Pre‐Treatment Serum Albumin Concentration Predicts Clinical Benefit of Long‐Term Albumin in Patients With Cirrhosis and Ascites

Background and Aims: The benefit of long-term albumin (LTA) in improving survival and reducing complications in patients with cirrhosis and ascites is not consistently observed across studies, possibly reflecting differences in patient populations and treatment regimens. This study aimed to determine whether baseline serum albumin (SA) levels can predict which patients are most likely to benefit from LTA therapy. Methods: A post hoc analysis of the ANSWER trial was performed in 431 patients randomized to receive standard medical treatment (SMT) alone or SMT plus human albumin (SMT + HA). The interaction between baseline SA and LTA was investigated using competing-risk survival analysis. The primary endpoint was 18-month survival. Secondary endpoints included the incidence of cirrhosis-related complications and hospitalizations. Results: A significant treatment-by-albumin non-linear interaction was found (p = 0.010), indicating heterogeneity of treatment effect across baseline SA levels with the upper bound of the region of statistically demonstrable benefit occurring at approximately 3.2 g/dL (sHR 0.53, 95% CI 0.28–0.99). In patients with SA ≤ 3.2 g/dL, 18-month survival was significantly higher in the SMT + HA group compared with SMT alone (HR 0.47, 95% CI 0.29–0.77; p = 0.0021). No significant survival difference could be demonstrated in patients with SA > 3.2 g/dL (HR 1.04, 95% CI 0.41–2.63; p = 0.93). Regardless of baseline SA levels, LTA was associated with improved ascites control and reduced rates of complications and hospitalizations. Conclusions: LTA provides survival and morbidity benefits in patients with mild-to-moderate hypoalbuminemia, whereas in patients with normal SA levels, its benefit appears mainly limited to morbidity reduction. Baseline SA may therefore help in prioritizing LTA therapy when resources are constrained.