Article Text

Download PDFPDF

Symptom prevalence of patients with end-stage liver disease: a systematic review
  1. Jen-Kuei Peng,
  2. Nilay Hepgul,
  3. Irene J Higginson and
  4. Wei Gao
  1. Cicely Saunders Institute, King’s College London, UK


Introduction End-stage liver disease (ESLD) is a major cause of morbidity and mortality. However, little is known about symptom prevalence among this population.

Aim(s) To systematically review the prevalence of symptoms and how they are measured in patients with ESLD

Method(s) Eight electronic databases (MEDLINE, EMBASE, PsycINFO, CINAHL, British Nursing Index, SCOPUS, Web of Science, and Cochrane Library) were searched from inception to December 2015 for studies investigating symptom prevalence in adult ESLD patients. No time or language limitations were applied. Articles focusing on acute liver failure, metabolic liver disease, cholestatic disease only, other terminal diseases, or on post liver transplantation were excluded.

Results We identified 31 studies with a total of 3630 ESLD patients. Most of them were middle-aged. The prevalence of pain ranged between 30% and 79%. Muscle cramps occurred in 56–68% of patients. Other most frequently reported physical symptoms were insomnia (26–77%), erectile dysfunction (53–93% in men), dyspnea (20–88%), and daytime sleepiness (33–71%). Surprisingly, fatigue and pruritus were only reported in one article for each, with a prevalence of 86% and 47%. Psychological symptoms included anxiety with a prevalence of 14–36%, while 4.5–64% of ESLD patients suffered from depression. The instruments for symptom measurement varied across studies.

Conclusion(s) We have identified the prevalence of a range of symptoms experienced by ESLD patients. There is high variability in symptom prevalence across different studies. Further studies on symptom prevalence and on developing consensus in symptom measurement are keys to improve the care of these patients.


  1. Abdel-Bary SA, Yousif M, Hussein HA. Respiratory muscle strength, hypoxemia and dyspnea in liver cirrhosis patients. Egypt J Chest Dis Tuberc 2014;63:1059–1064

  2. Abrams GA, Concato J, Fallon MB. Muscle cramps in patients with cirrhosis. Am J Gastroenterol 1996;91:1363–1366

  3. Angeli P, Albino G, Carraro P, et al. Cirrhosis and muscle cramps: evidence of a causal relationship. Hepatology 1996;23:264–273

  4. Baskol M, Ozbakir O, Coskun R, et al. The role of serum zinc and other factors on the prevalence of muscle cramps in non-alcoholic cirrhotic patients. J Clin Gastroenterol 2004;38:524–529

  5. Baumann AJ, Wheeler DS, James M, et al. Benefit of early palliative care intervention in end-stage liver disease patients awaiting liver transplantation. J Pain Symptom Manage 2015;50:882 e2–886 e2

  6. Bianchi G, Marchesini G, Nicolino F, et al. Psychological status and depression in patients with liver cirrhosis. Dig Liver Dis 2005;37:593–600

  7. Chatrath H, Liangpunsakul S, Ghabril M, Otte J, Chalasani N, Vuppalanchi R. Prevalence and morbidity associated with muscle cramps in patients with cirrhosis. Am J Med 2012;125:1019–1025

  8. Chien YC, Chiang HC, Lin PY, Chen YL. Erectile function in men with end-stage liver disease improves after living donor liver transplantation. BMC Urol 2015;15:83

  9. De Rui M, Schiff S, Aprile D, et al. Excessive daytime sleepiness and hepatic encephalopathy: it is worth asking. Metab Brain Dis 2013;28:245–248

  10. Gencdal G, Gunsar F, Meral CE, et al. Sleep disorders in cirrhotics; how can we detect? Liver Int 2014;34:1192–1197

  11. Grassi M, Albiani B, De Matteris A, et al. Prevalence of dyspepsia in liver cirrhosis: a clinical and epidemiological investigation. Minerva Med 2001;92:7–12

