Elevated Liver Function Tests as Predictors of Severe Maternal Outcomes in Women with Preeclampsia

By Sadia Chaudhary¹, Hafiza Ateeqa Mubarak², Anila Sabir³, Hina Sadaf⁴, Anas Khalil⁵, Zahid Mahmood⁵, Marium Shoukat¹, Farah Naz Tahir⁶

Doi: https://doi.org/10.36283/ziun-pjmd14-1/018

How to cite: Chaudhary S, Mubarak HA, Sabir A, Sadaf H, Khalil A, Mahmood Z, Shoukat M, Tahir FN Elevated Liver Function Tests as Predictors of Severe Maternal Outcomes in Women with Preeclampsia. Pak J Med Dent. 2025 Jan ;14(1): 116-120. Doi: https://doi.org/10.36283/ziun-pjmd14-1/018.

Received: Fri, August 30, 2024 Accepted: Tue, December 19, 2024 Published: Fri, January 10, 2025.

Background: Preeclampsia is a hypertensive disorder of pregnancy that ultimately led to high mortality and morbidity due to its complication HELP (Hemolysis, Elevated Liver Enzymes, and Low Platelet count), syndrome, and its association with elevated liver function tests. The main objective of this study is to investigate the association between elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) and severe maternal outcomes in women diagnosed with preeclampsia.

Methods: A cross-sectional study was conducted using convenience sampling at the Department of Obstetrics and Gynecology, Central Park Teaching Hospital Lahore Pakistan from April 18, 2024, to August 5, 2024. Group A with severe maternal outcome group eclampsia, HELLP, and group B without severe outcome. Liver function tests (AST, ALT, and ALP) were measured upon diagnosis. Severe maternal outcomes were statistically analyzed using SPSS version 26 applying a paired t-test.

Results: Among 300 women diagnosed with preeclampsia 90(30%) had increased LFTs and severe maternal outcomes were measured in 45 (50%) women with increased LFTs as compared to 30 (14.3%) women with normal LFTs(p=0.001). logistic regression analysis also showed that increased ALT (OR 3.7, 95%CI 2.01-7.02, p<0.001) and AST (OR 4.4, 95%CI 2.4-8.02, P<0.001) were significant predictors of severe maternal outcome while ALP was not associated with severe outcomes (OR 1.2, 95%CI 0.8-2.4, p=0.41).

Conclusion: This study provides new insight into the prognostic values of LFTs, which could increase their prognostic value and improve clinical decision-making and maternal care in preeclampsia.

Keywords: Preeclampsia, Liver Function Test, Maternal Mortality.

Preeclampsia is a critical hypertensive disorder and its complications cause maternal and perinatal mortality and morbidity globally and is characterized by the onset id hypertension and proteinuria after 20 weeks of gestation. Elevated levels of AST and ALT specifically reflect hepatocellular injury, while ALP can indicate cholestasis, albeit less sensitively in predicting severe outcomes¹. Other markers such as bilirubin, though relevant in hepatic dysfunction, were not included as they primarily indicate jaundice, which is not as commonly observed in the preeclampsia spectrum. Furthermore, physiological elevations in liver enzymes can occur during pregnancy due to increased hepatic load and altered hemodynamics. In Pakistan, preeclampsia is reported in approximately 7-10% of pregnancies, with severe outcomes such as eclampsia, HELLP syndrome (Hemolysis, Elevated Liver Enzymes, and Low Platelet count), and maternal death occurring in 10-14% of cases. This highlights the critical need for early identification of reliable prognostic markers, especially in LMICs, to improve maternal and fetal outcomes. By focusing on ALT, AST, and ALP, which are key indicators of liver dysfunction associated with systemic inflammation and endothelial damage in preeclampsia, this study aims to address the gap in predicting severe outcomes effectively. Despite the understanding of all mechanisms and advancements in obstetric care the complications are not entirely understood^2,3.  Recent data shows that increasing incidence of preeclampsia in low and middle-income countries where access to prenatal care is very limited⁴.The causes of preeclampsia are multifactorial and it involves placental implantation and a weak immune system in early pregnancy and ultimately leads to endothelial dysfunction that causes proteinuria and hypertension hallmark features of this disorder⁵. Critical organs affected by this condition are the liver and hepatic involvement damaged cells and raised transaminase levels that are seen in HELLP syndrome⁶. The main mechanism is hepatic microvascular injury and periportal necrosis due to which severe inflammatory response occurs and characterizes this disorder⁷. Liver function tests (LFTs) including alanine aminotransferases (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) are important components in the diagnostic workup for preeclampsia⁸. Increased levels of ALT and AST indicate hepatic injury while increased ALP shows cholestasis. However, interpretation of these tests during pregnancy can be challenging due to physiological changes that also affect liver enzymes⁹.

