Urgent Liver Transplantation for Acute Liver Failure in Pregnant Women: The Optimum Timing for Delivery : Transplantation

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Original Clinical Science—Liver

Urgent Liver Transplantation for Acute Liver Failure in Pregnant Women: The Optimum Timing for Delivery

Ichai, Philippe MD1,2,3; Bouchghoul, Hanane MD4; Laurent-Bellue, Astrid MD5; Sacleux, Sophie-Caroline MD1,3; Boudon, Marc MD1,2,3; Cherqui, Daniel MD, PhD2,3,6; Tortajada, Pauline MD6; Braun, Marius MD7; Lemaitre, Elise MD1; Pittau, Gabriella MD2,3,6; Ordan, Marie-Amélie MD1,3; Levi, Sharon MD1; Azoulay, Daniel MD, PhD2,3,6; Fernandez, Herve MD, PhD4; Guettier, Catherine MD, PhD2,3,5; Samuel, Didier MD, PhD1,2,3; Saliba, Faouzi MD1,2,3

Author Information
Transplantation 107(1):p 172-180, January 2023. | DOI: 10.1097/TP.0000000000004290
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Abstract

INTRODUCTION

The most common causes of ALF are viral infections, paracetamol, other medications, and toxins.1 Two other causes may also and specifically trigger ALF in pregnant women: acute fatty liver of pregnancy (AFLP) and haemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome.2-4 In these cases, the treatment is the emergency delivery, which in most cases enables a resolution of liver dysfunction.4,5 Perinatal death in AFLP and in HELLP syndrome is estimated between 10 and 27% and 7.4 and 34%, respectively.6,7 More recently, data from the ALF US study group estimated a perinatal death in AFLP/HELLP to 11.1%.8 Apart from these 2 etiologies, emergency delivery should not, in theory, modify the course of ALF. When liver transplantation (LT) is required, the issue is to determine the most appropriate timing for delivery before or after transplantation.

The onset of ALF during pregnancy (pregALF) remains a rare event with a very limited number of case reports in the literature. In a series reported by Casey et al, 70/3155 consecutive patients presented with ALF during pregnancy. Only 15.7% underwent LT. Thirty-five of these 70 patients were suffering from ALF due to HELLP syndrome or AFLP, whereas in 21 cases, it had been caused by paracetamol, and in 14 other patients, there was another cause.8 Overall fetal survival rates in the 3 patient groups were 96%, 43%, and 55%, respectively.

The principal aims of our study were to (1) define the optimum strategy regarding delivery in ALF during pregnancy and requiring LT, (2) clarify the survival of pregnant women presenting with ALF, and (3) based on our experience and that reported in the literature, propose a decision-making algorithm based on the outcomes of both mother and fetus.

MATERIALS AND METHODS

Patients

This is a retrospective observational analysis of liver transplant recipients for acute liver failure (ALF) during the period of 1986 and 2019. All females of childbearing age who were admitted to our center were recruited for the study. Pregnant women presenting with nonspecific ALF, defined as the onset of ALF during pregnancy, not due to HELLP or AFLP were selected (Figure 1). Ultimately, 5 patients who were pregnant when LT was indicated were analyzed for our study (Paul Brousse cohort).

F1
FIGURE 1.:
Study flowchart. AFLP, acute fatty liver of pregnancy; ALF, acute liver failure; HELLP, haemolysis, elevated liver enzymes, low platelet count; LT, liver transplantation; PB, Paul Brousse; pregALF, ALF during pregnancy.

In parallel, a systematic review was made of the literature, searching in the PubMed-Medline and Embase databases using the terms “acute liver failure and pregnancy” or “pregnancy and liver transplantation” or “ALF and pregnancy” during the same period of 1986–2020. Reviews and specific etiologies related to pregALF (that is, AFLP and HELLP syndrome) were excluded. From each selected manuscript, we extracted main parameters related to the mother (age, cause of ALF, delivery before or after LT, gestational age at the time of admission, transplantation and delivery, type of delivery) and to the infant (alive or not, intrauterine demise or perinatal death, termination of pregnancy, miscarriage, and birth weight).

