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1
National Perinatal Epidemiology
Unit, University of Oxford, UK;
2
Guys and St Thomas’ Hospitals
NHS Foundation Trust, London, UK
Correspondence to:
Dr M Knight, National Perinatal
Epidemiology Unit, University of
Oxford, Old Road Campus,
Oxford OX3 7LF, UK; marian.
knight@npeu.ox.ac.uk
Revised 25 February 2008
Accepted 29 February 2008
Published Online First
10 March 2008
Gut 2008;57:951–956. doi:10.1136/gut.2008.148676
A prospective national study of acute fatty liver of
pregnancy in the UK
M Knight,1 C Nelson-Piercy,2 J J Kurinczuk,1 P Spark,1 P Brocklehurst,1 on behalf of UK
Obstetric Surveillance System (UKOSS)
ABSTRACT
Objectives: To identify a national, population-based
cohort of women with acute fatty liver of pregnancy
(AFLP), to evaluate proposed diagnostic criteria and to
document accurately the incidence, management and
outcomes of the condition.
Subjects and methods: This was a population-based
descriptive study using the UK Obstetric Surveillance
System, carried out in all 229 hospitals with consultant-
led maternity units in the UK. The participants comprised
57 women in the UK diagnosed with AFLP between
February 2005 and August 2006 in an estimated cohort of
1 132 964 maternities (women delivering).
Results: The estimated incidence of AFLP was 5.0 cases
per 100 000 maternities (95% CI 3.8 to 6.5 per 100 000).
Fifty-five cases (90%) were confirmed by diagnostic
criteria and clinical assessment, two (3%) by clinical
assessment alone, representing 97% agreement (kappa
statistic = 0.78). 18% of women had twin pregnancies
and 20% were underweight (body mass index (BMI)
,20). 60% of women were admitted to intensive care
and 15% to a specialist liver unit. One woman received a
liver transplant. One woman died (case fatality rate 1.8%,
95% CI 0% to 9.4%). There were seven deaths among 67
infants (perinatal mortality rate 104 per 1000 births, 95%
CI 43 to 203).
Conclusions: The largest population-based cohort of
women with AFLP to date has been identified. Diagnostic
criteria previously proposed agree substantially with
clinical diagnosis. The incidence estimate from this study
is lower than documented by earlier hospital-based
studies, but maternal and neonatal outcomes are better
than previously reported, possibly related to improved
ascertainment. Women with twin pregnancies appear to
be at higher risk, but further studies are needed to
investigate the risk associated with low BMI.
Acute fatty liver of pregnancy (AFLP) is a rare but
potentially lethal condition of late pregnancy
which may be part of a spectrum of disorders
related to pre-eclampsia. It remains a cause of
maternal mortality in the UK1 and elsewhere.2
Because the condition is rare, it is difficult to
study, and the existing literature consists predo-
minantly of small hospital-based case series3 4 or
historical cohorts identified retrospectively over a
number of years.5 6 Both these study types have
limitations. Incidence estimates from these studies
vary widely between 1 in 900 and 1 in 16 000
deliveries7 8; maternal case fatality estimates range
between 12% and 18%, and neonatal mortality
estimates range from 7% to 58%.9 There has been
no comprehensive national study of the epidemiol-
ogy of this condition. Because the evidence base is
Hepatology
poor, information available to counsel women
with the condition is limited, and guidelines for
management are lacking.
The condition is closely related to the syndrome
of haemolysis, elevated liver enzymes and low
platelets (HELLP). However, widely accepted diag-
nostic criteria do not exist for AFLP, and the cases
included in different studies are not necessarily
diagnostically uniform. A set of standard diagnos-
tic criteria has been proposed in a recent UK study,3
but these criteria have not been evaluated in a large
series of cases.
The aims of this study were to identify a
national, population-based cohort of women with
AFLP using the UK Obstetric Surveillance System
(UKOSS), to evaluate the diagnostic criteria
proposed by Ch’ng et al3 and to document
accurately the incidence, management and out-
comes of this condition.
METHODS
We identified cases through the monthly mailing
of UKOSS10 between February 2005 and September
2006. Clinicians were asked to report any woman
diagnosed with AFLP with symptoms and signs
consistent with AFLP, or any woman in whom
AFLP was confirmed by biopsy or postmortem.
