolysis, elevated liver enzymes, and a low platelet count syndrome

Male fetal sex

Low body mass index (BMI <20 kg/m2)


PATHOGENESIS — The pathogenesis of acute fatty liver of pregnancy (AFLP) is unclear, but defects in fatty acid metabolism during pregnancy appear to play a role. Free fatty acids normally increase in pregnancy, particularly late in gestation, to fuel fetoplacental growth and development. If maternal-fetal fatty acid metabolism is defective, intermediate products of metabolism can accumulate in maternal blood and hepatocytes, with deleterious effects on maternal hepatocytes [9,10].

An overview of fatty acid oxidation disorders including the clinical manifestations is presented separately. (See "Overview of fatty acid oxidation disorders" and "Specific fatty acid oxidation disorders".)

Fetal long-chain 3-hydroxyacyl CoA dehydrogenase (LCHAD) deficiency — Approximately 20 percent of AFLP is associated with LCHAD deficiency [1]. LCHAD is one of the enzymes involved in fatty acid oxidation; it catalyzes a step in beta-oxidation of mitochondrial fatty acids in which 3-ketoacyl-CoA is formed from 3-hydroxyacyl-CoA. In fetuses homozygous for LCHAD deficiency, the fetoplacental unit cannot perform this step, so levels of intermediate products of fatty acid metabolism increase and enter the maternal circulation [11-13]. Because the mother is heterozygous for LCHAD deficiency, she has decreased ability to accomplish fatty acid oxidation, thus contributing to long-chain metabolites accumulating in maternal blood and hepatocytes, resulting in toxic effects.

However, not all mutations that lead to LCHAD deficiency result in AFLP [14,15]. The homozygous G1528C mutation, which alters amino acid 474 from glutamic acid to glutamine on the protein (E474Q), appears to be the most common genotype associated with development of AFLP [9,11]. The heterozygous and wild-type fetal genotype are not associated AFLP [16].

The G1528C mutation has also been associated with development of hemolysis, elevated liver enzymes, and a low platelet count syndrome [9,11,16] and preeclampsia [16], which share several phenotypic features with AFLP [17].

Other enzyme deficiencies — The following deficiencies of fetoplacental mitochondrial oxidation have also been associated with development of AFLP, but are less common than the G1528C mutation [10] (see "Specific fatty acid oxidation disorders", section on 'Medium- and short-chain fatty acid oxidation disorders'):

Short-chain acyl-CoA dehydrogenase deficiency [18].

Medium-chain acyl-CoA dehydrogenase deficiency [19].

Carnitine palmitoyltransferase deficiency [20].

Mitochondrial trifunctional protein deficiency [21,22].

It is important to recognize that genetic testing may not demonstrate an abnormality. As an example, a whole-exome genetic sequencing analysis of East Asian patients with AFLP found no gene mutation in enzymes involved in fatty acid metabolism [23].

PATIENT PRESENTATION — Acute fatty liver of pregnancy (AFLP) typically presents between the 30th and the 38th week of gestation, but the diagnosis has been made as early as 18 weeks [24] and as late as four days after delivery [3,25].

The initial symptoms of AFLP are often nonspecific (eg, nausea, vomiting, abdominal pain, malaise, headache, and/or anorexia). Many patients have hypertension, with or without proteinuria. Coexisting hemolysis, elevated liver enzymes, and low platelet count syndrome occurs in 20 percent, and 20 to 40 percent of patients are also diagnosed with preeclampsia [26]. (See "HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets)" and "Preeclampsia: Clinical features and diagnosis".)

Signs and symptoms of acute liver failure, including jaundice, ascites, encephalopathy, disseminated intravascular coagulopathy, and hypoglycemia rapidly develop. Most patients develop acute kidney injury, and often progress to multiorgan failure [4].