The study protocol was approved by the Ile-de-France Paris VII Ethics Committee (N° C0-16-006).

Definitions

ALF was defined by the presence of liver injury (INR > 1.5) associated with hepatic encephalopathy. The indication for LT in patients with ALF was determined in accordance with the Clichy-Villejuif criteria for transplant.9,10

Nonspecific pregALF was defined as the onset of ALF during pregnancy, not due to HELLP or AFLP.

According to the World Health Organization (WHO), fetal viability is defined by birth after 22 weeks of gestation (WG) and/or a birth weight >500 g.11 The outcome of the pregnancy was defined according to the gestational age at delivery: a late miscarriage if the gestational age at delivery was <22+0 WG, extreme preterm delivery if delivery occurred between 22+0 and 27+6 WG, and severe and moderate preterm delivery if delivery occurred between 28+0 and 36+6 WG, respectively (9). We therefore classified all cases reported in the literature according to the gestational age at admission and delivery following the WHO criteria.

Management of Patients

The initial screening of mothers included serological tests for hepatitis, a plasma assay of paracetamol levels and those of other medications/toxins, and a Doppler ultrasound of the liver. If these investigations produced negative results, further investigations were performed to search for other possible causes of hepatitis.1

When the criteria for LT were met, the patient was placed on the high-emergency list. All patients were managed in the Intensive Care Unit according to a standardized protocol for ALF.12 All native livers of our cohort were reviewed by 2 pathologists and excluded AFLP, and HELLP syndrome.

Fetal vitality was assessed by an obstetric ultrasound examination to record the presence of fetal movements and fetal heart rate. X-rays and scans were only performed if strictly necessary and depending on whether the pregnancy continued or not at the time of transplantation. The medications prescribed also depended on the outcome of pregnancy. The immunosuppressive regimen consisted of a triple regimen combining corticosteroids, calcineurin inhibitors, and antimetabolites. For those patients with ongoing pregnancy at time of LT, antimetabolites were excluded.

RESULTS

Paul Brousse Cohort

Among the 174 (70.5%) females of childbearing age who were admitted to our center between 1986 and 2019 for ALF, 12 (7%) were pregnant at the onset of ALF. Five of these 12 were suffering from specific pregnancy-related ALF and underwent an emergency cesarean section (2 with ALFP and 3 with HELLP syndrome). The 7 other patients presented with nonpregnancy-related ALF, defined as the onset of ALF during pregnancy, not due to HELLP or AFLP. None of the 7 females presented signs of preeclampsia, and the pathology of the native liver did not show histological signs in favor of HELLP or AFLP. Two of the 7 patients did not meet the criteria for emergency LT and were transplanted later at 1 and 1.5 mo after delivery. Ultimately, 5 patients who were pregnant when LT was indicated were analyzed in our study (Paul Brousse cohort) (Figure 1).

The median gestational age of pregnancy in the 5 patients presenting with nonspecific pregnancy-related ALF was 22 WG [16–23]. The obstetric ultrasound examination performed at admission revealed fetal vitality in the 5 pregnancies. ALF was due to a Delta virus superinfection in 1 patient with hepatitis B and an adverse drug effect in another patient (quinidine-phenylethylbarbiturate). In the 3 other cases, no etiology could be identified. All patients met the criteria for emergency LT (Table 1).