The UKOSS methodology has been described in
detail elsewhere.10 In brief, every month UKOSS
case notification cards were sent to nominated
reporting clinicians in each hospital in the UK with
a consultant-led maternity unit, with a simple tick
box to indicate whether they had seen a woman
with AFLP. They were also asked to return cards
indicating a ‘‘nil report‘‘, in order that we could
monitor card return rates and confirm the denomi-
nator to calculate the incidence rate. When a
clinician returned a card indicating a case, they
were then sent a data collection form asking for
details of disease presentation, management and
outcomes. They were also asked to report exclu-
sion of other causes of liver dysfunction such as
acute viral hepatitis and paracetamol overdose. All
data collected were anonymous.
Data were double entered into a customised
database. We assessed cases against the diagnostic
criteria for AFLP proposed by Ch’ng et al3
(‘‘Swansea criteria’’, see box) to confirm the
diagnosis objectively. As the Swansea criteria have
not been systematically assessed for their perfor-
mance in a population case series, two of the
authors (CNP, MK) reviewed all the cases to
determine independently whether AFLP was the
most likely diagnosis.
951
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Hepatology
Additional case ascertainment
To ensure all cases were identified, we independently contacted
all radiology departments and liver units, who were asked to
report any cases of AFLP, reporting only their year of birth and
date of diagnosis. Where a case was identified which had
apparently not been reported through UKOSS, the relevant
UKOSS reporting clinician was contacted and asked to complete
a data collection form. In addition, the Confidential Enquiry
into Maternal and Child Health (CEMACH) was contacted at
the end of the study and asked to identify any maternal deaths
from AFLP occurring during the study period, again providing
only their year of birth and date of diagnosis. These were
compared with maternal deaths reported through UKOSS. No
additional new cases were identified through these three other
sources.
Statistical analyses
Statistical analysis was carried out according to a prespecified
study protocol. All analyses were carried out using STATA v9
software.
Rates with 95% CI were calculated using the most recently
available birth data (2005) as a proxy for 2005 and 2006,11 with
the total number of maternities (women delivering) during the
study period estimated from this source as 1 132 964. A kappa
statistic (which takes into account chance agreement) was
calculated for the comparison of the diagnostic criteria and the
clinical assessment of the presence of AFLP.
Ethics committee approval
The UKOSS general methodology (04/MRE02/45) and this
study (04/MRE02/71) were approved by the London Multi-
centre Research Ethics Committee.
Results
All 229 UK hospitals with consultant-led maternity units
contributed data to UKOSS during the study period—that is,
100% participation. All women diagnosed with AFLP deliver in
consultant-led maternity units; this study therefore effectively
covered the entire cohort of UK maternities during the study
period. Ninety-two percent of monthly report cards were
Criteria for diagnosis of AFLP3*
Six or more of the following features in the absence of another
explanation:
c Vomiting
c Abdominal pain
c Polydipsia/polyuria
c Encephalopathy
c Elevated bilirubin (.14 mmol/l)
c Hypoglycaemia (,4 mmol/l)
c Elevated urate (.340 mmol/l)
9
c Leucocytosis (.11610 /l)
c Ascites or bright liver on ultrasound scan
c Elevated transaminases (aspartate aminotransferase or alanine
aminotransferase .42 IU/l)
c Elevated ammonia (.47 mmol/l)
c Renal impairment (creatinine .150 mmol/l)
c Coagulopathy (prothrombin time .14 s or activated partial
thromboplastin time .34 s)
c Microvesicular steatosis on liver biopsy
*Figures in parentheses indicate ranges used in the current study
952
returned, and data collection was complete for 97% of cases
(fig 1). Additional reports were received from 31% of intensive
care units and 26% of liver units, although no new cases were
identified through these sources.
Data collection forms were received for 61 women. Of these,
55 cases (90%) were confirmed by both the Swansea criteria and
clinical assessment, and a further two (3%) by clinical
assessment alone (table 1). These two cases each met five of
the Swansea criteria; the cases confirmed by both assessments
met between six and 11 criteria, with a median of eight criteria.
