Curr Gastroenterol Rep (2015) 17:18 DOI 10.1007/s11894-015-0440-6
LIVER (B BACON, SECTION EDITOR)
Palliative Care for Patients with End-Stage Liver Disease Anne M Larson 1
# Springer Science+Business Media New York 2015
Abstract Liver disease results in over four million physician visits and over 750,000 hospitalizations per year in the USA. Those with chronic liver disease frequently progress to cirrhosis, end-stage liver disease (ESLD), and death. Patients with ESLD experience numerous complications, including muscle cramps, confusion (hepatic encephalopathy), protein calorie malnutrition, muscle wasting, fluid overload (ascites, edema), bleeding (esophagogastric variceal hemorrhage), infection (spontaneous bacterial peritonitis), fatigue, anxiety, and depression. Despite significant improvements in palliation of these complications, patients still suffer reduced quality of life and must confront the fact that their disease will often inexorably progress to death. Liver transplantation is a valid option in this setting, increasing the duration of survival and palliating many of the symptoms. However, many patients die waiting for an organ or are not candidates for transplantation due to comorbid illness. Others receive a transplant but succumb to complications of the transplant itself. Patients and families must struggle with simultaneously hoping for a cure while facing a life-threatening illness. Ideally, the combination of palliative care with life-sustaining therapy can maximize the patients’ quality and quantity of life. If it becomes clear that life-sustaining therapy is no longer an
This article is part of Topical Collection on Liver * Anne M Larson [email protected] 1
Swedish Liver Center, 1101 Madison Street #200, Seattle, WA 98104, USA
option, these patients are then already in a system to help them with end-of-life care. Keywords End-stage liver disease . Palliative care . Death . Cirrhosis . End-of-life care
Introduction Chronic liver disease leads to over 4 million ambulatory physician visits annually in the USA (US), with >3.5 million visits for viral hepatitis alone [1]. Chronic liver disease often progresses to cirrhosis and subsequent liver failure, with an estimated US prevalence of cirrhosis of 0.27 % of the population (633,323 adults) [2]. Annually, over 750,000 hospitalizations can be attributed to acute and chronic liver disease [1, 3]. Health-care costs in this population approach almost $4 billion annually, and the incidence of hospitalizations due to cirrhosis and its complications is rising significantly [3–6]. Within a month following discharge, 37 % of cirrhotic patients are readmitted at a mean cost of nearly $30,000 [5]. The more frequent the readmission rate, the greater the risk of subsequent mortality. Up to 40,000 deaths per year can be attributed to cirrhosis—26.4 % per 2-year interval compared to 8.4 % in matched controls [1, 2, 7, 8]. Most patients with chronic liver disease feel well for decades, often completely unaware of the progressive nature of their illness [2]. As the disease progresses, however, patients may develop nonspecific symptoms such as fatigue, even in the absence of cirrhosis. Fatigue is in fact one of the most frequently identified symptoms of chronic liver disease and cirrhosis, and can lead to significant decrease in quality of life [9, 10]. Once chronic liver disease is diagnosed or complications abruptly present, patients often then experience psychologic distress which contributes to their poor quality of life
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[10, 11•]. There may be little time to adjust to the diagnosis— depression and anxiety frequently accompany the diagnosis [11•, 12–14]. The cirrhotic liver eventually decompensates, leading to end-stage liver disease (ESLD), the final phase in liver failure. Patients with ESLD then further experience significant morbidity, including abdominal pain, muscle cramps, cognitive dysfunction (encephalopathy), malnutrition and muscle mass loss, fluid overload (ascites, edema), profound fatigue, and pruritus [15]. Additionally, they may experience such life-threatening complications as variceal hemorrhage, spontaneous bacterial peritonitis, or hepatocellular carcinoma. Life-saving liver transplantation is available only to a small subset of these patients.