TABLE 1. - Clinical and biological characteristics at and following admission
Delivery or IUFD before LT Delivery or IUFD after LT
Patient (year of admission) 1 (1986) 2 (1989) 3 (1997) 4 (1997) 5 (2019)
At admission
 Patient
  Age (y) 19 23 29 30 30
  Obstetrical history Parous: 2Procedure: 1 Parous: 1Procedure: 1 Parous: 1Procedure: 1 6 IVFProcedure: 1 Parous: 2Procedure: 2
  Gestational age at admission (WG) 31 22 15 16 23
  Cause of ALF Drug (quinidine-phenylethylbarbiturate) B-Delta Undetermined Undetermined Undetermined
  HE (grade) 0 1 2 2 3
Interval between jaundice and HE (d) 5 12 3 28 5
  MV no no no no yes
  PT (Factor V) (%) 13 (10) 18 (43) 17 (15) 13 (20) 32 (24)
  Total bilirubin (µmol/L) 323 288 302 399 199
  ALT (IU/L) 800 2790 149 460 88
  Urea (mmol/L) 1 4 2 0.6 3,5
  Creatinine (µmol/L) 75 55 70 82 54
  Platelets (/mm3) 150 000 100 000 177 000 221 000
  Fibrinogen (g/L) 2.5 NA 0.8 1.01 1.1
 Infant
  Fetal vitality at ultrasound (yes/no) yes yes yes yes yes
After admission
 Patient
  OTI before LT yes yes no no yes
  Grade HE LT 4 (coma 3) 4 (coma 2) 3 3 4
  PT LT (Factor VLT)(%) 5 (10) 10 (10) 18 (18) 9 (14) 29 (19)
  Total bilirubin LT (µmol/L) 352 350 444 402 214
  YALT LT (IU/L) 110 90 307 87
  Delay between hospitalization and LT (d) 7 23 18 18 11
 Outcome of pregnancy (up to LT)
  Intrauterine fetal demise no yes yes no no
 Characteristics of LT
  Type of LT OLT OLT APOLT APOLT (left liver) OLT
  Duration of surgery (hours) NA 9 h 14 h 30 min 11 h 5 h 33 min
  Number of PRBC 2 31 32 14 0
  Number of SDP 41 57 41 32 0
  Cold ischemia time (h) 4 h 35 min 8 h 30 min 10 h 30 min 11 h 50 min 7 h 34 min
  Primary graft nonfunction No No Yes Yes No
  Repeat LT No No Yes Yes No
  Good functioning LT 2 1 1
After transplantation
 Intrauterine fetal demise (time) 1 (20 WG)
 Mother alive (last news) No a Yes (August 2019) Yes (2002) Yes (February 1999) Yes (June 2020)
 Infant alive and in good health (follow-up) Yes (at birth) No No No Yes (10 mo)
aShe died from AIDS, 10 y after LT.
Continuous variables were reported as medians and 25th–75th percentiles (Q1–Q3).
ALF, acute liver failure; APOLT, auxiliary partial orthotopic liver transplantation; HE, hepatic encephalopathy; IUFD, intrauterine fetal demise; IVF, in vitro fertilization; LT, liver transplantation; MV, mechanical ventilation; NA, no available; OLT, orthotopic liver transplantation; OTI, orotracheal intubation; PRBC, packed red blood cells; PSD, solvent/detergent-treated plasma; WG, weeks of gestation.

The median [IQR 25–75] time elapsing between admission and transplantation was 10 d [3–14]. Patients were analyzed according to the date of delivery.

Delivery or Intrauterine Fetal Demise Before Liver Transplantation (n = 3, Patients 1, 2, 3)

The gestational age of pregnancy at admission in these 3 patients was 31, 22, and 15 WG. One patient (patient 1) gave birth to a live infant before LT at 31 WG (Figure 2). After delivery, the patient developed disseminated intravascular coagulation and then hepatic encephalopathy and was finally transplanted as an emergency. In the 2 other patients (patients 2 and 3), it was decided to pursue their pregnancies as their terms were not compatible with fetal survival at the time of onset of ALF (22 and 15 WG, respectively). However, they lost their fetuses between admission and LT, suffering intrauterine demise at 25 WG and 17 WG, respectively. The times elapsing between admission and expulsion of the nonviable fetus were 17 and 13 d, respectively. The patients then underwent LT 3 and 1 d later, respectively.

