Gastroenterology

Gastroenterology

Volume 156, Issue 6, May 2019, Pages 1675-1682
Gastroenterology

Original Research
Full Report: Clinical—Liver
Frailty Associated With Waitlist Mortality Independent of Ascites and Hepatic Encephalopathy in a Multicenter Study

https://doi.org/10.1053/j.gastro.2019.01.028Get rights and content

Background & Aims

Frailty is associated with mortality in patients with cirrhosis. We measured frailty using 3 simple tests and calculated Liver Frailty Index (LFI) scores for patients at multiple ambulatory centers. We investigated associations between LFI scores, ascites, and hepatic encephalopathy (HE) and mortality.

Methods

Adults without hepatocellular carcinoma who were on the liver transplantation waitlist at 9 centers in the United States (N = 1044) were evaluated using the LFI; LFI scores of at least 4.5 indicated that patients were frail. We performed logistic regression analyses to assess associations between frailty and ascites or HE and competing risk regression analyses (with liver transplantation as the competing risk) to estimate sub-hazard ratios (sHRs) of waitlist mortality (death or removal from the waitlist).

Results

Of study subjects, 36% had ascites, 41% had HE, and 25% were frail. The odds of frailty were higher for patients with ascites (adjusted odd ratio 1.56, 95% confidence interval [CI] 1.15–2.14) or HE (odd ratio 2.45, 95% CI 1.80–3.33) than for those without these features. Larger proportions of frail patients with ascites (29%) or HE (30%) died while on the waitlist compared with patients who were not frail (17% of patients with ascites and 20% with HE). In univariable analysis, ascites (sHR 1.52, 95% CI 1.14–2.05), HE (sHR 1.84, 95% CI 1.38–2.45), and frailty (sHR 2.38, 95% CI 1.77–3.20) were associated with waitlist mortality. In adjusted models, only frailty remained significantly associated with waitlist mortality (sHR 1.82, 95% CI 1.31–2.52); ascites and HE were not.

Conclusions

Frailty is a prevalent complication of cirrhosis that is observed more frequently in patients with ascites or HE and independently associated with waitlist mortality. LFI scores can be used to objectively quantify risk of death related to frailty—in excess of liver disease severity—in patients with cirrhosis.

Section snippets

Patients

This study was conducted as part of the Multi-Center Functional Assessment in Liver Transplantation Study (FrAILT), which includes 9 liver transplantation centers in the United States: University of California, San Francisco (n = 770), Baylor University Medical Center (n = 51), Columbia University Medical Center (n = 50), Duke University (n = 40), University of Pittsburgh (n = 37), Johns Hopkins Medical Institute (n = 38), Loma Linda University (n = 32), University of Arkansas for Medical

Characteristics of Entire Patient Population

A total of 1044 patients with cirrhosis were included in this study. Baseline characteristics of the cohort are listed in Table 1. To briefly summarize, median age was 57 years, 43% were women, 61% were non-Hispanic white, and median body mass index was 28 kg/m2. Twenty-nine percent had chronic hepatitis C virus (HCV) as their primary etiology of liver disease, 25% had alcoholic liver disease, and 17% had nonalcoholic steatohepatitis. Rates of hypertension, diabetes, and coronary artery disease

Discussion

Cirrhosis most commonly leads to premature death through complications of portal hypertension. However, manifestations of hepatic synthetic dysfunction and portal hypertension present in an often unpredictable pattern: although one patient might develop ascites without ever experiencing HE, another might develop ascites, HE, and bleeding esophageal varices within a period of months. Similarly, physical frailty, an overt extrahepatic manifestation of cirrhosis, presents variably in patients with

Acknowledgments

Author contributions: Jennifer C. Lai conceived and designed the study; acquired, analyzed, and interpreted the data; drafted the manuscript; critically revised the manuscript for important intellectual content; performed statistical analysis; obtained funding; and supervised the study. Jennifer L. Dodge analyzed and interpreted of data, critically revised the manuscript for important intellectual content, and performed statistical analysis. Elizabeth C. Verna, Robert Rahimi, Matthew R. Kappus,

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Conflict of interest The authors disclose no conflicts.

Funding This study was funded by the National Institutes of Health (K23AG048337 and R01AG059183 to Jennifer C. Lai; F32AG053025 to Christine E. Haugen; P30DK026743 to Jennifer C. Lai and Jennifer L. Dodge; and K24DK101828 to Dorry Segev). These funding agencies played no role in the analysis of the data or the preparation of this manuscript.

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© 2019 by the AGA Institute