Letter to the Editor: Physical frailty is the most important predictor of early mortality in hospitalized patients with decompensated cirrhosis

Dear editor,

We have carefully reviewed the article titled “Physical frailty is the most important predictor of early mortality in hospitalized patients with decompensated cirrhosis,” published by Francesca D’Arcangelo et al in the journal “Hepatology Communications.” This prospective study assessed the impact of frailty and sarcopenia on hospitalized patients with decompensated cirrhosis. The results indicate that, independent of the severity of liver disease and the presence of acute-on-chronic liver failure (ACLF), frailty is the strongest independent predictor of early mortality in patients with decompensated cirrhosis.¹ However, we wish to put forward new perspectives to further advance academic development in this field.

One issue is that this study utilized the Liver Frailty Index to determine the presence of frailty, based primarily on 3 performance tests, including grip strength, balance and the chair stand test; it should be noted that neurological conditions such as cerebellar disorders, stroke, and brain tumors may influence the results of these performance tests, and as patients with such conditions were not included in the exclusion criteria for this study, this may have affected some of the findings. Furthermore, hepatic encephalopathy (HE) is one of the most serious complications of end-stage liver disease and the most common cause of death; it is frequently observed in patients awaiting liver transplantation. However, the calculation method for the hepatic frailty index may be biased by the presence of HE, and in such cases, it cannot be taken as indicative of frailty.² In the baseline data of this study, the incidence of HE was significantly higher among frail patients than among non-frail patients (35.5% vs. 23.1%).¹ The presence of HE influences the assessment of frailty and patient survival to some extent, thereby reducing the predictive value of frailty in this study.

Most importantly, the findings of this study indicate that frailty is the strongest independent predictor of early mortality in patients with acute decompensated cirrhosis, independent of the severity of liver disease and the presence of ACLF; in my personal view, this result should be interpreted with caution. In various post hoc analyses conducted by the authors based on ACLF status and Child–Pugh classification, it was found that, compared with ACLF patients without frailty, patients without ACLF but with frailty had similar post-transplant survival (p = 0.882),¹ suggesting that frailty may be a factor independently influencing patient mortality, irrespective of the severity of liver disease or the presence of extrahepatic organ failure. However, as mentioned in this paper regarding the prospective study by Gomez Perdiguero et al,³ the Liver Frailty Index, MELD-Na, and the Skeletal Muscle Index may independently predict the development of ACLF in patients awaiting liver transplantation; this indicates that frailty may be closely related to the progression of ACLF, and frail patients may be more prone to developing ACLF during the course of their illness. ACLF is a potentially reversible syndrome characterized by rapid progression and a high short-term (within 28 days) mortality rate;⁴ therefore, further investigation is required to determine whether frailty can be considered the strongest predictor of early mortality in patients with acute decompensated cirrhosis, independent of ACLF status. Should the authors conduct dynamic, stage-based observation and assessment of patients’ ACLF status, the evidence might be more robust.

In summary, the authors’ study highlights that frailty may have a significant impact on the prognosis of patients with decompensated cirrhosis; we should therefore enhance the assessment of frailty in hospitalized patients to improve risk stratification and clinical decision-making. I also hope that this paper will contribute to further exploration of the predictive value of frailty in relation to ACLF and overall survival in patients with cirrhosis.