Discussing End-of-Life Issues Once the diagnosis of cirrhosis and end-stage liver disease is made or complications occur, patients are often frightened and wonder how they could have reached this point. They may be angry that they were unaware of the consequences of their illness. They often absorb only bits and pieces of what is being told to them and have trouble piecing it all together. Patients suffer a significantly reduced quality of life and must ultimately confront the fact that their disease will inexorably progress to death. Liver transplantation may be a valid treatment option in this setting, increasing the duration of survival and palliating many of the symptoms. Up to 10–15 % of these patients die without receiving an organ, however, and there are many patients who are not candidates for liver transplantation. Furthermore, some patients receive a liver transplant but succumb to complications of the transplant itself. Receiving news of a terminal or life-limiting diagnosis is stressful and evokes strong emotions such as fear, anxiety, anger, depression, despair, hopelessness, and helplessness [16]. Early discussion of end-of-life issues is essential in the management of all patients with ESLD, including those being evaluated for liver transplantation. Patients and their families must understand their prognosis and be prepared for all potential outcomes in order to make realistic treatment decisions [17]. Physicians face the challenge of supporting hope while providing patients with accurate prognostic information [18]. This becomes particularly challenging in the presence of hepatic encephalopathy which further impedes communication and the patient’s ability to make decisions. Physicians and practitioners should anticipate this and engage the patient and their family early in advanced care planning. There is also a significant burden on the caregivers of patients in this setting, particularly in the presence of hepatic encephalopathy [19•, 20–23]. Family members must often make decisions for the patient. This is particularly stressful if the caregiver is not aware of the patient’s wishes. Those patients with liver disease associated with substance abuse may
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lack a strong social network. There may be no close family to provide support, which further complicates communication and long-term care planning [19•]. Palliative care discussions can become particularly difficult if the ESLD patient is being considered for or has been listed for liver transplantation. They must face dealing with the risk of an early death while at the same time focusing on the hope of receiving a life-saving transplant—Bhope for the best and prepare for the worst^ [24]. The patient must be helped to understand that they may experience a catastrophic decline in their condition before transplant can be provided, or may receive a transplant only to die of post-transplant complications. These competing outcomes lead to a Broller-coaster ride^ of emotions which is difficult for all involved. Those for whom liver transplant is not available or has failed face having their hopes dashed and confronting their terminal illness head on. The use of do not attempt resuscitation (DNAR) orders in the setting of ESLD remains even more controversial. The possibility of receiving a transplant adds complexity to the discussion of DNAR and many argue that liver transplant candidates should not carry this type of directive. Full code status may be reasonable for patients who are still healthy enough to survive resuscitation efforts without compromising future treatment options such as transplant. As ESLD progresses, however, and patients become more critically ill, the possibility of transplant futility must be addressed [25–27]. Resuscitation is rarely successful in the critically ill ESLD patient who experiences a catastrophic event (e.g., cardiopulmonary arrest) [28–33••]. Despite successful resuscitation, the event may further compromise transplant outcome or prevent transplant altogether. In this setting, DNAR orders may be appropriate.
Palliative Care and ESLD Palliative care is defined as an approach that improves the quality of life of patients and their families facing the problems associated with life-threatening illness, through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychosocial, and spiritual [34]. Palliative care is often confused with hospice care—a component of palliative care to aid the dying in their last 6 months of life. This confusion may lead to the avoidance of involvement of the palliative care team, particularly in the setting of potential liver transplantation. More recently, however, palliative care is being viewed as a distinct entity from hospice [35•, 36]. There has traditionally been very little guidance for the use of palliative care in the setting of ESLD [37••, 38]. Palliative and hospice care have more traditionally been used in the setting of illnesses whose progressive disease course is clear,
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such as end-stage cancer. Palliative care is of significant value, however, at any stage of disease for any patient with a serious or life-threatening illness [35•]. Patients involved with palliative care experience an improvement in quality of life, a decrease in depression and anxiety, and feel that there is better alignment of their goals with their medical care [35•, 39, 40]. There are many barriers to the consideration of palliative care in the setting of cirrhosis and ESLD. Cirrhotic patients may not appear Bsick^ to the casual observer and, therefore, may not be considered to need help with symptoms or to be at risk of dying. The symptom burden in these patients is frequently not identified as an issue by either physicians or caregivers [41]. The trajectory of liver failure is less predictable than in the setting of other chronic diseases, such as advanced cancer [19•, 42]. This is particularly true earlier in the course of disease or if symptoms (i.e., encephalopathy or ascites) have been medically well controlled. This makes care planning and projection regarding end-of-life issues much more complicated. The practitioner, patient, or caregivers may view palliative care as synonymous with hospice and appropriate only during the final days of life—seeing palliative care as giving up. Finally, discussing palliative care and advanced directives may appear to be at odds with pursuit of curative or life-prolonging therapies, such as liver transplant [37••]. Therefore, end-of-life issues in ESLD are frequently not addressed at all or addressed too late to be of benefit to the patient [43–45••]. Poonja et al. showed that only ∼10 % of patients who were removed from the liver transplant list were referred to palliative care, despite a high symptom burden [46••]. Additionally, they and others have found that goals of care and do not resuscitate status were rarely discussed in these dying patients [29, 47, 48]. Hansen et al. followed six ESLD patients who were hospitalized in the ICU and were either on the liver transplant list or being considered for liver transplant. Interviews were conducted with multiple staff and family members throughout the course of the hospitalization [49]. They found that what mattered most to all participants was the goal of liver transplant. There was no focus on comfort care until all treatment options had been exhausted and none of the patients received a palliative care consultation [49]. The lack of palliative and end-of-life care offered to those who are not candidates for transplant or have been removed from the list often leads to feelings of abandonment by patients [43].