Recent studies focused on the prognostic significance of increased LFTs in preeclampsia however the precise predictive values of these tests have not been systematically evaluated. Advancements in imaging and biomarker technology research have enhanced our understanding of early management of preeclampsia. Doppler ultrasound is a standard tool for early diagnosis of preeclampsia and biomarkers such as placental-derived growth factor has shown promise in the prediction of the onset and progress of the disease¹⁰.

This study aims to fill the gap by systematically analyzing the association between elevated LFTs and severe maternal outcomes in preeclamptic women. By identifying reliable predictors of adverse outcomes, we hope to improve clinical decision-making power and improve maternal outcomes.

A cross-sectional study was conducted using convenience sampling at the Department of Obstetrics and Gynecology, Central Park Teaching Hospital Lahore Pakistan from April 18, 2024, to August 5, 2024, with ethical approval letter number (IRB# CPMC/IRB-No/ 1475) focused on pregnant women diagnosed with preeclampsia providing a comprehensive analysis of liver function test and their prognostic value in predicting severe maternal outcomes in preeclamptic women. Statistical significance was determined with a p-value threshold of p < 0.05. A total of 300 women diagnosed with preeclampsia were included in this study and they were divided into two groups based on severity of outcomes. The sample size was calculated using epi software considering a confidence level of 95%, a power of 80 %, and an expected frequency of severe maternal outcome 105 preeclampsia. Based on these parameters minimum size of sample size 300 was taken to ensure sufficient power to detect significant differences between these two groups. Group A with severe outcomes including eclampsia, HELLP syndrome, and maternal mortality. Group B non-severe outcome women who did not develop severe maternal outcomes. Inclusion criteria pregnant women diagnosed with preeclampsia after 20 weeks of gestation, with a single pregnancy. Women having any preexisting liver disease hypertension, or multiple pregnancies were excluded. Data were collected and LFTs were measured upon diagnosis of preeclampsia. Statistical analyses were performed using SPSS version 26. Descriptive statistics were used to summarize the demographic data and continuous variables were expressed as mean ±SD deviation. Comparative analysis was done using the independent t-test for continuous variables and the chi-square test for categorical variables. Logistic regression analysis was performed to see the predictive values of increased LFT for severe maternal outcomes.

Table 1: Demographic and Clinical Characteristics of the Study Population

The demographic data highlights the statistical difference in age, BMI, and prevalence of hypertension and higher values observed in group A with severe outcomes (Table 1). Statistical comparisons were made using the independent t-test for continuous variables and the chi-square test for categorical variables. * Represents a significant p-value at 0.05, ^**represents a significant p-value at 0.01, and ^*** represents a significant p-value at 0.001.

Table 2: Liver Function Tests and Maternal Outcomes

Increased ALT and AST levels were significantly associated with severe maternal outcomes including eclampsia, HELLP syndrome, and maternal mortality which indicates their importance as a potential predictor of adverse outcomes in preeclamptic women Table 2.

Table 3: Logistic Regression Analysis for Predicting Severe Maternal Outcomes

 Logistic regression analysis shows elevated AST and ALT levels are significant predictors of severe maternal outcomes in preeclamptic women Table 3.

