Measurement of health-related quality of life in patients with chronic liver disease

Assessment of quality of life as an outcome measure among patients with various conditions has become common in clinical settings in the last two decades.1-9 This has led to the development of a number of instruments ranging from generic indices of well-being to disease-specific instruments. The popularity of these measures has been accompanied by challenges including increased psychometric efficiency and the burden of increasing costs with the inclusion of multiple quality of life instruments into studies. Consequently, many shortened versions of original instruments were created and validated, such as the Medical Outcome Study Short Form-36 (SF-36).10 Since quality of life outcomes have been found to be related to physiological function and mortality, a need for instruments more responsive to treatment effects and the natural history of particular diseases became evident. This caused a significant expansion of disease-specific quality of life assessment instruments for a number of diseases such as arthritis, cancer, stroke, heart disease, and more recently liver disease.1-11 HRQL, health-related quality of life; CLDQ, Chronic Liver Disease Questionnaire. Typically, disease-specific tools are developed by combining the most relevant disease-related items from existing generic measures, clinical expertise, and patient feedback.12, 13 In creating disease-specific instruments, it is challenging to balance test brevity and comprehensiveness, with practical efficiency and measurement precision. Some data suggest that disease-specific instruments are more suitable for clinical trials while generic instruments are beneficial for comparing chronic liver disease with other diseases. However, a more comprehensive understanding of the disease experiences can be obtained by investigators who administer both generic and disease-specific instruments. Such an approach can provide accurate assessments of both the global aspects of health-related quality of life, allowing for comparisons with other diseases, and the particulars of liver disease.1-9 “Chronic liver disease” covers a range of illnesses and with this range, individuals experience varying effects on their health-related quality of life (HRQL). In the early stages of liver disease, few or non-specific symptoms are present and patients thus report less significant effects of their illness on their HRQL. However, as the disease progresses to cirrhosis and the associated complications arise (ascites, muscle cramps, fatigue, etc.), HRQL tends to be more significantly affected. Data show that in patients with advanced cirrhosis, the etiology of the disease does not appear to influence individuals' HRQL scores.14 However, for those in the earlier stages of disease, this may not be true. For example, patients in the early stages of chronic cholestatic liver diseases (along with significant pruritus and fatigue) report significant impairment in their HRQL.15 These symptoms may not be present in those with other forms of chronic liver disease such as chronic hepatitis B or iron overload. The development of a single instrument to accurately capture the HRQL experiences across disease severity and etiology of liver disease is challenging because of these types of differences in the disease. Several types of instruments have been used specifically for those with liver disease: modular instruments, based mainly on generic instruments with a few additional disease-specific scales, and disease-specific instruments focused on those with chronic liver disease. The Chronic Liver Disease Questionnaire (CLDQ) is a validated instrument specific to chronic liver disease and can be utilized across all types of liver disease.1, 2, 15 Individuals in both the early and advanced stages of the disease can be administered the CLDQ. Additionally, a hepatitis C specific version of the CLDQ has been developed and is currently undergoing further validation (The Chronic Liver Disease Questionnaire Hepatitis C - CLDQ-HCV). In this issue of Liver Transplantation, Ferrer and colleagues report the results of their study that aimed to validate a Spanish version of the Chronic Liver Disease Questionnaire (CLDQ) and to assess its psychometric properties.16 The CLDQ was translated into Spanish, pilot tested, and finally administered (CLDQ and SF-36) to patients with chronic liver disease. Initially, forward and backward translations were performed and the instrument was given to a small number of patients who were interviewed about the questionnaire. The instrument was then administered to 149 subjects who presented to a hepatology clinic. These subjects were clinically stable and were diagnosed with either cirrhosis or non-cirrhotic liver disease. Based on their psychometric analysis, the authors' report that the Spanish version of the CLDQ is valid, reliable, and responsive. Factor analysis along with correlations with the SF-36 demonstrated validity. Reliability of each of the CLDQ scales was moderate to high, with the exception of the “Activity” scale. Responsiveness was also demonstrated through administration of the questionnaire to patients who had received a liver transplant. As expected, these patients showed significant improvements in their CLDQ scores after liver transplantation. The authors initially considered dropping item 29 (concerned with how worried the individual is about the availability of a liver if they would need a liver transplant) based on the fact that organs are more readily available in Spain and other European countries and also based on a recent study involving the translation of the CLDQ to Italian.17 However, they subsequently found that approximately one third of their study population still reported this concern. In contrast to the original version, the Spanish CLDQ instrument identified a seventh factor, with the two sleep items originally placed on the Emotion function scale loading onto a separate factor. Based on the exploratory factor analysis results and the additional factor of sleep, it is notable that the Spanish version is not perfectly equivalent to the original version. Although overall the Spanish version performed well in this particular study, further administration and testing of the Spanish version is needed in larger populations and across various Spanish-speaking cultures. Furthermore, the Spanish version of CLDQ must be validated in patients with earlier disease and its responsiveness in earlier stages of liver disease must be established. In sum, Ferrer et al. utilized a systematic approach to the translation and validation of the CLDQ. The psychometric properties of the CLDQ Spanish version remain strong, and comparable methodology has resulted in the translation and validation of the CLDQ in a number of other languages.17-19 Data continue to suggest that CLDQ and its properly translated and validated versions are useful for measuring HRQL in patients with chronic liver disease throughout the world. Future studies in different languages and cultures are needed to further test the applicability of the CLDQ in large scale multinational clinical trials. Availability of the CLDQ in several languages will allow clinicians to obtain a better understanding of how HRQL may be similarly or differentially impacted by chronic liver disease cross culturally.