Acta Colomb Cuid Intensivo.

2017;17(3):222---225

Acta Colombiana de
Cuidado Intensivo
www.elsevier.es/acci

CASE REPORT

Plasmapheresis for acute liver failure in acute fatty

liver of pregnancy
Karla Gabriela Peniche-Moguel ∗ , Jesús Salvador Sánchez-Díaz,
César López-Guzmán, María Verónica Calyeca-Sánchez, Edgar Castañeda-Valladares

Unidad Médica de Alta Especialidad, Hospital de Especialidades No. 14 Centro Médico Nacional ‘‘Adolfo Ruiz Cortines’’, Instituto
Mexicano del Seguro Social, Veracruz, Mexico

Received 5 April 2017; accepted 7 August 2017

Available online 16 October 2017

KEYWORDS Abstract Acute fatty liver of pregnancy (AFLP) is an obstetric emergency that complicates
Acute fatty liver of gestation in the last trimester or immediate post-partum period. It is associated with genetic
pregnancy; defects in the long chain 3-hydroxyacyl CoA dehydrogenase (LCHAD) enzyme, which is necessary
Plasmapheresis; for mitochondrial fatty acids beta-oxidation, resulting in hepatic micro-vesicular steatosis and
Swansea criteria; acute liver failure. Liver biopsy is the reference standard for its diagnosis, however the Swansea
HELLP syndrome criteria are also used.
A case is presented of a 16-year-old woman during week 37 gestation, with biochemical evi-
dence of acute liver failure progressing to multiple organ dysfunction. Pregnancy interruption
and treatment of acute liver failure with plasmapheresis lead to the resolution of the organ
dysfunction.
© 2017 Asociación Colombiana de Medicina Crı́tica y Cuidado lntensivo. Published by Elsevier
España, S.L.U. All rights reserved.

PALABRAS CLAVE Plasmaféresis para la insuficiencia hepática aguda en el hígado graso agudo del
Hígado graso agudo embarazo
del embarazo;
Plasmaféresis; Resumen El hígado graso agudo del embarazo (HGAE) es una emergencia obstétrica que com-
Criterios de swansea; plica la gestación en el último trimestre o en el posparto inmediato, se asocia con defectos
Síndrome HELLP genéticos en la enzima 3-hidroxiacil-CoA deshidrogenasa (LCHAD) de cadena larga, necesaria
para la beta-oxidación de ácidos grasos mitocondriales lo que resulta en la esteatosis micro
vesicular e insuficiencia hepática aguda. La biopsia del hígado es el estándar de oro para el
diagnóstico, sin embargo los criterios de Swansea también se utilizan.

∗ Corresponding author.
E-mail address: gabrielapenichemd@gmail.com (K.G. Peniche-Moguel).

http://dx.doi.org/10.1016/j.acci.2017.08.004
0122-7262/© 2017 Asociación Colombiana de Medicina Crı́tica y Cuidado lntensivo. Published by Elsevier España, S.L.U. All rights reserved.
Plasmapheresis for acute liver failure in acute fatty liver of pregnancy 223

Este reporte de caso es de una mujer de 16 años de edad quien durante la semana 37 de
gestación, cursó con pruebas bioquímicas de insuficiencia hepática aguda avanzando a dis-
función orgánica múltiple. La interrupción del embarazo y el tratamiento de la insuficiencia
hepática aguda con plasmaféresis condujeron a la resolución de la disfunción orgánica.
© 2017 Asociación Colombiana de Medicina Crı́tica y Cuidado lntensivo. Publicado por Elsevier
España, S.L.U. Todos los derechos reservados.

