AIM: To evaluate psychometrics of the Chinese (mainland) chronic liver disease questionnaire (CLDQ) in patients with chronic hepatitis B (CHB).

METHODS: A cross-sectional sample of 460 Chinese patients with CHB was selected from the Outpatient Department of the Eighth Hospital of Xi’an, including CHB (CHB without cirrhosis) (n = 323) and CHB-related cirrhosis (n = 137). The psychometrics includes reliability, validity and sensitivity. Internal consistency reliability was measured using Cronbach’s α. Convergent and discriminant validity was evaluated by item-scale correlation. Factorial validity was explored by principal component analysis with varimax rotation. Sensitivity was assessed using Cohen’s effect size (ES), and independent sample t test between CHB and CHB-related cirrhosis groups and between alanine aminotransferase (ALT) normal and abnormal groups after stratifying the disease (CHB and CHB-related cirrhosis).

RESULTS: Internal consistency reliability of the CLDQ was 0.83 (range: 0.65-0.90). Most of the hypothesized item-scale correlations were 0.40 or over, and all of such hypothesized correlations were higher than the alternative ones, indicating satisfactory convergent and discriminant validity. Six factors were extracted after varimax rotation from the 29 items of CLDQ. The eligible Cohen’s ES with statistically significant independent sample t test was found in the overall CLDQ and abdominal, systematic, activity scales (CHB vs CHB-related cirrhosis), and in the overall CLDQ and abdominal scale in the stratification of patients with CHB (ALT normal vs abnormal).

CONCLUSION: The CLDQ has acceptable reliability, validity and sensitivity in Chinese (mainland) patients with CHB.

Chronic hepatitis B (CHB), caused by persistent infection with hepatitis B virus (HBV), is a common chronic liver disease in mainland China. According to the latest national hepatitis B seroepidemiological survey[1], the estimated current HBV carriers in mainland China run up to 93 million, including 20-30 million patients with CHB[2]. CHB patients suffer recurrent symptoms in the long disease natural history and are at a high risk of developing fatal complications of cirrhosis and hepatocellular carcinoma[3,4]. Therefore, CHB may result in a heavy disease burden not only in premature death but also in health impairment[5-8].

Health-related quality of life (HRQoL) is defined as how the individual rates his/her life in terms of physical, psychological and social aspects[9]. In comparison with clinical parameters, HRQoL is a more holistic assessment of health status considering the individual’s functional health and well-being, especially in chronic disease in which mortality is not an immediate concern[3]. Due to the complex natural history and phases of CHB[10], it is particularly important to use HRQoL as the primary endpoint for evaluating health and treatment effects in patients with such disease.

Generally, HRQoL can be measured by generic and disease-specific instruments. Generic instruments are used to compare the HRQoL between groups of patients, but disease-specific questionnaires distinguish the impairment of a specific illness and are more sensitive to the change[11,12]. The 36-item short-form health survey version 2 (SF-36v2) performs well as a generic instrument in patients with CHB[13]. However, not every scale or summary component of the SF-36v2 has the required or eligible sensitivity[14]. Therefore, a disease-specific HRQoL instrument is recommended as a complement for clinical studies in CHB.

The chronic liver disease questionnaire (CLDQ) is the first liver specific instrument developed by Younossi et al[15]. It has been translated into different languages for cross-cultural adaptation[16-23] and proved as a valid tool for HRQoL measurement and evaluation in patients with chronic liver disease[24,25]. The Chinese (Hong Kong, China) CLDQ has been validated in patients with CHB infection[14]. However, a dearth of study assessed psychometrics of the Chinese (mainland) CLDQ in mainland Chinese patients with CHB[26].

The purpose of the study was to evaluate psychometrics including reliability, validity and sensitivity of the Chinese (mainland) CLDQ in CHB patients. The findings of this study will help find suitable disease-specific questionnaire in the management of CHB in mainland China and add to the body of evidence for expanding the use of the CLDQ.

The CLDQ is a non-generic, disease-specific instrument for assessing HRQoL in patients with chronic liver disease. We used the Chinese (mainland) CLDQ in patients with CHB and proved that this instrument has acceptable reliability, validity and sensitivity.

Internal consistency reliability of AB, FA, EM, WO scales and the overall CLDQ were satisfactory, with Cronbach’s α coefficient greater than 0.70. It was consistent with the reports from similar studies using the original and other different language versions of CLDQ[15,16,19,34]. However, Cronbach’s α of SY (0.65) and AC (0.66) scales were less than the recommended value of 0.70. This is probably due to heterogeneous manifestations of systematic symptoms severity and activity limitations in patients with CHB or CHB-related cirrhosis and, consequently, influences the corresponding scoring. Percentages of the floor and ceiling effects regarding the six scales and total score of the CLDQ were less than 20%, indicating that this instrument can capture the full range of potential responses and detect small changes in CHB patients during treatment process.

The convergent and discriminant validity of the CLDQ was satisfactory, proving that the items of each scale can reflect the major characteristics consistently. Lam et al[14] and Mahmoudi et al[35] reported similar results in their studies. However, “availability of a liver for transplant” (item 29) in the present study did not better correlate to WO scale (γ = 0.35), possibly due to few patients confronted with the problem of liver transplantation. Therefore, this item was less correlated to WO scale than the other four items within the same dimension.