Arginine vasopressin deficiency (AVP-D, previously called central diabetes insipidus) may occur and is thought to be caused by decreased levels of arginine vasopressin secondary to reduced clearance of vasopressinase by the impaired liver [27]. Acute pancreatitis, which can be severe, is rare and generally occurs in the setting of hepatic and renal dysfunction [28].

In cases of maternal hypovolemia combined with metabolic acidosis from liver injury, uteroplacental perfusion is diminished and, in turn, tests of fetal well-being are frequently nonreassuring [29].


Laboratory findings — All patients with acute fatty liver of pregnancy (AFLP) have elevations in aminotransferases (aspartate aminotransferase or alanine aminotransferase), usually ranging from 5 to 10 times the upper limit of normal (table 1) [26]. Other laboratory findings that may be present include:

Elevated serum bilirubin levels

Low serum glucose

Elevated serum creatinine

Elevated white blood cell count

Elevated ammonia level

Elevated urate level

Prolonged prothrombin time, international normalized ratio, activated partial thromboplastin time

Increased thrombin time

Reduced levels of coagulation inhibitors (eg, antithrombin)

Low platelet count

Low fibrinogen

Fragmented red blood cells and burr cells


Low cholesterol

Note: In normal pregnancy, the mean platelet count is slightly lower than in nonpregnant females, but usually remains within the normal range. Pregnancy is also associated with leukocytosis: The neutrophil count begins to increase in the second month of pregnancy and plateaus in the second or third trimester, at which time white blood cell counts range from 9000 to 15,000 cells/microL. The physiologic increase in the glomerular filtration rate during pregnancy results in a decrease in serum creatinine concentration, which falls by an average of 0.4 mg/dL (35 micromol/L) to a normal range of 0.4 to 0.8 mg/dL (35 to 70 micromol/L) (table 2).

Imaging — Radiologic findings thought to be characteristic of AFLP have been described in small case series and reports. Ultrasound of the liver may show nonspecific changes, including fatty infiltration or brightness but this is not diagnostic [26,30]. Other imaging modalities maybe more specific. For example, in one report of five patients with AFLP, serial magnetic resonance imaging (MRI) showed a transient increase in detectable fat (ie, >5 percent MRI-proton density fat fraction) that resolved within two weeks after delivery [31]. In a retrospective study of 19 patients with AFLP who underwent at least one imaging study, fatty infiltration of the liver was found on ultrasound in three of 11 patients, on computed tomography (CT) in five of 10 patients, and on MRI in none of five patients; three patients with normal ultrasound scans subsequently had fatty filtration seen on CT [32]. (See 'Diagnostic evaluation' below.)

Histologic findings — Biopsy is rarely needed for diagnosis or management. If performed, microvesicular fatty infiltration of swollen hepatocytes is strongly suggestive of AFLP [33,34]. The fat droplets surround centrally located nuclei, giving the cytoplasm a foamy appearance. The fatty infiltration is prominent in central and mid zonal parts of the lobule and usually spares a sharply defined rim of cells around the portal tracts [35]. Tissue should be set aside at the time of the procedure for special stains (oil red O on frozen section, or electron microscopy) for confirmation of diagnosis in patients without evident vacuolization (picture 1) [36,37].

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of acute fatty liver of pregnancy (AFLP) primarily involves the syndrome of hemolysis, elevated liver enzymes, and a low platelet count (HELLP) and preeclampsia with severe features (table 3 and table 1) [38]. There is a large clinical overlap between AFLP, HELLP syndrome, and severe preeclampsia [39]. Adding to the complexity, a patient may have both AFLP and HELLP or preeclampsia with severe features.

Hypertension is present in essentially 100 percent of patients with preeclampsia, 85 percent of patients with HELLP, and up to about 50 percent of patients with AFLP. Severe symptoms and signs of hepatic insufficiency such as hypoglycemia, encephalopathy, ascites and coagulopathy are more consistent with AFLP than HELLP or severe preeclampsia. AFLP is the most common cause of acute liver failure in pregnancy [40]. Multi-organ involvement, especially concurrent renal failure, is more common with AFLP than HELLP or severe preeclampsia, while hypertension and proteinuria are often more severe in HELLP and severe preeclampsia.