Introduction

Acute fatty liver of pregnancy (AFLP) is a rare complication

of pregnancy with an incidence of about 5 cases per 100,000
pregnancies,1 being an obstetric emergency with a morta-
lity up to 90%, however nowadays with medical treatment
including plasmapheresis reduces death to less than 10%.2
AFLP is a form of severe liver disease with development
of acute liver failure, jaundice, intravascular coagulation,
encephalopathy, renal injury and even pancreatitis, leading
to multiple organ dysfunction.
The gold standard for diagnosis is liver biopsy, which
demonstrate the microvesicular steatosis, however clinical
and biochemical Swansea criteria are currently used, having
a negative predictive value of 100%.3
Treatment of acute liver failure include pregnancy
interruption, blood transfusion support and more recently
plasmapheresis, which in different studies is the therapeutic
option with the highest success rate.4
Clinical case
16-Years-old female patient, without chronic diseases diag-
nosis. Among the gyneco-obstetric history, is the patient’s
first gestation denying previous pregnancies or abortions;
she referred to seek monthly prenatal care without any
complications.
The current condition started on June 3 of 2015 with
37 weeks of gestation, where epistaxis, gingival bleeding
and asthenia characterized the clinical picture. The pres-
ence of jaundice caught the attention of the family. The
first blood tests showed hyperbilirubinemia of 14.1 mg/dL
and direct bilirubin of 13.2 mg/dL, being the reason why this
patient was sent to the gyneco-obstetric Hospital, where
was received with a biochemical data of acute liver failure
and acute fetal distress, so it was decided to interrupt the
pregnancy. The product was died.
The patient was transferred to intensive care 36 h after
admission for further deterioration of biochemical para-
meters, multiple organ dysfunction with a SOFA of 18 pts,
hepatic, renal and hematological failure, also showing dis-
seminated intravascular coagulation with gastrointestinal
and pulmonary bleeding, requiring invasive mechanical ven-
tilation. Hem derivatives and factor VII were transfused,
stopping the bleeding; however, the patient developed lung
injury with refractory hypoxemia, needing ventilation in a
prone position 12 h for 2 consecutive days (Fig. 1).
For kidney injury, slow renal replacement therapy was
continuously provided for 72 h, observing renal bioche-
mistry improvement. However, with the biochemical data
of acute liver persistence, the beginning of plasmapheresis
Figure 1 Thorax axial section tomography, pulmonary win-
dow. Areas of alveolar collapse and air bronchograms are
observed.
therapy was performed seven days after pregnancy inter-
ruption. After five sessions of plasmapheresis with albumin,
liver failure biochemical data improved.
For the diagnostic approach infectious causes for acute
liver failure were discarded, determining them by proofs
against hepatitis A, B, C and E antibodies, serological HIV,
TORCH, as well as dengue virus. Among the non-infectious
causes antibodies to SLE, primary biliary cirrhosis were
requested, hepatic vein thrombosis was discarded, Swansea
criteria were applied, concluding with a final diagnosis of
pregnancy acute fatty liver (Table 1).
After 20 days of intensive care, the patient was dis-
charged for clinical improvement with a multiple organ
dysfunction diagnosis.
Discussion
AFLP is an acute mitochondrial liver disease, characterized
by the presence of micro and macro vesicular steatosis
on a histological level and by acute liver failure at a
biochemical level; presenting hyperbilirubinemia, elevated
transaminases, hypoglycemia, hyperammonemia and hyper-
lactatemia. Histological changes are the same as observed in
Reye’s syndrome and its evolution can reach hepatic necrosis
or progress to liver failure, requiring a transplant.5---7
The main differential diagnosis of AFLP is preeclampsia
and HELLP syndrome, the last one is a multisystem syn-
drome characterized by hypertension after 20 weeks of
gestation with systolic >140 mmHg and diastolic blood pres-
sure of 90 mmHg, associated with proteinuria of 300 mg/24 h
or any other organ dysfunction as acute kidney injury, liver
injury, coagulopathy or neurological disorders; the etio-
logy resides in alterations during placentation, leading to
hypo perfusion and endothelial dysfunction, where the tro-
phoblast fails not invading the lining of the uterus, resulting
in arterial placental perfusion defects getting worse as
224 K.G. Peniche-Moguel et al.

Table 2 Swansea criteria.

PLT: platelets. Leu: leukocytes. Cr: creatinine. TB: total bilirubin. DB: direct bilirubin. IB: indirect bilirubin. AST: aspartate aminotransferase. ALT: alanine aminotransferase. PT: prothrombin
PTT

109d
(s)

102

100
43
Clinical Biochemical Study of image
Vomit Total bilirrubin Ascites or hepatic
>0.8 mg/dLa steatosis by

30.2
38d
PT ultrasonographya
(s)

37
17
Low blood sugar
<72 mg/dLa
Abdominal Uric acid >5.7 mg/dL
(UI/L)

pain Serum creatinine

ALT

144d
218

100
44
>1.6 mg/dLa
Polyuria/ Ammonium >80 mmol/La Microvesicular
(mg/dL) (mg/dL) (UI/L)

polydipsia Leukocytes >11 × 109 /la steatosis on liver

AST

145d
202

130
45
Encephalopathya AST o ALT >42 UI/la biopsy
Coagulopathy (TP >14 s
to TTP >32 s)a
0.9
1.0
1.2
0.4
IB

a Clinical, biochemical and imaging criteria met by the patient.

13.5d
13.2

1.6

the pregnancy progresses and placental demand increases;

DB

14

nitric oxide, prostaglandins and endothelial placental tissue

are released from platelet aggregation, endothelial dysfunc-
14.5d
(mmol/L) (mg/

14.1

15.2
2.0
dL)

tion and hypertension.2,7

Ammonium TB

Acute liver failure is defined by the presence of three

criteria: 1) fast development of hepatocellular dysfunction
with jaundice and coagulopathy, 2) encephalopathy and 3)
167d

the absence of previous liver disease. Treatment consists on

NR

100
32

renal and ventilatory support, blood transfusion, decreasing

intestinal nitrogen production with antibiotics and lac-
(mg/dL)
Glucose

tulose, also hyperammonemia reduction with l-ornithine

45d

l-aspartate, the newest treatment called MARS (molecular

65

95
147

absorption recirculating system) and plasmapheresis, which

Biochemical patient evolution of hematological, renal and hepatic function.

is employed in most cases of liver failure associated with

(mg/dL)

AFLP.8,9
Urea

AFLP etiology and pathogenesis still a mystery, but it has

24
30
24
25

been identified as a genetic defect in which exists a mutation

(G1528C) in one allele of the enzyme complex on the alpha
(mg/dL)

d Swansea biochemical criteria fulfilled upon admission to intensive care.

subunit, called mitochondrial trifunctional protein (MTP),

2.8d

located on the chromosome 2p23. The LCHAD enzyme can be

2.5

0.8
0.8
Cr

found as part of the MTP complex, which participates in the

third step for fatty acids beta oxidation at the mitochondria,
this genetic defect could cause partial or total deficiency of
(10/L)

8.15
16.1d

time. PTT: partial thromboplastin time. NR: not registered.

