Liver Frailty Index could identify cirrhosis patients at highest risk of death while waiting for transplants

Cirrhosis is a common liver disease, affecting about 1 in 400 adults in the United States annually. Cirrhosis can lead to liver failure or end-stage liver disease, which requires a liver transplant for survival. But up to 25 percent of people who are on waitlists for liver transplants die before receiving one. A new way to measure physical frailty in people with cirrhosis of the liver may help to better identify patients who are most at risk of dying while waiting for a transplant, according to a new study. The research by an NIA- and NIDDK-supported team of investigators was published in the Jan. 17 issue of Gastroenterology.

Current methods of determining the individuals most at-risk for serious complications or death while waiting for transplant have relied on lab test results or the presence of physical complications like hepatic encephalopathy (HE, temporary problems with brain functioning and cognition due to a buildup of toxins in the blood) or ascites (abdominal swelling due to a buildup of protein-rich fluids).

However, cirrhosis is often accompanied by a cluster of related side effects, such as muscle wasting, poor nutrition, and decreased physical function. The research team designed a way to quantify these aspects of frailty, such as physical function/capacity, mobility, and weakness, into a composite Liver Frailty Index (LFI). They hypothesized that, combined with factoring in HE and ascites, the Index could be a more effective tool for clinicians to detect people most at risk for dying before they receive a transplant, or whose frailty puts them at risk for poor transplant outcomes.

In the study, the research team examined 1,044 adults on liver transplant waitlists at nine transplant centers across the United States. They performed three simple tests for frailty: grip strength, timed chair stands (how many seconds it takes a person to stand and sit in a chair with their arms folded across the chest), and balance testing. They then factored in HE and ascites, and calculated a total Liver Frailty Index score, with frailty being defined as a score of 4.5 or greater.

Overall, patients with HE or ascites were at least twice as likely to be frail as those without these conditions. The study authors suspect that frailty is likely an end manifestation of cirrhosis-related liver dysfunction, accompanied by muscle wasting and inadequate nutrition, and is sometimes made worse by related hypertension and other complications.

Using the Liver Frailty Index may help identify the most vulnerable on transplant waitlists and help guide those people and their caregivers to consider accelerated transplant options, such as living donor liver transplantation (receiving a portion of healthy liver donated by a friend or family member), accepting higher-risk donated livers, or considering alternate transplant centers.

The investigators will next seek to test how the LFI might inform development of physical activity and nutrition interventions that could help reduce physical frailty and the risk of adverse outcomes for people on waitlists for liver transplantation.

This research was supported by NIA grants K23AG048337, P30AG044281, and F32AG053025; and NIDDK grants P30DK026743 and K24DK101828.

Reference: Lai J, et al. Frailty associated with waitlist mortality independent of ascites and hepatic encephalopathy in a multi-center study. Gastroenterology. 2019 Jan 17. doi: 10.1053/j.gastro.2019.01.028.