Soluble fms-like tyrosine kinase 1 (sFlt-1): A novel biochemical marker for acute fatty liver of pregnancy.

Abstract

Acute fatty liver of pregnancy (AFLP) substantially contributes to maternal and neonatal morbidity and mortality. Other liver-associated pregnancy complications such as preeclampsia-associated HELLP (hemolysis, elevated liver enzyme, low platelet) syndrome may be difficult to differentiate from AFLP as these diseases overlap with regard to multiple clinical and laboratory features. The aim of this study was to investigate angiogenic profiles by measuring soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) in pregnancies compromised by AFLP and to compare them with those complicated by HELLP syndrome. Pregnant women affected by AFLP or HELLP syndrome were enrolled. The study population of women with HELLP syndrome was part of a larger data collection obtained in our clinic that has been used for previous work. Patients' angiogenic profiles were assessed by measuring sFlt-1 and PlGF serum levels. To assess the diagnostic potential of these angiogenic markers in AFLP, as well as discriminating it from HELLP syndrome, non-parametric tests were used and receiver operating curves were calculated. Six women with AFLP and 48 women with HELLP syndrome were included in the study. Patients with AFLP showed significantly higher sFlt-1 levels (median: 57570pg/mL; range 31609-147170pg/mL) than patients with HELLP syndrome (9713pg/mL; 1348-30781pg/mL; p<0.001). PlGF serum levels were higher in patients with AFLP compared with those with HELLP syndrome (197pg/mL; 127-487pg/mL vs. 40pg/mL; 9-644pg/mL, respectively; p<0.01). sFlt-1/PlGF ratios were not significantly different between AFLP and HELLP syndrome patients (192; 157-1159 vs. 232; 3-948, respectively; NS). In our study population, an sFlt-1 cut-off value of 31100pg/mL allowed differentiation between these two diseases with a sensitivity and specificity of 100%. A linear correlation was found between the cumulative numbers of Swansea criteria and sFlt-1 serum levels (r=0.97; p<0.01). AFLP is associated with very high sFlt-1 serum levels in particular in women fulfilling eight or more Swansea criteria. Besides the suggested Swansea criteria to diagnose AFLP, an sFlt-1 value above 31100pg/mL may be an additional biochemical feature improving discrimination between AFLP and HELLP syndrome. However, because of the small number of pregnancies affected by AFLP included in this work further studies are needed to corroborate our findings.