What is end-stage liver disease (ESLD)? Fast Fact #481 ESLD, also known as decompensated cirrhosis or chronic liver failure, is the final phase of the progression of chronic liver disease. It features cirrhosis accompanied by complications of portal hypertension and hepatic dysfunction such as ascites, variceal bleeding, spontaneous bacterial peritonitis, hepatorenal syndrome (HRS), hepatic encephalopathy, jaundice, and sarcopenia (1). Patients with ESLD often have an elevated Model for End-Stage Liver Disease (MELD) score of 20 or more, or a Child-Turcotte-Pugh (CTP) class C (2). While ESLD is a progressive disease that is ultimately terminal in the absence of liver transplantation (LT), the trajectory of illness can be unpredictable and unstable, with abrupt hepatic decompensation and organ failure leading to hospitalizations and even sudden death (3). See Fast Fact #188, Fast Fact #189, and Fast Fact #348 for more information. 

Role of LT: LT is potentially curative and significantly improves long-term survival in ESLD. However, out of approximately 10 million prevalent ESLD cases globally, only 35,000 LTs are performed annually (4,5).  Patients on the LT waitlist have 13% annual mortality (6). Access to timely LT is affected by donor availability, financial limitations, psychosocial issues such as substance use, disease progression (“too sick for transplant”), medical comorbidities, and patient preference (7). Therefore, for many patients with ESLD, the care shifts at some point from a curative focus to a supportive/palliative focus. 

What are the benefits of specialized palliative care (PC) involvement? Patients with ESLD often have a multitude of unmet PC needs. These include uncontrolled physical symptoms (fatigue, shortness of breath, fluid retention, and pain are especially common), emotional distress, lack of prognostic awareness, difficulty making healthcare decisions, caregiver burnout, and financial distress (8). Many patients and families living with ESLD are unaware of hospice care (8). Many do not have a designated health care power of attorney (HCPOA) (8). Specialized PC teams (which sometimes include clinical pharmacists) can enhance symptom management, quality of life, advance care planning, and medication dosing for patients with ESLD, while also promoting goal-concordant care, assessing decision-making capacity, and fostering honest and clear illness communication (9-14). Studies suggest that they neither reduce the likelihood of LT nor increase mortality in patients with ESLD (9,10).

Timing of a PC consult in ESLD: While evidence suggests that early involvement of specialized PC teams is beneficial, the optimal timing for involving PC consultation in ESLD has not been established (13). Expert opinion and specialty guidelines suggest that specialist PC consultation be considered for all patients with decompensated cirrhosis, advanced hepatocellular carcinoma, or HRS (2). Transplant candidacy should not discourage specialized PC consultation (2). 

When does specialized PC get involved in ESLD care? Despite its benefits and status as a quality indicator, specialized PC consultation is underutilized in ESLD care (14,15). Many clinicians struggle with identifying the optimal time for involving specialized PC teams due to the unpredictable disease trajectory and the possibility of curative LT.  Approximately 10% are referred to specialized PC teams or hospice care, and those who do are often referred within days to a few weeks before death (16,17). 

What are the barriers to specialized PC involvement? Clinician barriers to PC consultation that have been described in the published ESLD literature are (14,18-20): 

• Concern for conflicting messaging about the potential for cure with an LT and the high mortality. 
• Concern for diminishing hope or eliciting feelings of abandonment. 
• Unpredictable disease course and uncertain prognosis.  
• Lack of understanding of the role and benefits of specialized PC teams. 
• Discomfort and difficulty in having end-of-life conversations. 
• Concern about the use of opioids for pain increasing the risk for encephalopathy. 

How can clinicians better address the unmet PC needs of patients with ESLD?  Child’s class C or worse, MELD scores 21 or worse, frequent hospitalizations, and hepatic decompensation events such as ascites, hepatic encephalopathy, or variceal bleeding should be considered as disease progression milestones (21). Such events should prompt clinicians to screen for unmet PC needs by seeking answers to the following clinical questions (22): 

• Does the patient have a designated HCPOA? 
• Does the patient retain the capacity to make complex medical decisions? 
• Has the patient been assessed for physical, emotional, spiritual, and social distress? 
• Would I be surprised if the patient never got an LT? Died within a year? 
• Has the patient had a serious illness discussion with their treating clinicians addressing their illness severity, prognosis, and realistic treatment options? 
• Has the clinician explored care preferences on LT, future medical care, and code status?  
• Has the clinician considered whether hospice care services are appropriate?  

If there is any difficulty with addressing any of these questions, then a specialized PC consultation (outpatient or inpatient) is warranted. 

