AASLD Practice Guidance: Palliative care and symptom‐based management in decompensated cirrhosis

Palliative care is defined as multidisciplinary, specialized medical care that addresses the physical, spiritual, and psychosocial needs of patients with serious illness and their caregivers.[1, 2] The benefits of palliative care are increasingly recognized across disease states and for patients with decompensated cirrhosis (DC).[3-5] This American Association for the Study of Liver Diseases (AASLD) guidance to providing palliative care for patients with cirrhosis was developed with the support and oversight of the AASLD Practice Guidelines Committee. The AASLD Practice Guidelines Committee chose to commission a guidance, rather than a guideline, because of the paucity of randomized controlled trials (RCTs) on this topic. AASLD guidelines are supported by systematic reviews of the literature, formal ratings of evidence quality and strength of recommendations, and, if appropriate, meta-analysis of results using the Grading of Recommendations Assessment Development and Evaluation system. In contrast, this document was developed by consensus of an expert panel and provides guidance statements based on formal review and analysis of the literature on the topics and questions related to the palliative care needs of patients with cirrhosis and their caregivers. Although palliative care can be considered regardless of the stage of cirrhosis, this guidance document predominantly addresses issues pertinent to adult patients with DC because this group bears considerable physical, psychosocial, and financial burden. We specifically focus on topics that are not covered in existing AASLD practice guidelines/guidance documents and thus refer the readers to the AASLD practice guidelines for specific recommendations for the diagnosis and management of ascites, hepatic encephalopathy (HE), hepatocellular carcinoma (HCC), and portal hypertension.[6-9] In addition, the complex palliative care needs for patients with HCC are not specifically addressed by this guidance, but are addressed by other guidelines.[10, 11] Palliative care can be provided at any stage of a serious illness and concurrently with disease-directed and curative treatments (including organ transplants). Over the past decade, the body of evidence supporting early palliative care has expanded to include persons with nonmalignant conditions, such as cirrhosis.[3, 4] Palliative care takes a comprehensive, person-centered approach to care, focusing on the aspects of care most important to patients and their families/informal caregivers. Because of this comprehensive scope, management typically relies on a team, including physicians, nurses, chaplains, social workers, and other providers. Table 1 illustrates the conceptual distinctions between primary and specialty palliative care. Specialty palliative care refers to care delivered by specialists with advanced palliative care skills such as board-certified palliative care physicians or palliative-certified nurses, social workers, pharmacists, and chaplains.[12] However, primary palliative care describes care aligned with the principles of palliative care (e.g., person-centered, communication-focused symptom management) that can be delivered by any medical professional.[12] The National Consensus Project for Quality Palliative Care defined eight core domains of high-quality palliative care around which this guidance is framed (Figure 1).[13, 14] Although all eight domains can apply to patients with DC, their relative importance may vary across the illness trajectory.[5, 15] Advance care planning (ACP) is a component of palliative care that involves the iterative and longitudinal process of medical decision making for patients and their families over the course of their illness trajectory.[16, 17] ACP includes identifying surrogate decision makers, illness education and prognostic disclosure, and formal documentation of goals for medical and end-of-life care (EoLC) through advance directives that center on the goals, values, and preferences of patients and their families.[17] Hospice is EoLC focused on allowing people in the last phases of incurable disease to live as fully and comfortably as possible.[14] Hospice is different than palliative care in that it focuses exclusively on comfort, rather than disease-directed curative treatment, and includes only persons with a life expectancy measured in months. In the USA, the hospice benefit is provided under Medicare Part A, and patients must have a defined, time-limited prognosis (certified by one or more physicians as ≤6 months).[18] DC is in many cases incurable, and life expectancy, which can be predicted with models such as the Model for End-Stage Liver Disease (MELD) and Child-Pugh-Turcotte scores, may be well below 6 months.[6, 19-21] Because of the poor prognosis of DC, many patients with DC qualify for hospice benefits, which can help support patients and their caregivers. Attention to patients' families and support persons, herein called caregivers, is a core value and component of palliative care (Figure 1). Caregivers are discussed in The National Consensus Project under the heading of clinical implications. Throughout this document, we address the role of caregivers in each aspect of palliative care. Caregivers of patients with DC often face under-recognized psychological, physical, and financial burdens.[22-27] Their symptoms include stress, anxiety, depression, insomnia, decreased health-related quality of life (HRQoL), and worse physical health.[23, 25-27] Psychological symptom burden among caregivers is associated with patients' alcohol use, encephalopathy, ascites, liver disease (LD) severity, repeated hospitalizations, prognostic uncertainty, and lack of information.