Malnutrition, defined as deficiency, excess, or imbalance of nutrients, is a common complication in patients with liver disease, especially those with cirrhosis. Malnutrition may present as an isolated micronutrient deficiency, such as zinc deficiency, and it commonly presents as frailty and/or sarcopenia in patients with advanced liver disease. Patients with cirrhosis and/or alcohol-associated hepatitis should be assessed for malnutrition because it adversely affects patient outcomes including mortality, as well as waitlist and posttransplant outcomes among liver transplant candidates. The prevalence of malnutrition varies based on the method of assessment and disease severity, being higher in those with advanced liver disease. Among stable outpatients with cirrhosis, counseling should be done to eat small frequent meals, a night-time snack between 7 PM and 10 PM, and 2 or more cups of coffee daily. In selected patients with metabolic dysfunction-associated steatohepatitis, vitamin E 800 IU/d should be provided. Among hospitalized patients with cirrhosis, nutritional supplementation preferably by enteral route should be implemented in those with poor oral intake of daily requirements of proteins and/or calories. Protein intake should not be restricted including patients with decompensated cirrhosis and hepatic encephalopathy. A vegetable source of protein seems to be better tolerated than an animal source of protein in patients with hepatic encephalopathy. Branched chain amino acids augment the efficacy of lactulose and rifaximin in the treatment of hepatic encephalopathy. Level of evidence and strength of recommendations were evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations system. This guideline was developed under the auspices of the American College of Gastroenterology Practice Parameters Committee.

Background: Patients with end-stage liver disease (ESLD) have complex needs and may benefit from palliative care (PC), which is often underutilized or delayed. Objectives: To characterize patients with ESLD who received inpatient PC consultation and to explore differences in characteristics between those who received PC consultation before (pre-Pall) or after (post-Pall) PC participation at weekly liver transplant (LT) Patient Selection Committee (PSC) meetings. Design: Single-center retrospective cohort study. Setting/Subjects: Hospitalized patients with ESLD who received inpatient PC consultation between February 2017 and February 2019 at an academic LT center in the United States. Measurements: PC referral reasons and timing, code status, hospice referrals, discharge location, and mortality. Results: Two hundred five patients were included. The primary reason for PC was goals of care (88.8%; n = 182). Most (86.8%; n = 178) were Full Code at hospital admission, while 81% (n = 166) were do-not-resuscitate at discharge. Nearly one quarter (22.9%; n = 47) sought life-prolonging care at discharge, while 41.5% (n = 85) were discharged with hospice, and 34.1% (n = 70) died before discharge. By the end of the study, 85.9% (n = 176) were confirmed as deceased. Median time from PC to hospice referral was 12 days [95% confidence interval [CI]: 8-23]. Median time from PC consult to death was 13 days [95% CI: 9-17] and from hospice referral to death was 7 days [95% CI: 4-13]. There were no statistically significant differences between the pre- and post-Pall groups related to PC referral patterns or outcomes. Conclusions: Most PC contacts occurred near end of life, and many led to comfort-focused care. Late referrals may be due to reliance on inpatient consults during acute illness. PC presence at PSC meetings represents an important step in collaboration with LT teams but did not lead to direct impact on PC referral patterns or outcomes.

Objective: The prevalence and mortality of chronic liver disease has risen significantly. In end-stage liver disease (ESLD), the survival of patients is approximately 2 years. Despite the poor prognosis and high symptom burden, integration of palliative care in ESLD is reduced, and the majority of patients continue to die in inpatient care. We aim to assess predictors and outcomes of home palliative care, as well as factors associated with death at home in patients with ESLD. Methods: Retrospective cohort study of patients with ESLD, followed by a palliative care team between 2017 and 2022. Information regarding patient demographics, ESLD etiology, decompensations, and interventions was collected. Two-sided tests were used to identify factors associated with home palliative care. Results: We analyzed 75 patients: 44% had home palliative care and 33% died at home. ESLD patients with home palliative care were older (72.52 vs 64.45; p = 0.002), had a longer palliative care intervention time (149.97 ± 196.23 vs 43.69 ± 100.60 days; p = 0.007), higher rates of ascites or hepatic encephalopathy (χ2 = 11.024; p = 0.029), and hepatocarcinoma (90.9% vs 64.3%; p = 0.007). Patients with home palliative care had a reduction in-hospital admissions (2.61 vs 1.06; p = 0.000) and a greater probability of death at home (66.7% vs 33.3%; p = 0.000). Patients who died at home (33.3%) were older (72.20 vs 64.40; p = 0.000) and had longer palliative care intervention time (178.80 ± 211.78 vs 46.28 ± 99.67 days; p = 0.006). Conclusion: Home palliative care in ESLD differs based on demographics and disease complications, with a positive impact of homecare translated into a reduction in hospital admissions and an increased probability of death at home.

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer. Photon radiotherapy shows efficacy in treating HCC but carries risks of high exit dose and radiation-induced liver disease. Additionally, HCCs with portal vein tumor thrombosis (PVTT) have a poor prognosis and are associated with higher risk of death. In recent years, proton beam therapy (PBT) has emerged as a novel treatment with the ability to downstage HCC for liver transplant (LT).

This review will provide an overview of dosimetric benefits of PBT, efficacy of PBT in treating HCC, downstaging HCC-PVTT for LT, and a comparison of PBT with other non-surgical techniques. A search of PubMed until 3 September 2024 was conducted using free search and the following keywords: hepatocellular carcinoma, proton beam therapy, portal vein tumor thrombosis, local ablative therapy, trans-arterial chemoembolization, stereotactic body radiotherapy, Y-90 radioembolization.

Various clinical trials using PBT have shown promising tumor local control and overall survival rates. PBT is mostly safe and efficacious for downstaging HCC-PVTT for LT. PBT has also been shown to be non-inferior to various other treatment modalities. Future research should focus on combinations of PBT with other modalities.

A female patient in her mid-50s presented with left-sided effusion in the context of decompensated cirrhosis secondary to alcoholic hepatitis. She had a pre-existing injury to her left hemidiaphragm following a fall 2 years previously, at which point she had also developed a left-sided effusion. The diagnosis of hepatic hydrothorax (HH) was made following pleural fluid aspiration. Recurrent thoracocentesis was not sufficient to manage the effusion and diuretic use was limited by hyponatraemia. An indwelling pleural catheter (IPC) was subsequently inserted to facilitate routine drainage and management in the outpatient setting. To our knowledge, this is the first instance of IPC insertion for HH in Ireland.