Thus a total of 57 cases were defined as confirmed cases. A
further four cases were not confirmed by either the Swansea
criteria or clinical assessment. The clinical diagnoses in these
women were: HELLP syndrome (five of the Swansea criteria
met), obstetric cholestasis (five of the Swansea criteria met),
pre-eclamptic liver dysfunction (four of the Swansea criteria
met) and in one woman the diagnosis was unclear (three of the
Swansea criteria met). There was thus 97% agreement between
the clinical assessment and the use of the Swansea criteria, with
a kappa statistic of 0.78, indicating substantial agreement.
There were 57 confirmed cases in an estimated 1 132 964
maternities,11 representing an estimated incidence of 5.0 cases
per 100 000 maternities (95% CI 3.8 to 6.5).
Diagnosis and management
Characteristics of women with AFLP are shown in table 2. Of
particular note, 18% of the women were pregnant with twins.
Forty-two women (74%) were diagnosed antenatally, the
remainder postnatally (see fig 2). The diagnosis was made at a
median gestation of 36 weeks (range 22–40) in women
diagnosed antenatally. The majority of women diagnosed
antenatally (41/42, 98%) were delivered within 4 days of
diagnosis, with most (25/42, 60%) delivered within 24 h of
diagnosis. One woman, who had AFLP in a previous pregnancy,
was diagnosed 76 days before delivery, although she did not
meet the Swansea criteria until the week of delivery.
The women diagnosed postnatally delivered at a median
gestation of 36 weeks (range 28–39), and all were diagnosed
within 4 days of delivery. The majority (12/15, 80%) were
diagnosed within 48 h of delivery.
Forty-eight women (84%) experienced prodromal symptoms;
34 (60%) had vomiting, 32 (56%) had abdominal pain, 7 (12%)
had polydipsia and 5 (9%) had encephalopathy.
The diagnostic features of the women are shown in table 3.
Twenty-four (52%) of the 46 women tested had coagulopathy
in the absence of thrombocytopenia (platelet count ,10061012).
Forty-five women had an abdominal ultrasound scan per-
formed. Ascites or bright liver was seen in 12 women (27%). No
woman had a liver biopsy performed. Eleven women had labour
Figure 1 Case reporting and completeness of data collection.
AFLP, acute fatty liver of pregnancy.
Gut 2008;57:951–956. doi:10.1136/gut.2008.148676
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Table 1 Comparison of clinical assessment of acute Table 2 Characteristics of cases

fatty liver of pregnancy (AFLP) with use of the Swansea Number of women Estimated population
criteria in cases reported to the UK Obstetric Surveillance Characteristic (n = 57) (%) proportion12
System (n, %)
Primiparous 35 (61) 42%*
Swansea criteria
Non-white ethnicity 22 (39) NA
AFLP Not AFLP Age ,20 0 (0) 7%
Clinical AFLP 55 (90) 2 (3) Age >35 14 (25) 19%
assessment Not AFLP 0 (0) 4 (7) Single marital status 9 (16) NA
Twin pregnancy 10 (18) 1%
Smoked during pregnancy 9 (16) NA
induced (19%); 10 of the women diagnosed antenatally and one Professional or managerial 14 (29) NA
occupation
of the women diagnosed postnatally. Four of the women
History of pre-eclampsia 2 (4) NA
induced antenatally went on to have caesarean deliveries, two
History of AFLP 1 (2) NA
because of fetal distress and two for failed induction. Forty-two
BMI under 20 9 (20) NA
women in total were delivered by caesarean section (74%)
BMI >30 3 (7) NA
(table 4), with just over half (23) receiving a general anaesthetic Pre-eclampsia in the current 10 (18) NA
(GA) for the procedure. All three caesarean sections in labour in pregnancy
women diagnosed antenatally were carried out under GA for *Married women only.
fetal distress. Eighteen of the prelabour caesarean sections in AFLP, acute fatty liver of pregnancy; BMI, body mass index; NA, data not available
women diagnosed antenatally were carried out under GA; the from routine national statistics.