This study provides strong evidence that elevated liver function tests specifically AST and ALT are significant predictors for monitoring maternal outcomes in preeclamptic women. This evidence suggests that LFTs can be used as early biomarkers for predicting outcomes in preeclamptic women allowing for timely intervention and improved maternal and fetal outcomes. The elevated levels of AST and ALT are consistent with findings from recent research¹¹.

Another study highlights that increased liver enzymes are strongly associated with maternal outcomes in preeclamptic patients including eclampsia and HELLP syndrome¹². This study also shows a significant odds ratio calculated in logistic regression analysis. This inflammation causes hepatic microvascular damage and periportal necrosis which manifests itself as elevated liver enzymes This study’s findings corroborate the supposed hypothesis that ALT and AST elevation showed hepatic involvement and systemic severity in preeclamptic women^13-16.

A less significant association between ALP and preeclampsia aligns with a recent study suggesting that ALP is a less sensitive indicator for severe maternal outcomes as compared to AAST and ALT ¹⁷. This finding aligns with existing literature that suggests ALP is less sensitive as an indicator of hepatocellular injury. AST and ALT are primarily found in liver cells and are released into the bloodstream when liver tissue is damaged. In contrast, ALP is also present in other tissues such as bones, placenta, and bile ducts^18-19. As a result, elevated ALP can occur due to factors unrelated to liver dysfunction, such as bone growth during pregnancy or placental activity, potentially confounding its use as a specific marker for hepatic involvement in preeclampsia. This broader tissue distribution may dilute the predictive strength of ALP in identifying severe maternal outcomes^20-21. The pathophysiological link between endothelial dysfunction, systemic inflammation, and hepatic involvement in preeclampsia remains a topic of considerable interest and ongoing research. This link underscores the potential for LFTs to be integrated as part of a more extensive maternal monitoring system that assesses both liver function and other indicators of systemic health ^22,23.

One aspect that deserves attention is the variability of LFT responses across different demographic groups. Emerging research suggests that ethnic and genetic factors may influence enzyme activity, potentially affecting how AST and ALT levels correlate with severe maternal outcomes in different populations. For example, studies have indicated that African American women may have a higher baseline level of certain liver enzymes due to genetic variations, which could impact the interpretation of LFTs in clinical settings. This calls for further investigation into whether demographic factors should be accounted for when interpreting LFT results during pregnancy^24,25,26.

Furthermore, understanding the molecular mechanisms behind elevated liver enzymes in preeclampsia may yield new insights into the disease’s pathogenesis and open doors to novel therapeutic strategies. The hepatic response in preeclampsia involves a complex interplay of cytokines, reactive oxygen species, and inflammatory pathways, which collectively contribute to organ damage. Targeting these pathways with anti-inflammatory or antioxidant therapies could offer a promising avenue for reducing the severity of the disease and improving maternal outcomes.

This study establishes that elevated ALT and AST levels are strong predictors of severe maternal outcomes in preeclamptic women, highlighting their potential as early biomarkers for timely intervention. By providing robust evidence on the prognostic value of LFTs, this research fills a crucial gap in the preeclampsia management literature. Future studies should explore the integration of these biomarkers into routine clinical practice and investigate other potential indicators to enhance prediction and risk stratification.

AST – Aspartate Aminotransferase

ALT – Alanine Aminotransferase

ALP – Alkaline Phosphatase

LFTs – Liver Function Tests

HELLP – Hemolysis, Elevated Liver Enzymes, and Low Platelet count

CRP – C-reactive Protein

BMI – Body Mass Index

SBP – Systolic Blood Pressure

DBP – Diastolic Blood Pressure

LMICs – Low- and Middle-Income Countries

OR – Odds Ratio

CI – Confidence Interval

SD – Standard Deviation

 p-value – Probability Value

None

None

None

The Ethical approval letter number (IRB# CPMC/IRB-No/ 1475) from Central Park Teaching Hospital Lahore, Pakistan.

All authors contributed equally

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