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Impact of physical and psychological factors on health-related quality of life in adult patients with liver cirrhosis: a systematic review protocol

Polis, Suzanne BN, MPH; Fernandez, Ritin BSc, MN, PhD

JBI Database of Systematic Reviews and Implementation Reports: January 2015 - Volume 13 - Issue 1 - p 39–51
doi: 10.11124/jbisrir-2015-1987

Review question/objective What is the impact of physical and psychological factors on health-related quality of life in adult patients diagnosed with liver cirrhosis?

Background All chronic liver diseases stimulate a degree of repetitive hepatocyte injury that alters the normal liver architecture and ends in cirrhosis.1Liver cirrhosis and hepatocellular carcinoma secondary to livercirrhosis are a major public health burden, reporting increasing mortality and morbidity both in Australia and globally.2-6The four leading causes of cirrhosis include harmful alcohol consumption, viral hepatitis B and C and metabolic syndromes related to non-alcoholic fatty liver disease and obesity.7-9

A cirrhotic liver is characterized by the presence of regenerative nodules surrounded by fibrous bands that inhibit the passing of molecules between blood and functional units of liver hepatocytes, leading to liver dysfunction.1,10,11Additionally, the presence of fibrous bands disrupts the normal vascular architecture, increasing resistance within the liver sinusoids and contributing to increased portal vein pressure.10,12

The early stages of cirrhosis are referred to as compensated liver disease with no reported symptoms or evidence of impaired liver function.12,13However, the signs and symptoms of liver failure, as well as the mortality rate, increase as the severity of cirrhosis increases.13Transition from compensated to decompensated cirrhosis is marked by one or more physiological changes. The physiological changes include increased portal vein pressure, impaired synthetic function, electrolyte imbalance and malnourishment.13These physiological changes trigger the development of physical signs and symptoms and impact on the psychological wellbeing of the individual living with cirrhosis. The physical signs and symptoms include esophageal varices, ascites, hepatic encephalopathy, jaundice, irregular sleep patterns, muscle cramps, pruritus, fatigue, impaired mobility, breathlessness, abdominal discomfort, gastrointestinal symptoms, change of body image and pitting edema.14-17Psychological symptoms include stress, depression and anxiety.18,19

Living with liver cirrhosis has a marked impact on the quality of life of the individual. Health-related quality of life (HRQOL) is the individual's perception of their physical, cognitive, emotional and social functioning.20Studies report that physical and psychological factors affect the quality of life of patients with cirrhosis which can be problematic and debilitating.18,21-28There is strong evidence which indicates that disease severity is associated with an impairment of the patient's HRQOL.15,18,22,24-26,29For example, gross ascites causes abdominal discomfort, breathlessness, increased stress and anxiety related to body image, immobility and an increased likelihood of falls. In addition, the management of ascites involves frequent invasive procedures, an increase in pill burden and implementation of dietary restrictions, all of which impact on HRQOL.26

Despite the clear relationship between HRQOL and severity of disease, there has been no systematic review undertaken to determine the physical, psychological and physiological factors that affect the HRQOL of patients with liver cirrhosis. This systematic review will therefore identify the best available evidence related to the impact of physical, psychological and physiological factors on the health-related quality of life of adult patients with liver cirrhosis. The results of the review will increase clinicians' knowledge and highlight areas of clinical management that may require additional strategies and treatment plans to improve symptom relief and HRQOL.

1 St George Hospital, Kogarah, Sydney, New South Wales

2 Center for Evidence based Initiatives in Health Care: an Affiliate Center of the Joanna Briggs Institute

3 School of Nursing and Midwifery, University of Wollongong, New South Wales

Corresponding author: Suzanne Polis

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Inclusion criteria

Types of participants

This review will consider studies that include adult patients aged 18 years and over who have been clinically diagnosed with compensated or decompensated liver cirrhosis. Studies investigating non-liver disease-related cirrhosis, the use of herbal medications, pre- and post-liver transplant and/or hepatocellular carcinoma patients, include non-cirrhotic patients, inpatient data, non-liver-related co-morbidities, patients undergoing interferon therapies and clinical trial studies investigating the use of medications or alternate interventions on HRQOL will be excluded.