F2
FIGURE 2.:
Chronology of the principal events among 5 patients in the Paul Brousse (PB) cohort. The arrow indicates the day of admission to our center; PB, admission to Paul Brousse. 1, Vaginal delivery; 2, High-urgent listing for emergency LT but improvement in clinical status. Indication for LT suspended; 3, Intrauterine fetal demise. Extraction of the dead fetus; 4, Reactivation of emergency listing because of a worsening in clinical status; 5, Premature membrane rupture. Therapeutic termination of pregnancy. D, delivery; HE, hepatic encephalopathy; IUFD, intrauterine fetal demise; J, jaundice; LT, liver transplantation; Re-LT, repeat-LT; TOP, termination of pregnancy; WG, weeks of gestation.

At the time of LT, median prothrombin time values were 10%, and all 3 patients were suffering from grade 3 or 4 hepatic encephalopathy. One patient (patient 3) underwent an auxiliary liver transplant. After LT, she presented with graft dysfunction secondary to hepatic artery thrombosis and underwent repeat transplantation 6 d later, after failure to remove the arterial obstruction. Her liver function returned to normal after this repeat procedure. All 3 patients were alive after a 5-y follow-up.

Delivery or Intrauterine Fetal Demise After Liver Transplantation (n = 2; Patients 4 and 5)

These 2 patients (16 WG and 23 WG at admission) were transplanted during their pregnancies, and the fetuses displayed good vitality at the time of the procedure (Figure 2). The intervals elapsing between admission and transplantation were 3 d and 1 d, respectively. One of these 2 patients (patient 4) underwent auxiliary LT but was retransplanted (total liver) 3 d later because of thrombosis affecting the hepatic vein anastomosis and failed attempts to remove the obstruction and repair the anastomosis. Although the obstetric ultrasound examination revealed good fetal vitality at the time of transplantation, the pregnancy was terminated 22 d after the repeat LT at 20 WG because of premature rupture of the membranes and severe oligoanhydramnios. A therapeutic termination was therefore performed 24 h later.

In the second patient (patient 5), the pregnancy continued after LT. The outcome in the mother was marked by the onset of acute rejection on day 10, treated with corticosteroids and azathioprine (for 3 d) and a veno-occlusive disease, lobular hepatitis without plasma cell component, and lesions of cholangiolitis on day 28. An etiological assessment was negative. Empirical treatment with corticosteroids, under the hypothesis of an autoimmune cause, was initiated and followed by a brief improvement. As for the fetus, signs of good vitality and intrauterine development within the normal range were recorded until birth. Under the hypothesis of cholestasis of the graft related to pregnancy, a cesarean section was performed at 31 WG. The mother’s liver parameters improved 5 mo after birth, and the baby is now well with a follow-up of 17 mo and is displaying normal psychomotor development.

In most cases, the microscopic examination of liver explants confirmed the absence of any underlying chronic hepatopathy. Retrospectively, the extent of necrosis and the absence of significant hepatocellular regeneration confirmed the need for LT (Table S1, SDC, https://links.lww.com/TP/C517). The central position of necrosis and the presence of plasma cells in 2 of the ALF of unknown etiology patients could be suggestive of a dysimmune process (Figure 3).

F3
FIGURE 3.:
Microscopic images of explanted livers.

REVIEW OF THE LITERATURE

A total of 32 available and analyzable cases of pregnant women presenting with ALF who underwent LT were identified.13-44 Their principal characteristics are shown in Table 2. The main causes of ALF in these women were viruses (HAV, n = 1; HBV, n = 8; HEV, n = 1; HSV, n = 4), drugs (n = 3), autoimmune disease (n = 1), and Budd–Chiari syndrome (n = 1). Eleven patients had ALF of undetermined origin, and the cause was not specified in 2 others.