End stage liver disease (ESLD) represents a growing health concern characterized by elevated morbidity and mortality, particularly among individual ineligible for liver transplantation. The demand for palliative care (PC) is pronounced in patients grappling with ESLD and acute on chronic liver failure (ACLF). Unfortunately, the historical underutilization of PC in ESLD patients, despite their substantial needs and those of their family caregivers, underscores the imperative of seamlessly integrating PC principles into routine healthcare practices across the entire disease spectrum.

To comprehensively investigate the evidence surrounding the benefits of incorporating PC into the comprehensive care plan for individuals confronting ESLD and/or ACLF.

A systematic search in the Medline (PubMed) database was performed using a predetermined search command, encompassing studies published in English without any restrictions on the publication date. Subsequently, the retrieved studies were manually examined. Simple descriptive analyses were employed to summarize the results.

The search strategies yielded 721 references. Following the final analysis, 32 full-length references met the inclusion criteria and were consequently incorporated into the study. Meticulous data extraction from these 32 studies was undertaken, leading to the execution of a comprehensive narrative systematic review. The review found that PC provides significant benefits, reducing symptom burden, depressive symptoms, readmission rates, and hospital stays. Yet, barriers like the appeal of transplants and misconceptions about PC hinder optimal utilization. Integrating PC early, upon the diagnosis of ESLD and ACLF, regardless of transplant eligibility and availability, improves the quality of life for these patients.

Despite the substantial suffering and poor prognosis associated with ESLD and ACLF, where liver transplantation stands as the only curative treatment, albeit largely inaccessible, PC services have been overtly provided too late in the course of the illness. A comprehensive understanding of PC's pivotal role in treating ESLD and ACLF is crucial for overcoming these barriers, involving healthcare providers, patients, and caregivers.

Advanced cirrhosis confers a significant symptom burden and has a 50% 2-year mortality rate in those with decompensated disease. There is increasing demand for supportive and palliative care (SAPC) for these patients, yet no consensus on the best model of delivery. It is necessary to identify the needs of such patients and their carers, and evaluate whether they are being met.A literature search was conducted using key words pertaining to adult patients with liver cirrhosis and their SAPC needs. Study quality was assessed and findings grouped by theme. 51 full texts were selected for inclusion, 8 qualitative studies, 33 quantitative studies, 7 systematic reviews, 2 mixed methods studies and 1 Delphi methods. Key findings were grouped into three main themes: SAPC needs, access to SAPC and models of care.Patients with cirrhosis have significant psychological and physical symptom burden with many unmet needs. These data failed to identify the best service model of care. The impact of specialist palliative care (SPC) referral was limited by small numbers and late referrals. With the majority of studies conducted in the USA, it is unclear how well these findings translate to other healthcare systems. Comparison between hepatology led services and SPC was limited by inconsistent outcome measures and prevented pooling of data sets. These data also had limited evaluation of patient-reported outcome measures. We propose the development of a core outcome set to ensure consistent and meaningful evaluation of the SAPC needs of patients with advanced non-malignant liver cirrhosis.

Delays and limitations of palliative care in patients with liver transplantation-ineligible end-stage hepatocellular carcinoma according to Barcelona Clinic Liver Cancer staging system may be explained by different perceptions between hepatologists and palliative care physicians in the absence of shared guidelines.

To assess physicians' attitudes toward palliative care in end-stage hepatocellular carcinoma and to understand what the obstacles are to more effective management and co-shared between palliative care physicians and hepatologists.

Members of the Italian Association for the Study of Liver Disease and the Italian Society of Palliative Care were invited to a web-based survey to investigate practical management attitude for patients with liver transplant-ineligible end-stage hepatocellular carcinoma.

Physician members of the of the two associations, representing several hospitals and services in the country.

Ninety-seven hepatologists and 70 palliative care physicians completed the survey: >80% regularly follow 1-19 patients; 58% of hepatologists collaborate with palliative care physicians in the management of patients, 55% of palliative care physicians take care of patients without the aid of hepatologists. Management of cirrhosis differed significantly between the two groups in terms of prescription of albumin, esophagogastroduodenoscopy, anti-viral treatment, anticoagulation, indication to paracentesis and management of encephalopathy. Full-dose acetaminophen is widely used among hepatologists, while opioids are commonly used by both categories, at full dosage, regardless of liver function.

This survey highlights significant differences in the approach to patients with liver transplantation-ineligible end-stage hepatocellular carcinoma, reinforcing the need for shared guidelines and further studies on palliative care in the setting.

The growing evidence of increased life expectancy in the future reveals the high relevance of frailty in patients with chronic-degenerative diseases; identification and management of symptoms may improve significantly their quality of life. The objective of our study was to assess the symptom burden in patients with advanced chronic or prolonged infectious diseases.

A cross-sectional study was performed enrolling 88 patients, referred to palliative care consultation for chronic pain, and evaluated using the Edmonton Symptom Assessment System to define Total Symptom Distress Score (TSDS) and high symptom burden (HSB) when more than six symptoms along with Numerical Rating Scale ≥4 were present.

All participants reported moderate to severe pain; in addition, 86 (97.7%) experienced a lack of well-being, 81 (92%) tiredness, 67 (76.1%) lack of appetite, 66 (75%) drowsiness, 66 (75%) depression, 56 (63.6%) anxiety, 49 (55.6%) nausea, and 39 (44.3%) shortness of breath. Forty-four patients (50%) had high TSDS, greater than 40.5, and presented lower Karnofsky Performance Scale (KPS) (median 40 vs. 70, p=0.0005), higher comorbidities (median 7 vs. 4, p=0.00001), and higher drug burden (median 9 vs. 6, p=0.0003) than those with low TSDS. Furthermore, considering symptom intensity, 40 patients (45.4%) had HSB and presented lower KPS (median 50 vs. 70, p=0.0005), higher comorbidities (median 7 vs. 4, p=0.00001), and higher drug burden (mean 9 vs. 6, p=0.01) compared to patients without HSB.

Our population had an HSB, in addition to pain, revealing high frailty. A correct assessment of symptoms is, therefore, required to manage patients with chronic infectious diseases. In this setting, attention should be given to identifying patients at high risk of HSB through a correct diagnosis and effective management, which should be based on a multi-professional approach.

