Living and dying well with end-stage liver disease: Time for palliative care?


  • Kirsty Boyd M.B.Ch.B.(Hon.), F.R.C.P. (Edin.) M.Med.Sci.,

    Corresponding author
    1. The University of Edinburgh Centre for Population Health Sciences Primary Palliative Care Research Group Edinburgh, UK
    • The University of Edinburgh, Centre for Population Health Sciences, Primary Palliative Care Research Group, Medical School, Teviot Place, Edinburgh, EH8 9AG, UK
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    • fax: (0131)-650 9119

  • Barbara Kimbell BSc (Hon), MSC,

    1. The University of Edinburgh Centre for Population Health Sciences Primary Palliative Care Research Group Edinburgh, UK
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  • Scott Murray MD, F.R.C.P. (Edin.), F.R.C.GP.,

    1. The University of Edinburgh Centre for Population Health Sciences Primary Palliative Care Research Group Edinburgh, UK
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  • John Iredale DM, F.R.C.P, F.Med.Sci., F.R.C.P. (Edin.)

    1. MRC/University of Edinburgh Centre for Inflammation Research, Edinburgh, UK
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  • Potential conflict of interest: Nothing to report.

Chronic liver disease is a major cause of mortality worldwide. In the United Kingdom, liver deaths have been increasing for 30 years and currently constitute the fifth highest cause of mortality.1, 2 Liver transplantation is only available to a subset of patients who meet strict criteria. Comorbidities and limited donor organ supplies mean that many patients will not receive a graft and so stand to benefit from palliative care delivered in parallel with optimal disease-focused treatment.3


ESLD, end-stage liver disease.

End-stage liver disease (ESLD) is the final decompensation phase in the liver trajectory. It is characterized by episodic, acute exacerbations, often requiring hospitalization. Life-threatening complications, such as variceal hemorrhage or hepatoma, combine with multiple debilitating symptoms, including ascites, extreme fatigue, pruritus, and cachexia.4 Patients may also experience cognitive decline, ranging from mild chronic impairment to severe hepatic encephalopathy and coma. Many suffer from psychological distress and depression.5 Advanced liver disease generally affects younger people of working age. Financial and social problems as well as the stigma of liver disease can have a profoundly negative impact on the quality of life of the patient and their family.6

Given the plethora of complex physical, psychological, existential, social, and family problems that are the norm in advanced liver disease, it is perhaps surprising that so little attention has been paid to understanding and addressing the wider illness experience of these patients and families.3, 7, 8 The hepatology literature has largely focused on the clinical complications of liver disease and treatment options that may improve both prognosis and quality of life.9 Health-related quality-of-life research is starting to provide insights into the burden of advanced liver disease and how people cope with waiting for transplantation.10, 11 The liver illness trajectory is very different from that found in a typical progressive cancer, the disease paradigm for which most palliative care provision has been developed.12 These patients face an uncertain illness trajectory with the possibility of improvement, if they can stop drinking, or rapid deterioration and death during an acute admission for a life-threatening complication. Palliative care may be viewed incorrectly as only applicable once the patient is in the final days of life and all other treatment options have been exhausted.

Palliative care policies in the United Kingdom and internationally aim to ensure that patients with any life-limiting illness who are approaching the last months of life are identified and assessed.13-15 Given the lack of a clear “terminal phase” and the difficulties of accurate prognostication at an individual level, patients who are likely to be “at risk of dying” from advanced liver disease in the next year are candidates for palliative care.3, 8 We suggest that clinical judgement informed by generic indicators, such as recurrent, unplanned hospital admissions and multimorbidity, can help trigger a review.16, 17 Disease-specific prognostic tools, such as the Child-Pugh or Model for End-stage Liver Disease scores, are evidence-based markers of some of the major complications of decompensated disease, and patients on the transplant waiting list also have end-stage disease. Palliative care has well-defined, supportive care goals related to optimizing quality of life and addressing information needs about the illness and prognosis alongside symptom control, psychosocial support, and spiritual care of the patient and their family.3, 8 Continuity of care consistent with the patient's wishes should then be provided through effective care planning. Goals, interventions, and plans for managing progressive deterioration or a potential episode of acute decompensation can be agreed upon with patients and families and communicated to all those providing care.14, 15

In addition, expertise in symptom control for patients with other types of organ failure is more advanced, whereas a robust evidence base for safe prescribing in liver disease, with its complex pathophysiology and pharmacokinetics, is lacking. Pain may be caused by comorbidities, liver disease complications, or hepatoma. There are no long-term studies of paracetamol (acetaminophen) use in patients with cirrhosis, but at a reduced dose, it is the safest option for mild pain.18 Opioids can be problematic in a population with a high prevalence of substance abuse and are considered a risk for encephalopathy, so careful assessment followed by individualized management and regular review are needed. Opioids should be given in smaller doses and at less frequent intervals in patients with liver disease. Constipation must be managed actively. Two reviews suggest that fentanyl may be the best-tolerated opioid for moderate-to-severe chronic pain, but there is no low-dose oral formulation for dose titration or breakthrough pain.19, 20 Codeine and tramadol are not recommended. If the patient's renal function is not compromised, immediate-release oral morphine may be tolerated and the liquid preparation allows titration with very small doses. An alternative is the more potent, oral opioid, hydromorphone. Morphine and hydromorphone are metabolized by glucuronidation. This is impaired to a lesser extent than the metabolism of drugs cleared by the cytochrome pathways, such as oxycodone. Some clinicians use oxycodone for patients with hepatorenal failure intolerant of morphine who require a low-dose, immediate-release opioid. These patients need to be monitored very closely.8

There is a clear, timely need to generate a better understanding of the experiences and needs of those living and dying with advanced liver disease. Though their experiences may resemble that of people with other types of organ failure, much less is known about the archetypical illness trajectory of ESLD. When asked directly about their care preferences, many patients with end-stage organ failure, including those with liver disease, expressed a clear wish for a palliative care approach that focuses on reduction of morbidity.21 There is growing professional and public recognition that palliative care should be available on the basis of need, not diagnosis; prognostic paralysis should not delay the assessment of needs, and integrated, well-planned, holistic care shared by different teams and specialties in primary and secondary care should be the norm for any patient with a life-limiting illness and their family. Clear guidance exists for the palliative care of nonmalignant end-stage disease in the kidney, lung, and heart. There is currently a pressing need and opportunity to develop programs of research to inform the development of such guidelines for liver disease.