indications for GA were fetal distress (1), fetal distress in the
presence of maternal coagulopathy (3), maternal coagulopathy
alone (12) and maternal AFLP but with no documented was a prospective study of all pregnant women referred for
coagulopathy (2). Two caesarean sections were carried out biochemical testing of liver function in one unit in south west
under GA in women diagnosed with AFLP postnatally; these Wales. Each woman or her case records were reviewed by one of
were both for fetal distress. two doctors and a diagnosis made using the same criteria as we
used. The consequent estimate of disease incidence is much
higher than ours and than other estimates. This difference may
Outcomes be explained by the fact that this study was hospital-based;
One woman died (case fatality 1.8%, 95% CI 0% to 9.4%). The
affected women are likely to be referred to this tertiary centre
same woman received a liver transplant; no other transplants
from surrounding district hospitals. Hence the denominator
were undertaken. Sixteen women were reported to have other
number used to estimate the incidence almost certainly under-
severe morbidities, including eight with renal failure (two
estimated the true denominator of births from a number of
requiring dialysis) and four who required ventilation. Other co-
referral hospitals from which the cases were referred and reflects
morbidities reported in individual women were postpartum
the difficulties of estimating disease incidence from non-
haemorrhage, septicaemia, a cerebrovascular accident, convul-
population-based sources. It is also possible that more mildly
sions and multiorgan failure. Sixty percent of women (34) were
affected women were diagnosed with AFLP in the Welsh study.
admitted to intensive care for a median of 3 days (range 1–8);
This is supported by the observed laboratory values; the women
seven women were subsequently transferred to a specialist liver
unit. In total, 10 women (18%) were admitted to a specialist in our study had higher levels of transaminases and bilirubin. It
liver unit, where they were treated for a median of 9.5 days is possible that some cases in the UK were not notified to our
(range 4–44). study; however, we were not able to identify any additional
There were six stillbirths and one neonatal death amongst the cases through the three alternative reporting sources we used, and
67 infants, giving a perinatal mortality rate of 104 per 1000 total we feel it is unlikely that there was significant under-reporting.
births (95% CI 43 to 203).

Discussion
This is the largest prospective, population-based study to
estimate the incidence of AFLP, from an estimated cohort of
.1.1 million maternities. The UK incidence of AFLP as
estimated from this study is 5.0 cases per 100 000 maternities,
or approximately 1 case per 20 000 births. One other regional
population-based study in the UK,13 which included only three
cases of AFLP, reported an incidence of 6.1 cases per 100 000
maternities (95% CI 1.3 to 17.9 per 100 000), with which our
estimate is compatible. A second, hospital-based, study7
reported an incidence .20 times greater, at 111 cases per
100 000 births (95% CI 51 to 201 per 100 000), based on nine
cases of AFLP. The first study was in the context of a project to
report a variety of severe maternal morbidities in the South East
Thames region, identified through multiple sources including
maternity computer databases and labour ward records, as well
as staff (principally obstetric and midwifery) reporting. These Figure 2 Gestation at diagnosis (antenatal cases) or delivery (postnatal
methods are similar to those we employed. The second study cases).

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Hepatology

Table 3 Diagnostic features of women with acute fatty liver of pregnancy

Number of women with value outside of
normal range/n (%) Median highest* or lowest{ value (range)

Bilirubin 57/57 (100) 101 mmol/l* (17–677)

Glucose 43/55 (78) 3.1 mmol/l{ (1.0–8.2)
Urate 43/49 (88) 510 mmol* (49–830)
White cell count 56/57 (98) 20.76109* (8.5–46.5)
Platelet count 37/57 (65) 12261012{ (14–436)
Transaminases 57/57 (100) AST 310 IU/l* (37–3198)
ALT 300 IU/l* (21–1156)
Ammonia 2/4 (50) 43 mmol* (13–71)
Creatinine 33/57 (58) 169 mmol/l* (64–395)
Coagulopathy 40/46 (87) PT 22 s* (13–315)
APTT 49 s* (18–108)
ALT, alanine aminotransferase; APTT, activated partial thromboplastin time; AST, aspartate aminotransferase; PT, prothrombin
time.