While mortality rates from advanced chronic liver disease (ACLD) are rapidly increasing, patients with an advanced disease stage have a comparable or even higher symptom burden than those with other life-limiting diseases. Although evidence is limited there is increasing recognition of the need to improve care for patients with ACLD; however, there are many limiting factors to providing good palliative care for these patients, including unpredictable disease progression, the misconception of palliative care and end of life care as being equivalent, a lack of confidence in prescribing medication and a lack of time and resources. Health professionals working with these patients need to develop the skills to ensure effective palliative care, while referral to specialized palliative care centers should be reserved for patients with complex needs. Basic palliative care, along with active disease management, is best delivered by the treating hepatologists. This includes discussions about disease progression and advance care planning, alongside the active management of disease complications. Liver disease is closely associated with significant social, psychological, and financial burdens for patients and their caregivers. Strategies to engage the discussion in multidisciplinary teams early in disease progression help to ensure addressing these issues proactively. This review summarizes the evidence on palliative care for patients with ACLD, provides examples of current best practice and offers suggestions on how disease-modifying and palliative care can coexist, to ensure that patients do not miss opportunities for quality of life improving interventions.

Prevalence and mortality of chronic liver disease have risen significantly. In end stage liver disease, the survival of patients is approximately two years. Despite the poor prognosis and high symptom burden of these patients, integration of palliative care is limited. We aim to assess associated factors and trends in palliative care use in recent years.

A Multicenter retrospective cohort of patients with end stage liver disease who suffered in-hospital mortality between 2017 and 2019. Information regarding patient demographics, hospital characteristics, comorbidities, etiology, decompensations, and interventions was collected. Two-sided tests and logistic regression analysis were used to identify factors associated with palliative care use.

A total of 201 patients were analyzed, with a yearly increase in palliative care consultation: 26.7 % in 2017 to 38.3 % in 2019. Patients in palliative care were older (65.72 ± 11.70 vs. 62.10 ± 11.44; p = 0.003), had a lower Karnofsky functionality scale (χ=18.104; p = 0.000) and had higher rates of hepatic encephalopathy (32.1 % vs. 17.4 %, p = 0.007) and hepatocarcinoma (61.7 % vs. 26.2 %; p = 0.000). No differences were found for Model for End-stage Liver Disease (19.28 ± 6.60 vs. 19,90 ± 5.78; p = 0.507) or Child-Pugh scores (p = 0.739). None of the patients who die in the intensive care unit receive palliative care (0 % vs 31.6 %; p = 0.000). Half of the palliative care consultations occurred 6,5 days before death.

Palliative care use differs based on demographics, disease complications, and severity. Despite its increasing implementation, palliative care intervention occurs late. Future investigations should identify approaches to achieve an earlier and concurrent care model.

The prevalence and mortality of chronic liver disease has risen significantly. In end stage liver disease (ESLD) the survival of patients is approximately 2 years. Despite the poor prognosis and high symptom burden of these patients, integration of palliative care is reduced. We aim to analyze the agreement between palliative care and hepatology physicians of clinical scenarios that could require palliative care intervention.

A cross-sectional study was conducted. Palliative care and hepatology physicians were surveyed. Using a five-point Likert scale, their perceptions of palliative care in ESLD were rated. Their agreement in clinical scenarios that could require palliative care intervention were evaluated. Analyses were conducted to assess any differences by primary role (hepatology vs. palliative care) and length of practice (<10 years vs. 10 years).

A total of 123 responses were obtained: 52% from palliative care and 48% from hepatology. The majority (66.7%) work in the field for up to ten years. There was a great consensus in 4 of the 8 clinical scenarios. In scenarios with less consensus, the area of activity and length of practice influence the reliance of physicians on palliative care. Involvement of palliative care in ESLD was considered "rare" by 30% and 61% consider difficult to predict the prognosis. More than 90% support medical training in both areas of activity.

The current involvement of palliative care is considered low, but there are clinical conditions that reveal a clear consensus and there's a unanimous view of the relevance of training.

Patients with cirrhosis and acute kidney injury (AKI) are critically ill and have high health care resource utilization (HCRU). The impact and timing of goals of care discussions on HCRU are not well described.

221 patients enrolled in a prospective cohort study of patients admitted with AKI and cirrhosis were reviewed. Documentation and timing of a goals of care discussions were analyzed as predictors of HCRU, defined as a composite outcome of intubation, initiation of renal replacement therapy, and/or admission to the intensive care unit.

Median MELD score was 26 [IQR 19, 33]. 29% patients were listed for liver transplant. 90-day mortality was 61%. 51% patients had at least one HCRU episode. Code status changed from admission to discharge from 91%/7%/0% to 68%/14%18% (full code/do not resuscitate/comfort measures, p < 0.001). 28% patients underwent goals of care discussions, with change in code status at a median of 16 [9, 22] days into admission. Only 18% of discussions were within 7 days of admission and all were after an HCRU event. Being listed for liver transplant was not associated with whether goals of care discussions occurred (23% listed vs. 31% non-listed, p = 0.24) but was associated with higher HCRU (69% vs. 43%; p < 0.001).

Goals of care discussions occurred late into the hospital course, after episodes of HCRU. Efforts should be made to engage in these discussions earlier in the hospital stay, which may decrease HCRU rates in this critically ill population and align with patients' goals of care.

The purpose of this review is to describe an approach that emphasizes shared decision-making for patients with decompensated cirrhosis and acute kidney injury when liver transplantation is either not an option, or unlikely to be an option.

When acute kidney injury occurs on a background of decompensated cirrhosis, outcomes are generally poor. Providers can also be faced with prognostic uncertainty. A lack of guidance from nephrology and hepatology professional societies means that providers rely on expert opinion or institutional practice patterns.

For patients who are unlikely to receive liver transplantation, the occurrence of acute kidney injury represents an opportunity for a goals of care conversation. In this article, we share strategies through which providers can incorporate more shared decision-making when caring for these patients. The approach involves creating prognostic consensus amongst multidisciplinary teams and then relying on skilled communicators to share the prognosis. Palliative care consultation can be useful when teams need assistance in the conversations.

Hepatorenal syndrome (HRS) frequently complicates alcoholic hepatitis (AH) and portends poor survival in this population. Published literature indicates mixed benefits from renal replacement therapy (RRT) for HRS refractory to medical management. Therefore, we sought to assess the utilization of RRT in AH and clinical outcomes at a national level.

Using the International Classification of Diseases, Tenth Revision (ICD-10) codes, we identified adult patients with AH with a coexisting diagnosis of HRS from the National Readmission Database 2016 through 2019. Mortality, morbidity, and resource utilization were compared. We compared proportions using the Fisher exact test and computed adjusted P-values based on multivariate regression analysis. Analyses were performed using Stata, version 14.2, considering a two-sided P < 0.05 as statistically significant.

