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Review

Palliative Care in End-Stage Liver Disease

by
Luisa Sousa
1,
Sofia Marques Silva
1,
Francisca Rego
2,
Rui Nunes
2 and
Hugo M. Oliveira
2,3,*
1
Internal Medicine Service, Matosinhos Local Health Unit, 4460-301 Matosinhos, Portugal
2
Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
3
Palliative Care Unit, Matosinhos Local Health Unit, 4460-301 Matosinhos, Portugal
*
Author to whom correspondence should be addressed.
Livers 2025, 5(3), 39; https://doi.org/10.3390/livers5030039
Submission received: 6 July 2025 / Revised: 14 August 2025 / Accepted: 20 August 2025 / Published: 22 August 2025

Abstract

Chronic liver disease is a significant global cause of morbidity and mortality. While early-stage liver cirrhosis is often asymptomatic, it can progress to a decompensated phase known as end-stage liver disease (ESLD), resulting in a high symptom burden, diminished quality of life, and frequent hospitalizations. Palliative care is a form of specialized care aimed at addressing the needs of patients; however, it remains underutilized in ESLD patients. Globally, the integration of palliative care into ESLD is impeded by several barriers. Certain factors—such as advanced age, the presence of hepatocellular carcinoma (HCC), and transplant listing status—have been associated with higher rates of palliative care referral. This review provides a comprehensive analysis of the current literature, emphasizing the benefits of palliative care interventions in ESLD, including improved symptom control and enhanced quality of life. It also underscores the impact on caregivers and healthcare systems, notably in reducing hospital readmissions. We advocate for a paradigm shift toward proactive, patient-centered models that integrate symptom management, advance care planning, and psychosocial support alongside disease-specific treatments for patients with ESLD.

1. Introduction

Chronic liver disease is a leading cause of global morbidity and mortality, responsible for approximately 1 to 2 million deaths annually [1,2]. It frequently progresses to cirrhosis and its complications. Despite advancements in controlling viral hepatitis, alcohol consumption and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) remain predominant causes of cirrhosis [1,2,3]. Progression to decompensated stages, acute-on-chronic liver failure (ACLF) [4,5], or hepatocellular carcinoma (HCC) [6,7] is associated with high mortality and often necessitates liver transplantation. However, the shortage of donor organs leaves many patients without a curative option [8,9].
Patients with end-stage liver disease (ESLD) also experience high rates of hospitalization and readmissions [10,11], leading to increased healthcare costs [12,13], and a significant proportion of deaths occur in hospital settings [14,15].
Palliative care’s foundational principles were established by Cicely Saunders, who emphasized alleviating patient suffering at advanced stages while maintaining dignity [16]. Since then, palliative care has evolved considerably, with the World Health Organization (WHO) recognizing its importance in its 1990 document, which has been updated over the years [17].
Palliative care is defined as specialized, multidisciplinary medical care aimed at addressing the physical, psychological, social and spiritual needs of patients and their caregivers, regardless of prognosis [17,18]. It can be applied at any disease stage, integrated with other treatments to promote symptom relief, enhance quality of life, and support families—without aiming to hasten or delay death.
This approach relies on a team consisting of physicians, nurses, psychologists, and social workers, ensuring personalized care and effective communication. Despite its importance, access remains limited, with the Lancet Commission estimating that 80% of the 61 million people who could benefit from palliative care do not receive it [19]. Furthermore, basic palliative care skills that are relevant to daily clinical practice should, as pointed out by the European Palliative Care Association, be incorporated into core medical curricula [20,21].

2. Aims and Methods

This comprehensive literature review does not focus on pharmacological strategies for symptomatic control, as these were adequately addressed in the 2022 recommendations of the American Association for the Study of Liver Diseases (AASLD) [22]. Instead, it aims to provide a broad analysis of the current literature, emphasizing the benefits of palliative care interventions in ESLD, including improved symptom control and enhanced quality of life. It also highlights the impact on caregivers and healthcare systems. Integrating palliative care in the management of ESLD is vital to improve the quality of life and offer comprehensive support.
A literature search was conducted using the MeSH terms “Palliative Care” and “End Stage Liver Disease” combined with the “AND” command. The search strategy used the data bases located in PubMed, Scopus, and Web of Science and included all data published until 31 January 2025. Additionally, backward citation searching was conducted by examining the reference lists of articles retrieved to identify the relevant literature. All studies that directly addressed the topic of palliative care and ESLD were considered, excluding studies focusing solely on liver failure or liver cirrhosis. All publications not written in Spanish, French, English, or Portuguese were excluded.

