|Year : 2021 | Volume
| Issue : 2 | Page : 99-104
Postpartum fatal fulminant hepatic failure presenting with persistent hypoglycemia due to acute fatty liver of pregnancy
Anant Parasher1, Vandana Mohan2
1 Department of Medicine, Guru Teg Bahadur Hospital, Delhi, India
2 Department of Obstetrics and Gynaecology, Guru Teg Bahadur Hospital, Delhi, India
|Date of Submission||10-Jun-2020|
|Date of Decision||13-Jul-2020|
|Date of Acceptance||19-Aug-2020|
|Date of Web Publication||12-Sep-2020|
Dr. Anant Parasher
House No. 14/8, Model Town, Khandsa Road, Opposite Shivaji Nagar Police Station, Gurugram - 122 001, Haryana
Source of Support: None, Conflict of Interest: None
Acute fatty liver of pregnancy (AFLP) is a sudden and devastating illness which occurs mostly around the 36th week of gestation in pregnant females. It is characterized by microvesicular fatty infiltration of the liver which eventually results in encephalopathy and hepatic failure. It carries significant perinatal and maternal mortality and requires early diagnosis and intervention to prevent maternal and fetal death. The foremost cause of AFLP is thought to be due to a mitochondrial dysfunction in the oxidation of fatty acids leading to their continuous accumulation in the hepatocytes. Early diagnosis is extremely important and the only definitive therapy is delivery. Here, we present the case of a 28-year-old pregnant female presenting with abdominal pain, vomiting, and jaundice who was diagnosed with AFLP and gradually worsened postpartum. Due to persistent hypoglycemia and rapidly developing fulminant hepatic failure, the patient expired 5 days after admission.
Keywords: Acute fatty liver, encephalopathy, fatty infiltration, pregnancy
|How to cite this article:|
Parasher A, Mohan V. Postpartum fatal fulminant hepatic failure presenting with persistent hypoglycemia due to acute fatty liver of pregnancy. J Med Sci 2021;41:99-104
|How to cite this URL:|
Parasher A, Mohan V. Postpartum fatal fulminant hepatic failure presenting with persistent hypoglycemia due to acute fatty liver of pregnancy. J Med Sci [serial online] 2021 [cited 2021 Oct 25];41:99-104. Available from: https://www.jmedscindmc.com/text.asp?2021/41/2/99/294943
| Introduction|| |
Acute fatty liver of pregnancy (AFLP) is a sudden and devastating illness seen in pregnant females, where microvesicular fatty infiltration of the liver results in encephalopathy and hepatic failure., It carries significant perinatal and maternal mortality and requires early diagnosis and intervention to prevent maternal and fetal death. After being first explained by Sheehan as an “Acute yellow atrophy of the liver” in 1940, AFLP has been described numerous times thereafter in many case reports.
AFLP is usually seen to occur around the 36th week of gestation or immediately postpartum. Risk factors include primiparity, pregnancy with a male fetus, multiple gestations, advanced maternal age, and low body mass index of the mother. The condition is neither infectious nor inherited, and recurrence of the disease in a subsequent pregnancy is very rarely seen.,
| Case Report|| |
A 28-year-old pregnant female presented in a drowsy state to the casualty with a history of multiple episodes of vomiting and right upper abdominal pain and distension for 7 days and yellowish discoloration of skin and urine for 2 days prior to presentation. There was no history of fever or altered sensorium, bleeding manifestations, hypertension, diabetes, or tuberculosis. The patient's attendants did not give any history of paracetamol/acetaminophen or alcohol abuse, smoking, or illicit drug use. The patient was Gravida 2 Parity 1 Live 1 with a period of gestation (POG) of 37 weeks and 4 days.
