Cholestatic Liver Dysfunction and Systemic Congestion in Acute Heart Failure: Prognostic Interaction Between Alkaline Phosphatase and CA125 ​

<title>Abstract</title> <p> <bold>Background</bold> : Congestive hepatopathy is a recognized complication of right-sided venous congestion in acute heart failure (AHF). Alkaline phosphatase (AP) reflects cholestatic liver dysfunction, while CA125 serves as a surrogate of systemic serosal congestion. We aimed to evaluate the prognostic impact of AP and its interaction with CA125 in patients hospitalized for AHF. <bold>Methods</bold> : We conducted a retrospective observational study including 735 patients hospitalized for AHF. Patients were classified according to AP and CA125 levels using predefined cutoffs (AP &gt;141 U/L; CA125 &gt;54.6 U/mL). The primary outcome was a composite of all-cause mortality and unplanned heart failure rehospitalization during follow-up, censored at one year. All-cause mortality was evaluated as a secondary endpoint. Cox proportional hazards regression with interaction terms was used for multivariable analysis <bold>Results</bold> : Median age was 88 years and 66.9% were women. During follow-up, 387 patients (53.1%) experienced the primary composite endpoint. Elevated AP alone was not associated with increased risk of adverse outcomes (HR 0.94; 95% CI 0.53–1.66; p=0.830). However, concurrent elevation of AP and CA125 identified a high-risk subgroup with markedly increased composite endpoint risk (HR 1.98; 95% CI 1.40–2.80; p&lt;0.001) and all-cause mortality (HR 2.10; 95% CI 1.39–3.11; p&lt;0.001). The interaction between AP and CA125 was statistically significant for both endpoints (p&lt;0.001). <bold>Conclusions</bold> : In old patients with AHF, the prognostic impact of elevated AP is critically dependent on concomitant systemic congestion reflected by elevated CA125. In contrast, elevated AP without concomitant CA 125 elevation was not independently associated with adverse outcomes. </p>