Impact of Chronic Liver Disease and Cirrhosis on Health Utilities Using SF-6D and the Health Utility Index

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1 LIVER TRANSPLANTATION 14: , 2008 ORIGINAL ARTICLE Impact of Chronic Liver Disease and Cirrhosis on Health Utilities Using SF-6D and the Health Utility Index Amy A. Dan, 1,2 Jillian B. Kallman, 1,2 Ragini Srivastava, 1 Zahra Younoszai, 1 Amy Kim, 1 and Zobair M. Younossi 1,2 1 Center for Liver Diseases and 2 Outcomes Research Program, Inova Fairfax Hospital, Falls Church, VA Assessment of health-related quality of life (HRQL) and health utilities have become important aspects of clinical research. Patient-derived utility adjustments are frequently used in economic analysis. Although HRQL has been frequently studied among patients with liver disease, extensive data on the health utilities of patients with liver disease are not available. Recently, SF-6D has been developed to obtain utility scores from the widely used Short Form 36 questionnaire. To assess health utilities of patients with chronic liver disease using 2 utility assessments [SF-6D and Health Utility Index 2 (HUI-2)], a total of 140 patients were identified from our Liver Disease Quality of Life Database with HRQL data available, as well as clinical and demographic data. Of the 140 patients, 42% were female, had a mean age of 49.4 years (standard deviation 11.2) 36% had hepatitis B virus (HBV), 29% had hepatitis C (HCV), 24% had cholestatic liver disease, and 11% had another liver disease (for example, nonalcoholic steatohepatitis). Bivariate analyses indicated that HBV patients had the highest health status as measured by all of SF-6D and HUI-2 subscales and the overall SF-6D and HUI-2 utility measures, whereas patients with HCV and cholestatic liver disease had similar scores, and those with other liver diseases had the poorest quality of life. When controlling for the effects of gender, age, and cirrhosis, impact of chronic liver disease diagnosis on utility scores persisted only for the SF-6D, with HCV patients having significantly poorer health than HBV patients. In conclusion, SF-6D provides not only a generic assessment of HRQL but also a utility score that can be used for economic analysis of patients with chronic liver disease. Liver Transpl 14: , AASLD. Received June 18, 2007; accepted October 2, The importance of assessing health-related quality of life (HRQL) among patient populations is widely recognized in clinical research. These health status measures evaluate different domains of health, such as physical functioning and mental health. Measures of HRQL, however, have not been designed for use in economic analysis. An important development in health services research has been the emergence of patientderived health utility or preference adjustments. Many of the algorithms for these measures generate single preference-based summary scores. 1 The Medical Outcomes Study Short Form-36 (SF-36) index is a widely used measure of HRQL. The index consists of 36 questions that capture 8 dimensions of health: general health, physical functioning, social functioning, bodily pain, mental health, vitality, physical health role limitations, and emotional role limitations. The index also allows for calculation of composite scales of mental health and physical health. The SF-36 has been validated among several patient populations and is used internationally. The SF-36 uses a simple algorithm for the scales, assumes equal intervals between response choices, and assumes all items are of equal importance. The scoring is thus not based on preferences and cannot be used for health utility adjustments used in economic analysis. Abbreviations: ANOVA, analysis of variance; HBV, hepatitis B virus; HCV, hepatitis C virus; HRQL, health-related quality of life; HUI, Health Utility Index; SD, standard deviation; SF-36, Medical Outcomes Study Short Form-36; OLS, ordinary least squares; MR2, multiple regression coefficient squared. Address reprint requests to Zobair M. Younossi, MD, MPH, Center for Liver Diseases at Inova Fairfax Hospital, 3289 Woodburn Road, Suite 375, Annandale, VA Telephone: ; FAX: ; zobair.younossi@inova.com DOI /lt Published online in Wiley InterScience ( American Association for the Study of Liver Diseases.