[25-29] Caregivers of patients with DC report feeling unprepared to provide physical care, medication management, and transportation to their loved ones and often experience significant financial burdens.[23-25, 27, 30-32] Importantly, the financial, social, and psychological burdens of cirrhosis experienced by caregivers can continue to impact caregivers after patients die. As such, support for caregivers of patients with cirrhosis should start early and extend through the bereavement period. This support can include inquiring about how they are doing during a medical visit, acknowledging the challenges of caregiving, and referring to services for support. Hepatology providers should assess caregivers' goals and consider their needs. Being knowledgeable about and providing a list of ancillary services to caregivers is something that can occur in hepatology. Services of interest to caregivers may include pastoral care or spiritual support, mental health resources, bereavement support, grief counseling, caregiver support websites, and peer support groups. Cirrhosis is associated with poor HRQoL attributable to multiple physical, cognitive, psychological, and social stressors that are challenging to manage.[30, 33, 34] Although the prognosis for patients with DC is variable, with a 5-year mortality ranging from 20% to 80% across studies, the overall disease trajectory is progressive, with declining health and increasing symptom burden and frequent hospitalizations at the end of life.[19, 35-37] Though liver transplantation (LT) can be curative, few patients are ever waitlisted for or receive LT.[38] Palliative care needs of patients with cirrhosis and their caregivers are frequently underaddressed.[39] Only 11% of patients with cirrhosis receive specialty palliative care or hospice care referrals, and consultation often occurs very late in the disease course.[40-44] Consequently, patients with cirrhosis receive EoLC that is more resource intensive and invasive than that of patients with other serious, life-limiting illnesses.[27, 44, 45] There are several barriers to palliative care implementation that have been identified specifically in hepatology. These barriers include a shortage of specialty palliative care providers, absence of evidence-based referral criteria, lack of role clarity between specialists, stigma that palliative care is synonymous with "giving up" on curative treatments, lack of provider training, competing demands on providers' time, and prognostic uncertainty.[22, 27, 41, 46-50] In addition, many of the symptoms experienced by persons with DC are highly liver specific and managed longitudinally by liver teams. This is in contrast to oncology practice models in which palliative care teams frequently have a key role managing malignant pain syndromes throughout the disease course.[51] Transplant evaluation and listing may also present a unique barrier to palliative care for patients with cirrhosis, related to the perceived incompatibility of transplantation and palliative care. One study found that patients with cirrhosis undergoing transplant evaluation received lower-quality EoLC.[52] Similarly, a qualitative study of 42 patients and 46 clinicians found that transplant teams avoided discussing nonaggressive treatment options with patients, leading caregivers to feel unprepared to support their loved ones at the end of life.[53] Finally, hepatology training does not routinely include palliative care training, and palliative care competencies for hepatologists have not been developed. Despite these barriers, hepatology clinicians, especially those with a longitudinal relationship with patients and families, can play a key role in delivering primary palliative care to address patients' and caregivers' needs. Some elements of primary palliative care that could be provided as part of routine hepatology care include evaluating and managing symptoms, identifying and documenting surrogate decision makers, eliciting patient preferences about treatment and aligning care plans with these preferences, providing counseling about what to expect in the future, and referring patients for social services to increase support in the community. A growing body of evidence supports the integration of curative and palliative care approaches for patients with DC (Table 2).[54-57] Observational studies have demonstrated reduced resource use, decreased symptoms, and improved HRQoL for patients with cirrhosis who receive palliative care services.[50, 58, 59] A single-arm, single-center study found that outpatient specialty palliative care referral for all patients undergoing LT evaluation resulted in improved physical and psychological symptom scores.[54] Likewise, an outpatient primary palliative care intervention led by hepatology nurses with palliative care and communication training was feasible and acceptable to recently discharged patients and their health care teams.[57] The intervention was associated with improved HRQoL, care coordination, coping, and anticipatory planning. Two studies that examined inpatient palliative care also had favorable findings. A specialty palliative care intervention in a single academic surgical intensive care was associated with earlier consensus around goals of care, reduced length of stay, and earlier provision of comfort-focused care without any change in mortality.[55] Caregivers also reported having more time to say goodbye.