Incidence estimates of AFLP from non-UK studies are also 95% CI 6.4 to 28.6). A similar proportion of women with twin
based on hospital case series.4–6 8 14 These estimates vary from 1 pregnancies has been observed in other studies,2 and an
in 4000 deliveries to 1 in 16 000 births. All are compatible with increased risk has also been observed in triplet pregnancies.17
our estimate due to their small case numbers and hence wide These observations are consistent with the quantified increase
confidence intervals, with the exception of the largest case in risk of related conditions such as pre-eclampsia observed in
series,5 a retrospective review of 28 cases from Los Angeles multiple pregnancies.18 Although this substantial increase in risk
County Hospital, USA between 1982 and 1997. These authors is associated with a rare condition, the observation is of
estimated that AFLP occurred in 15 of every 10 000 deliveries in particular importance in the light of increasing multiple
their population (95% CI 10.0 to 21.7). This difference may pregnancy rates following assisted reproductive techniques in
again be explained by referrals of women from outside the area the UK and elsewhere.12
to this tertiary hospital; questions have also been raised by other Women with AFLP were also more likely to be primiparous
authors15 as to whether all the cases included were definitely and older than the general population of women giving birth in
AFLP. England and Wales. There was also a suggestion of an inverse
AFLP was first reported as a unique pregnancy syndrome relationship between body mass index (BMI) and AFLP. In our
more than 60 years ago.16 However, there is no clearly cohort, 20% of women were classified as underweight with a
established clinical definition to allow consistent comparison BMI ,20, and 7% were obese with a BMI of >30. There are no
across studies and which allows the syndrome to be clearly national comparative data on BMI in pregnant women;
distinguished from related disorders such as HELLP syndrome. however, a database analysis of 325 000 women with singleton
We used the diagnostic criteria proposed by Ch’ng et al3 in pregnancies in the North West Thames region of London
Swansea. In our large, national cohort, there was substantial between 1989 and 199719 reported that 12% of women were
agreement between the clinical diagnosis of cases and the underweight and 10% obese. A comparison between these data
Swansea criteria; we therefore suggest that these diagnostic and ours would give an estimated OR of 1.4 for AFLP in
criteria are adopted as an objective measure for future studies, underweight women (95% CI 0.6 to 2.9) and 0.5 in obese
enabling more consistent interstudy comparisons. women (95% CI 0.1 to 1.6). This relationship has not been
Nearly 20% of the women in this cohort had twin observed before, and is the opposite of the relationship observed
pregnancies. In comparison, only 1% of maternities in England between BMI and pre-eclampsia.19 20 Because of the rarity of
and Wales in 2005 were twin pregnancies;12 we can therefore AFLP, our national study covering .1.1 million maternities
estimate that women with a twin pregnancy have a .14-fold identified only 57 cases and does not have the power to
increase in the risk of AFLP (estimated odds ratio (OR) 14.3, determine whether this is a statistically significant relationship
or just a chance finding. A multinational study would be
Table 4 Mode of delivery and stated indication for caesarean section in required to investigate this further.
women with acute fatty liver of pregnancy (AFLP) As would be anticipated, all the women in this series had
Mode of delivery/indication for Women diagnosed Women diagnosed raised transaminases and bilirubin levels, and 98% also had a
caesarean section antenatally n (%) postnatally n (%) raised white cell count. More than 80% had either raised urate
Spontaneous vaginal delivery 7 (17) 4 (27) or coagulopathy, or both. More than half of the women had
Instrumental delivery 4 (10) 0 (0) abnormal levels of each of blood glucose, platelets or creatinine,
Prelabour caesarean section or reported prodromal vomiting. Vigil-De Gracia, in a compar-
Maternal AFLP 20 0 ison of 75 women with HELLP syndrome and 10 women with
Maternal pre-eclampsia 0 2 AFLP,21 also found low glucose levels, raised bilirubin levels, a
Fetal distress 5 4 raised white blood cell count and prodromal vomiting to be
Breech 2 1 useful distinguishing features of AFLP in comparison with
Cephalopelvic disproportion 1 0 HELLP. Transaminase levels were not consistently significantly
Total 28 (67) 7 (47)
different between AFLP and HELLP patients in their study,
Caesarean section during labour
although transaminitis in AFLP is generally reported to be
Fetal distress 3 4
higher than in HELLP or pre-eclampsia.9 Other investigators
Total 3 (7) 4 (27)
have also found coagulopathy to be a useful distinguishing

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feature of AFLP.22 23 In our cohort, .50% of women tested had
coagulopathy without thrombocytopenia, also suggesting that
these features may be used to discriminate between the two
conditions.