TABLE 2. - Characteristics of pregnant women presenting with ALF who underwent LT classified according to gestational week at admission following the WHO viability criteria: data reported in the literature
Theoretical degree of prematurity if delivery at admission Total Nonviable <22 WG Extreme prematurity 22–27 WG+6 Severe and moderate prematurity 28–36+6 WG
 N 32 15 9 8
 Age 29.1 [26.5–32] 28 [21–32] 30 [29–30.5] 31.5 [28–32]
 Gestational age at admission (30) 22 [18–28] 18 [14–19] 26 [22–27] 31 [31–33.25]
 References 13, 16–19, 21, 24, 28–30, 33, 35, 36, 38, 43 15, 20, 23, 25–27, 31, 39, 42 14, 22, 32, 34, 37, 40, 41, 44
Delivery or TOP before LT (N) 11 1 2 b 8
 Gestational age (WG) at
  admission 31 [29–32] 12 27 and 27 31 [31–33.25]
  delivery 31 [27–33] 12 27 and 27 32 [31–33.25]
  LT 31 [28–33] D+7 d 27 and 27 33 [31–34]
 Infant alive (n) 10 0 2 8
 Reason for termination of pregnancy TOP:1
 Mode of delivery
  Caesarean section 10 2 8
  Natural 1 1 0 0
 Infant weight at birth (g) 1717.5 [1475–2046.25] n = 6 1400/1156 1942.5 [1726.2–2179.5], n = 8
 Follow-up (mo) live infants 6.2 [0.77–12] 1/0.03 10 [1.2–12], n = 8
 Mother alive 11 1 2 8
Delivery or IUFD after LT (N) 21 14 7 c 0
 Gestational age (WG) at
  admission 19 [17–22] 18 [15.25–19] 25 [22–27]
  LT 21 [18–22] 18.5 [15.5–20.75] 25 [22.5–27]
 Gestational age (WG) at delivery
  in demise fetus (n = 9) 21.5 [19.75–24.5] 20 [19.25–22.25] 24 and 26
  in infants alive at birth (n = 12) 30 [27.75–37] 30 [27.5–33.5] 36 [28–37]
 Infant alive (n) 12 7 5
 Reason for termination of pregnancy MT:2 (Oligohydroamnios 2/2 and bilateral ventriculomegaly 1/2)TOP:1 (at the request of parents)IUFD: 4 IUFD: 2
Mode of delivery (infants alive) a
  Caesarean section 10 6 4 a
  Vaginal delivery 1 1
 Weight at birth of living infants 1925 [1195.5–2740] 1875 [1395.5–2237.5], n = 6 2700 [1800–3000], n = 5
 Follow-up (mo) (infants alive) 12 [2.77–22.5] 12 [0.03–24], n = 7 11 [1–12], n = 5
 Mother alive 21 14 7
Continuous variables were expressed as medians with their interquartile range (25th–75th percentiles [Q1–Q3]).
aNot available for 1 patient.
bThe same day as LT.
cD performed just after LT.
LT, liver transplantation; MT, medical termination of pregnancy; IUFD, intrauterine fetal demise; TOP, termination of pregnancy; WG, weeks of gestation.

All the fetuses displayed good vitality at admission. The median gestational age at admission for ALF was 22 WG (18–28). Delivery was performed before LT in 11 patients. Delivery or intrauterine fetal demise occurred after or during LT in 21 patients. Those pregnant for <22 WG (n = 15) at the time of admission were transplanted during pregnancy in 93.3% of cases. The rate of infants alive at birth reached 50% among these patients. All patients pregnant for longer than 27+6 WG (8 patients) were transplanted after delivery, with live births in all cases. Between 22 and 27+6 WG, 78% (7/9) of pregnant patients were transplanted while an ongoing pregnancy, with an overall infant survival rate at birth of 77.8%. In 2 of the 9 patients, LT was performed a few hours after delivery on the same day. Whatever the gestational age at admission and the timing of LT (before or after delivery), all these ALF patients survived (Figure 4).