13.7

14.5
Leu

the enzyme complex. Homozygous fetus for this mutation

do not undergo fatty acid oxidation, returning through the
heterozygous maternal placenta and deposited in the liver,
which cause apoptosis, oxidative stress and mitochondrial
dysfunction resulting in liver necrosis. Moreover, fatty acid
161
97
80
120
PLT

c Following five sessions of plasmapheresis.

beta-oxidation at peroxisomes level is altered causing hydro-

gen peroxide release, perpetuating the hepatic damage.
As well, during the third trimester of pregnancy, the main
26.5
18.6

source of energy production is fatty acids metabolism, com-

Hct
(%)

27
29
Admission to intensive care.

bined with maternal heterozygous phenotype for G1258C

mutation, makes the mother more susceptible to present
Prior to plasmapheresis.

this pathology.10
(g/dL)

6.36

In 2002, Ch’ng et al.11 through a prospective analysis

8.9

8.5
8.8
Hb

with a cohort of 142 patients, identified the most com-

mon liver disorders associated with pregnancy, grouping
them by trimester and proposing a diagnostic criteria named
11.06.15b
06.06.15a

17.06.15c

Swansea. These are fourteen criteria, having to complete six

04.06.15
Table 1

for AFLP diagnosis (Table 2).

In 2008, Knight et al.12 published the first prospective
a
b

multicenter study in UK hospitals, with an estimated cohort

Plasmapheresis for acute liver failure in acute fatty liver of pregnancy
of more than 1 million pregnant women who were clini-
cally evaluated with AFLP and then evaluated through the
Swansea diagnostic criteria. Reporting a 0.78 kappa coef-
ficient with considerable agreement and concluding that
these criteria should be applied when AFLP is suspected, so
the diagnosis could be homogenized. Moreover in 2011, Goel
et al.13 validated the Swansea criteria retrospectively in
24 patients, cataloged with hepatic disease associated with
pregnancy who had undergone liver biopsy; they compared
the presence of microvesicular steatosis in a liver biopsy
and the Swansea criteria, observing that of the 24 patients
included, 20 patients fulfilled the criteria and 17 patients
had microvesicular hepatic steatosis while the remaining
3 patients did not exhibit this hepatic impairment, estab-
lishing sensitivity and specificity for the Swansea diagnostic
criteria of 100% and 57% respectively with an 85% positive
predictive value and 100% negative predictive value.
Therapeutic plasmapheresis also known as therapeutic
plasma exchange, is defined as a method of extracorporeal
blood purification, which consists in extracting a pre-
determined volume of plasma, aimed to eliminate or remove
high molecular weight particles, pathogens or decrease the
rate of circulating immune complexes.14 Currently the gui-
dance of the American society for apheresis (ASFA) provides
recommendations for the use of plasmapheresis through four
categories and evidence levels.15
In our patient, the decision to use albumin for thera-
peutic plasmapheresis was the recommendation given in the
ASFA where plasma or albumin was suggested as a replace-
ment fluid, in the context of the patient who had presented
transfusion-related acute lung injury we chose albumin to
reduce the risk of perpetuating lung damage.
Jin et al.4 reported 39 AFLP cases registered in seven
years, diagnosed through the Swansea criteria; in these
patients plasmapheresis was used as standard treatment,
demonstrating its effectiveness in reducing up to 5% mater-
nal mortality, at the same time it was determined that
the use of plasmapheresis the first three days post partum
influence the number of plasmapheresis sessions required
for clinical improvement, with statistical significance of
p ≤ 0.01.
In summary, symptom recognition, diagnosis through
Swansea criteria, aggressive organic support and the use of
plasmapheresis have shown in retrospective studies to be
the best diagnostic and therapeutic option for AFLP. How-
ever more randomize prospective studies are needed to
establish this treatment as a guide to follow in pregnancy-
associated liver disease, which if is left untreated fetal and
maternal life may be threatened. Likewise genetic counsel-
ing for women who have presented AFLP could be an option
to prevent recurrence.
Ethical disclosures
Protection of human and animal subjects. The authors
declare that no experiments were performed on humans or
animals for this study.
Confidentiality of data. The authors declare that no patient
data appear in this article.
225
Right to privacy and informed consent. The authors
declare that no patient data appear in this article.
Funding
We declare the absence of external or internal financing of
pharmaceutical or non-pharmaceutical companies for the
preparation or publication of the manuscript.
Conflict of interests
The authors declare that they have no conflict of interest.
Acknowledgements
We thank the medical and nursing team who through team-
work successfully resolved the patient’s condition.
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