Integrating Palliative Care with ESLD Management The early integration of palliative care in the setting of chronic disease has been shown to improve quality of life (QOL) and actually results in longer patient survival [50•, 51, 52]. It has been suggested that palliative care could be considered in any patient who is at risk of dying within the next year from
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advanced liver disease [53–55]. The course of ESLD is unfortunately much less predictable than many other chronic illnesses—patients experience episodic periods of exacerbation and recovery [42]. This makes predicting the actual time course of progression to death difficult and contributes to the stress patients and caregivers feel. This also makes the timing of palliative care involvement unclear, probably contributing to the lack of palliative care referrals in this population. Early concurrent palliative care could significantly benefit the patient with ESLD and the health-care team providing this care must find ways to integrate palliative care with the possibility of life-prolonging therapy [44, 56]. Support for the concept of palliative care in this setting is growing [38, 57, 58]. It has been suggested that certain clinical findings, such as refractory ascites or hepatic encephalopathy, could be used as triggers for palliative care consultation [37••]. Despite significant improvements in the medical management and the potential for life-saving liver transplant, ESLD patients still suffer a profoundly reduced QOL and have an increase in health-care utilization [53, 59–69]. This poor QOL is comparable to that reported by patients with advanced chronic obstructive pulmonary disease or heart failure [70]. Additionally, these patients are frequently anxious and depressed which contributes to worse QOL and experiencing more physical symptoms [13, 37••, 71, 72]. As many as 60– 70 % of patients with ESLD experience pain—at least a third of which rate this as moderately severe most of the time [29, 73, 74]. In fact, patients with late ESLD have rates of moderate to severe pain similar to those with lung or colorectal cancer [29, 46••]. Additionally, hospital utilization is increased among ESLD patients with pain [3, 75]. As ESLD progresses, management of the complications of cirrhosis becomes a more time consuming endeavor and is all too often left to the busy primary care clinician [76]. Increased disease complexity is associated with increased hospitalizations [35•]. It is clear that aggressive management of symptoms improves QOL in these patients. Palliative care teams could assist with this management, as well as address the patient goals and plans for managing ever worsening disease [53]. Quality of life can be improved, and health-care utilization decreased, in the ESLD patient with aggressive symptom control [77–79]. Pain Management Unfortunately, the failing liver can make pain management in the ESLD patient more complicated. Pain is often undertreated for fear of complicating the liver disease. The basic principles of pain assessment and management apply to these patients just as they do to those without ESLD; however, clinicians must often modify standard treatments [80–82]. Selective and nonselective nonsteroidal antiinflammatory drugs should not be used in patients with cirrhosis. They inhibit platelet function, can cause gastrointestinal ulceration, and may lead to acute renal failure because they
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inhibit prostaglandin-regulated renal afferent arteriolar vasodilatation [83–85]. Acetaminophen is the preferred first-line analgesic. Its toxicity is dose-dependent, and it can be safely used in daily doses of 2 g or less [82, 86, 87]. Opioids may be used cautiously given that hepatic processing may be altered [83, 88]. This may result in decreased hepatic clearance (increased bioavailability) due to decreased first-pass metabolism (e.g., morphine, oxycodone, hydromorphone, pentazocine) [37••, 89]. Patients should be cautioned about this and avoid taking extra pills or taking them more frequently than prescribed. Certain opioids (e.g., codeine) rely on hepatic transformation to active metabolites and therefore will be less effective. Others are unaffected by the underlying liver dysfunction (e.g., fentanyl, sufentanil). All opioids can complicate hepatic encephalopathy, as can the opioid-related constipation [82]. Careful monitoring is therefore essential.
