Long-term use of human albumin for the treatment of ascites in patients with hepatic cirrhosis: The interim analysis of the ANSWER study

Introduction: Despite long-term human albumin (HA) administration for treating cirrhosis with ascites is commonly used in Italy, the scientific evidence of its efficacy is still lacking. Aim: To assess the efficacy of long-term HA administration in patients with cirrhosis and ascites. Methods: In this multicentre, prospective, randomized clinical trial, 420 patients with cirrhosis and uncomplicated ascites treated with anti-mineralocorticoids (≥200 mg/day) and furosemide (≥25 mg/day) are planned to be randomized 1:1 to either standard medical treatment (SMT) or SMT + HA (40 g twice weekly for 2 weeks, and then 40 g weekly). Death, liver transplantation, TIPS, refractory ascites requiring ≥3 paracentesis/month or 18 months follow-up terminate the study. The primary end-point is mortality. Among the secondary end-points, those related to the management of ascites and the incidence of complications of cirrhosis were assessed in this analysis. Results: 386 (SMT: 188; SMT + HA: 198) patients were included. Their respective median follow-up duration was 183 (129–233) and 301 (238–355) days (p = 0.021). Baseline demographics and clinical and laboratory parameters were well balanced between the two arms. Kaplan–Meier intention-to-treat analysis showed that mortality was significantly reduced in patients receiving HA (at 18 months: SMT + HA: 22%, SMT: 34%; p = 0.045). Statistically significant benefits were found in the SMT + HA arm in the incidence rate of paracentesis (−55%, p < 0.001), incidence of refractory ascites (−42%, p < 0.001), and need of ≥3 paracentesis/month (−62%; p < 0.001). HA arm also presented an advantage in the incidence rates of SBP (−57%; p = 0.004), hepatic encephalopathy grade III–IV (−37%; p = 0.005) and renal impairment (serum creatinine > 1.5 mg/dl) (−28%; p = 0.011). HA administration did not increase the risk of variceal bleeding, and the incidence of severe adverse effects was similar in the two arms. Conclusions: Long-term HA administration prolongs survival in patients with cirrhosis and ascites, improves greatly the management of ascites and reduces the incidence of severe complications of the disease.