  12. Gutteling JJ, De Man RA, Busschbach JJ, Darlington AS. Health-related quality of life and psychological correlates in patients listed for liver transplantation. Hepatol Int 2007;1:437–443

  13. Huyghe E, Kamar N, Wagner F, et al. Erectile dysfunction in end-stage liver disease men. J Sex Med 6: 1395–1401

  14. Kalaitzakis E, Josefsson A, Castedal M, et al. Gastrointestinal symptoms in patients with cirrhosis: a longitudinal study before and after liver transplantation. Scand J Gastroenterol 2013;48:1308–1316

  15. Kaltsakas G, Antoniou E, Palamidas AF, et al. Dyspnea and respiratory muscle strength in end-stage liver disease. World J Hepatol 2013;5:56–63

  16. Klein J, Tran SN, Mentha-Dugerdil A, et al. Assessment of sexual function and conjugal satisfaction prior to and after liver transplantation. Ann Transplant 18: 136–145

  17. Madan A, Barth KS, Ballier WE, et al. Chronic pain among liver transplant candidates. Prog Transplant 2012;22:379–384

  18. Margreiter M, Heinisch BB, Schwarzer R, et al. Lower urinary tract symptoms in patients with liver cirrhosis. World J Urol 2015;33:315–321

  19. Montagnese S, Middleton B, Skene DJ, Morgan MY. Night-time sleep disturbance does not correlate with neuropsychiatric impairment in patients with cirrhosis. Liver Int 2009;29:1372–1382

  20. Mostacci B, Ferlisi M, Baldi Antognini A, et al. Sleep disturbance and daytime sleepiness in patients with cirrhosis: a case control study. Neurol Sci 2008;29:237–240

  21. Poonja Z, Brisebois A, Van Zanten SV, et al. Patients with cirrhosis and denied liver transplants rarely receive adequate palliative care or appropriate management. Clin Gastroenterol Hepatol 2014;12:692–698

  22. Popovic D, Culafic DM, Tepavcevic DB, et al. Assessment of depression and anxiety in patients with chronic liver disease. Vojnosanit Pregl 2015;72:414–420

  23. Rodrigue, JR, Nelson DR, Reed AI, Hanto DW, Curry M. Fatigue and sleep quality before and after liver transplantation. Prog Transplant 2010;20:221–233

  24. Rogal SS, Bielefeldt K, Wasan AD, et al. Inflammation, psychiatric symptoms, and opioid use are associated with pain and disability in patients with cirrhosis. Clin Gastroenterol Hepatol 2015;13:1009–1016

  25. Rogal SS, Winger D, Bielefeldt K. Szigethy E. Pain and opioid use in chronic liver disease. Dig Dis Sci 2013;58:2976–2985

  26. Roth K, Lynn J, Zhong Z, Borum M, Dawson NV. Dying with end stage liver disease with cirrhosis: insights from SUPPORT. Study to understand prognoses and preferences for outcomes and risks of treatment. J Am Geriatr Soc 2000;48:S122–S130

  27. Singh N, Gayowski T, Wagener MM, Marino IR. Depression in patients with cirrhosis. Impact on outcome. Dig Dis Sci 1997;42:1421–1427

  28. Sorrell JH, Brown JR. Sexual functioning in patients with end-stage liver disease before and after transplantation. Liver Transpl 2006;12:1473–1477

  29. Stewart KE, Hart RP, Gibson DP, Fisher RA. Illness apprehension, depression, anxiety, and quality of life in liver transplant candidates: implications for psychosocial interventions. Psychosomatics 2014;55:650–658

  30. Trzepacz PT, Brenner R, Van Thiel DH. A psychiatric study of 247 liver transplantation candidates. Psychosomatics 1989;30:147–153

  31. Wang GS, Yang JX, Li MR, et al. Liver transplant may improve erectile function in patients with benign end-stage liver disease: single-center chinese experience. Exp Clin Transplant 2013;11:332–338

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.