Nearly 80% of the women with AFLP had an abdominal
ultrasound examination. Classical features of ascites or bright
liver were only seen in a quarter of these. This observation is
reflected in other studies which report that hepatic ultrasound
is not sufficiently sensitive or specific to make a definite
diagnosis.23 Diagnosis by CT scanning was not reported in our
study, although this has been recommended where the
diagnosis of AFLP remains unclear after ultrasound examina-
tion.9 We did not identify any women who underwent MRI
scanning; other series have suggested that the role of MRI still
has to be defined.24 Similarly, none of the women in our study
underwent a liver biopsy. This is unsurprising given the high
proportion of women with coagulopathy and current recom-
mendations that biopsy is not undertaken routinely.9
The current recommended management of AFLP is suppor-
tive,9 with expedited delivery in women diagnosed antenatally.
All the women in our study were diagnosed within 4 days of
delivery, with the exception of one woman who was diagnosed
very early in pregnancy with recurrent AFLP. This woman was
the only woman reported to have recurrent AFLP and, although
we cannot calculate a reliable recurrence rate from these data,
this suggests the rate is relatively low. There are no current
recommendations concerning the mode of delivery in women
with AFLP. Our data would suggest that current practice in the
UK favours caesarean section delivery. Three-quarters of the
women in our study were delivered by caesarean section; .80%
of caesarean deliveries were carried out electively before labour
onset. This high rate is perhaps surprising given the high rate of
reported coagulopathy, but may be a reflection of the perceived
severity of the condition. The choice of method of anaesthesia
for caesarean delivery is also difficult, with the options of GA
which has a potentially negative effect on hepatic encephalo-
pathy versus regional methods with increased risks of haema-
toma formation in the presence of coagulopathy.25 In this study,
half of the women had GA and half had regional anaesthesia for
caesarean section. No women who had regional anaesthesia
were reported to have had complications of the procedure,
including five women who received regional anaesthesia in the
presence of documented coagulopathy. Worsening encephalo-
pathy was not reported as a problem in any of the women who
had a GA.
The severe morbidity associated with AFLP is reflected in the
high proportion of women (65%) who were admitted to an
intensive care or specialist liver unit. One in six women was
admitted to a regional specialist liver unit. We are unable to
estimate what additional proportion was cared for within
obstetric high dependency units. However, only one woman
died, representing a case fatality rate of only 1.8%, although
with relatively small numbers involved the imprecision of this
estimate is reflected in the wide confidence intervals ranging
from 0% to 9%. There were no other deaths identified through
UKOSS or through the UK CEMACH. This case fatality rate is
lower than widely quoted rates of 12–18%,9 including a series
from a UK specialist liver unit with a case fatality of 13% (95%
CI 4% to 29%).26 There are several reasons possible for the better
maternal outcome we observed. All of the case series have
relatively small case numbers and therefore the confidence
intervals for their estimates of case fatality overlap with those
estimated from our national cohort study. In addition, as we
have previously noted, the majority of studies are hospital-based
Gut 2008;57:951–956. doi:10.1136/gut.2008.148676
Hepatology
series from specialist or tertiary referral units; the spectrum of
cases seen in these hospitals is likely to be more severe than that
of the population as a whole. It is also possible that care for
women with AFLP has improved over time, leading to a lower
case fatality in our study in comparison with older studies.
The outcome we observed for the fetus was poorer than the
maternal outcome, with a perinatal mortality rate of 104 per
1000 births, .10 times the overall national rate. Only one
neonatal death occurred, giving a neonatal case fatality rate
of 2%, which also compares favourably with quoted rates of
7–58%.9 The majority of the baby deaths in this study occurred
antepartum; six infants were stillborn (9%), which is similar to
or lower than rates quoted in other studies (7–66%).5 6 Further
investigation into earlier diagnosis and delivery may help to
determine whether any of these stillbirths are potentially
preventable.
Conclusion
We have identified the largest population-based cohort of
women with AFLP published to date, in a population of .1.1
million births. The diagnostic criteria proposed by Ch’ng et al3
agree substantially with clinical diagnosis in this series, and we
suggest that they are adopted for future studies to ensure
diagnostic consistency and thus comparability. The incidence
estimate from this study is lower than documented by earlier
hospital-based studies, but maternal and neonatal outcomes are
better than previously reported. The improvement in outcomes
may be due to improved care over time or due to improved case
ascertainment and the wider generalisability of the results of this
national population-based survey. Women with twin pregnancies
appear to be at higher risk of AFLP, but further studies are needed
to investigate the risk associated with low BMI.