In addition, non-pregnancy-related causes of abnormal liver chemistries need to be assessed, such as hepatitis (ie, hepatitis B virus, herpes simplex virus, hepatitis E virus, autoimmune), gallstone disease, Budd-Chiari syndrome and acetaminophen or other drug-induced liver injury.

Differential diagnosis is discussed in more detail separately. (See "Hypertensive disorders in pregnancy: Approach to differential diagnosis".)

DIAGNOSTIC EVALUATION — Pregnant patients in the second half of pregnancy who present with nausea, vomiting, abdominal pain, malaise, hypertension, headache, and/or anorexia should be evaluated for acute fatty liver of pregnancy (AFLP), severe preeclampsia, and hemolysis, elevated liver enzymes, and a low platelet count (HELLP) syndrome, as well as other disorders associated with these nonspecific symptoms (eg, hepatitis and other viruses, acetaminophen poisoning), when clinically appropriate.

The initial work-up includes maternal vital signs, cognitive assessment for encephalopathy, and:

Complete blood count



Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)

Lactate dehydrogenase



Urine protein (protein:creatinine ratio or 24-hour urine protein)

Prothrombin time, international normalized ratio

For patients with signs of liver failure (eg, encephalopathy, jaundice, coagulopathy) or ALT ≥5 times the upper limit of normal, additional laboratory study is performed urgently, including ammonia.

The role of imaging for patients with suspected AFLP is uncertain. While some imaging modalities may be more specific than noncontrast ultrasound, MRI and computed tomography (CT) should be used judiciously because the safety of MRI in pregnancy is not as well established as for ultrasound and CT exposes the mother and fetus to ionizing radiation [1,41]. (See 'Imaging' above and "Diagnostic imaging in pregnant and nursing patients".)

For pregnant patients with suspected biliary tract disease (eg, cholestatic pattern of liver biochemical tests), abdominal imaging with noncontrast ultrasound is typically performed [1]. (See "Approach to the patient with abnormal liver biochemical and function tests", section on 'Evaluation of elevated alkaline phosphatase'.)

Role of liver biopsy — Liver biopsy is not necessary for the diagnosis of AFLP in nearly all patients. It is reserved for rare cases in which the diagnosis is in doubt and the results will affect patient care (eg, for patients with persistent liver failure postpartum who are being evaluated for liver transplantation). Stabilization of the mother and emergency delivery of the fetus should not be delayed for liver biopsy in patients whose clinical presentation and laboratory findings are compatible with AFLP [25]. If liver biopsy is performed in a patient with coagulopathy, a transjugular approach is used because it carries a lower risk of bleeding compared with percutaneous liver biopsy [26]. (See "Transjugular liver biopsy".)

DIAGNOSIS — A presumptive diagnosis of acute fatty liver of pregnancy (AFLP) is usually made clinically based upon the presence of characteristic symptoms (nausea, vomiting, abdominal pain, malaise, and/or anorexia) in a pregnant woman with significant hepatic dysfunction in the second half of pregnancy, after other potential causes of these findings have been excluded. There is a large clinical overlap between AFLP, HELLP syndrome, and severe preeclampsia, and it is sometimes impossible to differentiate among them. Multisystem involvement, including acute kidney injury, encephalopathy, coagulopathy, pancreatitis, pulmonary edema, and/or adult respiratory distress syndrome, strengthens the diagnosis of AFLP [42-44]. (See 'Laboratory findings' above and 'Differential diagnosis' above.)

In addition, diagnosis of AFLP does not exclude another diagnosis of pregnancy-induced liver disease.

Small studies have identified biomarkers that could potentially contribute to diagnostic evaluation [45,46]; however, biomarkers are not routinely used in clinical practice.

Findings on imaging may support the diagnosis, but imaging is not required in all patients with suspected AFLP. (See 'Diagnostic evaluation' above.)

