Maternal Serum SIRT1 Concentrations in Intrahepatic Cholestasis of Pregnancy: Limited Diagnostic Utility in a Prospective Case-Control Study.

Objective

To investigate maternal serum silent information regulator-2 protein 1 (SIRT1) levels in pregnancies complicated by intrahepatic cholestasis of pregnancy (ICP) and evaluate their diagnostic performance.

Methods

This prospective case-control study included 44 pregnant women with ICP and 44 healthy pregnant controls matched according to gestational age at blood sampling and maternal body mass index. Maternal serum SIRT1 concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Clinical, laboratory, and obstetric outcomes were compared between groups. Correlation, receiver operating characteristic (ROC) curve, and exploratory multivariable logistic regression analyses were performed.

Results

Maternal serum SIRT1 levels were significantly lower in the ICP group compared with controls [1.06 (1.05) ng/mL vs. 1.54 (1.74) ng/mL, p = 0.005]. ROC analysis demonstrated modest discriminative performance of maternal serum SIRT1 alone for identifying ICP (AUC: 0.674, 95% CI: 0.559-0.788, p = 0.005). A SIRT1 cut-off value of ≤1.28 ng/mL yielded 63.6% sensitivity and 60.5% specificity. In contrast, ALT alone showed excellent discriminative performance (AUC: 0.927, 95% CI: 0.860-0.995, p < 0.001). Combined ROC analyses demonstrated further improvement with the ALT + albumin model (AUC: 0.962, 95% CI: 0.925-0.999), whereas addition of SIRT1 resulted in only a minimal incremental increase in AUC to 0.966 (95% CI: 0.933-0.998). Maternal serum SIRT1 concentrations were not independently associated with ICP after adjustment for laboratory parameters.

Conclusions

Although maternal serum SIRT1 levels were significantly reduced in pregnancies complicated by ICP, their diagnostic performance was modest and provided minimal incremental value beyond conventional biochemical markers. Nevertheless, reduced maternal serum SIRT1 concentrations may support the involvement of inflammatory and oxidative stress-related pathways in ICP pathophysiology and warrant further mechanistic investigation.