COMMENTS FROM THE EDITORS

End-Stage Chronic Liver Disease: Time to Define aGood Death

John Iredale

Much has been written about the epidemic ofchronic liver disease faced in the West as aresult of hepatitis C, alcohol use, and nonalco-

holic steatohepatitis and in the East as a result of chronicviral liver disease. For each of these examples, the endstage of years of repetitive cycles of inflammation andrepair is advanced fibrosis and cirrhosis with the attendantcomplications, which are challenging to treat and whichseriously affect patients’ quality of life. Additionally, end-stage cirrhotic liver disease is associated, of course, withthe development of hepatocellular cancer. Our approachto this challenge has been the development and refine-ment of hepatic transplantation. Transplantation repre-sents a real success story of the latter part of the 20thcentury because it has transformed the prognosis of dis-eases which until comparatively recently were consideredfatal.1

But for the cohort for which we can successfully per-form transplantation, we also manage a cohort of patientswho are either unsuitable for transplantation, because ofthe presence of comorbid factors, or who are unable toundergo transplantation for other technical reasons or be-cause of the shortage of donor livers. By definition, thisgroup of patients has an appalling prognosis. Indeed, dis-ease models, the Model for End-Stage Liver Disease andChild-Pugh scores, and the development of significantcomplications such as ascites and spontaneous bacterialperitonitis frequently predict an outlook for these patientsworse than many advanced cancers. Our patients withend-stage liver disease require increasingly complex med-ical support and manifest a spectrum of complicationsthat significantly impact on quality of life, such as thedevelopment of ascites, encephalopathy, and cachexia.2,3

At the same time, our flexibility to deploy pharmaceuti-

cal-based approaches is limited by the capacity of the end-stage diseased liver to metabolize many drugs commonlyused in advanced disease, such as opiates.2-4

The analogy with end-stage cancer is an importantone. In many developed countries, the cancer serviceshave established effective and dynamic systems of pallia-tive care ensuring that the final illness of the patient ischaracterized by as high as possible a quality of life. Theapproaches taken in this setting are becoming increasinglybased on evidence from studies in community and hospi-tal settings. These studies encompass the effects on qualityof life of specific interventions or treatments. But to eval-uate the effects on quality of life after an intervention, abaseline undertaking of patient needs and expectations isrequired. A key tool which has proven valuable in definingthis evidence in the palliative core setting has been quali-tative in-depth interviews with patients and their caregiv-ers during their final illnesses.6,7

This structured approach; defining the needs and re-quirements of patients with nonmalignant terminal dis-eases, together with clinical and epidemiological studiesthat allow a plotting of illness trajectory, has been success-fully deployed in the pulmonary and renal fields to pro-vide evidence-based guidelines to trigger specificinterventions and the institution of specific services andtreatments as the patient deteriorates.8 In the area of pal-liation for nonmalignant end-stage disease, we are fallingbehind our pulmonary, cardiology, and renal colleagues.The recently published Gold Standard Framework forprognostic guidance and engagement of palliative carepublished in the United Kingdom, for example, containsclear guidelines for identifying those with terminal (lifeexpectancy less than 1 year) illnesses based on clearly de-finable parameters applicable in primary and secondarycore settings for: cardiac failure, pulmonary disease, renaldisease, and degenerative neurological disorders.8 Liverdisease is notable by its absence.

With a few key exceptions, there is little in the litera-ture on the appropriate palliative approach for patientswith end-stage liver disease. While those publications arevaluable and authoritative,2-5 there is huge scope for us asa community to define what we need to do for thesepatients and to identify and evaluate the most appropriateway of treating the very distressing symptoms that occurto those with end-stage liver disease in the terminal set-

From the Queen’s Medical Research Institute, Medical Research Council Centrefor Inflammation Research, University of Edinburgh, Edinburgh, Scotland, UK.

Received February 19, 2008; accepted February 19, 2008.Address reprint requests to: John Iredale, Queen’s Medical Research Institute,

MRC/University of Edinburgh Centre for Inflammation Research, 47 Little FranceCrescent, Edinburgh, Scotland, UK EH 16 4TJ. E-mail: john.iredale@ed.ac.uk;fax: �44 131 242 6578.

Copyright © 2008 by the American Association for the Study of Liver Diseases.Published online in Wiley InterScience (www.interscience.wiley.com).DOI 10.1002/hep.22298Potential conflict of interest: Nothing to report.

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ting. Indeed, defining when to pull out of active treatmentwith such patients can be an extremely difficult and chal-lenging clinical decision.

In his excellent book “Hippocratic Oaths”, RaymondTallis illustrates the possible futures of old age in the formof a series of graphs.9 This type of plot could be used toillustrate what we should be aiming for in our patientswith end-stage liver disease. If we were to plot quality oflife on the y axis against time on the x axis, then I suspectthe experience of our end-stage liver failure patientswould be represented as an undulating line wandering(with variable steepness) from the top lefthand corner tothe bottom right, indicating a relentless decline in qualityof life. Whereas our aim should be that the plot runs to asgreat an extent as possible horizontal and as close to thetop of the y axis as possible before suddenly plummetingto the x axis in the days around death. We are not, ofcourse, able to alter the illness trajectory of the diseaseswhich underpin terminal hepatic failure in this setting.However, as clinicians in the 21st century, we need tomake it our business to understand the expectations,needs, and requirements of patients dying of end-stagehepatic disease and, on the basis of this data, define the

best and most effective approaches to make the final ill-nesses of our patients as symptom-free and fulfilling aspossible.

References1. Williams R. Hepatology: a personal story. Clin Med 2008;8:25-31.2. Larson AM, Curtis JR. Integrating palliative care for liver transplant can-

didates “too well for transplant, too sick for life”. JAMA 2006;295:2168-2176.

3. Sanchez W, Talwalkar JA. Palliative care for patients with end-stage liverdisease ineligible for liver transplantation. Gastroenterol Clin North Am2006;35:201-219.

4. Rhee C, Broadbent AM. Palliation and liver failure: palliative medicationsdosage guidelines. J Palliat Med 2007;10:677-685.

5. Tegeder I, Lotsch J, Geisslinger G. Parmacokinetics of opioids in liverdisease. Clin Pharmacokinet 1999;37:17-40.

6. Murray SA, Boyd K, Kendall M, Worth A, Benton TF, Clausen H. Dyingof lung cancer or cardiac failure: prospective qualitative interview study ofpatients and their carers in the community. BMJ 2002;325:929.

7. Kendall M, Harris F, Boyd K, Sheikh A, Murray SA, Brown D, et al. Keychallenges and ways forward in researching the “good death”: qualitativein-depth interview and focus group study. BMJ 2007;334:521.

8. Prognostic Indicator Guidance to Aid Identification of Adult Patients withAdvanced Disease, in the Last Months/Year of Life, Who Are in Need ofSupportive and Palliative Care. Royal College of General Practitioners;Gold Standards Framework, PIP 2.24. Published June 2006. Available at:http://www.goldstandardsframework.nhs.uk.

9. Tallis R. Hippocratic Oaths: Medicine and Its Discontents. London, UK:Atlantic Books; 2004.

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