Swansea criteria — The Swansea criteria, which include symptoms, laboratory findings, and imaging, are a diagnostic model for AFLP that have been validated in a cohort study where the incidence of AFLP was 5.0 cases per 100,000 births [3,47].

The Swansea criteria are listed below [3,26,48]. The number of criteria needed for a positive diagnosis has varied from six to nine in research studies, and the criteria are intended for use in patients without hemolysis, elevated liver enzymes, and a low platelet count (HELLP) syndrome or preeclampsia, which limits their clinical utility [26,49].

Signs and symptoms


Abdominal pain



Laboratory findings

Elevated bilirubin (>0.8 mg/dL or >14 micromol/L)

Hypoglycemia (glucose <72 mg/dL or <4 mmol/L)

Leukocytosis (>11,000 cells/microL)

Elevated transaminases (AST or ALT) (>42 international unit/L)

Elevated ammonia (>47 micromol/L)

Elevated urate (5.7 mg/dL or >340 micromol/L)

Acute kidney injury, or creatinine >1.7 mg/dL (150 micromol/L)

Coagulopathy or prothrombin time >14 seconds

Imaging: Ascites or bright liver on ultrasound scan

Histology: Microvesicular steatosis on liver biopsy

When the Swansea criteria were applied to a cohort of 24 patients with suspected pregnancy-related liver disease who underwent biopsy, the presence of ≥6 abnormal variables had positive predictive value of 85 percent and negative predictive value of 100 percent for finding microvesicular steatosis [47].

INITIAL MANAGEMENT — Initial management of the patient with acute fatty liver of pregnancy (AFLP) includes prompt delivery of the fetus, regardless of gestational age, because delivery initiates resolution of this life-threating disease. Medical treatment is provided to stabilize the mother while the liver recovers. Although it may not be possible to distinguish between AFLP, HELLP syndrome, and preeclampsia with severe features, the clinical management is the same (prompt delivery, maternal support) for the three diagnoses, and delivery should not be delayed while attempting to ascertain the underlying disorder.

Patients with signs of acute liver failure (eg, coagulopathy, encephalopathy) are transferred to a referral center for liver transplantation evaluation. Although most patients improve after delivery, transfer is required to avoid delay in liver transplantation evaluation and listing and to reduce risk of adverse outcomes. Management of patients with acute liver failure is discussed separately. (See "Acute liver failure in adults: Management and prognosis" and "Liver transplantation in adults: Patient selection and pretransplantation evaluation".)

Components of pregnancy management include:

Assessing for multi-organ dysfunction and severity of liver dysfunction – After a presumptive diagnosis of AFLP is made, close laboratory monitoring is important because these patients are at risk for multi-organ failure in addition to acute liver failure [50]:

Complete blood count

Comprehensive metabolic panel (which should include transaminases, bilirubin, creatinine, blood urea nitrogen, electrolytes, glucose)


Prothrombin time, partial thromboplastin time, fibrinogen

Amylase, lipase

In addition to monitoring laboratory studies, we follow the Model for End-stage Liver Disease (MELD) score because high MELD score (particularly MELD ≥30) was associated with increased risk of maternal complications [51]. (See "Model for End-stage Liver Disease (MELD)".)

Critical care support – The care of these patients requires a multidisciplinary team including maternal-fetal medicine, obstetric anesthesia, hepatology, neonatology, and a blood bank. Patients often require monitoring in an intensive care unit with close attention to their fluid status because aggressive fluid replacement in the setting of low plasmatic oncotic pressure can lead to pulmonary edema [4]. Patients are monitored by following physical examination with mental status assessment, pulse oximetry, and fluid balance, including urinary output. The use of invasive hemodynamic monitoring is balanced against the increased risk for bleeding in the setting of coagulopathy. However, if central venous access is necessary, use of an internal jugular approach with ultrasound guidance may decrease the risk of complications. The indications for central venous access and the approach to patients with coagulopathy and/or thrombocytopenia who require catheter placement are discussed separately. (See "Central venous access in adults: General principles".)