A total of 73 203 patients with AH were included in the analysis (mean age 46.2 years). A total of 3620 individuals had HRS diagnosis (5%), of which 14.7% (n: 532) underwent RRT. HRS patients receiving RRT had a higher mortality rate than those who did not (adjusted odds ratio [aOR] 1.8, 95% confidence interval [CI]: 1.3-2.6, P: 0.01), along with higher resource utilization. Only those patients with HRS who underwent liver transplantation (LT) experienced a mortality reduction (24.4% for those not receiving RRTs and 36.5% for those receiving RRT).

RRT is associated with higher mortality and morbidity when offered to patients with AH and HRS, who do not undergo LT. Therefore, our results suggest careful selection of AH patients when deciding to initiate RRT for HRS.

The incidence of chronic progressive diseases is rising and investment on quality of death and dying is of utmost importance to minimize physical and emotional suffering. There is still a gap in palliative care (PC) between patients with cancer and those with advanced chronic liver disease (ACLD). Our objectives were to characterize clinical attitudes and therapeutic interventions and to evaluate the differences in end-of-life care between inpatients with cancer and ACLD under gastroenterology care.

Retrospective cohort study, including patients with cancer or ACLD who died in a Gastroenterology department between 2012 and 2021. Demographic characteristics, clinical and endoscopic procedures and symptom control were compared between the groups.

From 150 patients, 118 (78.7%) died with cancer and 32 (21.3%) died from ACLD without concomitant hepatocellular carcinoma. ACLD patients were more frequently male ( P  = 0.001) and younger ( P  = 0.001) than patients with cancer. Median time of hospitalization in the last month of life was 16 days for both groups. Discussion of prognosis with the patient was more frequent for cancer patients (35.6% versus 3.2%, P  < 0.001). Referral to PC occurred in 18.8% and 61% of the patients with ACLD and cancer respectively ( P  < 0.001). Endoscopic procedures were performed in half of the patients and were more likely to be unsuccessful in those with cancer.

Clinical decisions were different between groups in terms of PC access and discussion of prognostic with the patient. It is urgent to define and implement metrics of quality of death and dying to prevent potentially inappropriate treatment.

Patients with end-stage liver disease (ESLD) who are not transplant candidates often have a trajectory of rapid decline and death similar to patients with stage IV cancer. Palliative care (PC) services have been shown to be underutilized for such patients. Most studies examining the role of PC in ESLD have been done at transplant centers. Thus, determining the utilization and benefit of PC at a non-transplant tertiary center may help establish a standard of care in the management of patients with ESLD not eligible for transplant.

We conducted a retrospective analysis of adult (>18 years) patients with ESLD admitted to Rochester Regional Health (RRH) system hospitals from 2012 to 2021. Patients were divided into groups based on the presence or absence of PC involvement. Baseline characteristics were recorded. The impact of PC was assessed by comparing the number of hospitalizations before and after the involvement of PC, comparing code status changes, health care proxy (HCP) assignments, Aspira catheter placements, and frequency of repeated paracentesis.

In our analysis of 576 patients, 41.1% (237 patients) received a PC consult (PC group), while 58.9% (339 patients) did not (no-PC group). Baseline characteristics were comparable. However, their mean number of admissions significantly decreased (15.66 vs. 3.49, p < 0.001) after PC involvement. Full code status was more prevalent in the no-PC group (67.8% vs. 18.6%, p < 0.001), while comfort care code status was more common in the PC group (59.9% vs. 20.6%, p < 0.001). Changes in code status were significantly higher in the PC group (77.6% vs. 29.2%, p < 0.001). The PC group had a significantly higher mortality rate (83.1% vs. 46.4%, p < 0.01). Patients in the PC group had a higher likelihood of having an assigned HCP (63.7% vs. 37.5%, p < 0.001). PC referral was associated with more frequent use of an Aspira catheter (5.9% vs. 0.9%, p < 0.001) and more frequent paracentesis (30.8% vs. 16.8%, p < 0.001).

In conclusion, our study provides compelling evidence of the diverse advantages of palliative care for patients with end-stage liver disease, including reduced admissions, improved goals of care, code status modifications, enhanced healthcare proxy assignments, and targeted interventions. These findings highlight the potential significance of early integration of palliative care in the disease trajectory to provide comprehensive, patient-centered care that addresses the unique needs and preferences of individuals with advanced liver disease.

Patients with advanced cirrhosis experience an unpredictable disease trajectory but are infrequently referred to palliative care (PC) services and rarely undertake advance care planning (ACP).

We assessed whether a novel model of care increased provision of meaningful PC in advanced cirrhosis compared with standard of care (SOC).

Thirty consecutive hepatology clinic outpatients with advanced cirrhosis, meeting one or more cirrhosis-related PC referral criteria, consented to treatment in the HepatoCare clinic (PC physician, specialist liver nurse, pharmacist) in parallel with usual specialist hepatology care. A control cohort of 30 consecutive outpatients with advanced cirrhosis undergoing SOC treatment was retrospectively identified for comparison. The primary outcome was provision of meaningful PC using HepatoCare versus SOC. Additional clinical outcomes were assessed over 12 months or until death and significant differences were identified.

The intervention and control cohorts had similarly advanced cirrhosis (mean Child-Pugh scores 8.7 vs 8.2, P = 0.46; mean model for end-stage liver disease scores 14.4 vs 14.6, P = 0.88) but a lower 12-month mortality rate (33% HepatoCare vs 67% SOC; P = 0.02). The intervention cohort experienced higher uptake of formal ACP (100% vs 25% for the control cohort) and outpatient PC referral (100% vs 40%), and were more likely to die at home or in a PC bed/hospice (80% vs 30%). The majority of the HepatoCare cohort (81%) had medications safely deprescribed and experienced fewer unplanned admission days (470 vs 794).

HepatoCare is a novel multidisciplinary model of care that integrates effective PC and specialist hepatology management to improve outcomes in advanced cirrhosis.

Patients with advanced chronic liver disease have a complex symptom burden and many are not candidates for curative therapy. Despite this, provision of palliative interventions remains woefully inadequate, with an insufficient evidence base being a contributory factor. Designing and conducting palliative interventional trials in advanced chronic liver disease remains challenging for a multitude of reasons. In this manuscript we review past and ongoing palliative interventional trials. We identify barriers and facilitators and offer guidance on addressing these challenges. We hope that this will reduce the inequity in palliative care provision in advanced chronic liver disease.

