Aust N Z J Obstet Gynaecol 2021; 61: 183–187

DOI: 10.1111/ajo.13293

SHORT REVIEW

Acute fatty liver of pregnancy – A short review

Marie Donck1 , Yoann Vercruysse2, Alexandros Alexis2, Serge Rozenberg1 and

Samantha Blaiberg1

1
Department of Obstetrics and
Gynaecology, University Hospital Acute fatty liver of pregnancy (AFLP) is a rare but dramatic condition associated
Saint-Pierre (Université Libre de with a high maternal and fetal morbidity and mortality. We present a short review
Bruxelles), Brussels, Belgium
2
of AFLP management, illustrated by a case report. We conducted a systematic lit-
Department of
Anesthesiology, University Hospital erature search for ‘acute fatty liver of pregnancy’, concerning its management. We
Saint-Pierre (Université Libre de found initially 11 studies, and three of them met the selection criteria. Prompt di-
Bruxelles), Brussels, Belgium
agnosis, maternal stabilisation and rapid delivery are mandatory. This illustrative
Correspondence: Dr Marie Donck, AFLP case fulfilled nine out of 14 Swansea criteria. Caesarean section is often re-
Department of Obstetrics
and Gynaecology, University quired (as illustrated in this case), reducing maternal and perinatal mortality rates.
Hospital Saint-Pierre, Université
Libre de Bruxelles, 322 rue KEYWORDS
Haute, 1000 Brussels, Belgium.
acute fatty liver of pregnancy, multidisciplinary management, secondary postpartum
Email: mariedonck90@gmail.com
haemorrhage, spinal anaesthesia, Swansea criteria
Conflict of Interest: The authors report
no conflict of interest.

Received: 1 June 2020;

Accepted: 29 November 2020

INTRODUCTION
Acute fatty liver of pregnancy (AFLP) is a rare obstetric emergency
that typically occurs during the third trimester, but can be ob-
served earlier in the pregnancy, as well as during the postpartum
period. It is characterised by an acute hepatic failure, secondary to
fatty infiltration of the liver. Its prevalence is estimated to be five
cases per 100 000 pregnancies.1,2 It is associated with high mor-
bidity and mortality rates for both mother and fetus. In the past
few decades, the maternal and fetal mortality rate reached up to
80%. 10,11
Nowadays, these rates range widely: maternal mortality
rate ranges from 1.8% to 18% and fetal mortality ranges from 9%
to 23%. 2,8
This decrease can be attributed to earlier diagnosis and
better management. 3 tory, histological and genetic findings but HELLP syndrome occurs
Pathogenesis of AFLP remains unclear. Deficiency in fatty acid
metabolism during pregnancy appears to play a key role. Several
associated genetic mutations are described: 20% of AFLP is asso-
ciated with long-chain 3-hydroxyacyl CoA dehydrogenase (LCHAD)
homozygous mutation, resulting in a fetal fatty oxidation defect,
causing an accumulation of metabolites toxic for the maternal
liver. The homozygous G1528C mutation and other pregnancy-re-
lated liver diseases like haemolysis, elevated liver enzymes, and
low platelets (HELLP) syndrome and preeclampsia have also been
associated with AFLP, although the link remains unclear. HELLP
and AFLP must therefore be considered as separate entities.4
The risks factors for AFLP include multiple gestations, male
fetuses, fatty acid oxidation disorder in the fetus and previous ep-
isodes of AFLP.3
Initial symptoms are often nonspecific, delaying the diagnosis.
It has been recommended to use the Swansea criteria, including
clinical symptoms, laboratory findings and imaging, for the diag-
nosis of AFLP (Table 1).3 Six or more criteria are needed for a pos-
itive AFLP diagnosis.3 The diagnosis can be challenging as there is
an overlap with other gestational (HELLP syndrome, preeclampsia,
cholestasis) and non-gestational pathologies involving the liver.
AFLP and HELLP syndrome have some common clinical, labora-
in most of the cases in patients with hypertension, and AFLP oc-
curs often in the absence of hypertension. Furthermore, around
50% of patients with AFLP do not have thrombocytopenia.9
This obstetrical pathology requires multidisciplinary manage-
ment. The initial management includes prompt delivery of the
fetus regardless of the gestational age (GA) and results in mater-
nal stabilisation and liver function improvement.3
We present here a short review of the literature and illustrate the
AFLP management based on a recent case experienced at our hospital.