Mental status should be evaluated since they are at risk of encephalopathy. Mechanical ventilation may be needed for management of acute respiratory distress syndrome.

Monitoring for and treatment of hypoglycemia – Plasma glucose concentration assessment should be done at six to eight hour intervals if the initial serum glucose is normal. If the glucose concentration is trending downward, more frequent monitoring is needed, in addition to evaluation for liver transplantation [2]. A continuous infusion of a 10 percent dextrose solution is administered, as needed to maintain a plasma glucose concentration above 65 mg/dL (3.6 mmol/L). Hypoglycemia is a common manifestation of acute liver failure. (See "Acute liver failure in adults: Management and prognosis", section on 'Metabolic abnormalities'.)

Monitoring for and treatment of coagulopathy – Coagulopathy is one of the most sensitive assessments of hepatic function. Platelet count, international normalized ratio, partial thromboplastin time, and fibrinogen levels are obtained every four to six hours until the patient beings to stabilize and improve. Worsening coagulopathy is an indication for expedited liver transplant evaluation. Management of disseminated intravascular coagulation in pregnancy is described in detail separately. (See "Disseminated intravascular coagulation (DIC) during pregnancy: Management and prognosis", section on 'Blood products'.)

Fetal monitoring – The fetal heart rate should be monitored continuously; abnormal fetal heart rate patterns would impact the urgency of delivery. (See "Intrapartum category I, II, and III fetal heart rate tracings: Management".)

Magnesium sulfate – In pregnancies <32 weeks of gestation, magnesium sulfate is administered until delivery to reduce the risk of cerebral palsy and severe motor dysfunction in offspring. Magnesium sulfate is also administered in patients with preeclampsia with severe features to prevent eclampsia regardless of gestational age. Dosing should be adjusted in patients with renal insufficiency. (See "Neuroprotective effects of in utero exposure to magnesium sulfate" and "Preeclampsia: Intrapartum and postpartum management and long-term prognosis", section on 'Dosing'.)

Other therapies – Data from case series suggested that therapeutic plasma exchange (TPE) may be an option for patients with progressive disease despite delivery [52]. TPE should not delay liver transplantation in patients with acute liver failure.

DELIVERY — Once a patient is diagnosed with acute fatty liver of pregnancy, plans should be made to proceed with prompt delivery. The route of delivery is contingent on the rate and degree of maternal/fetal decompensation and the probability of successful vaginal birth.

Labor induction is a reasonable option if standard tests for fetal well-being are reassuring, vaginal birth is likely to be accomplished within 24 hours, and the disease is not rapidly progressing within that time frame. Cervical ripening agents can be used if the cervix is unfavorable. (See "Induction of labor: Techniques for preinduction cervical ripening".)

If accomplishing a successful vaginal birth within 24 hours is unlikely, and there is concern about rapidly progressing maternal/fetal decompensation, then performing a cesarean delivery rather than induction is reasonable. In one review, the cesarean delivery rate was 66.7 percent (298/447) [29]. However, the mother should be stabilized before surgery, with special attention given towards correcting any coagulopathy [6]. (See "Disseminated intravascular coagulation (DIC) during pregnancy: Clinical findings, etiology, and diagnosis".)

Neuraxial anesthesia for labor and/or delivery may not be possible in patients with coagulopathy. The threshold platelet count for performing neuraxial techniques varies among clinicians, and is individualized based on patient factors. (See "Adverse effects of neuraxial analgesia and anesthesia for obstetrics", section on 'Neuraxial analgesia and low platelets'.)


Maternal monitoring and course — The three major causes of maternal morbidity and mortality are hemorrhage, liver failure, and acute kidney injury [29]. Over the past several decades, maternal mortality rates have decreased from >75 percent to <5 percent [3,4,37,53,54]. This improvement has been attributed to multiple factors: earlier diagnosis of acute fatty liver of pregnancy (AFLP), prompt delivery, and advances in critical care [26].