Introduction: Previous research has shown limited palliative care (PC) utilization among patients evaluated for liver transplantation (LT) despite the cohort's significant symptom burden, high frequency of hospitalization and risk of rapid decompensation. Our aim was to evaluate patient characteristics and end-of-life (EOL) outcomes (i.e. ICU utilization, code status, advance care planning) associated with the use of PC services in patients who were evaluated for LT. Methods: We performed a single-center cross-sectional study comprised of 223 deceased patients evaluated for LT between 1/1/2017 and 12/31/2021. We evaluated demographic characteristics and EOL outcomes for differences between patients who received PC consultation and those who did not. EOL outcomes associated with PC use were assessed using logistic and linear regression analysis adjusted for patient demographics. Results: Patients who received PC consultation were younger (mean 57 vs. 61; P = 0.048), had higher Model for end-stage Liver Disease (MELD) scores (27.5 vs. 22; P = 0.001), higher rates of hepatic encephalopathy (96% vs. 84%, P = 0.005), and were more frequently declined for LT (77% vs. 57%; P = 0.008). Patients who received PC services were less likely to die in the ICU (OR = 0.07 [0.02-0.18]) and were more likely to have documented advance care planning (OR = 3.16 [1.47-6.97]), family meetings (OR = 6.58 [2.72-17.08]), and goals-of-care discussions (OR = 14.83 [4.39-69.29]). Conclusion: For patients being evaluated for LT, PC utilization differed based on demographics, disease complications and severity, and transplant status. Those who received PC services had higher quality EOL care planning and fewer ICU admissions.

This observational study focuses on the characteristics and survival of patients taken off of the liver transplant waiting list. Assessment of post-delisting survival and a frequent follow-up of patients after delisting are important keys to improve the survival rate of patients with liver failure after being delisted. Within this study, delisted liver transplant candidates were divided into the following groups: (1) "too good" (54%) or (2) "too sick" (22%) for transplantation, (3) adherence issues (12%) or (4) therapy goal changed (11%). The 5-year survival after delisting within these groups was 84%, 9%, 50%, and 68%, respectively. Less than 3% of the delisted patients had to be relisted again. The clinical expert decision of the multidisciplinary transplant team was sufficiently accurate to differentiate between patients requiring liver transplantation and those who were delisted after a stable recovery of liver function. The assessment of post-delisting survival may serve as a complementary metric to assess differences in center practices and to estimate cumulative post-delisting mortality risk.

Background: Liver transplant is the only cure for cirrhosis. We studied the impact of palliative care on patient care by conducting a population-based cohort study. Methods: We queried the Explorys database (IBM, New York) database for a diagnosis of 'cirrhosis' followed by 'palliative care consultation' and collected demographic and clinical data. Results: We identified 316,970 patients with cirrhosis. Palliative care was consulted for 10.9% (n = 34,600) of patients. Patients aged >65 [OR 1.33 (1.30-1.36), P < .0001], men [OR 1.13 (1.11-1.16), P < .0001], a diagnosis of hepatocellular carcinoma (HCC) [OR 2.53 (2.45-2.60), P < .0001] were more likely to receive a palliative care consultation. Patients for whom palliative care were consulted were less likely to undergo surgical procedures [OR .49 (.47-.50)]. Conclusion: Only about 1 in 10 cirrhotics received a palliative care consultation. Older patients, males, and patients with a diagnosis of HCC are more likely to receive palliative care.

Background: End-stage liver disease (ESLD) patients carry heavy symptom burdens and risk receiving aggressive and sometimes unwanted care at end of life. Palliative care (PC), which aims to alleviate symptoms and facilitate goal-concordant care in serious illness, may offer substantial benefits for ESLD patients but is not widely provided. Objectives: To assess the impact of PC integrated within hepatology (PCIH) services on health care utilization, advance care planning (ACP), and hospice enrollment. Design: We compared patients who received PCIH (n = 55) to a retrospective cohort (n = 57) receiving usual care in an outpatient hepatology clinic. Setting/Subjects: From June 2016 to November 2017, we enrolled patients receiving care in a U.S. public hospital clinic who met the following inclusion criteria: (1) ESLD with a Model for End-Stage Liver Disease score ≥20, (2) hepatology approval for PC referral, and (3) at least one advanced complication of ESLD. Measurements: We assessed patient demographics, clinical information, health care insurance status, health care utilization, completion of psychosocial assessments, and ACP using two-sided Fisher's exact test and Mann-Whitney U tests. Results: Patients receiving PCIH more frequently had goals of care discussions (87.3% vs. 21.2% p ≤ 0.01), completed ACP documentation (56.4% vs. 7.0%, p ≤ 0.01), psychosocial assessments (98.2% vs. 35.1%, p ≤ 0.01), and hospice enrollment (25.5% vs. 7.0%, p = 0.01). Patients receiving PCIH who were hospitalized also had fewer mean hospitalization days (13 vs. 19.7 days, p ≤ 0.01). Conclusions: Embedding PC services in a hepatology clinic is a promising strategy to improve care for ESLD patients in public hospitals.

Symptom-focused trials are critically needed for patients with cirrhosis. However, this work would benefit from standard processes and validated measures.

A writing group was formed among hepatologists, nurses, palliative care providers, pharmacists, and clinical trial experts focused on symptom management in patients with cirrhosis to define the key (1) components of trial design, (2) symptom targets, (3) measurement, and (4) outcomes for each target. From July 2022 to January 2023, panelists participated in an iterative process of developing and arriving at a consensus for each component. The goal was to provide consensus definitions that can be operationalized in future clinical trials, including for patients with cirrhosis.

The panel reached a consensus on key reporting features for clinical trials, along with considerations for study design. Nine key symptom targets (muscle cramps, pruritus, pain, fatigue, sexual dysfunction, sleep disorders, depression and anxiety, nausea/vomiting, and dyspnea/breathlessness) were identified. The panel selected instruments that can be considered for clinical trials based on psychometric validation and previous experience. The panel identified ongoing needs, including instrument validation, safety data, evidence about non-pharmacologic interventions, and comparative effectiveness studies.

This expert panel identified key design, reporting, and measurement elements to standardize processes and measures in future symptom-focused clinical trials in the context of cirrhosis.