The factor structure of the Chinese (mainland) CLDQ conform to the six scale structure of the original US version, with a new scale of “sleep” (factor 6) covering the item “difficulty in sleeping at night” (item 16) and “difficulty in falling asleep at night” (item 20) being the only major difference. Such new factor was also found in the Spanish, Italian and German population[19,20,34]. It was reasonable to believe that sleeping habits vary among cultures (napping habits and bedtimes), so it may not be surprising that these items clustered differently. For patients with CHB or CHB-related cirrhosis, they may have sleep difficulties due to various reasons other than emotional problems, including pain or other disease-related factors. Except for the two items of “sleeping difficulty”, all other items of the EM scale loaded on factor 1 consistently.

The items of WO, AC and AB scales loaded on factor 2, 3 and 4. However, AC and AB scales also combined with other items. The finding showed that “decreased strength” (item 8) and “decreased energy” (item 11) of FA scale loaded on factor 3 (AC scale), whereas “bodily pain” (item 3) of SY scale loaded on factor 4 (AB scale), which demonstrated that decreased strength and energy highly correlate to activity[14], and bodily pain may be better related to AB, especially abdominal pain in CHB patients. “Tiredness or fatigue” (item 2), “feel sleepy during the day” (item 4) and “drowsiness” (item 13) were found loading on factor 5 as measuring fatigue symptoms. However, the FLC of “shortness of breath” (item 6) (0.32), “muscle cramps” (item 21) (0.35), “dry mouth” (item 23) (0.32) and “itching” (item 27) (0.28) were less than the recommended value of 0.45. It was probably because that most of the patients were in CHB stage and did not have distinct clinical manifestations as the items reflected.

By comparison between CHB and CHB-related cirrhosis groups, the CLDQ was sensitive in detecting differences in the overall and AB, SY and AC scale scores. It suggests that, based on measuring the physical and psychological health, the CLDQ could further detect the difference of hepatitis-related physical symptoms in CHB patients with or without cirrhosis. After controlling for influences of the disease (CHB and CHB-related cirrhosis), the CLDQ was very good in measuring differences in the overall and AB and SY scale scores between normal and abnormal ALT groups in CHB patients without cirrhosis. Multiple linear regression analysis also confirmed this result through further controlling other confounding factors such as sociodemographics.

However, due to close scores, FA, EM and WO scales did not show significant difference in CHB patients with or without considering ALT test results and controlling for influences of the disease (CHB and CHB-related cirrhosis). Specifically, the difference of between-group comparison in AC scale changed from significant to not significant after stratification, indicating the confounding role of the disease (CHB and CHB-related cirrhosis). Unlike such finding, Lam et al[14] used the Chinese (Hong Kong, China) CLDQ in patients with CHB infection and reported significant differences in FA, AC, EM and WO scales between uncomplicated and complicated CHB patients. Such discrepancy might be the result that CHB-related complications have impact on the patients’ health regardless of the disease (CHB and CHB-related cirrhosis) and, subsequently, influence the scoring of the corresponding scales. Therefore, the sensitivity of FA, AC, EM and WO scales of the CLDQ in patients with CHB or CHB-related cirrhosis need further examination.

In patients with CHB-related cirrhosis, the ES values of AB (0.27), FA (0.23), AC (0.23) scales and the overall CLDQ (0.21) were greater than 0.20, confirming the major impact of ALT on the hepatitis-related physical health. Other scales including SY (0.16), EM (0.13) and WO (-0.06) did not have the required ES value, indicating the similar conditions of hepatitis-related symptoms and mental health under the influence of ALT (normal vs abnormal) in cirrhotic patients. However, no statistical significance of independent sample t test was found in any scales and the overall CLDQ in the present study. The probable explanation for this might be the small sample size (n = 64). Different from such result, Lam et al[13] found significant differences in SY scale and the overall CLDQ between impaired liver function and cirrhosis groups in CHB patients. Accordingly, more attention should be paid to proving the sensitivity of the CLDQ in CHB-related cirrhosis patients under the influence of normal and abnormal ALT.

There were some limitations in the present study. First, the Chinese (mainland) CLDQ was administered using a face-to-face interview, the performance of the instrument by self-completion will need to be confirmed by future work. Second, the responsiveness of the Chinese (mainland) CLDQ in detecting changes with disease progression or ALT status will also need to be determined. Third, this study was conducted in the single-site of the Eighth Hospital of Xi’an. Therefore, it was limited to generalize the results to all of Chinese mainland CHB patients.

The Chinese (mainland) CLDQ has been proved as a valid tool for assessing HRQoL in patients with CHB. Both reliability and validity were demonstrated to be strongly satisfactory, and better sensitivity was confirmed in detecting the difference of AB, SY and AC scales and the overall CLDQ, especially the differences in AB scale and the overall CLDQ under the influence of ALT status. The Chinese (mainland) CLDQ can be a suitable disease-specific questionnaire for evaluating the change of HRQoL and treatment effects of CHB in clinical practice. Future work in a larger cohort of patients is needed to further prove the responsiveness of the Chinese (mainland) CLDQ.