Frailty is a multidimensional clinical state of decreased physiologic reserve and increased vulnerability for patients. It is a condition in which all body systems gradually lose their capabilities, and it usually occurs in older people (1). However, as the definition of frailty evolves day by day in modern research, it has been observed in other diseases involving multiple systems, including end-stage liver diseases (2). The pathogenesis of frailty is complicated, and the possible theory describes the process as the combined influence of chronic inflammation, immune activation, and environmental and lifestyle factors (3). Currently, no agreement has been reached on the diagnosis of frailty, so various assessment instruments have been developed, such as the Edmonton Frailty Scale (EFS), Fatigue, Resistance, Ambulation, Illness, Loss of Weight (FRAIL) Index, and the Liver Frailty Index (LFI) (4, 5). The cost and prevalence of frailty are hard to evaluate due to the differences in the study population, sample size, and measurement instruments (6). Therefore, a synthesized analysis is needed to evaluate the frailty of certain diseases and to better prevent them.

Cirrhosis, on the other hand, is described as the final stage of chronic liver disease, combined with a series of complications (7). As the 11th most common cause of death (8), cirrhosis caused 1.7 million deaths worldwide in 2017, and the age-standardized death rate of cirrhosis is still rising (9). Frailty in cirrhosis patients has a great impact on mortality and life quality, especially for those awaiting transplants (10). Thus, considering the prevalence of cirrhosis and the impact of frailty, identifying the prevalence and characteristics of frailty in cirrhosis patients can be a lifesaver in end-stage liver disease management and, in the end, contribute to the primary, secondary, and tertiary prevention of liver disease.

Although previous studies have described the impact of frailty in cirrhosis patients, no unified conclusions have been reached on the estimated prevalence. Many factors, including mental health, unplanned hospital admissions, liver transplant waitlist mortality, age, and increased hospitalization days, are associated with frailty in cirrhosis patients. In addition, several high-quality observational studies that were published in recent years reported the prevalence of cirrhosis patients (11–26). Thus, we systematically gathered data from these articles to evaluate the prevalence and characteristics of frailty in cirrhosis patients.

The study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (27). The protocol of this meta-analysis was registered by the Prospective Register of Systematic Reviews (PROSPERO) with the following registration number: CRD42023407442.

Our meta-analysis compared the outcomes of data collected from 16 observational studies regarding the prevalence of frailty in 8,406 patients with cirrhosis. An estimated prevalence of 27% was shown in cirrhosis patients with frailty. We further investigated the distribution of sex, age, and BMI in cirrhosis patients with or without frailty to characterize our target patients. As a result, the frail cohort has a higher average age, a larger proportion of male patients, and a lower BMI than the non-frail cohort. Such results can help clinicians to easily and swiftly identify frailty in patients with cirrhosis.

At the time our research is being conducted, few research studies have focused on the prevalence of frailty in cirrhosis patients. A previous meta-analysis (29) discussed the frailty assessment instruments in cirrhosis patients, including the Liver Frailty Index (LFI), the Short Physical Performance Battery, the 5-m gait speed, and routine nursing assessment, but it did not research the estimated prevalence of frailty as our study does. Currently, the most frequent tool is the LFI, which is a performance-based tool comprising three separate tests, including grip strength, chair stands, and balance testing. The other most commonly used tools are the Fried phenotype and the Fried Frailty Index (FFI), which cover weight loss, exhaustion, low physical activity, slowness, and weakness. Other tools include the Karnofsky Performance Scale (KPS), which assesses patients' ability to work and care for themselves, and the short physical performance battery (SPPB), which includes a balance test, gait speed test, and chair stand test. Several other meta-analyses (30–34) calculated the prevalence of frailty in different populations, which resulted in 11% in the older community-dwelling population, 53% in long-term care residents, 5%−29% in patients with human immunodeficiency virus (HIV) infections, and 37% in patients with end-stage renal disease. All the studies mentioned above discussed a specific population without cirrhosis. Overall, our study filled the gap in the prevalence of frailty in cirrhosis patients.

There have been several reports demonstrating the association of factors with frailty in cirrhosis patients, including mental health, unplanned hospital admissions, liver transplant waitlist mortality, age, and increased hospitalization days. For instance, researchers have identified age as a significant influencing factor for frailty (35). Our findings also reveal that the cirrhosis patients in the frail cohort tend to have a higher age when compared to the non-frail cohort. However, it should be noted that a recent report found that cirrhosis patients may also experience frailty at a younger age (23). Together with our findings, aged cirrhosis patients require more frequent evaluation in clinics.

In the current study, a male predominance of frailty among cirrhosis was found, which is against the published findings (19, 25). First, these studies and a few others included a lot more male than female patients, which may create bias. Second, male patients with cirrhosis are more likely to have comorbidities such as spontaneous bacterial peritonitis and hepatocellular carcinoma, which may also accelerate frailty.

With our findings, we hope cirrhosis patients can be identified swiftly and easily during outpatient visits and inpatient admissions to improve the quality of life and mortality in end-stage liver disease patients. Considering the prevalence of frailty in cirrhosis patients, all kinds of assessment instruments should be used regarding local demographics in hepatology clinical practice. After the diagnosis of frailty, a comprehensive intervention combining in-hospital treatment with community-based physical activity and nutritional programs (36) should be taken to reduce the prevalence and improve mortality in end-stage liver disease patients, especially those on the liver transplant waitlist.

To better summarize our meta-analysis, we are focusing on the prevalence of frailty in cirrhosis patients and calculating related parameters through subgroup analysis. The result of the sensitivity analysis and assessing the risk of bias in prevalence studies through the modified tool (28) indicated the credibility and stability of our study. There are also limitations in our meta-analysis. First, the study population in articles meeting the inclusion criteria comes from a diverse background, including age, nationality, race, etc., which can cause bias. Second, during the research, high heterogeneity was found. As limited data was retrieved, the cause of heterogeneity was unable to be identified. Third, we failed to acquire sufficient data regarding the complications, etiology, and other factors that might be influencing the prevalence of frailty in cirrhosis patients. Fourth, the data on the clinical impact of frailty, such as the severity of liver cirrhosis, in the reported papers chosen is limited. Future work could explore the clinical impact for the benefit of clinical practice. Finally, funnel plot asymmetry cannot discriminate between publication bias and other sources of asymmetry, and meta-regression could be employed to assess the heterogeneity.

This meta-analysis indicated that the estimated prevalence of frailty in cirrhosis patients stayed at a high level, and compared to the non-frail cohort, the frail patients tend to be male, older, and have a lower BMI with worse liver function. With these findings, we hope more resources and efforts can be directed toward reducing the prevalence of frailty in cirrhosis patients and improving their mortality. This approach could potentially lead to better health outcomes and quality of life for these patients.

The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author.

RX: Data curation, Validation, Writing – original draft, Writing – review & editing. XJ: Data curation, Validation, Writing – original draft, Writing – review & editing. CY: Data curation, Funding acquisition, Resources, Supervision, Validation, Writing – original draft, Writing – review & editing.