|ORIGINAL RESEARCH REPORTS
|Year : 2014 | Volume
| Issue : 1 | Page : 7-11
Liver function tests in Nigerian women with severe preeclampsia
Ifeoma C Udenze1, Adesina P Arikawe2, Elaine C Azinge1, Ephraim U Egbuagha1
1 Department of Clinical Pathology, Faculty of Clinical Sciences, University of Lagos, Idi Araba, Lagos, Nigeria
2 Department of Physiology, Faculty of Basic Medical Sciences, University of Lagos, Idi Araba, Lagos, Nigeria
|Date of Web Publication||21-Jul-2014|
Ifeoma C Udenze
Department of Clinical Pathology, Faculty of Clinical Sciences, College of Medicine of the University of Lagos, Idi Araba, Lagos 12003, Lagos
Source of Support: None, Conflict of Interest: None
Background: Preeclampsia is a common complication of pregnancy with high maternal and perinatal morbidity and mortality. The new American College of Obstetricians and Gynecologists (ACOG) guideline now includes elevation of liver enzymes as a criterion for the diagnosis of preeclampsia. Objectives: The objectives of this study is to compare liver function tests in preeclampsia and normotensive pregnancy and determine their relationship with systolic and diastolic blood pressure, plasma creatinine, and uric acid levels in Nigerian women with severe preeclampsia. Materials and Methods: This was a case-control study of 46 women with severe preeclampsia and 21 pregnant women as controls. These women attended the Antenatal Clinic at the Lagos University Teaching Hospital, Lagos where women were consecutively recruited. Results: There was a statistically significant difference in the systolic blood pressure (P = 0.002), diastolic blood pressure (P = 0.004), plasma creatinine (P = 0.007), uric acid (P = 0.0001), plasma albumin (P = 0.029), alkaline phosphatase (ALP) (P = 0.0001), aspartate aminotransferase (AST) (P = 0.0001), γ-glutamyl transferase (GGT) (P = 0.035), and unconjugated bilirubin (P = 0.023) between the group with severe preeclampsia and the normotensive pregnancy control group. Alanine aminotransferase (ALT) was however not significantly elevated. AST elevation was the most common anomaly in severe preeclampsia occurring in 54.3% of cases. There was no association between systolic and diastolic blood pressure, plasma creatinine, and uric acid in severe preeclampsia with and without abnormal liver function tests. Conclusion: Elevation of AST, ALP, GGT, and unconjugated bilirubin are common in Nigerian women with severe preeclampsia but may not all be of liver origin. These parameters were also not associated with indices of disease severity. The use of liver enzyme concentrations as adjuncts in preeclampsia diagnosis should be applied with caution in Nigerian women with preeclampsia.
Keywords: Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, severe preeclampsia, γ-glutamyl transferase
|How to cite this article:|
Udenze IC, Arikawe AP, Azinge EC, Egbuagha EU. Liver function tests in Nigerian women with severe preeclampsia. J Clin Sci 2014;11:7-11
| Introduction|| |
Preeclampsia is a multisystem disorder affecting the central nervous system, the liver, the kidney, and the coagulation system among others.  It occurs in a pregnant woman who develops new onset hypertension and proteinuria after 20 weeks gestation.  Preeclampsia complicates about 5-10% of pregnancies and is associated with maternal and perinatal mortality and morbidity. ,,, Until most recently, the diagnosis of preeclampsia is made when a pregnant woman, after 20 weeks gestation, presents with proteinuria (≥300 mg/24 hours or ≥100 mg/L, equivalent to ≥2+ on dipstix urinalysis) on at least two random urine samples at least 4-6 hours apart but not more than 7 days apart, and systolic blood pressure ≥140 mmHg or a diastolic blood pressure ≥90 mmHg measured using an appropriate sized cuff repeatable at least 4-6 hours apart but not more than 7 days apart and a remission of these symptoms by 6 weeks postpartum. , Severe preeclampsia is associated with systolic blood pressure ≥160 mmHg, or diastolic blood pressure ≥110 mmHg diastolic, with proteinuria ≥5 g in a 24-hour urine collection. 