[55] This intervention included early consultation with an interdisciplinary palliative care team, who provided a comprehensive evaluation within 24 h of admission, including discussion of prognosis, caregiver support, ACP, and symptom assessment. The palliative care team then participated in daily rounds and conducted a caregiver meeting within 72 h of admission. To the best of our knowledge, Shinall et al. conducted the only RCT of a palliative care intervention in inpatients with cirrhosis. The intervention included patients with a life expectancy <12 months and involved an inpatient specialty palliative care consultation and monthly postdischarge follow-up with the palliative care team, who reviewed medications, symptoms, and goals of care.[56] The comparison group received usual care that included palliative care at the discretion of the hepatologist (19% received palliative care), and results were analyzed on an intention-to-treat basis. Although this trial was prematurely terminated because of low enrollment, patients in the intervention group had significantly reduced readmission rates and more days alive outside of the hospital as compared with patients in the control group.[56] The researchers cited barriers to enrollment including patients and family feeling overwhelmed at the time of index hospitalization, concerns about whether insurance would cover palliative care, challenges with identifying caregivers, and a narrow screen-in to enrollment window.[56] Few interventions have included caregivers of patients with cirrhosis. A randomized trial of a cognitive behavior-based coping intervention delivered by trained nurses or social workers by telephone (as compared with LD education as an attention control) did not significantly impact mental health or HRQoL for patients or caregivers.[60] However, a mindfulness-based stress reduction and supportive group therapy intervention was associated with improved patient and caregiver mental health symptoms and HRQoL.[61] More trials are needed to understand how to best help caregivers of patients with cirrhosis. Although these early data generally support the effectiveness of palliative care interventions for patients with cirrhosis and their caregivers, larger trials are needed to further characterize the optimal timing and content of these interventions. Conducting palliative care trials in this population is especially challenging for several reasons. Such trials are resource and time intensive; the population is heterogeneous (in terms of illness severity, trajectory, and treatments) with considerable prognostic uncertainty; trials require rigorous, potentially intrusive study monitoring; and there is limited interest in the topic from commercial sources, among others. The ongoing PAL LIVER trial, funded by the Patient-Centered Outcomes Research Institute, is recruiting patients with advanced liver disease and their caregivers from 18 clinical centers in the United States, comparing the effectiveness of palliative care delivered by specialists versus trained hepatologists for improving patients' HRQoL, symptoms, caregiver burden, and health care use.[62] PAL LIVER and other studies are needed to establish which palliative outcomes matter most to patients and their caregivers. As cirrhosis-specific data accumulate, trials of palliative care in other similar populations may help to inform care. Over the past decade, several landmark studies have assessed the impact of multicomponent, interdisciplinary palliative care interventions in patients with advanced heart, lung, renal, and hematological diseases across multiple domains of palliative care (Table S1).[13, 14] Palliative care interventions have improved physical (e.g., fatigue, pain), psychological (e.g., depression, anxiety, and mood), social, spiritual, EoLC, ACP, caregivers' quality of life, and cost-effectiveness of care.[63-77] However, evidence for improvement in religious, existential, and cultural aspects of care remains limited.[14] In general, interventions with a comprehensive evaluation by palliative care specialists, including nurses, social workers, or physicians, were associated with improved quality of care and symptom management. ACP is a proactive, ongoing, collaborative process of decision making about health care preferences, goals, and values in the context of a life-limiting illness.[16, 17] Decisions around life-sustaining treatments, completing advance directives, and identifying surrogate decision makers are all part of ACP, which is based on continuous assessment and documentation of patients' personal values, preferences, and caregiver input.[14, 17] Written documentation (such as advance directives) can help ensure that these values and preferences are respected across clinical teams and health care settings. ACP interventions are also associated with greater concordance between patient preferences and care delivery, completion of advance directives, and improved end-of-life management.[78] Thus, facilitating ACP is an important component of caring for persons with DC. Table 3 outlines key ACP definitions, and Figure 2 illustrates key components of ACP, including assessing patients' capacity and willingness to engage in ACP, identifying surrogate decision makers who should be present for conversations, and eliciting and documenting preferences.[14, 17, 79] It is critical to document this information early in the trajectory of cirrhosis, before the onset of encephalopathy, for example. It is also notable that a person who is present at an outpatient appointment or at the hospital bedside may not be the person that local surrogacy laws identify as a default surrogate or the person that the patient wants to be making decisions on their behalf. Ideally, clinicians with a continuity relationship with a patient and an understanding of their prognosis should regularly engage in conversations regarding prognosis and goals of care.