wileyonlinelibrary.com/journal/anzjog © 2020 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists 183
184 Acute fatty liver of pregnancy

TABLE 1 Swansea criteria for diagnosis of acute fatty liver of pregnancy (AFLP) and differential diagnosis with preeclampsia

AFLP (Swansea criteria, n = 14) Preeclampsia/HELLP syndrome

Symptoms Vomiting Central nervous system disorder:

Abdominal pain • Photopsia, scotomata, cortical blindness, retinal vasospasm
Polydipsia/polyuria • Severe headacheSevere persistent right upper quadrant or
Encephalopathy epigastric pain unresponsive to medication and not accounted
for by another diagnosis.
Signs Blood pressure: normal Blood pressure: systolic blood pressure ≥140 mmHg or diastolic
No oedema of the lower limbs blood pressure ≥90 mmHg on at least two occasions at least four
No hyperreflexia hours apart after 20 weeks of GA in a previously normotensive
No pulmonary oedema patient.
Oedema of the lower limbs
Hyperreflexia
Pulmonary oedema
Laboratory Leucocytosis (>11 000 cells/μL) Low platelet count (<150 000/dL)
Elevated transaminases Haemolysis
Elevated ammonia (>47 μmol/L) Disseminated intravascular coagulation
Elevated bilirubin (>0.8 mg/dL or > 14 μmol/L) Elevated creatinine (>90 μmol/L; 1.02 mg/dL)
Elevated uric acid (>5.7 mg/dL or > 340 μmol/L) Elevated transaminases at least twice the upper limit
Acute kidney injury (creatinine > 1.7 mg/dL Proteinuria (spot urine protein/creatinine > 30 mg/mmol (0.3 mg/
or > 150 μmol/L) mg) or > 300 mg/day or at least 1 g/L (‘2 + ’) on dipstick testing)
Coagulopathy or prothrombin time > 14 s
Hypoglycaemia (< 72 mg/dL or > 4 mmol/L)
Imaging Ascites or bright liver on ultrasound scans Fetal growth restriction
Pathology Microvesicular steatosis on liver biopsy

The presence of at least six out of 14 Swansea criteria, in the absence of another explanation, confirms the diagnosis.
Adapted from Ch’ng et al. Prospective study of liver dysfunction in pregnancy in Southwest Wales, Gut. 51 (2002) 876–88010 and J. Ablett, A.
Ashcroft. Acute fatty liver of pregnancy (GL780), Matern Guidel Policies (2018). http://www.royal​berks​hire.nhs.uk (accessed February 17, 2020).11
Adapted from The classification, diagnosis and management of the hypertensive disorders of pregnancy: A revised statement from the ISSHP.
Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health. 4 (2014) 97-104.