F4
FIGURE 4.:
Outcome of pregALF patients of the Paul Brousse (PB) cohort and of the reported cases in the literature. IUFD, intrauterine fetal demise; PregALF, acute liver failure in pregnant women; LT, liver transplantation; TOP, termination of pregnancy; WG, weeks of gestation.

Based on our limited experience and those cases reported in the literature and considering infants survival rates as a function of gestational age at admission, we propose a management algorithm for the mother and fetus that require a multidisciplinary approach (Figure 5).

F5
FIGURE 5.:
Proposed algorithm for the management of pregnant women presenting with nonpregnancy-related ALF. ALF, acute liver failure; LT, liver transplantation; WG, weeks of gestation.

DISCUSSION

This consecutive series of 5 pregnant women presenting with nonpregnancy related ALF and undergoing LT, combined with our review of the literature concerning a further 32 patients, highlighted numerous points, which included (1) the rarity of ALF in this population of patients requiring LT (2.9%); (2) the time expected to be the most appropriate for delivery, that is, before or after LT, as a function of gestational age at admission; (3) the poor prognosis for the fetus (only 2 survived in our series and 21/32 [65%] in the literature); and (4) the satisfactory results of LT in this patient population (100% survival).

In the general population, fetal survival remains rare before 24 WG (0.7%). At 24 WG, 25 WG, and 26 WG in France, the rates of fetal survival are 31%, 59%, and 75%, respectively, and reach 94% (81% without major problems) between 28 and 31 WG and 99% at 32–34 WG.45,46 In addition, the percentages of infants who leave the neonatal ICU without being affected by a serious neonatal pathology are 0% if they were born before 24 WG, 12% at 24 WG, 30% at 25 WG, 48% at 26 WG, 81% between 27 and 31 WG, and 97% between 32 and 34 WG.45,46 Any decision regarding delivery before or after LT must therefore consider these survival rates.

When gestational age at the diagnosis of ALF is below the viability threshold (22 WG), transplantation should be performed before delivery. In 93% (14/15) of cases in the literature, LT was performed with an ongoing pregnancy, and the median gestational age at delivery was 30 WG [IQR 27.5–33.5]. The perinatal survival rate was low (7/15 infants, 46.1%), which could probably be explained by the severity of the liver failure and associated organ failures, its probable detrimental effects on the fetus, the treatments initiated, and the liver transplant surgery itself. This rate might probably be overestimated as it was based on case reports collected from the literature and it reflected survival at birth rather than neonatal survival. On the other hand, when gestational age was above 27+6 WG at admission, the survival of infants reached 100%. All these patients were delivered before undergoing LT. Thus, at a gestational age of >27+6 WG, delivery can be considered before LT.

Gestational age between 22 and 27+6 WG probably represents a grey zone during which the timing of delivery with respect to LT is difficult to define. The more gestation approaches 28 WG, the more delivery before LT should be considered. In the literature, 2 of the 9 patients, both pregnant at 27 WG at admission, gave birth before LT to a living infant. The 7 other patients, with a median gestational age of 25 WG [IQR 22–27] at admission, gave birth after LT at a median of 36 WG [IQR 28–37] to a living infant. Two fetuses died at 24 and 26 MG, respectively. In our series, 2 patients had reached 22 and 23 WG at the time of onset of ALF; 1 infant died in utero, and the second lived and was born at 31+2 WG.

Despite all the precautions taken, and even if pregnancy is pursued after LT, normal fetal development cannot be guaranteed. The literature offers few clues or data regarding the infant’s psychomotor development in the medium and longer terms. Furthermore, the effects of ALF on the fetus remain unknown and uncertain.47 The median follow-up postdelivery recorded in the literature was 11 mo [IQR 0.07–15.5].

