Clinical validation of the chronic liver disease questionnaire for the Chinese population in Singapore

Introduction

Chronic liver disease (CLD) is a major health burden to society and is estimated to be the fifth most common cause of death worldwide.1 Progression of CLD to cirrhosis, liver failure, and liver cancer is associated with increasing patient morbidity, frequency of hospitalizations, and worsening quality of life.2 Beyond the management of the physical components of the disease, attention must be directed to thee patient's health-related quality of life (HRQOL), which contributes to their overall state of health.3 HRQOL is defined as “the physical, psychological and social domains of health, seen as distinct areas that are influenced by a person's experiences, beliefs, expectations and perceptions.”4

To provide complete patient care, physicians involved in managing patients with CLD must assess patients' HRQOL in addition to physical symptoms. The assessment of HRQOL is conducted using generic and disease-specific instruments. Generic instruments such as the SF365 provide normative data that allow a cross-comparison between patient cohorts but are less sensitive to disease-specific changes. Conversely, disease-specific instruments provide a more accurate assessment of impairments caused by specific disease processes. The Chronic Liver Disease Questionnaire (CLDQ) is the most widely validated disease-specific HRQOL instrument developed for patients with CLD.6 The CLDQ has been cross-culturally validated and translated into several different languages worldwide and has demonstrated excellent validity and reliability for the assessment of HRQOL in CLD irrespective of language, cultural differences, educational level, and etiology of liver disease.7-16 Despite this, measurement of HRQOL is not commonly performed in clinical practice. This could be due to unfamiliarity with HRQOL instruments or a lack of evidence to support locally validated HRQOL instruments. This creates an important need for the local adaptation and clinical validation of such HRQOL tools.

In Singapore, a majority of the population is Chinese, and the major burden of CLD is due to chronic hepatitis B, which is endemic in the region.17 In addition, the rate of non-alcoholic fatty liver disease (NAFLD) has been rapidly increasing over the last two decades.18 Coupled with a low rate of liver transplantation compared to the West, this translates to a large burden of CLD patients who require regular HRQOL assessment. Although a Mandarin version of the CLDQ has been previously validated in China,19 the Singapore version of spoken and written Mandarin is different, thus limiting the utility of the China-Mandarin CLDQ in local clinical practice. To meet the need for a Singapore-Mandarin version of CLDQ, we performed a translation and cultural adaptation of the CLDQ to develop a Singapore-Mandarin version of the CLDQ (CLDQ-SG) (refer to Appendix S1, Supporting information), which was shown to be culturally acceptable by the Mandarin-speaking population in Singapore.20

In this study, we aim to validate the CLDQ-SG by examining the internal consistency and validity of this self-reported questionnaire in a population of CLD patients in a tertiary center in Singapore.

Methods

We performed a cross-sectional study of adult patients with CLD who were seen in the outpatient clinics in the Department of Gastroenterology & Hepatology, Singapore General Hospital between May 2014 and July 2015. A small proportion of the study cohort was admitted to the hospital directly from the outpatient clinics and was recruited during the participants' inpatient stay. Inclusion criteria for this study were adults ≥21 years of age with a diagnosis of CLD who were able to read and speak Mandarin. Exclusion criteria included patients with active hepatic encephalopathy or cognitive impairment, acute complications of CLD (e.g. acute variceal bleeding, acute liver failure, and spontaneous bacterial peritonitis), extrahepatic organ failure, active malignancy, and active psychiatric diseases.

Diagnosis of CLD was made on clinical grounds and included patients with chronic viral hepatitis B and C, alcoholic liver disease, autoimmune liver disease, NAFLD, methotrexate-related liver fibrosis, and cryptogenic liver cirrhosis. The presence of liver cirrhosis was based on radiological findings of coarse liver echogenicity with irregular margins and/or histopathological criteria. The severity of liver cirrhosis was determined clinically using the Child-Pugh criteria. The presence of ascites was determined either clinically or via abdominal ultrasound. The presence and severity of hepatic encephalopathy was assessed clinically using the West Haven criteria. CLD patients were categorized into three groups for comparison: noncirrhotic, compensated cirrhosis (Child-Pugh A), and decompensated cirrhosis (Child-Pugh B and C).

The study received ethical approval from the SingHealth Centralized Institution Review Board (CIRB Ref: 2014/359/A). All subjects provided written consent to participate in the study. Permission to adapt and translate the original and Mandarin versions of the CLDQ instrument was obtained from the original authors Younossi6 and Zhou,18 respectively. Patients who fulfilled the inclusion criteria for the study were asked to complete two questionnaires, the SF-36v2 and the CLDQ-SG, on their own but could seek clarification from a research coordinator if required. The original CLDQ is a disease-specific instrument developed by Younossi et al. to evaluate the HRQOL of patients with CLD. It consists of a 29-item self-administered questionnaire that assesses six separate domains—“Fatigue,” “Emotional Function,” “Abdominal Symptoms,” “Systemic Symptoms,” “Worry,” and “Activity”. The questions relate to symptoms or emotions experienced over the past 2 weeks and are rated on a 7-point scale ranging from 1 (“all of the time”) to 7 (“none of the time”). The domain score represents the mean score of the items related to that domain. The overall CLDQ score represents the mean score for all six domains. A lower score (closer to 1) represents a poorer state of health compared to a higher score (closer to 7).