CASE One dose of betamethasone was administered for lung mat-

A 29 year old primigravida of Northern African origin, with no
relevant medical history, was admitted to the emergency unit
at 33weeks and four days GA. During the previous two weeks
she had developed generalised skin rashes associated with
pruritus and jaundice. She also described polyuria, polydipsia,
loss of appetite and extreme tiredness. Polyuria and poly-
dipsia are clinical signs of central diabetes insipidus that
may occur in patients suffering from AFLP caused by the de-
creased levels of arginine vasopressin secondary to reduced
clearance of vasopressinase by the impaired liver. 18
The pa-
tient did not have any symptoms or clinical signs of preec-
lampsia, no proteinuria and her blood pressure at admission
was normal.
Blood test revealed abnormal kidney and hepatic function, el-
evated bilirubin, elevated ammonia, elevated uric acid, very low
haptoglobin, leucocytosis and coagulopathy. Abdominal ultra-
sound showed vesicular microlithiasis, but no intracapsular liver
hematoma or fatty infiltration.
At vaginal examination, the cervix was closed. AFLP was diag-
nosed promptly, based on the Swansea criteria, scoring nine out
of 14 (Table 1).
uration. After discussion, we decided to perform an emergency
caesarean section (CS).
Prior to the spinal anaesthesia, two units of fresh frozen
plasma (FFP) and 1 g of fibrinogen were administered.
Following prophylactic antibiotic administration, we per-
formed a classic Misgav-Ladach CS.5 A newborn female of 1890 g
was born and immediately taken care of by the neonatologist.
Apgar score was 1-3-8 at 1-5-10 min. Umbilical cord arterial pH was
7.24 with a base excess of − 2.6. Oxytocin (10 IU) was administered
as per protocol for uterine tonicity. We reported no complication
during our CS. During the CS, 1 g of fibrinogen was administered.
The blood loss during the CS was estimated at 750 mL.
Immediately after the CS, the patient was transferred to the
intensive care unit (ICU) with a continuous IV infusion of oxyto-
cin at 10 IU per 24 h. She suffered from a secondary postpartum
haemorrhage due to uterine atony, which started approximately
one hour after the ICU admission. The team decided to perform a
uterine manual revision under spinal anaesthesia. A thromboelas-
tometry test was performed and showed normal values. The pa-
tient lost in total 3000 mL of blood and received a total of four
units of red blood cells (RBC), four units of FFP, 2 g of fibrinogen,
10 units of platelets and 1 g of tranexamic acid. After the manual
D. Marie et al. 185

revision, a Bakri balloon was inflated in the uterine cavity with Citations from PubMed N=11
240 mL of saline solution, under ultrasound control, and oxytocin - Systematic reviews N=2
- Clinical trials N=1
was switched to intravenous dinoprostone (prostaglandin E2) as - Guidelines N=2
- Observational studies N=6
per protocol. The patient was transferred back to the ICU.
During the postpartum period, the patient’s biological mark-
Citations excluded after screening titles and/or
ers and clinical status progressively improved. The patient did not abstracts because they were off-topic content
have any clinical signs of preeclampsia. The patient left the hospi- N=8

tal on the sixth day postpartum.

The study was approved by the local hospital ethics committee Studies included N=3
of the Saint-Pierre University Hospital Centre (O.M. 007) (Approval
no.: 45.137.832) and the patient gave her written consent, allow-
DISCUSSION
ing this publication.

Establish the diagnosis

REVIEW
Method of research
A systematic literature search on PubMed database was con-
ducted from inception until the 4 July 2020. Our search term was
‘acute fatty liver of pregnancy’, restricted to ‘systematic reviews,
clinical trials, guidelines and observational studies’. In addition,
to be eligible, the articles needed to address the management of
patients with AFLP.
We found initially 11 studies, and three of them met the
selection criteria.
Even though AFLP is a rare condition, it should be immediately
recognised by healthcare providers in obstetric units, since
prompt diagnosis and management improves the outcome.
Distinguishing between AFLP and preeclampsia/HELLP syndrome
may be challenging since there is an overlap in clinical and biologi-
cal criteria (Table 1).9
We established the diagnosis of AFLP of this case based on
the Swansea criteria (Table 1),10,11 which are recognised as a
reliable tool to establish the diagnosis.3 Antithrombin activ-
ity of less than 65% may facilitate diagnosis of AFLP against
preeclampsia/HELLP syndrome.9

Results Delivery

The principal methodological aspects and results of these three We decided to perform an emergency CS based on the patient’s
studies are summarised in Table 2. deterioration and the blood test showing multiple organ failure.

TABLE 2 Studies concerning the management of acute fatty liver of pregnancy (AFLP)