Delivery before LT is associated with a higher risk of postpartum hemorrhage due to severe hemostatic disorders. Although it has not been demonstrated, support should therefore be provided by the administration of plasma and platelet concentrates during the first 24 h after surgery, and above all, close surveillance should be ensured of any locoregional complications that might require local hemostasis and/or specific treatments for postpartum hemorrhage (intrauterine balloon tamponade, vascular ligation). In the event of intrauterine fetal demise at the time ALF is diagnosed, delivery must be delayed until after LT to minimize the risks of postpartum hemorrhage, unless sepsis or another obstetric reason necessitates delivery. The same applies to any termination of pregnancy.

Management of a pregnant patient presenting with ALF is more complex than that of a nonpregnant patient as it must take account of both the mother and fetus. Standard management should be supplemented by specific precautions, such as maintaining a satisfactory hemodynamic status that will ensure optimum feto-maternal circulation, only using medicinal products that are authorized in pregnant women, and preventing any risk of exposure to ionizing radiation, although this risk is lower during the second and third trimesters of pregnancy than during the first. These measures must be pursued after transplantation and until birth. If a premature birth threatens, treatment with betamethasone must be initiated to accelerate fetal pulmonary maturation. Screening for ischemic lesions and other brain consequences linked to low cardiac output during the perioperative period can be achieved using ultrasound and fetal brain MRI.

Among the clinical cases recorded in the literature, the very short-term survival of mothers reached 100%, as it did in our series.

Two of our 5 patients (patients 3 and 4) underwent auxiliary LT. In both cases, the surgical procedure was complex and lengthy, and hemorrhage was complicated by vascular thrombosis that caused severe liver dysfunction and resulted in repeat transplantation. Although the fetus was viable before LT in 1 of these patients, intrauterine fetal demise was diagnosed after the procedure; this had probably been caused by the complexity of the surgical procedure chosen.48 Overall, in these exceptional circumstances, the surgical procedure should be simplified and adapted as much as possible so as not to accumulate risks, for example, by ensuring the maintenance of feto-maternal circulation during the perioperative period (clamping of the lateral vena cava).

Our patient series and this review gather the largest number of patients presenting with ALF during pregnancy and offer a synthetic vision of the principal results. However, it does have several limitations. Most important is the small population studied because of the rarity of onset of ALF during pregnancy that requires LT. In the series studied by Casey et al, only 5 out of 3155 patients (HELLP syndrome and AFLP excluded) undergoing transplantation presented with ALF during pregnancy.8 This confirms the rarity of this patient population and means that a recruitment bias was improbable in our series. Thus, the strategy proposed is based on our experience and the only data available in the literature. This implies that the gestational age thresholds we propose regarding LT before or after delivery can only be indicative. However, they have the advantage of offering guidance to clinicians when they need to deal with this situation.

The second limitation of our study was its retrospective nature, which did not enable any evaluation or prediction of the consequences for the fetus of pursuing the pregnancy. There are currently no data concerning the short-, medium, or long-term survival of infants born to mothers who presented with ALF and were transplanted before or after delivery. Only a prospective study with short- and long-term follow-up would be able to determine the optimum strategy. Finally, we cannot exclude that the excellent outcome regarding pregnant women might be linked to a recruitment bias in the literature and that some cases of AFLP/HELLP, which lead to maternal death, were never reported.

CONCLUSION

The onset of nonpregnancy-related ALF in pregnant women is rare. The prognosis for the fetus is poor (survival of 64.8% in the literature and in our series), whereas for the mother, it is excellent. Birth before or after LT depends on gestational age at the time of diagnosis of ALF. In the case of a pregnancy shorter than 22 WG, it should be pursued after LT, and all therapeutic precautions should be taken for as long as they have no consequences for the mother. In pregnancies longer than 28 WG, delivery can be considered before LT. Between these 2 time points, there is a divergence of views. The psychomotor development of the infant in the short and longer terms remains unknown.

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