On examination, the patient was conscious but semi-oriented and drowsy. The patient seemed quite lean and malnourished, with a BMI of 17.6 kg/m2. The blood pressure was 98/70 mm Hg and pulse was 96 beats/min. There was moderate pallor with pedal edema but no cyanosis, clubbing, or lymphadenopathy. Icterus was present in the sclera. Abdominal examination revealed mild tenderness in the right hypochondrium and a palpable liver just below the right subcostal margin. Fundal height corresponded to POG with fetus in cephalic presentation and reassuring fetal heart rate. On central nervous system examination, the patient had Glasgow Coma score of 13/15. Pupils were mid-dilated and reacting normally. Reflexes were normal and the bilateral plantar response was indeterminate. There was slight rigidity noted in both the upper and lower limbs. Power was adequate in both the upper and lower limbs, and sensory examination was grossly normal. Respiratory and cardiac examinations were unremarkable.
After complete blood investigations, a provisional diagnosis of viral hepatitis with thrombocytopenia was made and treatment started with intravenous (IV) fluids and IV antibiotics (ceftriaxone and metronidazole). IV fluids comprised of 2% dextrose which was supplemented with thiamine and given 8 hourly to counter hypoglycemia. Anemia and thrombocytopenia were corrected through red cell concentrate and platelet transfusions. An emergency ultrasound of the whole abdomen revealed a mildly enlarged liver with fatty infiltration, along with moderate ascites. The hepatobiliary tree was normal with no signs of obstruction or dilatation of the common bile duct. Tests for HIV, HBV, and HCV done by ELISA were negative and IgM antibodies to HAV and HEV were not found. Screening was done and found negative for antinuclear antibodies, Smooth muscle antibodies, and anti-liver kidney microsome type 1 antibodies. The serum ceruloplasmin levels and urinary copper levels were normal, and on slit lamp examination no evidence of Kayser–Fleischer ring was found. The serum ferritin and transferrin levels were found to be in normal range, and so were the levels of alpha-fetoprotein. Primary biliary cirrhosis could not be ruled out due to unavailability of the antimitochondrial antibody test. Serum cortisol levels were normal, and the levels of thyroid hormones (T3, T4, and thyroid-stimulating hormone) were also observed to be in normal range.
A urine toxicology screen obtained was negative. Other investigations that were sent comprised of serum uric acid and ammonia levels, and ascitic fluid for sugar, protein, and cytology. In view of the clinical findings, the patient was prepped for immediate delivery but soon went into spontaneous labor, and had a normal vaginal delivery of a healthy male newborn. In view of the excessive blood loss during delivery, another two units of platelets and one unit of red cell concentrate were transfused.
Over the next couple of days, the patient's condition started to deteriorate with deepening of jaundice, persistent nausea and vomiting, and persistent bouts of hypoglycemia in spite of dextrose supplementation. Although the blood pressure was maintained in the range of 96–100/70–74 mm hg on IV fluids, the deteriorating hepatic function tests and increasing serum ammonia and creatinine levels signified worsening of hepatorenal function. Even on continued antibiotic cover and supportive treatment, the patient maintained the same status with no signs of improvement. She gradually became altered with worsening sensorium and irrelevant talk, for which an emergency noncontrast computed tomography (NCCT) brain was done which was suggestive of non-specific changes of encephalopathy. Soon, vasopressor support was required to maintain optimum blood pressure, and continuous dextrose infusions were maintained to counteract the persistent hypoglycemia. The patient's condition was worsened by decreasing urine output secondary to acute kidney injury, which was suspected due to the nonresolving septicemia.
A diagnosis of fulminant hepatic failure with hepatic encephalopathy due to AFLP was strongly suspected in view of blood work and ultrasound findings, and the antibiotic cover was upgraded to a combination of IV Piperacillin-Tazobactam (4.5 g stat f/b 2.25 g 8 hourly), teicoplanin (400 mg stat f/b 200 mg every alternate day), and metronidazole (500 mg eight hourly). Subsequently, in view of the continuously falling SpO2 levels even on high-flow oxygen, the patient was intubated and shifted to the intensive care unit. A noncontrast CT whole abdomen was done, which was suggestive of an enlarged liver with fatty infiltration.
