MohammadJafari R,MD1, 2, Saadaty N1, 4, Rezaei M1, 2,Haghighizadeh.MH3, MSC ,Ghasemi M, M.D1*.
1. Fertility, Infertility and Perinatology Research Center. Ahvaz Jundishapur University of
Medical Sciences, Ahvaz, Iran
2. Department of Gynecology, Imam Khomeini Hospital and Razi hospital, Ahwaz
3. Department of Biostatistics, Health school, Ahvaz Jundishapur University of Medical
Sciences. Ahvaz. Iran
4. School of Medicine, Department of Community Medicine
* Corresponding Address: P. O. Box: 6193673166 Dr. Marziyeh Ghasemi, general physician,
Fertility Infertility and Perinatology Research Center , Ahvaz Jundishapur University of Medical
Sciences, Ahvaz. Iran.
Email: gmarziyeh18@yahoo.com
Authors address:
1. Razieh mohammadjafari.
Department of Gynecology and Obstetrics, head of
Fertility,
Infertility and Perinatology Research Center. Ahvaz Jundishapur University of Medical Sciences,
Rmj41@yahoo.com
Ahvaz, Iran.
2. Nasrin Saadati - School of Medicine, Department of Community Medicine, Fertility Infertility and
Perinatology Research Center. Ahvaz Jundishapur University of Medical Sciences . Ahvaz. Iran
Nsaadaty@ajums.ac.ir
3. Misam resaei .
Medical Student of Ahvaz Jundishapur University of Medical Sciences,
Ahvaz. Iran. maysamrezaei@yahoo.com
4. Mohammad hossein haghighizade . MSc in Statistics , Department of Biostatistics, Health
school, Ahvaz Jundishapur University of Medical Sciences. Ahvaz. Iran.
Mhhaghighy@yahoo.com
5. Marziyeh Ghasemi. GP . Fertility Infertility and Perinatology Research Center ,Clinical
Research Development Center, Imam Khomeini Hospital , Ahvaz Jundishapur University of
Medical Sciences, Ahvaz. Iran. gmarziyeh18@yahoo.com
1
Acute fatty liver of pregnancy: Clinical, Paraclinical
2
Abstract
Introduction: Acute fatty liver of pregnancy is one of the serious complications of the pregnancy
period. Surveying the laboratory and clinical signs is effective in on time prognosis and fast
treatment of this illness.
Materials and Methods: The present study is a retrospective study conducted on records of 25
women with acute fatty liver of pregnancy in the years 2000- 2009. The patients were divided
into three groups under the age of 25, ages 25 to 35 and over age 35. The data were analyzed by
SPSS- 19. The qualitative variables were described by percentage, and the quantitative variables
were described by mean and standard deviation. The chi- square and T- tests were used for
analyzing the results.
Results: The patients were between 16 to 45 years old with the number of pregnancies between
one and four and they were 24 to 39 weeks pregnant with the average of 33.56 weeks. The forty
–four percent of the patients were nulliparous women and 56% were multiparous women. The
most prevalent clinical symptoms were nausea, vomiting, abdominal pain, headache, pruritus and
icterus. The laboratory signs included disorders of liver, coagulation, kidney, and hypoglycemia.
Based on the age, nausea and vomiting in the groups one and two, and abdominal pain (100%) in
the third group were the most prevalent symptom. No patient had fever, ascites and polydipsia.
There was one case of mother’s death with fetal death.
Discussion: In our study, the clinical and paraclinical signs of acute fatty liver of pregnancy were
mostly about the liver, coagulation, kidney and hypoglycemia disorders. Considering that the
patients mostly refer in three phases of clinical, laboratory and complications, it is essential to
evaluate the patients with suspected clinical symptoms especially nausea, vomiting and
abdominal pain.
Keyword: fatty liver, pregnancy, Clinical, Paraclinical
3
Introduction: Acute fatty liver of pregnancy is mostly with the first pregnancies in women
under 25 years old and is accompanied by the pregnancy with a male fetus (75%) (1, 2), and is
more prevalent is nulliparous women (3, 4). The incidence rate has been estimated from one in
10000 to one in 16000. Its maternal mortality and fetal mortality rates are 18% and 23%,
respectively (3). For the first time, it was described with hepatic microvascular steatosis in the
year 1940 (5). In this disease, no ethnical, regional varieties and diseases of pregnancy period are
effective. In addition, the immature girls and menopause women did not have it (4).
