Physiological responses to the six-minute walk test in frail/pre-frail patients with cirrhosis awaiting transplantation

Background and Aims: Patients with cirrhosis awaiting transplantation have well-documented reductions in aerobic capacity, yet the physiological responses during functional assessments that underlie these limitations are not fully understood. This study compared the physiological responses during a six-minute walk test (6MWT) in patients with cirrhosis awaiting transplantation to age-matched controls. Methods: Thirty participants with cirrhosis awaiting transplantation (11 female, 58±7 y, 77% Child Pugh B/C) and 20 controls (5 female; 62±11 y) were enrolled. Heart rate (HR), oxygen consumption (VO₂; portable device), and calf muscle oxygenation (SmO₂; near-infrared spectroscopy) were continuously measured prior to (5-min), during, and after (5-min) the 6MWT. HR and VO₂ recovery kinetics were analyzed using non-linear exponential decay modeling (OriginLab, 2023b) to calculate the mean response time (MRT), while calf muscle oxygenation (SmO₂) was assessed using the half-time recovery metric (t₅₀). Results: At rest, the cirrhosis group had a higher HR ( p =0.020) and lower calf SmO₂ ( p =0.036) compared to controls, while VO₂ was not significantly different between groups. The cirrhosis group walked a shorter distance than controls (414±131 m vs. 624±72 m; p <0.001), and had a significantly lower HR, VO₂, and tissue deoxygenation during exercise. Despite these exercise-related impairments, recovery kinetics, measured by HR MRT and SmO₂ t₅₀,were comparable between groups ( p >0.999 and p =0.151, respectively). In contrast, VO₂ MRT was significantly slower in the cirrhosis group (85±23 s vs. 61±18 s; p <0.001). Conclusions: Individuals with cirrhosis awaiting transplantation have reduced aerobic endurance and delayed VO₂ recovery reinforcing the rationale for prehabilitation and suggesting that extended recovery periods during exercise training may be beneficial.