A recent review by the American College of Obstetricians and Gynecologists (ACOG) has introduced a few changes. It is now possible to make a diagnosis of preeclampsia in the absence of proteinuria that meets or exceeds the diagnostic threshold in a pregnant woman with hypertension plus any of the following: New onset thrombocytopenia, impaired liver function, renal insufficiency, pulmonary edema, or visual or cerebral disturbances.  Impaired liver function was defined as liver transaminases elevated to twice the normal concentration.  Abnormalities of the liver in preeclampsia has been documented in literature.  Liver Function Test (LFT) abnormalities occur in 3% of pregnancies, and preeclampsia is the most frequent cause.  The pathophysiologic changes in preeclampsia include disturbances in the vascular development of the placenta resulting in placental hypoperfusion and ischemia. The damaged placenta, in turn, secretes a wide range of anti-angiogenic factors into the maternal circulation that is believed to cause a systemic endothelial cell dysfunction and microangiopathy.  In the liver, these endothelial damages can cause periportal hemorrhagic necrosis with the release of hepatocellular enzymes into circulation. The hemolysis elevated liver enzymes and low platelets (HELLP) syndrome which complicates severe preeclampsia is also a consequence of liver affectation in preeclampsia.  In preeclampsia, an elevation in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels have been noted and hyperbilirubinemia may also occur. , The role of liver enzymes in predicting preeclampsia has been studied  and their relationship with disease severity has been investigated.  However, there is scarcity of data from the Nigerian population. With a new role for the liver in diagnosing preeclampsia, it becomes important to evaluate liver function tests in Nigerian women with preeclampsia and their relationship with disease severity prior to the adoption of this guideline for the population.
| Materials and Methods|| |
Pregnant women who were attending the Antenatal Clinic at the Lagos University Teaching Hospital, Lagos, Nigeria diagnosed with severe preeclampsia and gestational age matched pregnant women without hypertension or proteinuria as controls were consecutively recruited into the study. Severe preeclampsia was defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥110 mmHg and ≥2+ of proteinuria. , Pregnant women with multiple gestation were excluded from the study. Approval of the study protocol was obtained from The Research and Ethics Committee of the hospital. Patients who consented to participate in the study signed an informed consent form. Information obtained included demographic information including age, ethnicity, level of education, marital status, medical history, and history of index and previous pregnancies, using a structured questionnaire.
Pregnancy was dated from the last menstrual period and confirmed by clinical examination and ultrasonography scanning. Blood was collected for biochemical analysis. Plasma ALT, AST, alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), direct and total bilirubin were estimated in plasma with reagents from Randox Laboratories Limited Antrim, UK using spectrophotometric methods. 
| Results|| |
The study participants did not differ in their socio demographic characteristics. Ninety-eight percent (98%) of the group with preeclampsia were married and 2% were unmarried. In the normal pregnancy control group, 95% were married and 5% unmarried. Forty-nine percent (49%) of the group with preeclampsia were of the Yoruba tribe, 42% were Igbo, and 9% were from other tribes. In the normal pregnancy control group, 48% were Yoruba, 43% were Igbo, and 9% were from other tribes. The mean gestational age for both groups was 32 weeks. Neither the study participants differed in their age distribution nor in their educational status. [Figure 1] and [Figure 2] show the age distribution and educational levels of the study participants.
|Figure 1: Age distribution of participants with and without preeclampsia. The preeclamptic group and the normal pregnancy control group did not differ in their age distribution (P = 0.569)|
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|Figure 2: Level of education of the participants, with and without preeclampsia. The preeclamptic group and the normal pregnancy control group did not differ in their level of education (P = 0.217)|
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When the preeclamptic group was classified based on an elevated level of at least one liver enzyme, there was no difference in the markers of disease severity (systolic and diastolic blood pressures, serum creatinine, and uric acid levels) between preeclamptics with normal and abnormal liver function.
| Discussion|| |
This study reports a significant increase in plasma levels of AST, ALP, GGT, and unconjugated bilirubin in women with severe preeclampsia compared to normotensive pregnancy controls, but there was no significant difference in plasma ALT level [Table 1]. Increased plasma levels of AST, ALP, ALT, GGT, and unconjugated bilirubin in severe preeclampsia was also found by Munazza et al.,  Dermir et al., and Garling et al.,  working in the Middle East and Europe. This study differed in not finding significantly increased plasma ALT levels in severe preeclampsia. The observed difference may be racially determined.
