# Investigating the role of frailty on outcomes in acutely ill patients with cirrhosis undergoing liver transplantation in the acute care setting

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $678,273

## Abstract

PROJECT SUMMARY
For patients with cirrhosis, liver transplantation is a well-established therapy, restoring liver function and
reversing portal hypertension within days to weeks of the surgery itself. But cirrhosis also leads to insidious
extra-hepatic effects such as muscle wasting, malnutrition, and functional impairment that may take months to
reverse, if at all, which can compromise health and wellbeing (“global functional health”) after transplantation.
In the ambulatory setting, these chronic cirrhosis manifestations can be captured by measures of “frailty”, the
chronic biological state of decreased physiological reserve and increased vulnerability to health stressors, and
operationalized using the Liver Frailty Index (LFI)—which our team developed from grip strength, chair stands,
and balance. When assessed in the ambulatory setting, LFI predicts adverse health outcomes including
hospitalizations and mortality. Frailty is now a well-accepted construct in hepatology/transplantation: in 2019,
the American Society of Transplantation (AST) endorsed the use of standardized frailty metrics, including the
LFI, for ambulatory liver transplant evaluation. However, approximately 1/3 of cirrhosis patients are
hospitalized with acute illness immediately prior to transplant, in whom pre-morbid, ambulatory, frailty metrics
may not be available. In this setting, transplant clinicians have, in many instances, been applying this construct
in the acute care setting to inform transplant decisions—often informally through an “eyeball test”—despite a
lack of studies evaluating the construct of frailty or tools to measure frailty in acutely ill patients. Unlike in the
ambulatory setting where frailty represents factors that would not reverse with liver transplantation, a single
frailty assessment in the acute setting may simply reflect the severity of acute liver-related decompensation,
which, in theory, could reverse with a new liver. On the other hand, frailty trajectories may be informative of a
patient’s ability to recovery a major stressor such as transplant surgery, so application of frailty as a trajectory
may be more clinically appropriate. But testing of these hypotheses has not yet been done. In this proposal, we
will leverage our 9-center research network to develop and validate a novel inpatient frailty index optimized for
this acutely ill population, investigate models incorporating single and longitudinal assessments of frailty for the
prediction of 1-year post-transplant global functional health, and associate inpatient frailty assessments with 1-
year post-transplant healthcare utilization. Impact: Our proposal will result in a pragmatic, objective tool to
standardize assessment of frailty in acutely ill patients with cirrhosis undergoing liver transplantation and
clinical prediction models to guide use of single and longitudinal assessments of frailty for transplant decision-
making in this clinically dynamic population. Understanding the preci...

## Key facts

- **NIH application ID:** 10880602
- **Project number:** 5R01DK133527-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Jennifer C. Lai
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $678,273
- **Award type:** 5
- **Project period:** 2023-07-15 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10880602

## Citation

> US National Institutes of Health, RePORTER application 10880602, Investigating the role of frailty on outcomes in acutely ill patients with cirrhosis undergoing liver transplantation in the acute care setting (5R01DK133527-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10880602. Licensed CC0.

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