References:  

1. Philips CA, Kedarisetty CK. Palliative Care for Patients with End-Stage Liver Disease. J Clin Exp Hepatol. 2023 Mar-Apr;13(2):319-328. 
2. Walling, A.M., Ahluwalia, S.C., Wenger, N.S. et al. Palliative Care Quality Indicators for Patients with End-Stage Liver Disease Due to Cirrhosis. Dig Dis Sci 2017; 62:84–92. 
3. Haep N, Florentino RM, Squires JE, et al. The Inside-Out of End-Stage Liver Disease: Hepatocytes are the Keystone. Semin Liver Dis. 2021 May;41(2):213-224. 
4. GBD 2017 Cirrhosis Collaborators. The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol. 2020;5(3):245-66. 
5. Terrault N, Francoz C, Berenguer M, et al. Liver Transplantation 2023: Status Report, Current and Future Challenges. Clin Gastroenterol Hepatol. 2023;21(8):2150-66. 
6. Kwong AJ, Ebel NH, Kim WR, et al. OPTN/SRTR 2021 Annual Data Report: Liver. Am J Transplant. 2023;23(2 Suppl 1):S178-63. 
7. Jadlowiec CC, Taner T. Liver transplantation: Current status and challenges. World J Gastroenterol. 2016 May 14;22(18):4438-45 
8. Peng JK, Hepgul N, Higginson IJ, et al. Symptom prevalence and quality of life of patients with end-stage liver disease: A systematic review and meta-analysis. Palliat Med. 2019 Jan;33(1):24-36. 
9. Baumann AJ, Wheeler DS, James M, et al Benefit of early palliative care intervention in end-stage liver disease patients awaiting liver transplantation. J Pain Symptom Manage. 2015;50(6):882–6.e2.  
10. Lamba S, Murphy P, McVicker S, et al. Changing end-of-life care practice for liver transplant service patients: structured palliative care intervention in the surgical intensive care unit. J Pain Symptom Manage. 2012;44(4):508-19. 
11. Shinall MC, Karlekar M, Martin S, et al. COMPASS: a pilot trial of an early palliative care intervention for patients with end-stage liver disease. J Pain Symptom Manage. 2019;58(4):614–22.e3. 
12. Kimbell B, Murray SA, Byrne H, et al. Palliative care for people with advanced liver disease: a feasibility trial of a supportive care liver nurse specialist. Palliat Med. 2018;32(5):919–29. 
13. Woodland H, Hudson B, Forbes K, et al. British Association for the Study of the Liver (BASL) End of Life Special Interest Group. Palliative care in liver disease: what does good look like? Frontline Gastroenterol. 2019 Sep 10;11(3):218-227. 
14. Dunn SH, Rogal SS, Maier MM, et al. Access to comprehensive services for advanced liver disease in the Veterans Health Administration. Digestive Diseases and Sciences 2019; 64:3471-3479. 
15. Shehadah A, Yu Naing L, Bapaye J, et al. Early palliative care referral may improve end-of-life care in end-stage liver disease patients: A retrospective analysis from a non-transplant center. Am J Med Sci. 2024 Jan;367(1):35-40. 
16. Gupta K, Hans B, Khan A, et al. A retrospective study on use of palliative care for patients with alcohol related end stage liver disease in United States. World J Hepatol. 2022 Sep 27;14(9):1817-1829. doi: 10.4254/wjh.v14.i9.1817. PMID: 36185714; PMCID: PMC9521455. 
17. Patel AA, Walling AM, Ricks-Oddie J, et al. Palliative care and health care utilization for patients with end-stage liver disease at the end of life. Clin Gastroenterol Hepatol 2017; 15: 1612–19. 
18. Ufere NN, Donlan J, Waldman L, et al. Barriers to Use of Palliative Care and Advance Care Planning Discussions for Patients With End-Stage Liver Disease. Clin Gastroenterol Hepatol. 2019 Nov;17(12):2592-2599.. 
19. Donlan J, Ufere NN, Indriolo T, et al. Patient and Caregiver Perspectives on Palliative Care in End-Stage Liver Disease. J Palliat Med. 2021 May;24(5):719-724.  
20. Esteban JPG, Rein L, Szabo A, et al. Attitudes of Liver and Palliative Care Clinicians toward Specialist Palliative Care Consultation for Patients with End-Stage Liver Disease. J Palliat Med. 2019 Jul;22(7):804-813. 
21. Ferrarese A, Bucci M, Zanetto A, et al. Prognostic models in end stage liver disease. Best Pract Res Clin Gastroenterol. 2023 Dec;67:101866 
22. Weissman DE, Meier DE. Identifying patients in need of a palliative care assessment in the hospital setting: a consensus report from the Center to Advance Palliative Care. J Palliat Med. 2011 Jan;14(1):17-23.

Author Affiliations: 1Department of Supportive Care, University Health Network, Toronto, Ontario Canada; 2Medical College of Wisconsin, Milwaukee, WI
Version History: First electronically published in March 2024
Conflicts of Interest: None to report