[14] Unfortunately, these conversations often do not occur until the end of life for patients with DC.[36, 43, 48, 53, 59, 80-83] Insufficient and delayed discussions likely contribute to receipt of high-intensity EoLC.[84] Conversely, early palliative care referral has been associated with higher rates of goals-of-care discussions in retrospective cohort studies.[58, 59] One pilot trial found that provider education and standardized documentation were associated with a 23% increase in advance directive completion and a 51% increase in goals-of-care conversations.[85] Similarly, specialty palliative care consultation with transplant evaluation led to early identification of surrogate decision-maker and ACP documentation.[54] In a single-site pilot RCT, a 5-min ACP video decision support tool for transplant-ineligible patients with DC significantly improved their knowledge about EoLC, informed their preferences for resuscitation and intubation, and was highly acceptable to patients (Table 2).[86] An expert panel, supported by modified Delphi methods, provided guidance on the timing of ACP in patients with DC.[87] They recommended that advance directives should be completed as early in the course of cirrhosis as possible and preferably before hepatic decompensation and potentially loss of decision-making capacity. Similarly, goals-of-care discussions, with or without the support of specialty palliative care services, should be prioritized when LT is being considered or if death is anticipated within 6 months.[87, 88] Resources that can support hepatologists in leading ACP include patient-facing visual aids, communication training, and goals-of-care communication training workshops and webinars (Table S2).[16, 89-95] Communication skills are a key component of ACP and palliative care. Uncertainty of the illness trajectory in cirrhosis complicates communication about prognosis. Furthermore, care preferences can fluctuate with a patient's changing clinical status. Clinicians may struggle to effectively communicate the complexity and uncertainty associated with the fluctuating and unpredictable clinical course—indeed, 80% of respondents in a large survey of hepatologists felt that the communication training they had received (in this study, around end-of-life communication) was inadequate.[48] Patients and families struggle to get the information they need or desire, particularly in the setting of critical illness.[84] Several published communication frameworks may be well suited to address the unpredictability associated with cirrhosis (Figure 3).[89-95] Although communication training is associated with improved person-centered outcomes, more work is needed to tailor approaches to training and communication in hepatology settings.[90] The medical team should also ensure that communication occurs in the language preferred by patients and families using a professional medical interpreter, if the preferred language is different than that of the provider.[96] Psychosocial, spiritual, and cultural aspects of care are understudied in all patient populations, despite being important to patients.[44] In general, an interdisciplinary, person-centered approach is recommended when addressing these potentially sensitive topics, and it is important to be aware of the local supportive care resources through ongoing conversations with social work, pharmacy, patient navigation, chaplaincy, spiritual care, and pastoral care, where available.[14] A key component of person-centered palliative care is assessing patient and caregiver psychosocial needs across social determinants of health, including financial stability, employment, food insecurity, housing, transportation, and access for necessary equipment/supplies.[14] Assessing financial burden is also important for patients with DC, who often report high rates of cost-related nonadherence to medications and food insecurity.[31, 97, 98] The question "Are you having difficulty paying for your medical care?" is an effective early screen for financial burden and engaging social work and pharmacy services to help support patients and their families in mitigating financial stress.[31, 97, 98] Cirrhosis carries a significant financial burden for patients and families. Patients with DC require a high number of informal caregiving hours each week compared with persons with other illnesses, which can lead to difficulty maintaining employment for family caregivers.[31] Patients differ in their beliefs and approaches to ACP, palliative care, and death and dying related to their spiritual and cultural frames of reference.[20] The limited relevant spirituality research in cirrhosis includes two qualitative studies that identified spirituality as a key determinant of HRQoL and perceptions of medical care.[99, 100] General palliative care guidelines recommend routinely evaluating the spiritual and cultural needs of patients and their families through understanding their preferred communication preferences, values, of spiritual and approaches to death and medical chaplaincy, and spiritual care providers as in the care of patients and families may in providing sensitive palliative care that also their spiritual beliefs and and can also help to support caregivers during the time of Although and spiritual care providers are not across health care patients and their families to include or spiritual from the to in their care can be in work has demonstrated and in palliative care and pain More work is needed to the to which these in health care access versus cultural or in preferences for care. 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