In most patients, AFLP usually resolves completely after delivery, with return of normal liver function within 7 to 10 days [4]. Liver function and coagulopathy typically begin to improve within days after delivery. A transient worsening of liver and renal functions and coagulopathy peripartum have been reported, reinforcing the need for continued monitoring following delivery [4].

We check liver chemistries, creatinine, and coagulation tests every six hours until we observe a clear downward trend, at which point the frequency of testing is reduced. Some patients have a prolonged course with multi-organ failure, requiring supportive management in an intensive care unit, including mechanical ventilation, dialysis for acute renal failure, nutritional support because of associated pancreatitis, or transfusion of blood products for ongoing hemolysis or postpartum hemorrhage from atony or incisional bleeding [1]. Management of these patients is the same as other adult patients with acute liver failure or postpartum hemorrhage, and is discussed in detail separately. (See "Acute liver failure in adults: Management and prognosis" and "Postpartum hemorrhage: Medical and minimally invasive management".)

Liver transplantation for fulminant hepatic failure caused by AFLP has been reported, but transplantation is unlikely to be needed with early diagnosis, supportive care, and prompt delivery of the fetus [25,55,56]. There are also reports of plasma exchange being used following delivery in patients who fail to improve with delivery and supportive care within two to eight days [57].

Long-term maternal consequences of AFLP are uncertain as most studies have not followed patients beyond the immediate postpartum phase of the illness, and the disease is rare [26]. Limited data suggest that there are no sequelae of the liver disease itself [4,26,58].

Genetic testing — Given the association between LCHAD deficiency in the fetus and AFLP in the mother, children born to mothers with AFLP should be monitored for manifestations of LCHAD deficiency, especially hypoglycemia. Molecular testing for long-chain 3-hydroxyacyl CoA dehydrogenase (LCHAD) in infants is performed because early diagnosis of LCHAD deficiency in the newborn can be life-saving [59,60]. Testing should be coordinated with a metabolic or genetic specialist. If the newborn has a positive test for LCHAD deficiency, the mother and father are screened. If they are positive, family screening may be indicated.

At a minimum, testing for the G1528C mutation should be performed since it is most common. If the patient tests negative for this mutation, LCHAD deficiency is still possible since it may be caused by a number of other mutations. In this setting, we suggest testing for other defects in fatty acid oxidation (eg, medium-chain acyl CoA dehydrogenase, short-chain acyl-CoA dehydrogenase) [10,18]. (See "Overview of fatty acid oxidation disorders" and "Specific fatty acid oxidation disorders".)

A list of laboratories that provide genetic testing is available at Genetic Testing Registry.

Perinatal outcome — AFLP is associated with an increased risk of perinatal mortality and morbidity [3,4]. It is likely then that the majority, if not all, fetal and neonatal deaths are secondary to maternal decompensation and/or preterm birth. Maternal acidosis is associated with a reduction in uterine blood flow, which can result in fetal hypoxia, and ultimately fetal asphyxia. In the setting of LCHAD deficiency, the unoxidized fatty acids are transferred to the mother through the placenta, rather than accumulating in the fetus, and thus are not a direct cause of fetal demise.

If no fatty acid oxidation defect is identified in the infant, offspring of mothers with AFLP appear to have no long-term adverse effects from the disorder itself. If a fatty acid oxidation defect is identified in the infant, long-term prognosis depends upon the clinical manifestations of the defect, which can range from mild to severe (table 4) [10,26,61]. Clinical presentation and prognosis of disorders of fatty acid oxidation are discussed separately. (See "Overview of fatty acid oxidation disorders".)

Recurrence in subsequent pregnancies — AFLP has been reported in subsequent pregnancies, even if testing for LCHAD deficiency mutation is negative; however, the exact risk of recurrence is unknown [14,49,62-66].

