Observational Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 21, 2018; 24(15): 1650-1657
Published online Apr 21, 2018. doi: 10.3748/wjg.v24.i15.1650
Development and predictive validity of the cirrhosis-associated ascites symptom scale: A cohort study of 103 patients
Agnete Nordheim Riedel, Nina Kimer, Anne-Sofie Houlberg Jensen, Emilie Kristine Dahl, Mads Israelsen, Luise Aamann, Lise Lotte Gluud
Agnete Nordheim Riedel, Nina Kimer, Anne-Sofie Houlberg Jensen, Emilie Kristine Dahl, Lise Lotte Gluud, Gastro Unit, Medical Davison, Copenhagen University Hospital Hvidovre, Hvidovre 2650, Denmark
Nina Kimer, Abdominal Center K, Medical Section, Copenhagen University Hospital Bispebjerg, København 2400, Denmark
Anne-Sofie Houlberg Jensen, Department of Gastroenterology and Hepatology, University Hospital Zealand Slagelse, Slagelse 4200, Denmark
Mads Israelsen, Department of Gastroenterology and Hepatology, Odense University Hospital, Odense C 5000, Denmark
Luise Aamann, Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus C 8000, Denmark
Author contributions: Gluud LL designed the study and drafted the protocol; Gluud LL, Jensen AS and Dahl EK collected questionnaires and conducted interviews for the pilot-testing of the cirrhosis-associated ascites symptom (CAS); Riedel AN, Jensen AS, Dahl EK, Gluud LL, Aamann L, Israelsen M and Kimer N collected questionnaires for the validation of CAS; Riedel AN and Gluud LL performed the analyses; Kimer N, Riedel AN and Gluud LL drafted the first version of the manuscript. All authors critically revised and approved of the final version of the manuscript.
Institutional review board statement: The study was approved by the Danish Data protection Agency, journal no: 04054, ID: AHH-2015-075.
Informed consent statement: All participants signed an informed consent.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Lise Lotte Gluud, DSc, MD, Associate Professor, Chief Doctor, Research Fellow, Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Kettegaard Alle 30, Hvidovre 2650, Denmark. lise.lotte.gluud.01@regionh.dk
Telephone: +45-31-353212
Received: November 28, 2017
Peer-review started: November 29, 2017
First decision: December 13, 2017
Revised: December 20, 2017
Accepted: January 18, 2018
Article in press: January 18, 2018
Published online: April 21, 2018
Research background

Cirrhosis is associated with a detrimental effect on health related quality of life (HRQL). Disease-specific questionnaires have been developed for the assessment of HRQL in patients with liver disease and cirrhosis. The questionnaires include aspects that are of particular relevance to patients with cirrhosis, such as concerns about complications and liver transplantation.

Research motivation

No previous studies have specifically evaluated the association between the severity of ascites related symptoms and HRQL. However, it is likely that the severity of symptoms is important.

Research objectives

We therefore developed and evaluated the predictive ability of a symptom assessment scale specifically made to assess symptoms related to cirhosis-associated ascites. We subsequently undertook a multicenter cohort study to evaluate the association between our scale and a disease specific scale (CLDQ) as well as a generic HRQL questionnaire (EQ-5D-5L).

Research methods

Development of the cirrhosis-associated ascites symptom (CAS) scale included a literature review, and a qualitative study to evaluate face and content validity as well as discriminatory ability. We initially searched for previously validated scales in MEDLINE and EMBASE. The searches were combined with manual searches of reference lists in potentially relevant articles and conference proceedings. We then proceeded with a qualitative study, where ten independent experts identified and listed what they believed were the most important symptoms with an expected negative impact on HRQL. Symptoms should occur frequently or be severe enough to have substantial impact on daily function in order to be considered for our scale.

We then conducted open interviews followed by structured interviews of ten patients with cirrhosis and moderate (n = 4) or severe ascites (n = 6). The selected domains were initially presented and patients were asked to rate them according to the patient’s perceived ‘importance’, on the extent to which the symptom had bothered them.

We revised the questionnaire instrument based on the answers.

After the development of the questionnaire, we prospectively enrolled a validation cohort consisting of patients with cirrhosis of any aetiology and severe, moderate or no ascites. All gave their informed consent to participate.

Subjects completed the following scales and questionnaires: CAS scale; Chronic Liver Disease Questionnaire; and EQ-5D-5L questionnaire.

We used the Crohnbach’s alpha to assess equivalent reliability. Discriminant validity was evaluated using Dunnett’s test to adjust for multiple comparisons. We originally planned to evaluate convergent validity with previously validated scales assessing symptoms or HRQOL associated with ascites. Since no previous scales were identified, we used the CLDQ and the EQ-5D-5L. We compared scale scores using Spearman correlation and included the CAS scale, CLDQ, CLDQ subscale parameters, and EQ-5D-5L. Correlations higher than 0.70 were considered strong and values below 0.40 were interpreted as poor.

Research results

The final scale included 14 items. Chronbach’s alpha was 0.88 for the total score, which we considered as acceptable. The validation cohort included 103 patients.

The proportion of patients with Child Pugh A was 24%, Child Pugh B: 58% and Child Pugh C: 19%. Fourty-four percent had severe ascites and 27 percent had moderate ascites. A control group of 30 percent had no ascites. The mean scores for each question in the CAS scale suggested that symptoms were worse for patients with severe ascites than for controls. The CAS scale score found that patients with severe ascites or moderate ascites had significantly worse scores compared with controls. Based on the CLDQ questionnaire, severe ascites had a detrimental impact on HRQOL compared with controls as did moderate ascites. The EQ-5D-5L also found a lower HRQOL in patients with severe or moderate ascites. We found a strong correlation between the CAS and the CLDQ total score as well as the CLDQ subscores; fatigue, activity and systemic symptoms.

Research conclusions

This study has developed and tested a symptom assessment scale for the impact of ascites in cirrhosis. The CAS scale is easy to use and correlates well with more extensive QoL questionnaires.

Research perspectives

This study has brought focus to the impact and importance of effective management of ascites in chronic liver disease.

The CAS scale should be tested in larger clinical and interventional trials, preferably in combination with CLDQ or other generic health related quality of life questionnaires.

The CAS scale should be tested in larger cohorts with various etiologies for chronic liver disease and ascites, also in malignant ascites. The CAS scale should also be tested in interventional trials in which the effect of a given intervention on the CAS scale is evaluated, to demonstrate whether the CAS scale is applicable as a monitoring tool in ascites.