Extra-hepatic comorbidity burden significantly increases 90-day mortality in patients with cirrhosis and high model for endstage liver disease

Scott Coppel,Lauren Nephew,Burcin Ekser,Archita P Desai,Eduardo Vilar-Gomez,Karan Mathur,Eric Orman,Marwan Ghabril,Naga Chalasani,Kavish R Patidar,Chandrashekhar Kubal

doi:10.1186/s12876-020-01448-z

Abstract

BackgroundWe examined how extra-hepatic comorbidity burden impacts mortality in patients with cirrhosis referred for liver transplantation (LT).MethodsAdults with cirrhosis evaluated for their first LT in 2012 were followed through their clinical course with last follow up in 2019. Extra-hepatic comorbidity burden was measured using the Charlson Comorbidity Index (CCI). The endpoints were 90-day transplant free survival (Cox-Proportional Hazard regression), and overall mortality (competing risk analysis).ResultsThe study included 340 patients, mean age 56 ± 11, 63% male and MELD-Na 17.2 ± 6.6. The CCI was 0 (no comorbidities) in 44%, 1–2 in 44% and > 2 (highest decile) in 12%, with no differences based on gender but higher CCI in patients with fatty and cryptogenic liver disease. Thirty-three (10%) of 332 patients not receiving LT within 90 days died. Beyond MELD-Na, the CCI was independently associated with 90-day mortality (hazard ratio (HR), 1.32 (95% confidence interval (CI) 1.02–1.72). Ninety-day mortality was specifically increased with higher CCI category and MELD ≥18 (12% (CCI = 0), 22% (CCI = 1–2) and 33% (CCI > 2), (p = 0.002)) but not MELD-Na ≤17. At last follow-up, 69 patients were alive, 100 underwent LT and 171 died without LT. CCI was associated with increased overall mortality in the competing risk analysis (Sub-HR 1.24, 95%CI 1.1–1.4).ConclusionsExtra-hepatic comorbidity burden significantly impacts short-term mortality in patients with cirrhosis and high MELD-Na. This has implications in determining urgency of LT and mortality models in cirrhosis and LT waitlisting, especially with an ageing population with increasing prevalence of fatty liver disease.

Highlights

We examined how extra-hepatic comorbidity burden impacts mortality in patients with cirrhosis referred for liver transplantation (LT)
Among the 387 patients evaluated for LT 47 were excluded, including 30 patients who were referred for multi-organ transplant, 7 with prior LT and 10 without underlying cirrhosis
There were no differences in mean Charlson Comorbidity Index (CCI) in females and males, females had a trend for higher frequency of connective tissue disease (6.2% vs. 2.3%, (p = 0.06))

Summary

Introduction

We examined how extra-hepatic comorbidity burden impacts mortality in patients with cirrhosis referred for liver transplantation (LT). Cirrhosis is a serious consequence of chronic liver diseases, and represents a substantial burden of morbidity, mortality and health-care expenditure It carries a poor prognosis in the setting of decompensation or development of hepatocellular carcinoma, with liver transplantation (LT) being the only definitive and lifesaving therapy. In this context, extra-hepatic comorbidities may carry multiple hazards to patients with cirrhosis in need of LT. The CCI predicts 1-year mortality in general populations and in patients with organ specific disease such as acute and chronic heart disease [5,6,7,8] Both liver disease severity, reflected in MELD, and HCC are known to impact mortality and LT considerations in patients with cirrhosis. The assessment of overall comorbidity burden, rather than individual comorbid conditions considered by transplant centers, may provide an aggregate measure of risk posed by the burden of extra-hepatic conditions

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