Acknowledgements: This study would not have been possible without the
contribution and enthusiasm of the UKOSS reporting clinicians who notified cases and
completed the data collection forms. We would particularly like to thank Carole Harris
who administered the data collection. We would also like to acknowledge the
members of the UKOSS Steering Committee who provided advice throughout the
study and supplied useful comments on earlier drafts of the paper. The support of the
Royal College of Obstetricians and Gynaecologists, Royal College of Midwives,
Obstetric Anaesthetists Association, Faculty of Public Health, National Childbirth Trust
and the Confidential Enquiry into Maternal and Child Health has greatly contributed to
the success of UKOSS.
Funding: MK is funded by the National Coordinating Centre for Research Capacity
Development of the Department of Health. JJK was partially funded by a National
Public Health Career Scientist Award from the Department of Health and NHS R&D
(PHCS022). The National Perinatal Epidemiology Unit is funded by the Department of
Health in England. The views expressed in this paper are those of the authors and do
not necessarily reflect the views of the Department of Health
Competing interests: None.
Ethics approval: The UKOSS general methodology (04/MRE02/45) and this study
(04/MRE02/71) were approved by the London Multicentre Research Ethics Committee.
MK designed the study, coordinated data collection, coded the data, carried out the
analysis and wrote the first draft of the paper. CNP provided clinical input to the study
and contributed to the analysis and writing of the paper. JJK assisted with the design
of the study, supervised the data collection and analysis, and contributed to writing
the paper. PS assisted with data coding, and conducted validation of the data and
some analysis. PB had the original idea for the surveillance system, provided advice at
every stage of the study and contributed to the writing and editing of the paper. PB
will act as study guarantor.
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8. Reyes H, Sandoval L, Wainstein A, et al. Acute fatty liver of pregnancy: a clinical
study of 12 episodes in 11 patients. Gut 1994;35:101–6.
9. Rajasri AG, Srestha R, Mitchell J. Acute fatty liver of pregnancy (AFLP)—an
overview. J Obstet Gynaecol 2007;27237–40.
10. Knight M, Kurinczuk JJ, Tuffnell D, et al. The UK Obstetric Surveillance System for
rare disorders of pregnancy. Br J Obstet Gynaecol 2005;112:263–5.
11. Office for National Statistics. Key population and vital statistics 2005. Available at
http://www.statistics.gov.uk/downloads/theme_population/KPVS32_2005/
KPVS2005.pdf (accessed 10 April 2008).
12. Office for National Statistics. Birth statistics. Review of the Registrar General on
births and patterns of family building in England and Wales, 2005. London: Office for
National Statistics, 2006.
13. Waterstone M, Bewley S, Wolfe C. Incidence and predictors of severe obstetric
morbidity: case–control study. BMJ 2001;322:1089–93.
14. Pockros PJ, Peters RL, Reynolds TB. Idiopathic fatty liver of pregnancy: findings in
ten cases. Medicine (Baltimore) 1984;63:1–11.
15. Goodlin RC. Not all cases in a reported series were acute fatty liver of pregnancy.
Am J Obstet Gynecol 2000;182:1650.
16. Sheehan HL. The pathology of acute yellow atrophy and delayed chloroform
poisoning. J Obstet Gynecol 1940;47:49–62.
17. Davidson KM, Simpson LL, Knox TA, et al. Acute fatty liver of pregnancy in triplet
gestation. Obstet Gynecol 1998;91:806–8.
18. Duckitt K, Harrington D. Risk factors for pre-eclampsia at antenatal booking:
systematic review of controlled studies. BMJ 2005;330:565.
19. Sebire NJ, Jolly M, Harris JP et al. Maternal obesity and pregnancy outcome: a study of
287,213 pregnancies in London. Int J Obes Relat Metab Disord 2001;25:1175–82.
Editor’s quiz: GI snapshot
ANSWER
From the question on page 877
The computed tomography (CT) scan (Fig 1) shows the ‘‘hyper-
attenuating ring sign’’, characteristic of epiploic appendagitis,1
produced by a pericolonic fat-containing mass with surrounding
hyper-attenuation.
Epiploic appendages are fat-filled pockets on the serosal
surface of the colon. They can become acutely inflamed due to
either torsion on their pedicle or spontaneous venous throm-
bosis of draining veins. This results in the clinical syndrome
known as epiploic appendagitis (EA).
EA is a benign, self-limiting condition that can occur at any
age with a peak in the 5th decade.2 It presents with focal
peritonitis and a normal or moderately raised white cell count.
