Should the routine use of the 6-minute walk test be implemented in liver disease assessment: Not so fast

Abstract

End-stage liver disease (ESLD) is a debilitating condition that often leads to death. Once diagnosed with ESLD, a patient’s quality of life decreases significantly. Well-established markers, such as the model for end-stage liver disease and Child-Pugh scores, are used to diagnose, monitor, and predict survival. Another tool, the 6-minute walk test (6MWT), has shown promise as an adjunct measure but remains underutilized despite its strong results and ease of reproducibility. Previous research has demonstrated that the 6MWT, as in many other conditions, helps predict survival, mortality, and outcomes in individuals with ESLD. A recent observational study by Corrêa et al found that the 6MWT is a reliable measure of functional capacity in patients with liver cirrhosis. Although the study’s small sample size of 20 patients limits its generalizability, the findings align with prior evidence showing that the 6MWT is an independent predictor of mortality and that poor test performance is associated with greater liver dysfunction. However, the 6MWT is a nonspecific test, and patient performance can be influenced by comorbidities such as heart failure, pulmonary disease, and frailty. Additionally, the optimal timing for administering the test has not been clearly established in the literature. Overall, although well-validated markers already exist for diagnosing and assessing outcomes in liver disease, the addition of the 6MWT-a low-cost, reliable, easily reproducible, and objective measure-may provide valuable prognostic and functional information if standardized protocols and covariates are better controlled.

Key Words: 6-minute walk test; Liver transplant; Liver failure; Cirrhosis; Functional capacity

Core Tip: The 6-minute walk test is a simple, low-cost, and reproducible assessment that has been shown to serve as a clinical predictor of survival, mortality, and other outcomes in individuals with end-stage liver disease. However, prior to its routine clinical implementation, additional research is needed to standardize testing protocols and to define the optimal timing for both administration and repeat assessment. Furthermore, the test should be interpreted as an adjunct measure of overall functional capacity and health status, rather than as a standalone indicator of hepatic function.

TO THE EDITOR

The six-minute walk test (6MWT) has served as an effective and objective tool for assessing functional capacity across a wide range of diseases. The test is simple, reproducible, and low-cost. Research has demonstrated that the 6MWT also has significant prognostic value, including predicting survival, clinical outcomes, and disease progression in cardiopulmonary disorders, liver disease, and organ transplantation. Cirrhosis, end-stage liver disease (ESLD), is a morbid condition that affects not only the liver but can also be the cause/driver of multiorgan failure and has systemic effects. There are well-established scores, such as the model for end-stage liver disease (MELD) and the Child-Pugh scores, that are used to diagnose, monitor, and predict survival. However, the only cure for ESLD is liver transplantation, and with the scarcity of organs, more prognostic indicators can be used. In patients with liver disease, the six-minute walk distance has been shown to be an independent predictor of survival in individuals with cirrhosis[1,2]. It has also been found to perform comparably to the MELD score and serves as an indicator of mortality in both patients on the transplant waiting list and those who have undergone transplantation[3]. Although the test holds considerable promise and has proven reliability, its results can be influenced by inadequate standardization and multiple confounding factors.

DISCUSSION

According to the centers for disease control and prevention, approximately 4.5 million people in the United States have cirrhosis, and the disease causes about 52000 deaths annually[4]. The mean age of individuals with cirrhosis is rising and they often experience multiple complications, and are typically frail and deconditioned[5]. Many studies suggest that the 6MWT should occur at the baseline evaluation for liver transplantation; however, this approach fails to consider several essential factors. Many evaluations begin while patients are hospitalized, and some may undergo transplantation during that same admission. Conversely, other patients may wait years for a liver transplant, during which their clinical status can change significantly-either improving or deteriorating. Additionally, patients with recent hospitalizations are often frailer and more deconditioned, which can further influence their performance on the 6MWT. Lai et al[6] reported a consensus that liver transplant candidates should undergo longitudinal monitoring using a frailty assessment tool that includes both objective and subjective measures, such as the 6MWT; however, this test should not serve as the sole criterion for delisting a patient. At different stages of the disease, patients have various levels of frailty and nutrition, which can influence muscle mass and overall performance in the test.

Corrêa et al[7], in a recent cross-sectional quantitative study, demonstrated that the 6MWT is a reliable tool for assessing the functional capacity of patients with liver disease. The study concluded that the test should be incorporated into routine clinical practice; however, its findings lack generalizability and statistical power, as the cohort included only 20 patients[7]. Before widespread implementation, it is essential to establish standardized procedures for conducting the test. Although the American Thoracic Society has published guidelines detailing how the 6MWT should be performed[8], these recommendations are not consistently followed across research studies. Updated and revised guidelines are needed, as advances in clinical knowledge, patient management, and treatment modalities have changed.

It is believed that after two tests, the change in performance is minimal; however, this part of the guidelines does not take into account the progression of the disease or the current clinical status of the patient. Morkane et al[9] in a cohort feasibility study of patients on a liver transplant waiting list, showed that an established exercise program can improve overall aerobic fitness compared with patients who did not participate in any exercise training. These exercise programs have been shown to improve overall functional capacity, test performance, and, more importantly, survival[3,8-10]. The test itself is not an accurate representation of liver disease alone, as it reflects multisystem function rather than solely the physiological mechanisms of liver failure. The test can be helpful, as it has proven to be an indicator of mortality in people with cirrhosis, liver failure, and those on the transplant list. However, before routine implementation, the technical aspects and timing of the test should be further investigated, as patient performance and clinical status can change over time.

CONCLUSION

Developing a clearer understanding of how the six-minute walk distance relates to clinical outcomes is key to integrating the six-minute walk test into standard assessments for patients with ESLD and to justify the use of structured rehabilitation programs. The 6MWT can be used currently, as an adjunct tool, particularly in patients who have been on the transplant list for a prolonged period. It can help characterize frailty and monitor changes in functional capacity over time until more evidence becomes available regarding how and when it should be used appropriately. However, before this can be achieved, the 6MWT must be standardized with clear, practical guidelines regarding how and when the test should be performed. Factors that should be standardized to improve its usefulness include the timing of when the patient should take the test, the frequency with which it should be administered, the patient’s baseline clinical status, and the specific instructions provided to the patient. Even slight variations in these parameters can alter outcomes and produce inconsistent results across different patient groups. Therefore, more randomized prospective studies are needed in which these variables are standardized, while also focusing on assessing changes in performance and examining how these relate to further liver disease decompensation and mortality.