Physiopathologically, the most important factor for the illness is a mitochondrial disorders in the
oxidation of fatty acids and as a result their accumulation in the hepatocytes. Penetration of fatty
acids causes acute hepatic failure and signs that if not be diagnosed or treated early, it will cause
irreparable complications like the death of the mother and the embryo (4), cardiomyopathy,
neuropathy, myopathy, nonketonic hypoglycemia, hepatic failure and asphyxia (6). Although its
cause is not known, the viral, dietary and poisoning reasons are included (1, 2). The role of the
placenta is also important in this disease, because it is observed that after delivery, the liver’s
function highly returns to its normal condition (4, 7, and 8). Oxidation of fatty acids is normal in
these women in a natural situation, but in pathologic conditions, the embryo is not able to oxidize
the fatty acids (1,2) and by transferring them to mother, while the mother cannot metabolize the
extra fatty acids, causes and diffuses acute fatty liver of pregnancy.
The clinical signs and laboratory abnormalities of the acute fatty liver of pregnancy has been
mostly reported as unspecific, and the incidence rate is different and the differential diagnosis is
in the third trimester of pregnancy (9). Clinical signs usually begin from the second trimester (2)
and aggravates in the third trimester (10, 11). Moreover, the most prevalent signs are nausea and
vomiting reported to be between 70% and 75% (6, 12). Abdominal pain (50-80%), tenderness in
the right upper quadrant (2,13), fever, headache, backache, reflux, diarrhea, gastrointestinal
bleeding, hypertension, jaundice, acute tubular necrosis, hepatorenal syndrome (14), pancreatitis,
reduction in the liver’s size, hepatoencephalopathy, ascites (50%), coma, and reduction in the
level of consciousness are other mentioned clinical signs in different studies (2). The death rate
of mothers has been decreased because of the improvement in diagnosis and the supportive
actions, (6, 15, 16), as it has been reduced from 90% in the past to 20% (8, 17). Martin. Et all
(2008) and (Seyyed
4
Majidi MR and Vafaeimanesh,2012)show that the plasma exchange
especially in severe cases, cause remission of the laboratory signs and indexes (18). Although the
patient will be recovered after labor, its laboratory abnormalities remain after the delivery for a
period of time and rarely, progress to hepatic failure and liver transplantation (19).
Temmerman et al. (2009) reported the prevalence of laboratory abnormalities about 3 to 5%. As
the rise in some blood markers is used in the diagnosis of fatty liver, so, the prognosis of
laboratory disorders in pregnant women with acute fatty liver is effective in the treatment and in
the reduction of the complications of the mother and the embryo (3, 20). These laboratory
abnormalities include hypoglycemia, hyperbilirubinemia (1, 20); increase of the hepatic enzymes
(1, 20), alkaline phosphatase (1, 20), Kreatinin, Uric acid; metabolic disorders (21), lactic
acidosis, reduction of coagulation factors (22), an increase in the prothrombin time (PT) (20),
low fibrinogen and antithrombin (22). Other laboratory abnormalities are reduction of platelet
life, leukocytosis, neutrophilia, thrombocytopenia, norm oblasts; giant platelet, basophilic
stippling, breaks down of blood cells (RBC) (1). Besides determining the most basic clinical and
in-vitro results of acute fatty liver of pregnancy in pregnant women, properly analyze of the liver
function test (LFT), and recognizing different clinical and laboratory abnormalities in early
phases (9) can be effective in proper care and can reduce the complications of the illness (20, 23,
24). So this study was conducted to survey the demographic characteristics;, clinical and
laboratory signs on pregnant women with acute fatty liver in Imam Khomeini and Razi hospitals
of Ahvaz during the years 2000- 2009.
Materials and Methods:
The studied population: The studied society was the whole medical records (25 persons) of
pregnant women with acute fatty liver of pregnancy in Imam Khomeini and Razi hospitals of
Ahvaz in the years 2000- 2009, which was confirmed by the ethic committee of the Ahvaz
Jundishapur University of Medical Sciences. The patients entered the study with their agreement.