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Types of intervention(s)/phenomena of interest

Studies will be included if they have assessed the impact of the following physical and psychological factors on the HRQOL of patients. The physical factors will include but not limited to esophageal varices, ascites, hepatic encephalopathy, jaundice, irregular sleep patterns, muscle cramps, pruritus, fatigue, impaired mobility, breathlessness, abdominal discomfort, gastrointestinal symptoms, muscle wasting and pitting edema. The psychological factors include stress, depression and anxiety.

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Types of outcomes

Studies will be included if they have objectively measured HRQOL including measuring any of the following domains: physical, social and family wellbeing; and emotional, psychological and functional wellbeing.

Studies will be included if quality of life has been measured using objective scales including but not limited to Liver Disease Quality of Life 1.0 (LDQOL), Short Form 36 Profile (SF-36), Chronic Liver Disease Questionnaire (CLDQ), Liver disease symptom index 2.0 (LDSI 2.0), Hepatitis Quality of Life Questionnaire.

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Types of studies

This review will consider experimental study designs including prospective and retrospective cohort studies and descriptive studies for inclusion.

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Search strategy

The search strategy aims to find both published and unpublished studies. A three-step search strategy will be utilized in this review. An initial limited search of the Cochrane Library, MEDLINE and CINAHL will be undertaken, followed by analysis of the text words contained in the titles and abstracts, and of the index terms used to describe the articles. A second search using all identified keywords and index terms will then be undertaken across all included databases. Thirdly, the reference lists of all identified reports and articles will be searched for additional studies. Studies published in the English language will be considered for inclusion in this review due to limited resources. Studies published from 1999 will be considered for inclusion in the review as this is when HRQOL data specific to chronic liver disease and excluding chronic hepatitis C were first reported.30-32

The databases to be searched include: Medline, CINAHL, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and Scopus

The search for unpublished studies will include: ProQuest Dissertation & Theses and MedNar

Initial key words to be used will be:


Quality of life

Health related quality of life



Portal hypertension

Esophageal varices

Muscle cramps

Cognitive impairment

Sleep disturbance

Pitting edema



Health distress







Abdominal bloating

Abdominal pain


Fecal incontinence.

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Assessment of methodological quality

Quantitative papers selected for retrieval will be assessed by two independent reviewers for methodological validity prior to inclusion in the review using standardized critical appraisal instruments from the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) (Appendix I). Any disagreements that arise between the reviewers will be resolved through discussion, or with a third reviewer.

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Data collection

Quantitative data will be extracted for papers included in the review using the standardized data extraction tool from JBI-MAStARI (Appendix II). The data will be extracted independently by one author and checked by a second author. The data extracted will include specific details about the interventions, populations, study methods and outcomes of significance to the review question and specific objectives. Authors of primary studies will be contacted for missing information or to clarify unclear data.

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Data synthesis

Quantitative papers will, where possible, be pooled in statistical meta-analysis using JBI-MAStARI. All results will be subject to double data entry. Effect sizes expressed as odds ratios (for categorical data) and weighted mean differences (for continuous data) and their 95% confidence intervals will be calculated for analysis. Heterogeneity will be assessed statistically using the standard chi-square and also explored using sub-group analyses based on different quantitative study designs included in this review. Where statistical pooling is not possible, the findings will be presented in narrative form including tables and figures to aid in data presentation where appropriate.

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Conflicts of interest

No conflicts of interest can be identified or foreseen in relation to this proposed systematic review.

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                                        Appendix I: Appraisal instruments

                                        MAStARI appraisal instrument







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                                        Appendix II: Data extraction instruments

                                        MAStARI data extraction instrument






                                        Cirrhosis; health related quality of life; encephalopathy

                                        © 2015 by Lippincott williams & Wilkins, Inc.