End-stage liver disease (ESLD) is the culmination of progression of chronic liver disease to cirrhosis, decompensation, and chronic liver failure, featuring portal hypertension or hepatocellular failure-related complications. Liver transplantation offers improved long-term survival for these patients but is negatively influenced by donor availability, financial constraints in developing countries, active substance abuse, progression of disease or malignancy on wait-list, sepsis and extrahepatic organ involvement. In this context, palliative care (PC), an interdisciplinary medical practice that aim to prevent and relieve suffering, offers best possible quality of life and is not limited to end-of-life care. It also encompasses achievable goals such as symptom control and aggressive disease-modifying treatments or interventions that beneficially alter the natural course of the disease to offer curative intend. In this narrative review, we discuss the prognostic factors that define disease course in ESLD, various indications and challenges in PC for advanced cirrhosis and management options for major symptom burden in patients with ESLD based on evidence-based best practice.

Frailty is a known predictor of outcome and mortality in patients undergoing liver transplantation. However, most patients remain unsuitable transplant candidates. It is not yet known if the assessment of frailty in non-transplant candidates can aid prognostication.

To collate and interrogate the various frailty tools presently used to predict mortality in the non-transplant cirrhosis setting.

A comprehensive review of MEDLINE and EMBASE databases for articles published from inception to March 2022 was undertaken, excluding those where patients underwent transplantation or had hepatocellular carcinoma.

We identified 12 observational cohort studies, featuring 9 frailty indices. These were from various global healthcare settings and of fair or good quality. Most were objective tools utilising clinician-based assessments. All frailty scores predicted prognosis, with variability in the method of application, and utilisation in long- or short-term mortality. Three studies directly compared different indices in the same population. There was some evidence that simple tools could perform as well, if not better, than more complex, time-consuming scores.

Various frailty tools can reproducibly evaluate mortality in patients with cirrhosis who are ineligible for transplant. However, further prospective head-to-head comparative studies are needed. In addition to determining model utility, studies should focus on important relative considerations which may limit widespread implementation including, ease of use and limited resources, given the global disparity of liver care provision. These tools may positively identify specific patient cohorts at risk of impending deterioration, thereby stratifying those patients likely to benefit from early integration with palliative care.

Patients with liver disease struggle to access palliative care. We aimed to compare carers' perceptions of end-of-life care for decedents with non-malignant liver disease, malignant liver disease and other non-malignant diseases, and to identify associated factors in non-malignant liver disease.

A retrospective analysis of individual-level data from the National Survey of Bereaved People 2011-2015.

More decedents with non-malignant liver disease died in hospital than other diseases (76.9% vs. 40.9% vs. 50.2%, p < .001), despite 89% wishing to die at home. Fewer decedents received home/hospice specialist palliative care compared with those with malignant liver disease (10.0% vs. 54.6%, p < .001). Carers of decedents with non-malignant liver disease were less likely to rate overall end-of-life care quality as outstanding/excellent (29.3% vs. 43.9% vs. 42.3%, p < .001). For this group, poorer care was associated with younger (65-74 vs. 18-64 years, OR [odds ratio] 1.39, p = .01), more socially deprived decedents (OR .78, p = .02), and better care with greater social support (OR 1.82, p < .001) and community specialist palliative care involvement (OR 1.80, p < .001). There was no association between outstanding/excellent rating and underlying cause of non-malignant liver disease (alcohol-related vs. non-alcohol-related, p = .92) or place of death (hospital vs. non-hospital, p = .476).

End-of-life care could be improved by integrating hepatology and community services, particularly specialist palliative care, and advance care planning to facilitate care and death (where desired) at home. However, death in hospital may be appropriate for those with non-malignant liver disease.

Hepatocellular carcinoma (HCC) is a deadly and burdensome form of liver cancer with an increasing global prevalence. Its course is unpredictable as it frequently occurs in the context of underlying end-stage liver disease, and the associated symptoms and adverse effects of treatment cause severe suffering for patients. Palliative care (PC) is a medical specialty that addresses the physical, emotional, and spiritual needs of patients and their carers in the context of life-limiting illness. In other cancers, a growing body of evidence has demonstrated that the early introduction of PC at diagnosis improves patient and carer outcomes. Despite this, the integration of palliative care at the diagnosis of HCC remains suboptimal, as patients usually receive PC only at the very terminal phase of their disease, even when diagnosed early. Significant barriers to the uptake of palliative care in the treatment algorithm of hepatocellular carcinoma fall under four main themes: data limitations, disease, clinician, and patient factors. Barriers relating to data limitations mainly encapsulated the risk of bias inherent in published work in the field of PC. Clinician-reported barriers related to negative attitudes towards PC and a lack of time for PC discussions. Barriers related to the disease align with prognostic uncertainty due to the unpredictable course of HCC. Significantly, there exists a paucity of evidence exploring patient-perceived barriers to timely PC implementation in HCC. Given that patients are often the underrepresented stakeholder in the delivery of PC, future research should explore the patient perspective in adequately designed qualitative studies as the first step.

Hepatorenal syndrome (HRS) contributes to significant morbidity and mortality in hospitalised patients with cirrhosis.

To examine recent trends, magnitude and outcomes of HRS in the National Inpatient Sample (NIS) database METHODS: Among the NIS database on cirrhosis hospitalisations (2016-2019) due to alcohol (ALD), chronic viral hepatitis (CVH), or NASH and complicated by acute kidney injury (AKI) were analyzed.

Of 113,454 hospitalisations, 18,735 (16.5%) had HRS (mean age 56 years, 36% females, 68% whites, 80% ALD, 7% NASH) with a stable trend over time. Among 1:1 propensity-matched 36,090 hospitalisations, the odds of HRS were 12% higher in NASH versus CVH. Based on weighted national estimates, there were 27,180 (8.3 per 100,000 US population) HRS hospitalisations in 2019, with economic burden of $4.2 billion USD. Mean hospitalisation and total charges (ALD vs. CVH vs. NASH) were 11 versus 10.8 versus 9.2 days and 151,000 versus 157,000 versus 120,000 USD, respectively; p < 0.001. In-hospital mortality was 18.9%, higher in HRS (25.8 vs. 12%, p < 0.001), and decreased by 15% annually. Survivors were more likely to be discharged to short- or long-term care facilities (HRS vs. non-HRS [42 vs. 27%, p < 0.001]); only 28.7% received palliative care.

HRS was the cause of AKI in 16.5% of patients hospitalised with cirrhosis and conferred significant healthcare burden with 27,180 HRS hospitalisations in 2019 and requiring an estimated 4.2 billion USD for hospital care. While there has been a decrease in in-hospital mortality over time, it remained high at 23.7% in 2019 in those with HRS.