A questionnaire, including demographic characteristics, and clinical and laboratory findings
(symptom and sign) was arranged, and the data of the records were included, too. Designing the
questionnaire was according to the opinions of a number of sociomedical experts, gynecologists,
and based on the context validity by the referral to the similar studies. The patients were divided
into three groups under age 25, ages 25 to 35 and over age 35. The data of each group were
analyzed separately.
5
Statistical analysis: This study was a retrospective cross- sectional and qualitative study. after
collecting and coding the data, SPSS- 19 analyzed them. The qualitative variables description
was by percentage; and the mean and SD quantitative variables were described by. Chi-square
and T- tests were used for analyzing the results.
Results:
We surveyed the clinical and Para clinical signs of acute fatty liver of pregnancy (Table 1 and 2).
The age of patients in this study was between 16 and 45 and the mean age was 27.2 (S= 7.05).
Eight patients were under age 25 (32%), 14 patients were between ages 25 and 35 (56%) and
three patients were over age 35 (12%). The number of pregnancies was between one and four
and the mean was 1.96 (S=1.02). They were 24 to 39 weeks pregnant with the average of 33.56
weeks. As one patient was between 14 and 27 (4%) and the rest were over 27 weeks (96%). 11
patients were nulliparaous (44%) and 14 patients were multiparous (56%). As six persons
experienced the second pregnancy (24%), six patients experienced the third (24%) and two
persons experienced more than three pregnancies (12%) . The clinical symptoms were nausea
and vomiting 44%, abdominal pain 36%, headache 20%, pruritus 16%, and icterus 8%,
respectively (Table 1). In the women under age 25 nausea and vomiting 27.5%, abdominal
pain25%, headache 12.5% and in the group between the ages 25 and 35 nausea and vomiting
50%, abdominal pain and headache 28.6% and in the group over age 35 abdominal pain 100%,
nausea and vomiting 33% were observed, respectively. No patient were with fever, ascites and
polydipsia.The frequencies of Para clinical signs in percentage were hyperbilirubinemia 44% ;
increase in PT 32%, thrombocytopenia 24%; hypoglycemia and increase of alkaline phosphatase
and kreatinin each 20%; prothrombin activity 16%, increase of albumin 12%; increase of partial
thromboplastin time (PTT) and leukocytosis 8%; neutrophilia and uric acid’s increase 4% (Table
2). Only a 39- year- old mother died with fetal death. Her clinical and paraclinical signs included
abdominal pain, leukocytosis, thrombocytopenia; increase in alkaline phosphatase and kreatinin;
coagulation disorder, and increase in bilirubin; 64% of the women had medico illness and 36%
did not have any. In this study hyperbilirubinemia (P-value= 0.010), hypoglycemia (P- value=
0.005), and pruritus (P-value= 0.014) were significant in nulliparaous women.
6
Table 1: The clinical signs of acute fatty liver of pregnancy according to the age (n=25)
Clinical signs
NumberGroup 1
Group 2
Group 3
Percentage
Nausea and
11- 44%
3
7
1
vomiting
Abdominal pain
9- 36%
2
4
3
Headache
5- 20%
1
4
0
Pruritus
4- 16%
2
2
0
Icterus
2- 8%
1
1
0
Impatience
1- 4%
0
1
0
Lethargy
1- 4%
0
1
0
Fatigue
1- 4%
0
1
0
Polyuria
1- 4%
1
0
0
Table 2: Laboratory signs according to age (n=25)
Laboratory signs
NumberGroup 1
Percentage
Hyperbilirobinemia
11- 44%
3
PT
8- 32%
2
Thrombocytopenia
6- 24%
2
Alkaline
5- 20%
1
phosphatase
Kreatinin
5- 20%
2
Hypoglycemia
5- 20%
3
Prothrombin
4- 16%
0
activity
Albumin
3- 12%
1
PTT
2- 8%
0
Leuko cytosis
2- 8%
1
Neutrophilia
1- 4%
1
Uric acid
1- 4%
1
7
Group 2
Group 3
6
4
3
3
2
2
1
1
2
1
2
1
1
2
2
0
0
0
0
0
2
1
0
0
Discussion:
Acute fatty liver of pregnancy is a pathological process related to pregnancy period without
known reasons, which does not have very specific signs (24). It has a wide spectrum of clinical
and laboratory signs. It sometimes becomes so serious that needs physician’s intervention. All
the physicians, gynecology staff and carers are suggested to survey the clinical and laboratory
signs before labor. Moreover, after observing suspecting signs, proper surveys should be
conducted for final diagnosis.