Statistical analysis

Descriptive statistics were computed for patient demographics and clinical characteristics and are given as frequencies with percentages (%) for categorical variables and medians with interquartile range for continuous data. For the SF36v2 scoring, Singapore norm-based T-scores were computed using the mean and standard deviation scale scores from published literature.21

Results

Discussion

This is the first study to validate the Singapore-Mandarin version of the CLDQ-SG in a clinical setting. Our results confirm the validity of the CLDQ-SG for the reliable assessment of HRQOL in a large cohort of patients with CLD. The key finding in our study is the demonstration that the overall CLDG-SG score declines in tandem with declining liver function. We observed a statistically significant decreasing trend in five of the six domains in addition to the overall CLDQ-SG score across the three groups, from noncirrhotic to compensated cirrhosis and decompensated cirrhosis patients. This observation strongly supports the construct validity of the CLDQ-SG for the assessment of severity of liver disease in the different groups of CLD patients. Our findings are consistent with similar studies of translation and validation of the CLDQ in various ethnic populations.7-16 Clinicians can thus rely on the CLDQ-SG to assess the deterioration of HRQOL as CLD progresses. Conversely, the CLDQ-SG can be used to evaluate the efficacy of therapeutic interventions on improving HRQOL.

When comparing HRQOL between the noncirrhotic and decompensated cirrhosis groups, the difference in the mean CLDQ-SG scores for almost all domains exceeded the minimal clinically important difference (MCID) of 0.5. The concept of MCID describes changes in patient-related outcome scores that are clinically meaningful to the patient and the physician. A change of 0.5 in the CLDQ domain score (on a 1–7 scale) has been suggested as the MCID.24 Changes of this magnitude in the CLDQ score should signal to the managing physician that a change in treatment may be warranted. This provides the clinician with reassuring evidence that the CLDQ-SG is clinically useful to detect significant deterioration in the patient's HRQOL as his or her CLD progresses. This allows for early identification and therapeutic interventions to address these specific issues.

The CLDQ-SG is a valid instrument for evaluating the specific domains of interest in the assessment of HRQOL. The only domain in which a significant trend was not observed between the three groups was EF. This observation is not unique to our study. In the validation of the China-Mandarin version of the CLDQ, Bao et al. similarly reported the lack of a significant trend in the EF domain between noncirrhotic and cirrhosis patients with chronic hepatitis B.10 The lack of significant change in the EF domain across severity of CLD was also reported in the Persian and Serbian cohorts.14, 15 This suggests that the CLDQ may not be sensitive enough to detect significant differences in the EF domain. Indeed, in the original development of the CLDQ, the EF domain showed the smallest changes in CLDQ score across the severity of disease when compared to the other five domains.6

Through exploratory factor analysis, we identified six factors that accounted for a total variance of 69.1%. However, compared to the original CLDQ study, we found that the items for the FA domain were not distinct and instead coloaded with the EF domain into a single factor. Poor factor loading of the FA domain was similarly observed by Lam12 and Zhou18 in the Cantonese and Mandarin versions of the CLDQ, respectively. However, in the German11 and Spanish9 validation studies of the CLDQ, items in the FA domain loaded well on a single factor, similar to the original description by Younossi.6 This finding may suggest that, in Chinese-speaking populations, questions relating to FA (e.g. “feeling sleepy during the day,” “feeling decreased strength,” or “decreased level of energy”) may be misinterpreted as affecting activity or emotional dysfunction instead, possibly due to linguistic peculiarities.

We identified a new factor that assessed sleep, which is unique from the original six factors described by Younossi et al.6 However, this is not a unique finding and has been consistently described in previous validations of the original CLDQ instrument.8-12, 15 Our data thus add to the collective literature that calls for a modification of the CLDQ to add a separate seventh domain specifically to assess sleep. In the original CLDQ construct, items #16 and #20 are included in the EF domain. However, sleep difficulties in patients with CLD may not be related to emotional concerns but may instead be caused by physical discomfort (e.g. from ascites) or by the disease process itself (e.g. hepatic encephalopathy).

We acknowledge several limitations of our study. First, being a single-center study, there may be concerns regarding the applicability of the results to the general Singapore population. However, as one of the two tertiary centers in the country, our hospital sees a large proportion of CLD and cirrhosis patients in Singapore, and the large sample size provides confidence in the validity of the study findings. Second, we did not assess test–retest reliability in this study as this has already been well established in previous studies. Finally, the relatively low numbers of decompensated cirrhosis patients may have limited the sensitivity of the CLDQ-SG to demonstrate meaningful differences between the various Child-Pugh classes.

In conclusion, this is the first study to validate the Singapore-Mandarin version of the CLDQ. The CLDQ-SG is easy to administer, easily understood, and acceptable to patients. Most importantly, our study provides evidence of the reliability and validity of the CLDQ-SG as a disease-specific HRQOL instrument for CLD patients. This will enable all health-care professionals involved in the management of CLD patients to routinely incorporate the assessment of HRQOL using this validated tool to optimize the holistic care of CLD patients.