Long-term Albumin Treatment Improves Outcomes in Patients with Cirrhosis and Ascites

Background and Aims: While the ANSWER trial has demonstrated improved survival with long-term albumin treatment in patients with ascites, a benefit was not observed in some other studies. Study design, heterogeneity in study cohorts and albumin dose have been hypothesized to explain these discrepancies. We aimed to assess the effects of long-term albumin treatment – administered in a real-life outpatient setting – on liver-related mortality in cirrhosis patients with ascites.Methods: 878 cirrhosis patients with ascites as index decompensation between 2003-2024 from four tertiary care centers in Europe were included. 106 patients (11.7%) receiving longterm (i.e., more than > 30 days) i.v. albumin therapy. Patients were characterized from time of albumin treatment initiation or first decompensation. We performed inverse probability of treatment weighting (IPTW) adjusting for age, sex, MELD-Na and etiologic cure to account for differences in disease severity in multivariable cox regression analyses of liver-related mortality.Results: The main patient characteristics were balanced between patients receiving long-term albumin [ivALB (+)] and those w/o albumin treatment [ivALB(-)]: median age: 60.2 vs 56.9 years (p = 0.008) and MELD-Na 14 vs 15 (p = 0.231). Median ivALB(+) treatment dose was 40 grams per week (mostly 20% 200mL) and patients were treated for 11.1 (IQR: 5.0 – 20.3) months. During a median follow-up of 46.5/36.4 months in ivALB(-)/ivALB(+) patients, 44.4%/35.9% died including 39.0%/27.2% liver-related deaths, and 12.3%/17.5% underwent liver transplantation (LT). Incidence of liver-related mortality at 36 months was 38.8% in the ivALB(-) vs. 34.4% in the ivALB(+) patients (log-rank p = 0.100). Cox proportional hazards regression with IPTW for ivALB(+) treatment showed that next to age (aHR per year: 1.04 [95%CI: 1.02-1.06]; p < 0.001), MELD-Na (aHR per point: 1.07 [95%CI: 1.04-1.10]; p < 0.001), female sex (aHR: 0.58 [95%CI: 0.42-0.81]; p = 0.001) and etiologic cure (aHR: 0.56 [95%CI: 0.36-0.88]; p=0.012) - long-term ivALB(+) therapy was associated with significantly reduced risk of liver-related death (aHR: 0.65 [95%CI: 0.42-0.99]; p = 0.048).Conclusions: Acknowledging the limitations related to retrospective design and nonstandardized treatment schedules, long-term ivALB(+) treatment significantly reduced liverrelated mortality in our cohort of cirrhosis patients with ascites.