On the 5th day of admission, the patients were planned for hemodialysis in view of the decreasing urine output and rising serum potassium levels. Multiple petechial hemorrhages were seen over the abdomen, arms, and thighs which led to the suspicion of disseminated intravascular coagulation (DIC), and were treated by transfusion of platelets and fresh frozen plasma. The patient had her first episode of hematemesis few hours after her dialysis, which was followed the next day by generalized tonic–clonic seizures. In spite of supportive care and anti-epileptic medication, SpO2 levels collapsed to 78%, with a blood glucose level of 46 mg/dl. The patient went into cardiorespiratory arrest soon after, and acute respiratory distress syndrome was suspected. Cardiopulmonary resuscitation was continued but despite intense critical care support and mechanical ventilation, the patient expired later in the day.
The various investigations done throughout the course of hospital stay have shown in [Table 1]. The imaging studies (ultrasound whole abdomen, NCCT abdomen, and NCCT Head) have shown in [Figure 1],[Figure 2],[Figure 3], respectively.
|Figure 1: (Ultrasound fatty liver) – Ultrasound of the whole abdomen showing increased hepatic echogenicity|
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|Figure 2: (Acute fatty liver of pregnancy non-contrast computed tomography) – Non-contrast computed tomography whole abdomen with findings of hepatomegaly and fatty infiltration|
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|Figure 3: (Non-contrast computed tomography head hepatic encephalopathy) – Non-contrast computed tomography head showing changes of encephalopathy|
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|Table 1: Investigations and blood parameters throughout the course of treatment|
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| Discussion|| |
AFLP is a universally dreaded complication in obstetrical units, which mostly manifests in the third trimester of pregnancy or sometimes in the early postpartum period. It is a condition unique to pregnancy, and is characterized by microvesicular steatosis in the liver due to incessant fatty acid infiltration. This infiltration of fatty acids causes acute liver insufficiency, which leads to most of the symptoms that present in this condition. AFLP can result in high fetomaternal morbidity and mortality if not diagnosed and treated early. Maternal mortality is now estimated to be 12.%–18%, with a neonatal mortality rate of 7%–66%. While the majority of cases resolve after delivery, rarely, some patients may progress to fulminant hepatic failure with the need for liver transplantation.
The pathogenesis is proposed to be an abnormality in the metabolism of long chain fatty acids in the fetus due to a deficiency in the enzyme long-chain 3-hydroxyacyl-CoA dehydrogenase. This defect leads to an excess of fetal long chain fatty acids entering the maternal circulation, overwhelming the capacity of the maternal liver to adequately metabolize these fatty acids. This subsequently leads to their deposition in the maternal liver, which substantially decreases the hepatic metabolic activity, leading to an increase in the serum bilirubin levels.,
The typical patient is ill-looking and presents with a couple of weeks of anorexia, nausea and vomiting, headache, and a right upper quadrant pain. Some pathognomonic features include severe jaundice, coagulopathy, encephalopathy, hypoglycemia, and ascites in the presence of a normal erythrocyte morphology. Intrauterine complications including death are not uncommon in severe cases. About 50% of patients with AFLP have a background of preeclampsia, and some patients may also show features of HELLP syndrome.,,,,,,,,
AFLP is considered as an obstetrical emergency because of its potential for rapid progression to coma and death. If untreated, AFLP can lead to complications such as DIC, renal failure, clotting disorders and coagulopathy, hypoglycemia, fulminant hepatic failure, and eventually multiorgan dysfunction. Morbidity in the infant includes increased risk of cardiomyopathy, neuropathy, myopathy, nonketotic hypoglycemia, and hepatic failure.
Although the gold standard for diagnosis of AFLP is liver biopsy, it is rarely necessary and frequently evaded as it can cause complications in the presence of coagulopathy. The Swansea diagnostic criteria are an alternative to liver biopsy, according to which six or more of the following findings are required for diagnosis of AFLP in the absence of another cause:
- Abdominal pain
- Elevated bilirubin >14 μmol/l
- Hypoglycemia <4 mmol/l
- Elevated urea >340 μmol/l
- Leukocytosis >11 × 109/l
- Ascites or bright liver on ultrasound scan
- Elevated transaminases (AAT [Alanine Aminotransferase] or aminotransferases alanine transferase [ALT]) >42 IU/l
- Elevated ammonia >47 μmol/l
- Renal impairment: creatinine >150 μmol/l
- Coagulopathy: prothrombin time >14 s or APPT >34 s
- Microvesicular steatosis on liver biopsy.