Conclusions
Hepatic Encephalopathy Hepatic encephalopathy (HE) presents with a wide spectrum of neurologic or psychiatric abnormalities which range from minimal (subclinical or covert) alterations to frank coma [90]. Minimal HE, the earliest stage of HE, occurs in up to 80 % of cirrhotics. It manifests with significant impairment in attention, psychomotor speed, visuospatial perception, response inhibition, and delayed information processing [91, 92]. The presence of HE, even at the subclinical level, complicates significantly the patient’s quality of life and their medical management [91, 93, 94]. Patients may make mistakes at work, leading to loss of employment. Independence is lost—driving is not an option once HE develops [95]. The encephalopathic patient should be accompanied to their physician visits by a trusted family member or friend—someone to help make decisions, write out plans, and remember details. Encephalopathy can generally be managed successfully with lactulose therapy and, if necessary, the addition of rifaximin [96•, 97].
Conflict of Interest Anne M Larson has received honorarium/speakers bureau fees from Gilead and Salix not related to this article.
Ascites In addition to other symptoms, the development of ascites is one of the most distressing symptoms for the cirrhotic patient. It is also the most common complication and at least 50 % of patients will develop it over the 10-year period following diagnosis of cirrhosis [98, 99]. Additionally, it is associated with only a 56 % 3-year survival after onset [99, 100]. Therefore, it is associated not only with an increased shortterm mortality but markedly a decreased quality of life during that time period [99]. Management of ascites is labor intensive as it progresses, but crucial for patient well-being. A full review of the management of all complications of cirrhosis is beyond the scope of this article. However, it is clear that these patients suffer from a wide spectrum of symptoms which need continual management. Careful attention to this management improves their quality and quantity of life.
Chronic liver disease carries significant morbidity and mortality. These patients suffer a significantly reduced quality and quantity of life. Their management is labor intensive and constant throughout the course of their disease. Combining palliative care with potential life-sustaining therapy can improve not only their quality of life but their length of survival. Involvement of the palliative care team should not be seen as Bgiving up^ but as integral to management of these complicated patients. When life-sustaining therapy is no longer an option, these patients are already in a system to help them with further end-of-life care.
Compliance with Ethics Guidelines
Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.
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LIVER (B BACON, SECTION EDITOR)
Palliative Care for Patients with End-Stage Liver Disease Anne M Larson 1
# Springer Science+Business Media New York 2015
Abstract Liver disease results in over four million physician visits and over 750,000 hospitalizations per year in the USA. Those with chronic liver disease frequently progress to cirrhosis, end-stage liver disease (ESLD), and death. Patients with ESLD experience numerous complications, including muscle cramps, confusion (hepatic encephalopathy), protein calorie malnutrition, muscle wasting, fluid overload (ascites, edema), bleeding (esophagogastric variceal hemorrhage), infection (spontaneous bacterial peritonitis), fatigue, anxiety, and depression. Despite significant improvements in palliation of these complications, patients still suffer reduced quality of life and must confront the fact that their disease will often inexorably progress to death. Liver transplantation is a valid option in this setting, increasing the duration of survival and palliating many of the symptoms. However, many patients die waiting for an organ or are not candidates for transplantation due to comorbid illness. Others receive a transplant but succumb to complications of the transplant itself. Patients and families must struggle with simultaneously hoping for a cure while facing a life-threatening illness. Ideally, the combination of palliative care with life-sustaining therapy can maximize the patients’ quality and quantity of life. If it becomes clear that life-sustaining therapy is no longer an
This article is part of Topical Collection on Liver * Anne M Larson [email protected] 1
Swedish Liver Center, 1101 Madison Street #200, Seattle, WA 98104, USA
option, these patients are then already in a system to help them with end-of-life care. Keywords End-stage liver disease . Palliative care . Death . Cirrhosis . End-of-life care
Introduction Chronic liver disease leads to over 4 million ambulatory physician visits annually in the USA (US), with >3.5 million visits for viral hepatitis alone [1]. Chronic liver disease often progresses to cirrhosis and subsequent liver failure, with an estimated US prevalence of cirrhosis of 0.27 % of the population (633,323 adults) [2]. Annually, over 750,000 hospitalizations can be attributed to acute and chronic liver disease [1, 3]. Health-care costs in this population approach almost $4 billion annually, and the incidence of hospitalizations due to cirrhosis and its complications is rising significantly [3–6]. Within a month following discharge, 37 % of cirrhotic patients are readmitted at a mean cost of nearly $30,000 [5]. The more frequent the readmission rate, the greater the risk of subsequent mortality. Up to 40,000 deaths per year can be attributed to cirrhosis—26.4 % per 2-year interval compared to 8.4 % in matched controls [1, 2, 7, 8]. Most patients with chronic liver disease feel well for decades, often completely unaware of the progressive nature of their illness [2]. As the disease progresses, however, patients may develop nonspecific symptoms such as fatigue, even in the absence of cirrhosis. Fatigue is in fact one of the most frequently identified symptoms of chronic liver disease and cirrhosis, and can lead to significant decrease in quality of life [9, 10]. Once chronic liver disease is diagnosed or complications abruptly present, patients often then experience psychologic distress which contributes to their poor quality of life