Ageing with a chronic hepatitis B (HBV) or hepatitis C (HCV) infection is an emerging public health priority. For people living with chronic viral hepatitis, their disease progression into old age is both underpinned by their existing blood borne virus and the potential emergence of other infectious and non-infectious conditions. These twinned pathways bring additional challenges to the care and support for people as they near end of life. This scoping review sought to examine what is known about the experiences of the end-of-life phase of an increasing population ageing with HBV and HCV in studies conducted in high-income settings and published in peer reviewed literature (2010-2021). In interpreting this literature, we found that challenges in determining the end-of life phase for people with lived experience of HBV or HCV are exacerbated by the conflation of aetiologies into a singular diagnosis of end-stage liver disease. Studies overwhelmingly reported the clinical aspects of end-of-life care (i.e. prognosis assessment and symptom management) with less attention paid to educative aspects (i.e. advance care directives and surrogate decision makers, discussion of treatment options and determining goals of care). Psychosocial interventions (i.e. quality of life beyond symptom management, including emotional/spiritual support and family and bereavement support) received limited attention in the literature, though there was some recognition that psychosocial interventions should be part of end-of-life care provision. Given the focus on the prominent disease presentation of liver cirrhosis and/or end-stage liver disease, the social and cultural dimensions of these infections have received less attention in the literature on end-of-life in the context of chronic viral hepatitis.

Alcohol-associated liver disease is one of the main causes of chronic liver disease. It comprises a clinical-histologic spectrum of presentations, from steatosis, steatohepatitis, to different degrees of fibrosis, including cirrhosis and severe necroinflammatory disease, called alcohol-associated hepatitis. In this focused update, we aim to present specific therapeutic interventions and strategies for the management of alcohol-associated liver disease. Current evidence for management in all spectra of manifestations is derived from general chronic liver disease recommendations, but with a higher emphasis on abstinence and nutritional support. Abstinence should comprise the treatment of alcohol use disorder as well as withdrawal syndrome. Nutritional assessment should also consider the presence of sarcopenia and its clinical manifestation, frailty. The degree of compensation of the disease should be evaluated, and complications, actively sought. The most severe acute form of this disease is alcohol-associated hepatitis, which has high mortality and morbidity. Current treatment is based on corticosteroids that act by reducing immune activation and blocking cytotoxicity and inflammation pathways. Other aspects of treatment include preventing and treating hepatorenal syndrome as well as preventing infections although there is no clear evidence as to the benefit of probiotics and antibiotics in prophylaxis. Novel therapies for alcohol-associated hepatitis include metadoxine, interleukin-22 analogs, and interleukin-1-beta antagonists. Finally, granulocyte colony-stimulating factor, microbiota transplantation, and gut-liver axis modulation have shown promising results. We also discuss palliative care in advanced alcohol-associated liver disease.

Palliative care remains suboptimal in advanced cirrhosis, in part relating to a lack of evidence-based interventions. Ascites remains the most common cirrhosis complication resulting in hospitalisation. Many patients with refractory ascites are not candidates for liver transplantation or transjugular intrahepatic portosystemic shunt, and therefore, require recurrent palliative large volume paracentesis in hospital. We review the available evidence on use of palliative long-term abdominal drains in cirrhosis. Pending results of a national trial (REDUCe 2) and consistent with recently published national and American guidance, long-term abdominal drains cannot be regarded as standard of care in advanced cirrhosis. They should instead be considered only on a case-by-case basis, pending definitive evidence. This manuscript provides consensus to help standardise use of long-term abdominal drains in cirrhosis including patient selection and community management. Our ultimate aim remains to improve palliative care for this under researched and vulnerable cohort.

Inequalities in access to hospice care is a source of considerable concern; white, middle-class, middle-aged patients with cancer have traditionally been over-represented in hospice populations.

To identify from the literature the demographic characteristics of those who access hospice care more often, focusing on: diagnosis, age, gender, marital status, ethnicity, geography and socioeconomic status.

Systematic literature review and narrative synthesis.

Searches of Medline, PsycINFO, CINAHL, Web of Science, Assia and Embase databases from January 1987 to end September 2019 were conducted. Inclusion criteria were peer-reviewed studies of adult patients in the UK, Australia, New Zealand and Canada, receiving inpatient, day, outpatient and community hospice care. Of the 45 937 titles retrieved, 130 met the inclusion criteria. Narrative synthesis of extracted data was conducted.

An extensive literature search demonstrates persistent inequalities in hospice care provision: patients without cancer, the oldest old, ethnic minorities and those living in rural or deprived areas are under-represented in hospice populations. The effect of gender and marital status is inconsistent. There is a limited literature concerning hospice service access for the LGBTQ+ community, homeless people and those living with HIV/AIDS, diabetes and cystic fibrosis.

Barriers of prognostic uncertainty, institutional cultures, particular needs of certain groups and lack of public awareness of hospice services remain substantial challenges to the hospice movement in ensuring equitable access for all.

The number of patients coming to hospital with liver disease is increasing. There was a worrying trend before the pandemic, and this has intensified. Despite improvements in the management of patients with advanced cirrhosis many patients will die within 6-12 months of first presentation, and, despite this, the field of palliative and supportive care in liver disease is still in its infancy. This is a narrative review. Evidence is often thin in this field. Where it exists it is cited, but much of the commentary here is based on the authors own experience and readers are free to consider it and debate it. Most patients who die of liver disease receive palliative care very late in their illness (if at all). There are many barriers to supportive and palliative care in liver disease which are discussed. Symptom control is often poor because of these barriers. Before symptomatic control can be established, patients in need of it must to be identified and conversations had about the severity of their situation and what their wishes would be. Interest in palliative and supportive care for patients liver disease is growing as is the number of hepatologists and palliative care clinicians within the UK with an interest. It is important that this enthusiasm and interest can be rolled out and scaled up across the UK so that all patients, wherever they are, can benefit. The aims of these articles are first to highlight and bring into focus the unmet need for palliative and supportive care in liver disease and second to provide suggestions for its integration into liver services. Ask yourself the question: where would I start in my hospital to help these patients?

Studies of palliative care (PC) in hospitalized patients with cirrhosis have been retrospective, with limited evaluation of patient-reported measures and outcomes.

To examine the relationship between PC, patient-reported measures (quality of life and functional status), and outcomes.

We performed a prospective cohort study of patients with cirrhosis hospitalized from 2014 to 2019. We recorded PC consultation details, quality of life (chronic liver disease questionnaire), and functional status (functional status questionnaire). Patients were followed for 90 days to assess readmissions, costs, and mortality.