Affected patients should be counseled about the possibility of recurrence if they are considering future pregnancy. Such patients should be co-managed with a maternal-fetal medicine specialist.

Patients with a history of AFLP should be closely monitored in a subsequent pregnancy. They should be advised to seek medical attention if they develop any signs or symptoms of AFLP (eg, malaise, new onset nausea and vomiting, headache, upper abdominal pain, jaundice). In addition to routine prenatal care (weight, blood pressure, urine dipstick), they should be asked about signs and symptoms of AFLP, examined for jaundice, and undergo frequent laboratory screening. If AFLP previously occurred in the third trimester, we obtain labs (eg, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen/creatinine, prothrombin time/activated partial thromboplastin time) at the initial prenatal visit, once again in the second trimester, then at every visit in the third trimester. In the third trimester, visits are scheduled every one to two weeks and weekly after 34 weeks. If AFLP previously occurred in the second trimester, we begin this surveillance approximately one month before the gestational age of the previous diagnosis.


Epidemiology and risk factors – Acute fatty liver of pregnancy (AFLP), characterized by maternal liver dysfunction and microvesicular fatty infiltration of hepatocytes, is rare, with an approximate incidence of 1 in 7000 to 20,000 deliveries. Risk factors include multiple gestation, prior history of AFLP, and male sex of the fetus. (See 'Epidemiology and risk factors' above.)

Patient presentation – AFLP typically presents between the 30th and the 38th gestational week, although it is not always diagnosed prior to delivery. The initial symptoms of AFLP may be nonspecific (eg, nausea, vomiting, abdominal pain, malaise, and/or anorexia). However, patients may develop manifestations of acute liver failure including jaundice, encephalopathy, coagulopathy and/or hypoglycemia. (See 'Patient presentation' above.)

Diagnostic evaluation – The diagnosis of AFLP is usually made clinically, based upon the presentation and compatible laboratory results. Laboratory tests that support the diagnosis include the following (see 'Diagnostic evaluation' above and 'Laboratory findings' above):

Elevated aminotransferases (5 to 10 times the upper limit of normal)

Elevated serum bilirubin

Elevated prothrombin time

Elevated urate level

Elevated ammonia level

Elevated creatinine

Elevated white blood cell count

Low serum glucose

Low fibrinogen

Initial management – For patients with AFLP, initial management includes prompt delivery of the fetus, regardless of gestational age. Treatment is otherwise largely supportive with the goals of maternal stabilization and recovery of liver dysfunction. (See 'Initial management' above.)

Pathogenesis – An enzyme deficiency associated with AFLP is fetal long-chain 3-hydroxyacyl CoA dehydrogenase (LCHAD) deficiency that results in fetal fatty oxidation defects. LCHAD catalyzes a step in beta-oxidation of mitochondrial fatty acids that forms 3-ketoacyl-CoA from 3-hydroxyacyl-CoA. Homozygous deficient offspring cannot perform this step and unmetabolized, long-chain fatty acids enter the maternal circulation. The accumulation of long-chain 3-hydroxyacyl metabolites produced by the fetus or placenta is toxic to the liver and may be the cause of maternal liver disease. (See 'Pathogenesis' above.)

Postpartum management – We suggest that all patients with AFLP and their children undergo molecular testing for LCHAD, at least for the most common G1528C mutation. Additional testing for other defects in fatty acid oxidation can be pursued if this mutation is not detected. A list of laboratories that provide genetic testing is available at Genetic Testing Registry, and testing should be coordinated with a metabolic or genetic specialist. (See 'Genetic testing' above.)

AFLP can recur in subsequent pregnancies, even if testing for LCHAD mutation is negative. Patients with a history of AFLP who are contemplating another pregnancy should be co-managed with a maternal-fetal medicine specialist. (See 'Recurrence in subsequent pregnancies' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff thank Dr. Yannick Bacq and Dr. Tram Tran for their past contributions as authors to prior versions of this topic review.

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Topic 3619 Version 37.0


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