Richard Parker1, Matthew J Armstrong, Tony Bruns, James Hodson, Ian A C Rowe, Chris D T Corbett, Philip A Reuken, Bridget K Gunson, Diarmaid D Houlihan, Barney Stephenson, Christina Malessa, William Lester, James W Ferguson. 1. 1 Centre for Liver Research and NIHR Biomedical Research Unit for Liver Disease, University of Birmingham, Birmingham, UK. 2 Liver Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. 3 Department Internal Medicine, Division of Gastroenterology, Hepatology and Infectious Disease, Jena University Hospital, Jena, Germany. 4 Department of General, Visceral and Vascular Surgery, Jena University Hospital, Jena, Germany. 5 Department of Haematology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. 6 Address correspondence to: Richard Parker, M.D., NIHR Centre for Liver Research, 5th Floor, Institute for Biomedical Research, University of Birmingham, Birmingham, B15 2TT, UK.
Abstract
BACKGROUND: Prognostic scores are used to assess the likelihood of mortality in cirrhosis and the necessity of liver transplantation. These models are imperfect and refinement would allow more accurate prognostication and selection of patients for transplant. This study investigated association of red cell parameters and mortality in liver transplant candidates. METHODS: Data from patients with cirrhosis assessed for transplantation from 2008 to 2010 at Queen Elizabeth Hospital Birmingham, UK were reviewed retrospectively. Kaplan-Meier analysis and Cox regression models were used to generate indices predicting mortality. Accuracy of existing and updated models was tested by calculation of c-statistics. Results were validated in a cohort of patients assessed for liver transplant in Jena, Germany. RESULTS: Data were collected from 386 patients in the study cohort. Median follow-up was 15 months (0-45). During follow-up, 151 patients (39%) were transplanted, 138 (36%) died, and 97 (25%) survived without transplant. Abnormal reticulocyte count (P<0.001, c-statistic 0.623) and hemoglobin concentration (P<0.001, c-statistic 0.609) predicted mortality in Cox regression analysis. Abnormal reticulocyte count was also found to predict mortality in competing risk analysis. Refining the Model for End-Stage Liver Disease (MELD) to incorporate reticulocyte count and hemoglobin concentration (MELD-red) improved predictive power from 0.701 to 0.731 (c-statistics). This was confirmed in an independent validation cohort of 157 patients with c-statistics of 0.787 and 0.816, respectively, for MELD and MELD-red. CONCLUSIONS: Abnormal red cell indices, in particular increased reticulocyte count and decreased hemoglobin concentration, are associated with increased risk of death in liver transplant candidates. Refining MELD to incorporate these indices improves prediction of mortality.
BACKGROUND: Prognostic scores are used to assess the likelihood of mortality in cirrhosis and the necessity of liver transplantation. These models are imperfect and refinement would allow more accurate prognostication and selection of patients for transplant. This study investigated association of red cell parameters and mortality in liver transplant candidates. METHODS: Data from patients with cirrhosis assessed for transplantation from 2008 to 2010 at Queen Elizabeth Hospital Birmingham, UK were reviewed retrospectively. Kaplan-Meier analysis and Cox regression models were used to generate indices predicting mortality. Accuracy of existing and updated models was tested by calculation of c-statistics. Results were validated in a cohort of patients assessed for liver transplant in Jena, Germany. RESULTS: Data were collected from 386 patients in the study cohort. Median follow-up was 15 months (0-45). During follow-up, 151 patients (39%) were transplanted, 138 (36%) died, and 97 (25%) survived without transplant. Abnormal reticulocyte count (P<0.001, c-statistic 0.623) and hemoglobin concentration (P<0.001, c-statistic 0.609) predicted mortality in Cox regression analysis. Abnormal reticulocyte count was also found to predict mortality in competing risk analysis. Refining the Model for End-Stage Liver Disease (MELD) to incorporate reticulocyte count and hemoglobin concentration (MELD-red) improved predictive power from 0.701 to 0.731 (c-statistics). This was confirmed in an independent validation cohort of 157 patients with c-statistics of 0.787 and 0.816, respectively, for MELD and MELD-red. CONCLUSIONS: Abnormal red cell indices, in particular increased reticulocyte count and decreased hemoglobin concentration, are associated with increased risk of death in liver transplant candidates. Refining MELD to incorporate these indices improves prediction of mortality.