Seventy-four of 679 patients saw PC, often later in the hospitalization (median hospital day 8; IQR 4-16). Those who saw PC had greater Charlson comorbidity index (mean 6.8 vs. 5.9), MELD (mean 25 vs. 20), and prior 30-day admission (47% vs. 35%). Compared to those who did not see PC, PC patients had greater impairments in intermediate activities of daily living (83% vs. 72%), social activity (72% vs. 59%), quality of interactions (49% vs. 36%), abdominal symptoms (mean score 3.1 vs. 3.6), activity (mean 3.3 vs. 3.6), and overall quality of life (mean 3.6 vs. 3.8). PC was associated with fewer transfusions and upper endoscopies and with greater completion of advanced directives. After multivariable adjustment, PC was not associated with intensive care, 30-day readmissions, 90-day costs, or mortality.

PC occurs infrequently and late in those with more severe liver disease and functional impairment. PC may be associated with reduction in utilization and greater completion of advanced directives. Randomized trials are needed to evaluate PC for this population.

Content available: Author Interview and Author Audio Recording.

Hepatobiliary diseases and their complications cause the accumulation of toxic bile acids (BA) in the liver, blood, and other tissues, which may exacerbate the underlying condition and lead to unfavorable prognosis. To develop and validate prognostic biomarkers for the prediction of complications of cholestatic liver disease based on urinary BA indices, liquid chromatography-tandem mass spectrometry was used to analyze urine samples from 257 patients with cholestatic liver diseases during a 7-year follow-up period. The urinary BA profile and non-BA parameters were monitored, and logistic regression models were used to predict the prognosis of hepatobiliary disease-related complications. Urinary BA indices were applied to quantify the composition, metabolism, hydrophilicity, and toxicity of the BA profile. We have developed and validated the bile-acid liver disease complication (BALDC) model based on BA indices using logistic regression model, to predict the prognosis of cholestatic liver disease complications including ascites. The mixed BA and non-BA model was the most accurate and provided higher area under the receiver operating characteristic (ROC) and smaller akaike information criterion (AIC) values compared to both non-BA and MELD (models for end stage liver disease) models. Therefore, the mixed BA and non-BA model could be used to predict the development of ascites in patients diagnosed with liver disease at early stages of intervention. This will help physicians to make a better decision when treating hepatobiliary disease-related ascites.

Background: End-stage liver disease (ESLD) is associated with high morbidity and mortality, with liver transplantation as the only existing cure. Despite reduced quality of life and limited life expectancy, referral to palliative care (PC) rarely occurs. Moreover, there is scarcity of data on the appropriate timing and type of PC intervention needed. Aim: To evaluate PC utilization and documentation in ESLD patients declined or delisted for transplant at a tertiary care medical center with a large liver transplantation program. Methods: We performed a retrospective cohort study of all patients discussed in Liver Transplant Committee (LTC) at our academic medical center between August 2018 and May 2020 in the United States. Patients declined or delisted for liver transplantation were included. Baseline demographics, model for end-stage liver disease (MELD) score, decompensation events, and reason for transplant ineligibility were recorded. The primary outcome was PC referral. Secondary outcomes included survival from LTC decision, time from LTC decision to PC referral, and code status in relation to PC referral. Results: Of 769 patients discussed at LTC, 135 were declined for transplantation. Thirty-seven (27%) received referral to PC. When adjusting for body mass index and age, MELD score of 21-30 had odds ratio (OR) of 4.5 (95% confidence interval [CI]: 1.7-12.3) and MELD score >30 had OR of 12.8 (95% CI: 3.9-47.7) for PC referral when compared with MELD score <20. When adjusting for MELD score, presence of ascites had OR of 4.6 (95% CI: 1.1-19.1) and presence of multiple complications had OR of 2.2 (95% CI: 2.2-3.8). Conclusions: Only 37 (27%) patients delisted or declined for liver transplantation were referred to PC. MELD score and degree of decompensation were important factors associated with referral. Continued exploration of these data could help guide future studies and help determine timing and criteria for PC referral.

Patients with end-stage liver disease undergo repetitive patterns of recovery and deterioration and are burdened with uncertainty. Although quality of life is low in patients with end-stage liver disease and their family members, few studies have been conducted to identify what palliative care should be provided for them. This integrative review aimed to explore palliative care for patients with end-stage liver disease, focusing on the components and outcome measurements for further research. After searching for studies on palliative care for end-stage liver disease published between 1995 and 2017, 12 studies that met the inclusion criteria were analyzed. The common components of palliative care for patients with liver disease were: (a) an interdisciplinary approach, (b) early palliative care, (c) discussion goals of care with patient and family members, (d) symptom management, and (e) psychosocial support. It was reported that patients who were provided palliative care had improved itching, well-being, appetite, anxiety, fatigue, and depression, increased the number of do-not-resuscitate orders, palliative care consultations, and decreased length of stay. These findings could guide the development of palliative care for end-stage liver disease patients.

It is essential to determine contributors around impairment in health-related quality of life (HRQoL) in patients with cirrhosis aiming at improving health care and therapeutic strategy. Studies simultaneously incorporating disease severity based on biochemical parameters and other physical/psychological effects (i.e., sleep disturbance and frailty) are heterogeneous and the subject of the present study. We analyzed and compared HRQoL, using the EuroQol Group 5 Dimension (EQ-5D) questionnaire and the utility index retrieved, in patients with cirrhosis and across groups stratified by sleep disturbance or frailty phenotype. Sleep disturbance and frailty were determined by the Pittsburgh Sleep Quality Index (PSQI) and Frailty Index, respectively. Multiple linear regression was implemented to clarify contributors of poor HRQoL. In this cohort of 227 patients with mean age of 61.7 years and 47.2% male, more than half of the study population represented impairment in HRQoL in at least one domain, according to EQ-5D. Furthermore, sleep disturbance and frailty have proved to be independently associated with poor HRQoL in two separate regression models, whereas conventional scoring systems such as Child-Pugh classification and Model for End-Stage Liver Disease are not closely relevant. Intriguingly, not all health domains within EQ-5D correlated well with PSQI and Frailty Index, with the exception of usual activities. Pain and anxiety/depression were the most frequently affected HRQoL domains even in patients without sleep disturbance or frailty. Conclusion: Impaired HRQoL is prevalent in patients with decompensated cirrhosis. Sleep disturbance and frailty are independently associated with poor HRQoL. It is imperative to timely intervene with these symptoms and deliver tailored health care.