|Table 1: Clinical and laboratory characteristics of women with severe preeclampsia compared to controls |
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Clinical significance of elevated levels of plasma AST, ALT, ALP, GGT, and bilirubin is in the assessment of liver disease; however, other factors occurring in the setting of preeclampsia can also cause increases in the plasma level of these enzymes. The transaminases, ALT, and AST are markers of hepatocellular disease. ALT is found mainly in the liver with lesser amounts occurring in the skeletal muscle and kidneys, whereas AST is widely distributed in equal amounts in the heart, skeletal muscle, and liver with smaller amounts in erythrocytes; hence, ALT is considered more liver specific than AST.  In liver disease, ALT elevation is expected to be higher than AST elevation.  The increased plasma levels of AST found in this study, without a similar increase in ALT levels between the study groups suggest other sources of AST elevation beyond the liver. Hemolysis and renal insufficiency which occur in severe preeclampsia , could contribute to the AST elevation found in this study.
ALP elevation is used clinically to differentiate hepatobiliary disease from osteogenic bone disease.  Both ALP and GGT are markers of extrahepatic and intrahepatic cholestasis. GGT is not elevated in bone disorders and elevation of both enzymes as found in this study would suggest the presence of hepatobiliary affectation in women with severe preeclampsia. Placental ischemia and endothelial dysfunction, both of which are linked to the pathophysiology of preeclampsia,  could also contribute to the elevation of ALP and GGT observed in this study.
This study showed a decrease in conjugated bilirubin with a corresponding increase in unconjugated bilirubin in severe preeclampsia compared to controls [Table 1]. These results in conjugated and unconjugated bilirubin is in line with other reports. , The decreased conjugation of bilirubin would suggest affectation of the secretory and excretory function of the liver in severe preeclampsia. Hemolysis could also contribute to the increased unconjugated bilirubin observed.  Furthermore, this study also showed decreased plasma albumin levels in preeclampsa compared to normotensive pregnancy controls [Table 1]. Gojnic et al.,  in their study found hypoalbuminemia in severe preeclampsia, which correlated with disease severity. These findings would suggest a reduction in the synthetic function of the liver in severe preeclampsia. Salako et al.,  however reported increased plasma albumin levels in preeclampsia compared to normotensive controls. The observed differences may be because the Salako study consisted of only primigravidae before 20 weeks gestation, whereas this study involved also multigravidae with a mean gestational age of 32 weeks.
In this study, 70% of the group with severe preeclampsia had at least an abnormality of a liver enzyme [Table 2]. Plasma AST elevation was the most common enzyme anomaly occurring in 54.3% of women with severe preeclampsia [Table 3]. Only 8.7% of the severe preeclampsia group had an elevated ALT level [Table 3]. Girling et al.,  reported a prevalence of 54% for abnormal LFT in preeclampsia, and Demir et al.,  reported AST elevation occurring in 21% of the group with preeclampsia. The observed differences in prevalence rates may be because the Demir  and Girling  studies included women with both mild and severe preeclampsia.
|Table 2: Clinical and laboratory characteristics of preeclamptics with normal and abnormal liver function tests |
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When the new ACOG guideline requiring elevation of ALT and AST above twice the upper reference value was applied, only 17.4% of the women with severe preeclampsia were identified [Table 4].
This study found no association between abnormal LFT and indices of disease severity: Hypertension, plasma creatinine, and uric acid in preeclampsia [Table 2]. One study found an association between abnormal LFT and renal compromise but not blood pressure,  another study found no association between complicated and uncomplicated preeclampsia and renal insufficiency.  The varied findings may be because some studies did not discriminate between mild and severe preeclampsia and the definitions of complicated preeclampsia also differed between studies. In this study despite significant differences in plasma enzyme levels between severe preeclamptics with and without abnormal liver function, the systolic blood pressure (SBP), diastolic blood pressure (DBP), creatinine and uric acid levels remained similar in both groups.
| Conclusion|| |
Severe preeclampsia is associated with abnormalities of liver function tests. However, other pathologies in preeclampsia, beyond the liver, may contribute to this. The abnormal liver function tests were not associated with disease severity in severe preeclampsia. Interpretation of liver function tests should be with caution in Nigerian women with severe preeclampsia.
Limitations of the study
Cost of procurement of reagents and materials used for the study
High noncompliance rate of subjects approached to consent for the study
Relatively small sample size used for the study (50 subjects with 50 controls was the minimum significant sample size required for the study).
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]