General information of the AFLP patients in our study
A retrospective analysis was performed on 13 patients with final clinical diagnosis of AFLP admitted from March 2012 to February 2020, ranging from 23 years old to 39 years old, with an average age of 29.2 years. There were 5 cases of multipara and 8 cases of primipara. The onset time ranged from 32 to 38+6 weeks, with an average time of 34+5 weeks. Among them, there were 4 cases (31%) with gestational weeks less than 34 weeks, 7 cases (54%) with 34~36+6 weeks, and 2 cases (15%) with 37 weeks or more. Visibly, this kind of disease is concentrated in the third trimester. The patients' visit time is generally 0-30 days after the onset and the diagnosis time is 0-2 days after the visit. All pregnancies were terminated within 24 h of definitive diagnosis. Two pregnant women (case 1 and case 2) were accompanied by serious coagulopathy and DIC due to delayed care seeking, among which 1 pregnant woman died. There were 11 cases of cesarean section and 2 cases of vaginal delivery. Above details are given in Table 1 and Additional file 1.
Table 1. The overall summary of clinical features of AFLP patients (n= 13).
Number of cases
nausea and vomiting
Fatty liver on ultrasound (n=12)
AFLP: Acute fatty liver of pregnancy.
Clinical manifestations of the 13 AFLP patients
Among the 13 patients, the initial symptoms of AFLP varied differently, with jaundice (9/13, 69%), fatigue (8/13, 62%) and nausea and vomiting (6/13, 46%) being the most common. Besides, three pregnant women (23%) were combined with HELLP syndrome or preeclampsia (see Table 1 and Additional file 1 for details). The relevant laboratory examination results of 13 AFLP patients were shown in Table 2 and Additional file 2 (the recorded values are the maximum outliers from the onset to the outcome of the disease). Liver damage occurred in all patients (100%) enrolled during hospitalization with significantly increased TBIL (56~300μmol/L) dominated by DBIL and a mild-moderate elevated level of ALT (79~647U/L) and AST (91~498U/L). Raised uric acid (535 ± 85μmol/L) was found in all patients (100%) and blood glucose decreased in 6 patients (46%) with a minimum of 2.4μmol/L. Moreover, the main maternal complications were different degrees of coagulopathy (13/13, 100%), followed by acute renal dysfunction (10/13, 77%). In this study, a total of 12 of the 13 patients received abdominal ultrasound examination, among which five individuals fulfilled the ultrasonic characteristics of fatty liver, suggesting a diagnostic coincidence rate of 42%. It indicates that imaging examination is helpful for the diagnosis of AFLP.
Treatment and outcome of the AFLP patients and their infants
Thirteen patients were definitively diagnosed with AFLP 0-2 days after the visit. Once the diagnosis was made, the pregnancy was terminated on the same day or next day. One (7%) maternal death occurred and all neonates (100%) survived delivery. The newborns delivered were all single births, including 8 boys, 5 girls, 10 premature infants and 3 full-term infants (Table 1). Plasma exchange was performed in 2 patients (15%) after termination of pregnancy, and 5 patients (38%) were transfused with blood products. Most patients had a good prognosis as a result of timely visit, while case 1 and case 2 unfortunately suffered from serious complications for delaying in seeking health care. In case 1 the pregnant women developed disseminated intravascular coagulation (DIC), intraperitoneal hemorrhage, acute pulmonary edema, multiple organ dysfunction and hemorrhagic shock at admission and finally discharged after a comprehensive treatment including cesarean section, blood transfusion, liver protection, anti-infection and blood purification. In case 2 the patient came to see the doctor at 10 days from the disease onset. She had severe liver injury and coagulation dysfunction on admission. Hence, termination of pregnancy was performed by cesarean delivery within 24 hours after admission. However, the disease progressed rapidly. She developed abdominal hemorrhage and DIC, a serious life-threatening event, thus uterine artery embolization was immediately performed. Unfortunately, the patient was unsuccessfully resuscitated and died due to hemorrhagic shock.
Biopsy pathology of the liver in the AFLP patients
Due to abnormal coagulation function of AFLP patients, liver biopsy is at high risk. In this study, 2 patients (case 8 and case 10) underwent liver biopsy guided by B-ultrasound 16 days and 23 days postpartum during the recovery period, respectively. The main pathological feature is characterized by microvesicular hepatic steatosis in figure 1, which meets the gold standard for the diagnosis of AFLP . Other patients and their family members had concerns about the safety of liver biopsy and found it difficult to accept the invasive examination.
Table 2. The laboratory results and imageological examinations of AFLP patients (n=13).
Mean ± SD
Onset time (weeks)
Uric acid (μmol/L)
Blood glucose (mmol/L)
WBC count (×109/L)
29.2 ± 5.1
34+5 ± 1.8
324 ± 212
252 ± 156
143 ± 59
92.7 ± 51.5
27.6 ± 3.9
22.1 ± 9.1
1.9 ± 0.7
535 ± 85
4.9 ± 2.2
186 ± 46.6
18.3 ± 6.4
AFLP: acute fatty liver of pregnancy; ALT: serum alanine aminotransferase; AST: serum aspartate aminotransferase; TBIL: total bilirubin; DBIL: direct bilirubin; PT: prothrombin time; INR: international normalized ratio; Cr: serum creatinine; WBC: white blood cell.
Genetic test results in five patients and one newborn with high-throughput methods
Many foreign studies have pointed out that the development of AFLP is related to genetic mutations in pregnant women or newborns. Mutations reported so far are common defects in enzymes involved in fatty acid oxidation, such as LCHAD, CPTl, MCAD or SCAD [7, 10]. Combined with the notion that the diagnostic gold standard of AFLP is microvesicular hepatic steatosis, we speculated that any genetic defects affecting maternal or fetal fatty acid metabolism and resulting in the accumulation of fatty acid metabolites, may cause severe maternal liver damage, thus leading to AFLP. Therefore, we performed whole-exon sequencing in five patients and one newborn with high-throughput methods, hoping to explore gene mutations in Chinese AFLP patients at the gene level. We found that none of the five patients had mutations in the enzyme involved in fatty acid metabolism. In addition, whole-exon sequencing of peripheral blood in the newborn infant of his mother with AFLP still showed no related gene mutations in fatty acid oxidation.