First-Trimester Hepatobiliary and Inflammatory Composite Indices as Candidate Markers for Subsequent Intrahepatic Cholestasis of Pregnancy: A Case–Control Study

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Background/Objectives: Intrahepatic cholestasis of pregnancy (ICP) typically becomes apparent in the second or third trimester, although hepatobiliary susceptibility may be present earlier. We evaluated associations between first-trimester hepatobiliary and inflammatory composite indices and subsequent ICP. Methods: This retrospective case–control study included 96 women who developed ICP and 197 controls. The S-index, De Ritis ratio, albumin–bilirubin score (ALBI), gamma-glutamyl transferase-to-platelet ratio (GPR), transaminase complex-to-platelet ratio (TACPR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and systemic inflammation response index (SIRI) were calculated from measurements from 8 + 0 to 13 + 6 weeks of gestation. ROC analysis, DeLong comparisons, and multivariable logistic regression were performed. Results: Hepatobiliary indices showed numerically higher AUCs than inflammatory indices. The S-index had the numerically highest observed AUC (0.808; 95% CI, 0.727–0.889), with 66.7% sensitivity and 95.1% specificity at a cutoff of ≥0.045. The De Ritis ratio had an AUC of 0.717. DeLong comparisons showed that the S-index had a significantly higher AUC than ALBI but did not differ significantly from the De Ritis ratio, GPR or TACPR. After adjustment for age, body mass index and gestational age at blood sampling, the S-index and De Ritis ratio remained associated with ICP. No inflammatory index had an AUC significantly greater than 0.50. Conclusions: First-trimester hepatobiliary indices, including the S-index and De Ritis ratio, were associated with subsequent ICP and may reflect an early hepatobiliary pattern. These indices warrant prospective validation as adjunctive markers for ICP risk stratification and for identifying women who may benefit from closer surveillance and timely or repeated bile acid testing.