3. Palliative Care in End-Stage Liver Disease

3.1. The Needs of Patients with ESLD

The SUPPORT study revealed that ESLD patients experience significantly reduced quality of life, marked by multiple complex physical, cognitive, and social symptoms [10]. Common symptoms include pain, dyspnea, asthenia, and mental confusion [10,23]. These findings have been corroborated by other studies and synthesized in a 2019 meta-analysis by Peng et al., which reported symptom prevalence rates of approximately: 30–79% for pain, 20–88% for dyspnea, 56–68% for cramps, 52–86% for asthenia, and 7–64% for pruritus—the latter considered a diseased-specific symptom in this population [24].
Symptom management remains suboptimal, often due to fear of pharmacological toxicity [25,26,27]. However, evidence suggests that the adverse effects of opioids are minimal or not clinically significant, particularly regarding hepatic encephalopathy, when used appropriately for pain control [28]. As physical deterioration progresses, symptoms tend to worsen, often leading to frequent hospitalizations near the end of life [12,27]. Studies also indicate that patients in terminal phases are subjected to aggressive treatments during hospitalization [10,29].
Beyond the physical the symptom burden, patients with ESLD also experience high levels of emotional distress [30], with studies highlighting limited disease knowledge and substantial uncertainty regarding the course of their illness [31,32]. On the other hand, patients perceive a lack of integration of care, with recurrent changes in care teams and a lack of communication between hospital-based and community-based providers [31,32,33], although evidence supports the benefits of coordinated and integrated care among the various specialties that treat patients with cirrhosis [34].

3.2. The Evolution of the Implementation of Palliative Care in ESLD

Although the SUPPORT data highlights the particularity and complexity of ESLD patients [10], it was the study published by Poonja et al. in 2014 that has driven future research on palliative care in this population [35]. This study showed that, following exclusion from the liver transplant list, only 11% of patients were referred to palliative care [35]. In the following years, research in this area expanded, with most studies involving cohorts from the United States of America (USA) [13,29,36,37,38,39] and the United Kingdom [40,41,42], and additional data emerging from Canada [35], Portugal [43,44], Taiwan [45] and Australia [46,47]. However, globally, data remain limited, and findings from the USA may not be fully applicable elsewhere due to differences in healthcare systems [48]. Studies have shown that palliative care utilization has increased from initial rates of 10–20% to approximately 50%, with these differences found to be statistically significant [35,37,46,49,50,51,52]. However, in recent years the rates have remained stable, which seems to suggest a plateau effect in referral to palliative care [51]. Several studies have also highlighted that palliative care interventions often occur late in the disease course [29,39,41,46,53]. In one study, 50% of patients were assessed by palliative care services only three days before death [37].
Growing evidence in this field led to the publication of the first recommendations by the AASLD regarding the implementation of palliative care and symptom management in patients with decompensated cirrhosis [22]. In 2023, the same organization recommended integrating palliative care components within multidisciplinary teams to support therapeutic decision-making for patients with HCC [54].

3.3. Factors Associated with the Implementation of Palliative Care in ESLD

From the outset, determining the optimal timing for referring patients with ESLD to palliative care has been a key challenge. Multiple studies have examined factors associated with the implementation of palliative care in this population. Table 1 summarizes (in alphabetical order) the factors that have consistently shown significance in multivariate analyses.
The most frequently investigated factors in relation to palliative care referral include age, the presence of HCC, and status on the liver transplant list. Consistent evidence indicates that referral to palliative care is more likely for older patients [36,41,42,44,50,53,55,56,57] and those diagnosed with HCC [13,36,42,43,44,46,49,50,51,53,55,56]. Conversely, being listed for a liver transplant appears to act as a barrier to palliative care referral [29,36,39,51,52,53,57]. Studies by Esteban et al. and Ufere et al. highlighted that listing for transplantation reduces consensus among specialists regarding the appropriateness of such referrals [58,59].
Several studies have attempted to demonstrate a relationship between Model for End-Stage Liver Disease (MELD) score, the associated mortality and the implementation of palliative care [52,53,60,61]. However, findings have been inconsistent, with some studies showing contradictory results [37,44,46,49,57]. Notably, evidence suggests that even with low MELD scores, up to 70% of these patients can have a high symptomatic burden and poor quality of life [62].
Additional factors associated with increased palliative care referral include ongoing alcohol consumption [36,46] and treatment at larger hospitals [13,50,51,55,63]. This last finding can be explained by greater availability of resources and thus structured palliative care services. The type of decompensation also influences referral patterns; chronic and predictable conditions such as ascites or hepatic encephalopathy are linked to greater palliative care engagement [36,37,41,44,51,52,53,55,60]
Recently, in a study published by Homann et al., the Surprise Question (“would I be surprised if a patient were to die?”) was shown to be a good prognostic indicator of mortality when answered by hepatologists. Additionally, it proved to be a useful screening tool with good sensitivity for identifying patients with ESLD at higher risk of death who may benefit from palliative care [64].
Table 1. Factors associated with the implementation of palliative care in ESLD.
Table 1. Factors associated with the implementation of palliative care in ESLD.
Favors ReferralDoes Not Favor Referral
Active alcohol consumption[36,46][49,60]
Hospital size[13,50,51,55,63][50]
Gender[63][36,46,50,51,52,53,56,60]
Older age[36,41,42,44,50,53,55,56,57][13,29,37,46,52,60]
Presence of HCC[13,36,42,43,44,46,49,50,51,53,55,56][29,52,60]
Presence on liver transplant list [29,36,39,51,52,53,57]
MELD score[52,53,60,61][37,44,46,49,57]
Type of decompensation
(ascites or hepatic encephalopathy)
[36,37,41,44,51,52,53,55,60][46]