2 322 DAN ET AL. Recently, the SF-6D has been derived from of the SF-36 score, which is a single summary utility-based (preference) measure of health status. 2,3 The overall single SF-6D measure of health is computed from 6 preference-based subscales of physical functioning, social functioning, mental health, vitality, pain, and role limitations. The SF-6D was primarily developed to allow for economic evaluations, while retaining the sensitivity to change in health status of the SF-36. Although only recently developed, the SF-6D is already a commonly used utility index. 4 Several alternative health utility measurements are available. Some studies have compared the various approaches to health preference measurement 4-6 and concluded that the preference-based approaches are based on different algorithms, which can lead to differential conclusions affecting health care and resource allocation decisions. Upon comparing 10 utility instruments, Pickard et al. 6 concluded that the SF-6D is the most favorable due to its theoretical and methodological strengths. Researchers, however, tend to agree that it is valuable to use multiple utility instruments to increase the accuracy of decisions based on these measures. 6 Despite widespread use of SF-36, SF-6D utility data for patients with chronic liver disease have not been previously reported. In addition to the SF-6D, another popular instrument for measuring health utility is the Health Utilities Index 2 (HUI-2). The HUI-2 has been commonly used because it includes a general health profile and preference-based health measures, has been validated across many health conditions, has been translated into several languages, and is useful in cost-utility economic evaluations. 7,8 The HUI-2 can measure effects of comorbidities and covers multiple attributes of health. 6 However, it is not very responsive to small but important changes in health status. In this work, we assess the health utilities of patients with chronic liver disease using the SF-6D and HUI-2. We also compare utility scores among patients with different types of liver disease. PATIENTS AND METHODS Patients with chronic hepatitis B virus (HBV), chronic hepatitis C virus (HCV), or cholestatic liver disease (primary biliary cirrhosis and primary sclerosing cholangitis) were selected from our Liver Disease Quality of Life Database ( ). This data set consists of patients with established diagnosis of chronic liver disease who were referred for evaluation, monitoring, and treatment. Patients completed a paper survey with 2 questionnaires at their initial clinical visit the Medical Outcomes Study Short Form 36 (SF-36) and Health Utilities Index-2 (HUI-2). These patients also had clinical and laboratory data available from the time of questionnaire administration. Coinfected patients (human immunodeficiency virus, or HBV-HCV coinfection), patients receiving interferon, as well as those with active neuropsychiatric problems, chemical dependency, excessive alcohol use, and liver transplantation, were excluded. Cirrhosis was defined histologically or clinically as evidenced by the presence of ascites, gastroesophageal varices, or hepatic encephalopathy. This retrospective study was approved by the Institutional Review Board. Measures SF-6D The SF-36 was revised into a 6-dimensional health state measure called the SF-6D. 2,3 The 6 dimensions are physical functioning, role limitations, social functioning, pain, mental health, and vitality. These 6 dimensions each have between 2 and 6 levels, with higher scores on the dimensions reflecting poorer health. This preference-based index is based on 11 items from the original SF-36 questionnaire. For every patient, each score on the 6 SF-6D dimensions defines a health state. The single preference-based measure is scored on a 0.29 to 1.00 scale, with 1.00 indicating complete/full health. HUI-2 The HUI-2 measures health status on 7 dimensions: mobility, emotion, cognition, sensation, self-care, pain, and fertility (this dimension was omitted from this study). Each dimension describes health on 3 to 5 levels, with higher scores reflecting better health. The overall utility score for the HUI-2 is calculated so that 0.00 represents the worst health state and 1.00 represents perfect/full health. Analytic Strategy A series of one-way analyses of variance (ANOVAs) was used to examine whether mean scores on the HRQL subscales differed between 4 patient groups: patients with HCV, HBV, cholestatic liver disease, and other chronic liver diseases. ANOVA Bonferroni tests were also conducted to identify which patient groups scores were statistically significantly different from each other. We also tested whether utility scores differed by gender, age, and whether patients had cirrhosis. To begin, we conducted bivariate analyses. t