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Gentilini et al enrolled 126 patients with refractory ascites and showed that long-term albumin infusion reduced the recurrence of ascites and ascites-related readmission without improving subjects ’ overall survival . 22 A follow-up study by Romanelli et al evaluated the outcomes of long-term albumin infusion with an extension of the follow-up period to a median of 84 months . 23 Again there was less recurrence of ascites ( 39 % albumin vs 85 % SMT ) in the albumin group compared with the control . Long-term albumin infusion importantly improved 5-year transplant-free survival ( 62 % in the albumin group vs 26 % SMT ) for the first time , even though the sample size was relatively small .
In the midodrine and albumin for cirrhotic patients in the waiting list for liver transplantation trial ( MACHT ), 24 Sola-Vera et al randomised 196 patients on the transplant waiting list to receive either SMT or albumin infusion plus midodrine . The primary endpoint of the study was cirrhosis-related complications . The cirrhosis-related complications , ascites control and overall survival were similar between the albumin and SMT group .
The ANSWER ( the human Albumin for the TreatmeNt of aScites in patients With hEpatic cirRhosis ) study evaluated long-term albumin infusion ( 40g twice-weekly for two weeks , followed by 40g weekly ) in 431 patients with decompensated cirrhosis and ascites versus patients treated with SMT . Albumin infusion was well-tolerated and associated with significantly lower mortality , fewer ascites-related complications , and reduced bacterial infection in decompensated cirrhosis .
Long-term albumin infusion was also deemed a costeffective approach , primarily from associated reductions in hospital admissions , and a lower risk of paracentesis and HRS . However , while exciting , it is worth noting that the ANSWER study excluded patients with refractory ascites .
Di Pascoli et al demonstrated a significant improvement in 24-month survival in the long-term albumin group when compared with SMT ( 58 % vs 35 %). 26 The albumin group had a lower risk of emergency hospitalisations from SBP , non-SBP infection and HE . The liver transplantation rate was similar in both groups ( 11 % vs 8 % in SMT ), but it should be highlighted that none of the patients with refractory ascites received transjugular intrahepatic portosystemic shunt ( TIPS ). More data are required to evaluate the comparative efficacy of long-term albumin and TIPS for refractory ascites .
The Albumin to prevent infection in chronic liver failure ( ATTIRE ) study by China et al showed that the risk of renal impairment , infection and death were similar between the albumin infusion and control group in hospitalised cirrhosis patients with acute decompensation and hypoalbuminaemia . 27
Conclusion The improved knowledge of the pathophysiological background of decompensated cirrhosis presents novel therapeutic perspectives for patient management . The therapeutic role of albumin infusion in decompensated cirrhosis is established and indications include SBP , HRS and in patients undergoing LVP and positive results for long-term albumin infusion will likely increase the global demand for intravenous albumin . Studies evaluating the role of long-term albumin infusion to improve systemic inflammation and cirrhosis-related complications are expected in the future and should focus on areas such as refining the dosages , scheduling of long-term albumin infusion and on specific patient populations that would benefit the most .
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