It has been reported in up to 7% of patients thought to have
diverticulitis and 1% of those thought to have appendicitis.3 4
EA is an important diagnosis to make as it may obviate
unnecessary surgical intervention and antibiotic therapy.
Complete resolution usually occurs within in 1 week5 with
simple analgesia.
Patient consent: Informed consent was obtained for the publication of this figure.
Gut 2008;57:956. doi:10.1136/gut.2007.128181a
956
20. Sebire NJ, Jolly M, Harris J, et al. Is maternal underweight really a risk factor for
adverse pregnancy outcome? A population-based study in London. Br J Obstet
Gynaecol 2001;108:61–6.
21. Vigil-De Gracia P. Acute fatty liver and HELLP syndrome: two distinct pregnancy
disorders. Int J Gynaecol Obstet 2001;73:215–20.
22. Knox TA, Olans LB. Liver disease in pregnancy. N Engl J Med 1996;335:569–76.
23. Usta IM, Barton JR, Amon EA, et al. Acute fatty liver of pregnancy: an experience in
the diagnosis and management of fourteen cases. Am J Obstet Gynecol
1994;171:1342–7.
24. Castro MA, Ouzounian JG, Colletti PM, et al. Radiologic studies in acute fatty liver of
pregnancy. A review of the literature and 19 new cases. J Reprod Med
1996;41:839–43.
25. Gregory TL, Hughes S, Coleman MA, et al. Acute fatty liver of pregnancy; three
cases and discussion of analgesia and anaesthesia. Int J Obstet Anesth
2007;16:175–9.
26. Pereira SP, O’Donohue J, Wendon J, et al. Maternal and perinatal outcome in
severe pregnancy-related liver disease. Hepatology 1997;26:1258–62.
Appendix 1: UKOSS steering committee
Catherine Nelson-Piercy (Chair), Guys and St Thomas’ Hospital; Jenny Furniss (Vice-
chair), Lay Member; Sabaratnam Arulkumaran, Royal College of Obstetricians and
Gynaecologists; Jean Chapple, Faculty of Public Health; Cynthia Clarkson, National
Childbirth Trust; Andrew Dawson, Nevill Hall Hospital; James Dornan, Royal College of
Obstetricians and Gynaecologists; Kate Fleming, Confidential Enquiry into Maternal and
Child Health; Shona Golightly, Confidential Enquiry into Maternal and Child Health; Ian
Greer, Hull York Medical School, York; Mervi Jokinen, Royal College of Midwives;
Gwyneth Lewis, Department of Health; Richard Lilford, Department of Public Health
and Epidemiology, University of Birmingham; Mary Mackintosh, Confidential Enquiry
into Maternal and Child Health; Margaret McGuire, Scottish Executive Health
Department; Richard Pebody, Health Protection Agency; Kate Taylor-Weetman,
National Childbirth Trust; Derek Tuffnell, Bradford Hospitals NHS Trust; James Walker,
National Patient Safety Agency; Steve Yentis, Chelsea and Westminster Hospital;
Members from the National Perinatal Epidemiology Unit: Carole Harris, Marian Knight,
Jennifer Kurinczuk, Peter Brocklehurst.
Figure 1 Arrow shows inflamed appendage.
REFERENCES
1. Rioux M, Langis P. Primary epiploic appendagitis: clinical, US and CT findings in 14
cases. Radiology 1994;191:523–6.
2. Carmicheal DH, Oran CH. Epiploic disorders. Arch Surg 1985;120:1167–72.
3. van Breda Vriesman AC. The hyperattenuating ring sign. Radiology 2003;226:556–7.
4. Molla E, Ripolles T, Martinez MJ, et al. Primary epiploic appendagitis: US and CT
findings. Eur Radiol 1998;8:435–8.
5. Breda Vriesman AC, Lohle PNM, Coerkamp EG, et al. Infarction of omentum and epiploic
appendage:diagnosis, epidemiology and natural history. Eur Radiol 1999;9:1886–92.
Gut July 2008 Vol 57 No 7
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A prospective national study of acute fatty

liver of pregnancy in the UK
M Knight, C Nelson-Piercy, J J Kurinczuk, et al.

Gut 2008 57: 951-956 originally published online March 10, 2008
doi: 10.1136/gut.2008.148676

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