Studies Method Results

Wu Z et al. Treating AFLP with artificial liver
support therapy. A systematic review. 2018.6
Wang HY et al. Effect of CS on maternal and
foetal outcomes in AFLP: a systematic review
and meta-analysis. 2016.7
Italian Association for the Study of the Liver
(AISF) position paper on liver disease and
pregnancy. 2016.8
Retrospective review of 15 patients treated
with postpartum artificial liver support
therapy (ALST) between 2010–2016 in
their hospital; 104 cases of AFLP having
postpartum ALST coming from a public
database which included nine studies.
Systematic review of 80 observational
studies evaluating the association between
caesarean section (CS) and perinatal
outcomes in AFLP searched in PubMed,
Embase, China national knowledge
infrastructure databases (until July 2015).
Guidelines were established by a panel of
experts, using the level of evidence and
strength of recommendations, based on a
review of data available in literature for:
specific liver diseases of pregnancy;
liver diseases occurring during pregnancy;
pregnancy in patients with pre-existing
chronic liver disease.
Postpartum ALST improves the outcome of
AFLP patients but more studies are needed
to confirm this fact.
Occurrence of multiple organ dysfunction
(MODS) carries a bad prognosis even when
treated using ALST.
CS compared to vaginal delivery improved:
the maternal mortality rate by 48% (rela-
tive risk (RR) 0.52 (95% CI 0.38-0.71));
the perinatal mortality rate by 44% (RR
0.56 (95% CI 0.41-0.76)).
Management of AFLP:
1-Prompt diagnosis is crucial because
interval from AFLP onset to delivery should
not exceed one week (Class IIa, Level B);
2-Maternal stabilisation in ICU and adequate
supportive therapy (Class IIa, Level B);
3-Rapid delivery: if vaginal delivery cannot
be achieved quickly, CS is the preferred
method (Class IIa, Level B).

The principal methodological aspects and results of these three studies are summarised in this table.
186
This decision was in line with the systematic review of Wang
et al., who reported that CS reduced the maternal mortality
rate by 48% and the perinatal mortality rate by 44% compared
to vaginal delivery7 and with the Italian guidelines which focus
on the management of AFLP in three points: prompt diagno-
sis, maternal stabilisation with an adequate support therapy
in ICU and a rapid delivery.8 These guidelines consider that
CS is the preferred method when vaginal delivery cannot be
achieved quickly.8
Anaesthesia
Neuraxial anaesthesia for labour, as well as for CS, has been re-
2,12–14
ported in patients with AFLP with a low complication rate.
Resolution
The clinical condition usually resolves within four days after de-
livery, but normalisation of the biological findings can take up
to eight weeks.3
Management of complications
Successful management of patients with AFLP is challenging.
Thromboelastometry is an efficient method for prompt diagnosis
and as a consequence, treating adequately coagulopathy in pa-
tients with AFLP.15,16. Wu et al. reported that postpartum artificial
liver support therapy (ALST) improves the outcome of AFLP pa-
tients except when the patient suffers from multiple organ dys-
function, as our patient did.6
Future prevention
There are no exact data about AFLP risk of recurrence. Patients
who developed an AFLP should have preconception counselling
and their pregnancy should be monitored closely by an experi-
enced obstetrician. Hepatic and renal function and coagulation
tests should be performed at the first prenatal visit, once again
in the second trimester, then every one to two weeks and weekly
after 34 weeks of GA or one month prior to the onset of the AFLP
if it occurred earlier on.17 As mentioned above, 20% of AFLP is
associated with LCHAD homozygous mutation. All women with
AFLP and their offspring should be tested for LCHAD mutation.
However, AFLP can recur in subsequent pregnancies even if test-
ing for LCHAD mutation is negative.4
Limitation of the study
We may have missed some studies since we included in our litera-
ture search only systematic reviews, clinical trials, guidelines and
observational studies and excluded case reviews.
To conclude, AFLP is a rare but serious condition associ-
ated with a high morbidity and mortality rates for both mother
Acute fatty liver of pregnancy
and fetus. Swansea criteria are a reliable tool for AFLP diag-
nosis. Differentiating this pathology from others can be chal-
lenging. Obstetricians should be able to identify rapidly AFLP
because prompt delivery (often by CS) improves maternal and
perinatal outcomes.7,8
F U ND ING
This study was not funded.
A U T H O R C O NT R IB U T IO NS
Marie Donck and Samantha Blaiberg equally participated in the
acquisition and interpretation of data, drafting the article and ed-
iting before submission. Yoann Vercruysse and Alexandros Alexis
equally participated in the acquisition and interpretation of data
concerning the anaesthesiology part. Serge Rozenberg was in-
cluded and conducted the short review.
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