3.4. Barriers to Early Implementation of Palliative Care in ESLD

Despite the high morbidity and mortality, which underscore the importance of early palliative care integration, several barriers hinder its implementation (Table 2). These obstacles can be grouped into three main categories: system-dependent factors (mainly due to the scarcity of resources within palliative care teams), clinician-related factors (particularly the uncertainty surrounding prognosis and the fear that referring patients to palliative care may negatively influence their outlook), and patient-related factors (often due to the negative stigma associated with palliative care) [33,59,65,66].
In fact, a study conducted by Donlan et al. concluded that ESLD patients had limited knowledge of palliative care, which was generally associated with end-of-life care [65]. In that study, as well as in the study by Abasseri et al., once a more contemporary definition of palliative care was presented, there was near-unanimous agreement on the need for its early implementation along the disease trajectory [65,67].
Furthermore, being on the liver transplant waiting list represents another major limitation to the implementation of palliative care. Studies have shown that ESLD patients listed for liver transplant receive lower-quality care in advanced stages of the disease, including during the end-of-life phase [68].
Table 2. Barriers to the implementation of palliative care in ESLD (adapted from references [48,59,66,69,70]).
Table 2. Barriers to the implementation of palliative care in ESLD (adapted from references [48,59,66,69,70]).
Dependent on the Healthcare SystemDependent on Clinical Care TeamsDependent on the Patient
Lack of comprehensive palliative care coverageLimited training or unclear role of palliative care in ESLDLack of understanding of disease trajectory and prognosis
Shortage of human resources in palliative care teamsLimited time during routine consultationsSometimes unrealistic prioritization of curative options
Limited training in palliative careDifficulty in addressing end-of-life careAssociation of palliative care with end-of-life care
Fear of the negative impact that referral to palliative care may have on patients listed for liver transplant
Late referral
Examples of multidisciplinary models of care, such as HepatoCare, that integrate effective palliative care and specialist hepatology management in ELSD have been published [47,71]. Despite their small sample sizes and single-center nature, they have shown positive results [47,71]. A multicenter randomized controlled trial (PAL-LIVER) is currently underway and may demonstrate an appropriate model of care [72], contributing to breaking down the barriers to the implementation of palliative care in ESLD.

3.5. The Impact of Palliative Care Intervention in ESLD

3.5.1. On the Patient

Multiple studies have demonstrated that palliative care improves symptom control and enhances quality of life in ESLD patients [38,73,74]. The pioneering study by Baumann et al. demonstrated that referring patients on the liver transplant waiting list to palliative care led to symptom improvement [38]. In this study, the researchers were able to significantly reduce several symptoms—such as pruritus, appetite loss, and fatigue—which had previously been perceived as moderate in intensity, in addition to improving patients’ overall sense of well-being [38].
A pilot study conducted by Quinn et al. showed that close follow-up by palliative care specialists enabled early recognition and stabilization of symptoms [75]. Another study by Shinall et al., despite facing recruitment challenges, was able to demonstrate that regular palliative care follow-up increased the number of days patients remained out of hospital [73].
In 2023, a study demonstrated that patients with ESLD often have a misperception of their prognosis, tending to be overly optimistic [76]. Another study highlighted the importance of clear and empathetic communication when delivering the diagnosis of ESLD, and how this influences the patients’ emotional response [32].
Discussions about advance care planning provide opportunities to inform patients about disease expectations, clarify doubts, and align care with personal values [77]. Although evidence suggests that ESLD patients are generally open and willing to discuss advance care planning—especially with their usual care team [78,79]—these conversations rarely take place and typically occur in an inpatient setting during acute episodes of decompensation [66,77,80]. Such discussions are even less frequent among patients on the liver transplant waiting list [81].
One commonly cited barrier to implementing advance care planning is the limited time available during outpatient consultations [31,66]. A study by Lamba et al. showed that early integration of palliative care increased the rate of advance care planning discussions from 2% to 38% [82]. This finding has been supported by more recent studies, which confirmed a higher frequency of advanced care planning among ESLD patients followed by palliative care teams [46,71].
In fact, research has highlighted the role of palliative care in providing educational and emotional support to ESLD patients, facilitating the development of a personalized care plan [83,84]. Several models have already been proposed to assist healthcare professionals in communicating prognosis with ESLD patients, including the Best Case/Worst Case framework [85], and even video-based informational tools delivered through digital platforms [86].