Typical laboratory findings are elevated aminotransferases-aspartate transferase elevation greater than alanine transferase (ALT), both <6 times above upper limit of normal, hyperbilirubinemia, hyperuricemia, high white blood cell count (above 15,000 cells/μL), hypoglycemia, high ammonia levels, and coagulopathy with or without DIC. The important differential diagnoses to be considered are fulminant viral hepatitis and severe HELLP syndrome. HELLP is usually encountered in the setting of severe pre-eclampsia, with prominent periportal hemorrhages, and fibrin deposition seen on liver histology. AFLP, on the other hand, is seen to be frequently associated with encephalopathy, coagulopathy, hypoglycemia, and renal failure, along with characteristic histological findings of microvesicular fatty infiltration.,,
Prompt induction of labor and immediate termination of pregnancy through delivery/caesarean section is the only true definitive therapy for AFLP. The suspected patient should be transferred to a tertiary care hospital as soon as possible to ensure early stabilization of the mother and efficient fetal monitoring. Supportive management should be initiated before delivery, which includes maintenance of an adequate airway, prevention/treatment of hypoglycemia, and correction of electrolyte and coagulation abnormalities.
The management of severe and persistent hypoglycemia with continuous dextrose infusions supplemented with thiamine is necessary to avoid coma and death. Blood glucose should be monitored closely until hepatic function recovers and the patient can tolerate a regular diet. Careful maintenance of intravascular volume with necessary IV fluids and blood products, frequent assessment of maternal vital signs, and evaluation of changes in mental status are crucial. Supportive care and management of complications should be instituted along with the management of acute hepatic failure.
Recently, few cases have been reported with successful treatment through the use of molecular adsorbent recirculating system (MARS) in patients with severe AFLP. Plasma exchange/plasmapheresis with continuous renal replacement therapy has also been tried in some complicated cases with severe encephalopathy, patients on ventilator support, severe liver, or renal insufficiency who failed to respond to conventional management, and patients with multiorgan dysfunction.,,
The majority of females with AFLP show gradual improvement in symptoms, and in hepatic function soon after delivery. Genetic screening for β-fatty acid oxidation defects should be advised for these patients, as most homozygous fetuses are seen to be carried by heterozygous mothers with AFLP. Although most females recover post-partum, some cases might decompensate with hepatic encephalopathy, fulminant hepatic failure and death. Early diagnosis and management with prompt termination of pregnancy has been seen to improve the prognosis, with better maternal and fetal outcomes.,
| Conclusion|| |
AFLP is an uncommon but potentially fatal complication seen mostly in third trimester of gestation. The patient usually presents with anorexia, nausea, vomiting and abdominal pain, along with jaundice developing over 1–2 weeks. Primiparous females and females with low BMI are seen to be more commonly predisposed for this condition. Early diagnosis becomes quite essential to improve prognosis and to anticipate hepatic failure in these cases. As in our case, the patient was a malnourished female with term pregnancy who had presented with symptoms of AFLP. Although an early diagnosis was made and the delivery was induced on the 1st day of admission, the patient's condition worsened rapidly postdelivery. This was quite a rare occurrence as most cases of AFLP usually start improving and resolve in a few weeks' postpartum. This event could be attributed to the patient's poor BMI and nutritional status, associated with possible herbal medication intake which was not reported in the history. Unfortunately, the patient could not be saved in spite of our best efforts, signifying the fact that AFLP is a lethal condition, even with early diagnosis and the best possible management.
Even though induction of labor with delivery remains the only real cure for this disease, some other therapies for complicated cases include plasmapheresis with renal replacement, and the use of MARS. Orthotopic liver transplantation has proved to be effective in cases with multiorgan failure in spite of aggressive therapy, but is neither widely feasible nor available in most centers today.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understand that her names and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed.
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Conflicts of interest
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[Figure 1], [Figure 2], [Figure 3]