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[10, 11•]. There may be little time to adjust to the diagnosis— depression and anxiety frequently accompany the diagnosis [11•, 12–14]. The cirrhotic liver eventually decompensates, leading to end-stage liver disease (ESLD), the final phase in liver failure. Patients with ESLD then further experience significant morbidity, including abdominal pain, muscle cramps, cognitive dysfunction (encephalopathy), malnutrition and muscle mass loss, fluid overload (ascites, edema), profound fatigue, and pruritus [15]. Additionally, they may experience such life-threatening complications as variceal hemorrhage, spontaneous bacterial peritonitis, or hepatocellular carcinoma. Life-saving liver transplantation is available only to a small subset of these patients.
Discussing End-of-Life Issues Once the diagnosis of cirrhosis and end-stage liver disease is made or complications occur, patients are often frightened and wonder how they could have reached this point. They may be angry that they were unaware of the consequences of their illness. They often absorb only bits and pieces of what is being told to them and have trouble piecing it all together. Patients suffer a significantly reduced quality of life and must ultimately confront the fact that their disease will inexorably progress to death. Liver transplantation may be a valid treatment option in this setting, increasing the duration of survival and palliating many of the symptoms. Up to 10–15 % of these patients die without receiving an organ, however, and there are many patients who are not candidates for liver transplantation. Furthermore, some patients receive a liver transplant but succumb to complications of the transplant itself. Receiving news of a terminal or life-limiting diagnosis is stressful and evokes strong emotions such as fear, anxiety, anger, depression, despair, hopelessness, and helplessness [16]. Early discussion of end-of-life issues is essential in the management of all patients with ESLD, including those being evaluated for liver transplantation. Patients and their families must understand their prognosis and be prepared for all potential outcomes in order to make realistic treatment decisions [17]. Physicians face the challenge of supporting hope while providing patients with accurate prognostic information [18]. This becomes particularly challenging in the presence of hepatic encephalopathy which further impedes communication and the patient’s ability to make decisions. Physicians and practitioners should anticipate this and engage the patient and their family early in advanced care planning. There is also a significant burden on the caregivers of patients in this setting, particularly in the presence of hepatic encephalopathy [19•, 20–23]. Family members must often make decisions for the patient. This is particularly stressful if the caregiver is not aware of the patient’s wishes. Those patients with liver disease associated with substance abuse may
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lack a strong social network. There may be no close family to provide support, which further complicates communication and long-term care planning [19•]. Palliative care discussions can become particularly difficult if the ESLD patient is being considered for or has been listed for liver transplantation. They must face dealing with the risk of an early death while at the same time focusing on the hope of receiving a life-saving transplant—Bhope for the best and prepare for the worst^ [24]. The patient must be helped to understand that they may experience a catastrophic decline in their condition before transplant can be provided, or may receive a transplant only to die of post-transplant complications. These competing outcomes lead to a Broller-coaster ride^ of emotions which is difficult for all involved. Those for whom liver transplant is not available or has failed face having their hopes dashed and confronting their terminal illness head on. The use of do not attempt resuscitation (DNAR) orders in the setting of ESLD remains even more controversial. The possibility of receiving a transplant adds complexity to the discussion of DNAR and many argue that liver transplant candidates should not carry this type of directive. Full code status may be reasonable for patients who are still healthy enough to survive resuscitation efforts without compromising future treatment options such as transplant. As ESLD progresses, however, and patients become more critically ill, the possibility of transplant futility must be addressed [25–27]. Resuscitation is rarely successful in the critically ill ESLD patient who experiences a catastrophic event (e.g., cardiopulmonary arrest) [28–33••]. Despite successful resuscitation, the event may further compromise transplant outcome or prevent transplant altogether. In this setting, DNAR orders may be appropriate.