This study was aimed to survey clinical and laboratory signs of women with acute fatty liver of
pregnancy. Nausea, vomiting, abdominal pain, headache, pruritus and icterus are the most
prevalent clinical signs in our study, respectively. These signs are more prevalent in the group
aged between 25 and 35 compared to the other two groups, probably due to more number of
women of this group compared to the other two groups (Table 1). In most similar studies, nausea
and vomiting were the most prevalent clinical signs. As the studies of Fesenmeier MF et al. (6),
Vigil- de Gracia et al. (12), and C L Ch̕ng et al. (23), which were similar to ours from this
viewpoint, it seems that due to the difference in the sample sizes of this study and Fesenmeier
MFs̕ study, the prevalence is more than ours is. The on time diagnosis of this finding has special
importance because of the differential diagnosis with gastrointestinal signs in the second and
third trimester of pregnancy, and health carers should pay attention to this point while visiting
pregnant women.
However, our study is retrospective and C L Ch̕s study (23) is prospective, the abdominal pain is
the second most prevalent sign in two studies. In our study, the frequency percentage of
abdominal pain rises as age increases, as 100% of women over age 35 years had abdominal pain.
This result shows the importance of this sign compared to other clinical signs in this age group.
We suggest surveying this result more by bigger sample size in a prospective study. In our study,
laboratory abnormalities exist that is disorders of the liver, coagulation and kidney; and
hyperglycemia in order of prevalence, which is more similar to the study of lau Hui- hsuan (24).
Nevertheless, Vigil- de Garcia’s study (12), found disorders of the kidney, coagulation, liver and
hypoglycemia.To survey this difference a bigger study with more sample size is necessary. In our
study, comparing all multiparaous women (56%) with nulliparaous women (44%), the
multiparaous women were affected with the acute fatty liver disease (AFLD) more. However,
comparing the number of pregnancies, nulliparaous women
8
more than multiparaous women,
have been diagnosed with the acute fatty liver of pregnancy
Although the type and the sample size of our study are different from the studies of Hui- Husan
and Michael f.Fesenmerier, the results are consistent. It seems that fatty liver of pregnancy is
more related to the number of pregnancies. In addition, the most prevalent laboratory signs are
the same in two groups of multiparaous and nulliparaous women. In addition, the most clinical
symptom in nulliparaous women is pruritus, and in multiparaous women are nausea, vomiting
and abdominal pain.
In the present study, the prevalent age of the disease is between 25 and 35 years old, but in the
studies of Hui- Husan and Michael f. Fesenmerier (1 and 2); it is under age 25 which probably
this difference is because the pregnancies under age 25 had been more prevalent in the year
1999-1992.
Our study showed that the clinical signs begin from the second trimester and aggravates in the
third trimester of pregnancy; but HinHinko et al. (10) believe that the signs appear in the third
trimester or at the beginning of the pregnancy period. It seems that this disease appears from the
late of the second trimester to the beginning of the post labor period.
In our study, there was one case of neonate and mother’s death. In Michael f.Fesenmerier’s
study, there were two cases of mother’s death and three cases of embryo’s death. Because the
signs of this disease are unspecific, the mortality probably is due to not on timely diagnosis of
the disease.
Conclusion: We found a triad for diagnosis of acute fatty liver of pregnancy in pregnant women
referring to clinics, Para clinical, clinical and complication phase. Awareness of therapeutic
attendants and accurate analysis of pregnant women with suspected clinical symptoms especially
nausea, vomiting and abdominal pain from the late of the second trimester at the beginning of the
post labor period is suggested to prevent the dangerous complications of this disease.
9
Acknowledgement: This study was a thesis presented for the degree of Medical Doctor (MD) of
Mr. Rezaei .M, which was supported by Ahvaz Jundishapur University of Medical Sciences. The
authors sincerely appreciate the Clinical Research Development Centre of Imam Khomeini
Hospital of Ahvaz for their support. The authors appreciate and thank the Research Deputy vicechancellor for research affairs of the Ahvaz Jundishapur University of Medical Sciences,
particularly the Research Consultation Centre (RCC) for technical support.
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