3.5.2. On the Caregivers

Several studies have demonstrated the negative impact that ESLD has on caregivers, particularly regarding psychological and financial burdens [25,33,65,87]. Commonly reported symptoms include anxiety, depression, and insomnia [88,89]. This symptomatic burden is often associated with factors such as alcohol use, the presence of hepatic encephalopathy, the severity of underlying liver disease, uncertainty regarding prognosis, and frequent hospitalizations [31,33,65,87].
Furthermore, when hepatic encephalopathy occurs, family members or caregivers often become primary decision-makers. One study revealed that family members have significant difficulty coping with the end-of-life process [31], and a lack of information about the disease may shift the family’s focus toward the curative goal of liver transplantation [83]. In many cases, family members serve as informal caregivers—roles frequently marked by uncertainty [31,87,90].
One study showed that regular support for the patient helped improve the quality of life of informal caregivers [74]. Many interventions focus on caregiver education and empowerment, particularly in managing treatment regimens and recognizing warning signs—needs widely acknowledged by caregivers themselves [65]. This is especially important because family members play a crucial role in providing emotional support and assisting with decision-making [32].

3.5.3. On the Healthcare System

Shinall et al. demonstrated that regular palliative care intervention following hospital discharge resulted in reduced hospital readmission rates and a greater number of days spent out of the hospital [73]. These findings are supported by other studies showing significant decreases in 30- and 90-day hospital readmission rates [36,55,56,91], as well as a reduction in average length of hospital stays [13,36,47,55,71]. Additionally, referral to palliative care has been associated with increased referrals to long-term care facilities such as nursing homes or hospice services [46,47,52,56,71,80].
Multiple studies have also shown that implementing palliative care leads to direct healthcare cost reductions—up to 50% in some cases [13,36,39,46,51]. This is achieved either through decreased utilization of diagnostic tests [13,46,51] or by more appropriate resource allocation, such as reducing intensive care admissions through predefined care limits [52,91].

4. Discussion

This review highlights that ESLD poses a substantial global health burden. Patients with ESLD patients often experience a significantly diminished quality of life, characterized by a high symptom burden, elevated emotional stress, and frequent hospitalizations. Although there has been increase integration of palliative care in the management of ESLD, recent years suggest that referral rates have remained stable [51]. This may reflect the scarcity of resources within palliative care teams—a barrier highlighted in several studies [48,59,66]. Notably, palliative care interventions are often introduced late in the disease trajectory—typically near the end of life [29,39,41,46,53], thereby limiting the potential therapeutic and psychosocial benefits. Delayed referrals reduce opportunities for symptom management, advance care planning, and psychosocial support.
Although most studies are retrospective, single-center cohorts, which may limit generalizability, studies have consistently shown that certain patient or disease characteristics, such as patient age [36,41,42,44,50,53,55,56,57] and the diagnosis of HCC [13,36,42,43,44,46,49,50,51,53,55,56] favors referral to palliative care. Being listed for a liver transplant act as a barrier to palliative care referral [29,36,39,51,52,53,57]. In fact, the dominant clinical emphasis on liver transplantation, the only curative modality, seems to overshadow the need for supportive and palliative care.
A growing body of evidence reveals that palliative care has a positive impact on ESLD patients. This translates into improved symptom control of ESLD patients, caregiver support and reduce resource utilization by preventing and decreasing recurring cycles of avoidable hospital admissions [36,55,56,74,75,91]. However, most available data originate from the USA and factors such as the hospital culture and the existence of structured hepatology and palliative care services, may influence the global applicability of this approach. Interdisciplinary models that combine hepatology and palliative care expertise are emerging as promising strategies for management of ESLD patients and their families [47,72]. The replication of these models of care, such as HepatoCare, and the insights that would be driven by the PAL-LIVER trial may help to further demonstrate the benefits of palliative care interventions in ESLD. We believe that the recognition and publication of guidelines by scientific associations in the field of hepatology regarding palliative care and ESLD can undoubtedly contribute to a paradigm shift. Furthermore, the creation of international research protocols could contribute to the solidification of palliative care intervention in ESLD.
We recognize that clinical trajectory of ESLD is unpredictable, often characterized by episodic decompensations. This fluctuating course complicates timely prognostication and the initiation of goals-of-care discussions. However, referrals to palliative care should be based on patient needs rather than on prognosis. Also, misconceptions about the role of palliative care among clinicians and patients can serve as barriers. It is imperative to reframe the role of palliative care within the healthcare system: it should not be viewed as a sign of therapeutic failure but as an essential component of comprehensive care for patients with liver cirrhosis and other serious illnesses. Timely and adequate referrals to palliative care should be recognized as hallmark of quality of care. Based on the data found, and adapting the model proposed by HepatoCare and Mazzarelli et al., we propose that referral to palliative care should be considered in at least 7 situations, described in Figure 1 [47,92].

