Paolo Caraceni1, Manuel Tufoni1, Giacomo Zaccherini1, Oliviero Riggio2, Paolo Angeli3, Carlo Alessandria4, Sergio Neri5, Francesco G Foschi6, Fabio Levantesi7, Aldo Airoldi8, Loredana Simone9, Gianluca Svegliati-Baroni10, Stefano Fagiuoli11, Giacomo Laffi12, Raffaele Cozzolongo13, Vito Di Marco14, Vincenzo Sangiovanni15, Filomena Morisco16, Pierluigi Toniutto17, Antonio Gasbarrini18, Rosanna De Marco19, Salvatore Piano3, Silvia Nardelli2, Chiara Elia4, Andrea Roncadori20, Maurizio Baldassarre21, Mauro Bernardi22. 1. Department of Medical and Surgical Sciences, University of Bologna, Italy; Bologna University Hospital Authority St. Orsola-Malpighi Polyclinic, Italy. 2. Department of Clinical Medicine, "Sapienza" University of Rome, Italy. 3. Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padua, Italy. 4. Division of Gastroenterology and Hepatology, "Città della Salute e della Scienza" Hospital, University of Turin, Italy. 5. Department of Clinical and Experimental Medicine, University of Catania, Italy. 6. Internal Medicine, Hospital of Faenza, A.U.S.L. of Romagna, Italy. 7. Internal Medicine, Hospital of Bentivoglio, A.U.S.L. of Bologna, Italy. 8. Liver Unit, Department of Hepatology and Gastroenterology, Niguarda Hospital, Milan, Italy. 9. Gastroenterology Unit, University Hospital, Ferrara, Italy. 10. Department of Gastroenterology, Polytechnic University of Marche, Ancona, Italy. 11. Gastroenterology and Transplant Hepatology, Papa Giovanni XXIII Hospital, Bergamo, Italy. 12. Careggi University Hospital, University of Florence, Italy. 13. Division of Gastroenterology, National Institute of Gastroenterology "S. De Bellis", Castellana Grotte (Bari), Italy. 14. Unit of Gastroenterology and Hepatology, Biomedical Department of Internal and Specialistic Medicine, University of Palermo, Italy. 15. A.O.R.N. dei Colli - "Cotugno" Hospital of Naples, Italy. 16. Gastroenterology Unit, Department of Clinical Medicine and Surgery, "Federico II" University of Naples, Italy. 17. Hepatology and Liver Transplantation Unit, Department of Medical Area, University of Udine, Italy. 18. Gastroenterology, Gemelli Foundation, Catholic University, Rome, Italy. 19. Gastroenterology Unit, Hospital of Cosenza, Italy. 20. Cineca Interuniversity Consortium, Bologna, Italy. 21. Department of Medical and Surgical Sciences, University of Bologna, Italy; Center for Applied Biomedical Research (CRBA), University of Bologna, Italy. 22. Department of Medical and Surgical Sciences, University of Bologna, Italy. Electronic address: mauro.bernardi@unibo.it.
Abstract
BACKGROUND & AIMS: The ANSWER study reported that long-term albumin administration in patients with cirrhosis and uncomplicated ascites improves survival. During treatment, serum albumin increased within a month and remained stable thereafter. In this post hoc analysis, we aimed to determine whether on-treatment serum albumin levels could guide therapy. METHODS: Logistic regression was used to assess the association between baseline serum albumin and mortality, as well as to determine on-treatment factors associated with mortality and to predict the achievement of a given on-treatment serum albumin level. Survival was assessed by Kaplan-Meier estimates and second-order polynomial regression. Patients whose on-treatment serum albumin remained below normal were compared with a subset of patients from the control arm matched by principal score. RESULTS: Baseline serum albumin was closely associated with 18-month mortality in untreated patients; albumin treatment almost effaced this relationship. On-treatment serum albumin and MELD-Na at month 1 were the sole independent variables associated with mortality. Second-order polynomial regression revealed that survival improved in parallel with increased 1-month on-treatment serum albumin. Kaplan-Meier estimations showed that any value of 1-month on-treatment serum albumin (0.1 g/dl intervals) in the range 2.5-4.5 g/dl discriminated patient survival. In the normal range of serum albumin, the best discriminant value was 4.0 g/dl. Compared to untreated patients, survival even improved in patients whose on-treatment serum albumin remained below normal. CONCLUSION: Baseline serum albumin per se should not guide the decision to start albumin therapy. Conversely, 1-month on-treatment serum albumin levels are strongly associated with outcomes and could guide the use of albumin - 4.0 g/dl being the target threshold. However, even patients whose serum albumin remains below normal benefit from long-term albumin administration. LAY SUMMARY: The ANSWER study has shown that long-term albumin administration improves survival and prevents the occurrence of major complications in patients with cirrhosis and ascites. This study shows that the achievement of these beneficial effects is related to a significant increase in serum albumin concentration. Even though the best results follow the achievement of a serum albumin concentration of 4 g/dl, a survival benefit is also achieved in patients who fail to normalise serum albumin.
BACKGROUND & AIMS: The ANSWER study reported that long-term albumin administration in patients with cirrhosis and uncomplicated ascites improves survival. During treatment, serum albumin increased within a month and remained stable thereafter. In this post hoc analysis, we aimed to determine whether on-treatment serum albumin levels could guide therapy. METHODS: Logistic regression was used to assess the association between baseline serum albumin and mortality, as well as to determine on-treatment factors associated with mortality and to predict the achievement of a given on-treatment serum albumin level. Survival was assessed by Kaplan-Meier estimates and second-order polynomial regression. Patients whose on-treatment serum albumin remained below normal were compared with a subset of patients from the control arm matched by principal score. RESULTS: Baseline serum albumin was closely associated with 18-month mortality in untreated patients; albumin treatment almost effaced this relationship. On-treatment serum albumin and MELD-Na at month 1 were the sole independent variables associated with mortality. Second-order polynomial regression revealed that survival improved in parallel with increased 1-month on-treatment serum albumin. Kaplan-Meier estimations showed that any value of 1-month on-treatment serum albumin (0.1 g/dl intervals) in the range 2.5-4.5 g/dl discriminated patient survival. In the normal range of serum albumin, the best discriminant value was 4.0 g/dl. Compared to untreated patients, survival even improved in patients whose on-treatment serum albumin remained below normal. CONCLUSION: Baseline serum albumin per se should not guide the decision to start albumin therapy. Conversely, 1-month on-treatment serum albumin levels are strongly associated with outcomes and could guide the use of albumin - 4.0 g/dl being the target threshold. However, even patients whose serum albumin remains below normal benefit from long-term albumin administration. LAY SUMMARY: The ANSWER study has shown that long-term albumin administration improves survival and prevents the occurrence of major complications in patients with cirrhosis and ascites. This study shows that the achievement of these beneficial effects is related to a significant increase in serum albumin concentration. Even though the best results follow the achievement of a serum albumin concentration of 4 g/dl, a survival benefit is also achieved in patients who fail to normalise serum albumin.