Palliative Care and ESLD Palliative care is defined as an approach that improves the quality of life of patients and their families facing the problems associated with life-threatening illness, through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychosocial, and spiritual [34]. Palliative care is often confused with hospice care—a component of palliative care to aid the dying in their last 6 months of life. This confusion may lead to the avoidance of involvement of the palliative care team, particularly in the setting of potential liver transplantation. More recently, however, palliative care is being viewed as a distinct entity from hospice [35•, 36]. There has traditionally been very little guidance for the use of palliative care in the setting of ESLD [37••, 38]. Palliative and hospice care have more traditionally been used in the setting of illnesses whose progressive disease course is clear,
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such as end-stage cancer. Palliative care is of significant value, however, at any stage of disease for any patient with a serious or life-threatening illness [35•]. Patients involved with palliative care experience an improvement in quality of life, a decrease in depression and anxiety, and feel that there is better alignment of their goals with their medical care [35•, 39, 40]. There are many barriers to the consideration of palliative care in the setting of cirrhosis and ESLD. Cirrhotic patients may not appear Bsick^ to the casual observer and, therefore, may not be considered to need help with symptoms or to be at risk of dying. The symptom burden in these patients is frequently not identified as an issue by either physicians or caregivers [41]. The trajectory of liver failure is less predictable than in the setting of other chronic diseases, such as advanced cancer [19•, 42]. This is particularly true earlier in the course of disease or if symptoms (i.e., encephalopathy or ascites) have been medically well controlled. This makes care planning and projection regarding end-of-life issues much more complicated. The practitioner, patient, or caregivers may view palliative care as synonymous with hospice and appropriate only during the final days of life—seeing palliative care as giving up. Finally, discussing palliative care and advanced directives may appear to be at odds with pursuit of curative or life-prolonging therapies, such as liver transplant [37••]. Therefore, end-of-life issues in ESLD are frequently not addressed at all or addressed too late to be of benefit to the patient [43–45••]. Poonja et al. showed that only ∼10 % of patients who were removed from the liver transplant list were referred to palliative care, despite a high symptom burden [46••]. Additionally, they and others have found that goals of care and do not resuscitate status were rarely discussed in these dying patients [29, 47, 48]. Hansen et al. followed six ESLD patients who were hospitalized in the ICU and were either on the liver transplant list or being considered for liver transplant. Interviews were conducted with multiple staff and family members throughout the course of the hospitalization [49]. They found that what mattered most to all participants was the goal of liver transplant. There was no focus on comfort care until all treatment options had been exhausted and none of the patients received a palliative care consultation [49]. The lack of palliative and end-of-life care offered to those who are not candidates for transplant or have been removed from the list often leads to feelings of abandonment by patients [43].
Integrating Palliative Care with ESLD Management The early integration of palliative care in the setting of chronic disease has been shown to improve quality of life (QOL) and actually results in longer patient survival [50•, 51, 52]. It has been suggested that palliative care could be considered in any patient who is at risk of dying within the next year from
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advanced liver disease [53–55]. The course of ESLD is unfortunately much less predictable than many other chronic illnesses—patients experience episodic periods of exacerbation and recovery [42]. This makes predicting the actual time course of progression to death difficult and contributes to the stress patients and caregivers feel. This also makes the timing of palliative care involvement unclear, probably contributing to the lack of palliative care referrals in this population. Early concurrent palliative care could significantly benefit the patient with ESLD and the health-care team providing this care must find ways to integrate palliative care with the possibility of life-prolonging therapy [44, 56]. Support for the concept of palliative care in this setting is growing [38, 57, 58]. It has been suggested that certain clinical findings, such as refractory ascites or hepatic encephalopathy, could be used as triggers for palliative care consultation [37••]. Despite significant improvements in the medical management and the potential for life-saving liver transplant, ESLD patients still suffer a profoundly reduced QOL and have an increase in health-care utilization [53, 59–69]. This poor QOL is comparable to that reported by patients with advanced chronic obstructive pulmonary disease or heart failure [70]. Additionally, these patients are frequently anxious and depressed which contributes to worse QOL and experiencing more physical symptoms [13, 37••, 71, 72]. As many as 60– 70 % of patients with ESLD experience pain—at least a third of which rate this as moderately severe most of the time [29, 73, 74]. In fact, patients with late ESLD have rates of moderate to severe pain similar to those with lung or colorectal cancer [29, 46••]. Additionally, hospital utilization is increased among ESLD patients with pain [3, 75]. As ESLD progresses, management of the complications of cirrhosis becomes a more time consuming endeavor and is all too often left to the busy primary care clinician [76]. Increased disease complexity is associated with increased hospitalizations [35•]. It is clear that aggressive management of symptoms improves QOL in these patients. Palliative care teams could assist with this management, as well as address the patient goals and plans for managing ever worsening disease [53]. Quality of life can be improved, and health-care utilization decreased, in the ESLD patient with aggressive symptom control [77–79]. Pain Management Unfortunately, the failing liver can make pain management in the ESLD patient more complicated. Pain is often undertreated for fear of complicating the liver disease. The basic principles of pain assessment and management apply to these patients just as they do to those without ESLD; however, clinicians must often modify standard treatments [80–82]. Selective and nonselective nonsteroidal antiinflammatory drugs should not be used in patients with cirrhosis. They inhibit platelet function, can cause gastrointestinal ulceration, and may lead to acute renal failure because they
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inhibit prostaglandin-regulated renal afferent arteriolar vasodilatation [83–85]. Acetaminophen is the preferred first-line analgesic. Its toxicity is dose-dependent, and it can be safely used in daily doses of 2 g or less [82, 86, 87]. Opioids may be used cautiously given that hepatic processing may be altered [83, 88]. This may result in decreased hepatic clearance (increased bioavailability) due to decreased first-pass metabolism (e.g., morphine, oxycodone, hydromorphone, pentazocine) [37••, 89]. Patients should be cautioned about this and avoid taking extra pills or taking them more frequently than prescribed. Certain opioids (e.g., codeine) rely on hepatic transformation to active metabolites and therefore will be less effective. Others are unaffected by the underlying liver dysfunction (e.g., fentanyl, sufentanil). All opioids can complicate hepatic encephalopathy, as can the opioid-related constipation [82]. Careful monitoring is therefore essential.
Conclusions
Hepatic Encephalopathy Hepatic encephalopathy (HE) presents with a wide spectrum of neurologic or psychiatric abnormalities which range from minimal (subclinical or covert) alterations to frank coma [90]. Minimal HE, the earliest stage of HE, occurs in up to 80 % of cirrhotics. It manifests with significant impairment in attention, psychomotor speed, visuospatial perception, response inhibition, and delayed information processing [91, 92]. The presence of HE, even at the subclinical level, complicates significantly the patient’s quality of life and their medical management [91, 93, 94]. Patients may make mistakes at work, leading to loss of employment. Independence is lost—driving is not an option once HE develops [95]. The encephalopathic patient should be accompanied to their physician visits by a trusted family member or friend—someone to help make decisions, write out plans, and remember details. Encephalopathy can generally be managed successfully with lactulose therapy and, if necessary, the addition of rifaximin [96•, 97].
Conflict of Interest Anne M Larson has received honorarium/speakers bureau fees from Gilead and Salix not related to this article.
Ascites In addition to other symptoms, the development of ascites is one of the most distressing symptoms for the cirrhotic patient. It is also the most common complication and at least 50 % of patients will develop it over the 10-year period following diagnosis of cirrhosis [98, 99]. Additionally, it is associated with only a 56 % 3-year survival after onset [99, 100]. Therefore, it is associated not only with an increased shortterm mortality but markedly a decreased quality of life during that time period [99]. Management of ascites is labor intensive as it progresses, but crucial for patient well-being. A full review of the management of all complications of cirrhosis is beyond the scope of this article. However, it is clear that these patients suffer from a wide spectrum of symptoms which need continual management. Careful attention to this management improves their quality and quantity of life.
Chronic liver disease carries significant morbidity and mortality. These patients suffer a significantly reduced quality and quantity of life. Their management is labor intensive and constant throughout the course of their disease. Combining palliative care with potential life-sustaining therapy can improve not only their quality of life but their length of survival. Involvement of the palliative care team should not be seen as Bgiving up^ but as integral to management of these complicated patients. When life-sustaining therapy is no longer an option, these patients are already in a system to help them with further end-of-life care.
Compliance with Ethics Guidelines
Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.
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