5. Conclusions

ESLD is a progressive, life-limiting disease that demands a comprehensive, patient-centered approach. Palliative care has been shown to enhance quality of life, alleviate symptom burden, and support complex decision-making in patients with chronic illnesses, including ESLD. The timely and routine incorporation of palliative care principles into ESLD management should become a standard component of best practices in hepatology.

6. Future Directions

We identified some areas that warrant further analysis. Future research should focus on evaluating the effectiveness of specific palliative interventions and identifying the most appropriate models of care that can have a global application. Clear, consensus-based guidelines are needed to define the timing, scope, and structure of palliative care in ESLD—particularly whether it should be delivered as a consultation service or through co-management. Innovative care models, such as embedding palliative care specialists within hepatology teams or establishing joint hepatology-palliative care clinics, may enhance care coordination and outcomes.
Additionally, particular attention must be given to ESLD patients on the liver transplant waiting list. Despite their complex needs, studies consistently report low rates of palliative care involvement in this population.

Author Contributions

Conceptualization, L.S., S.M.S. and H.M.O.; methodology, H.M.O.; software, L.S. and S.M.S.; validation, F.R., R.N. and H.M.O.; formal analysis, H.M.O.; investigation, L.S., S.M.S. and H.M.O.; data curation, H.M.O.; writing—original draft preparation, L.S. and S.M.S.; writing—review and editing, L.S., S.M.S., F.R., R.N. and H.M.O.; visualization, H.M.O.; supervision, F.R., R.N. and H.M.O.; All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

No new data were created or analyzed in this study. Data sharing is not applicable to this article.

Conflicts of Interest

The authors declare no conflicts of interest.

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Figure 1. Consider referral to palliative care (regardless of transplant criteria) for patients with any of these 7 conditions. ACLF—acute-on-chronic liver failure; BCLC—Barcelona Clinic Liver Cancer; SPICT—Supportive & Palliative Care Indicators Tool; NECPAL—NECesidades Paliativas tool.
Figure 1. Consider referral to palliative care (regardless of transplant criteria) for patients with any of these 7 conditions. ACLF—acute-on-chronic liver failure; BCLC—Barcelona Clinic Liver Cancer; SPICT—Supportive & Palliative Care Indicators Tool; NECPAL—NECesidades Paliativas tool.
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Sousa, L.; Silva, S.M.; Rego, F.; Nunes, R.; Oliveira, H.M. Palliative Care in End-Stage Liver Disease. Livers 2025, 5, 39. https://doi.org/10.3390/livers5030039

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Sousa L, Silva SM, Rego F, Nunes R, Oliveira HM. Palliative Care in End-Stage Liver Disease. Livers. 2025; 5(3):39. https://doi.org/10.3390/livers5030039

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Sousa, Luisa, Sofia Marques Silva, Francisca Rego, Rui Nunes, and Hugo M. Oliveira. 2025. "Palliative Care in End-Stage Liver Disease" Livers 5, no. 3: 39. https://doi.org/10.3390/livers5030039

APA Style

Sousa, L., Silva, S. M., Rego, F., Nunes, R., & Oliveira, H. M. (2025). Palliative Care in End-Stage Liver Disease. Livers, 5(3), 39. https://doi.org/10.3390/livers5030039

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