tests were used to examine gender differences and whether the presence of cirrhosis impacted utility scores. Because age is a continuous variable, Pearson s correlations were used to explore the relationship between age and utility scales. Ordinary least squares regression was used to test the simultaneous effects of age, gender, diagnosis (HBV was the reference group), and having cirrhosis on the overall SF-6D and HUI scales. For all analyses, probability values less than 0.05 were considered statistically significant. RESULTS One hundred forty patients were identified from the database that had HRQL data available, as well as clinical and demographic data. Of the 140 patients, 36% had HBV, 29% had HCV, 24% had cholestatic liver disease, and 11% had another liver disease (for exam-

3 CHRONIC LIVER DISEASE AND HEALTH UTILITIES 323 TABLE 1. Characteristics of Patient Groups Other Liver Cholestatic Liver Disease (n 33) HCV (n 41) HBV (n 51) Disease (n 15) Comparison Test % Female (n) 69.7 (23) 36.6 (15) 25.5 (13) 53.3 (8) ** Mean age (SD) 54.9 (9.4) 48.1 (8.7) 47.3 (12.4) 48.3 (13.6) F 3.67 * % Cirrhosis (n) 57.6 (19) 46.3 (19) 3.9 (2) 86.7 (13) *** % Child-Turcotte-Pugh A (n) 39.4 (13) 17.1 (7) 3.9 (2) 40.0 (6) *** % Child-Turcotte-Pugh B/C (n) 18.2 (6) 29.3 (12) 0 (0) 46.7 (7) Abbreviation: 2, chi-squared; HBV, hepatitis B virus; HCV, hepatitis C virus; SD, standard deviation. TABLE 2. SF-6D and HUI Scores by Health Condition All Patients (n 142) Cholestatic Liver Disease (n 33) HCV (n 41) HBV (n 51) Other Liver Disease (n 15) Possible Range SF-6D Overall 0.71 (0.16) 0.68 (0.16) 0.67 (0.16) 0.78 (0.14) 0.62 (0.13) *** Physical functioning 2.57 (1.5) 2.78 (1.4) 2.85 (1.6) 2.04 (1.3) 3.20 (1.2) ** 1-6 Role limitation 2.18 (1.3) 2.45 (1.3) 2.32 (1.4) 1.57 (1.0) 3.13 (1.2) *** 1-4 Social functioning 2.11 (1.3) 2.12 (1.2) 2.51 (1.4) 1.61 (1.0) 2.67 (1.5) ** 1-5 Bodily pain 2.78 (1.5) 3.00 (1.4) 3.17 (1.4) 2.04 (1.4) 3.60 (1.6) *** 1-6 Mental health 2.42 (1.1) 2.33 (1.0) 2.66 (1.1) 2.14 (1.0) 2.87 (1.0) ** 1-5 Vitality 3.02 (1.2) 3.24 (1.2) 3.22 (1.2) 2.53 (1.0) 3.60 (1.0) * 1-5 HUI-Mark 2 Overall 0.80 (0.19) 0.79 (0.17) 0.75 (0.22) 0.87 (0.16) 0.71 (0.19) ** 0-1 Cognition 0.93 (0.09) 0.92 (0.09) 0.91 (0.10) 0.96 (0.09) 0.93 (0.07) 0-1 Emotion 0.90 (0.14) 0.90 (0.10) 0.88 (0.17) 0.93 (0.10) 0.86 (0.19) 0-1 Mobility 0.96 (0.11) 0.96 (0.13) 0.95 (0.12) 1.00 (0.02) 0.90 (0.18) * 0-1 Pain 0.89 (0.20) 0.89 (0.20) 0.85 (0.22) 0.94 (0.16) 0.87 (0.25) 0-1 Self-care 0.97 (0.15) 0.96 (0.18) 0.99 (0.16) 0.99 (0.07) 0.90 (0.26) 0-1 Sensation 0.85 (0.16) 0.85 (0.09) 0.81 (0.22) 0.88 (0.15) 0.81 (0.12) 0-1 Abbreviations: HBV, hepatitis B virus; HCV, hepatitis C virus; HUI, Health Utility Index. Higher scores reflect better health. Higher scores reflect poorer health. ple, nonalcoholic steatohepatitis, autoimmune hepatitis, and cryptogenic cirrhosis). A total of 42% of patients were female, and patients mean age was 49.4 years [standard deviation (SD) 11.2]. Of the total sample, 38% had cirrhosis; 20% of the sample had Child-Turcotte-Pugh class A cirrhosis, 12% had Child-Turcotte- Pugh class B, and 6% had Child-Turcotte-Pugh class C. Table 1 presents these characteristics by type of chronic liver disease. The mean SF-6D score for patients with chronic liver disease was 0.71 (SD 0.16) and their mean HUI-2 score was 0.80 (SD 0.19). Table 2 presents the mean scores on the SF-6D and HUI-2 subscales and overall utility scales for patients with cholestatic liver disease, HCV, HBV, and other liver diseases. A series of one-way ANOVAs was conducted to explore whether there were differences in HRQL subscales and overall utility scales among the 4 patient groups. Analyses indicated that HBV patients had the highest health utility scores as measured by all the SF-6D subscales and overall utility score. Patients with HCV and cholestatic liver disease had similar levels of quality of life, but scores indicated poorer quality of life compared to HBV patients. Patients with other liver diseases had the poorest SF-6D health utility scores (Table 2). Comparisons of patient groups on HUI-2 scores parallel findings of the SF-6D analyses. Patients with other liver diseases also had the poorest health utility scores and HBV patients had the highest utility scores as measured by the HUI-2. T-tests were used to examine gender differences in

4 324 DAN ET AL. TABLE 3. SF-6D and HUI Scores by Cirrhosis and Child-Turcotte-Pugh Type Patients without Cirrhosis (n 88) Patients with Cirrhosis (n 54) Patients with Child- Turcotte-Pugh A (n 28) Patients with Child- Turcotte-Pugh B or C(n 26) Range SF-6D Overall 0.75 (0.1) 0.64 (0.2) *** 0.71 (0.2) 0.57 (0.1) ** Physical functioning 2.16 (1.4) 3.25 (1.4) *** 2.74 (1.4) 3.80 (1.2) ** 1-6 Role limitation 1.82 (1.2) 2.76 (1.3) *** 2.14 (1.2) 3.42 (1.1) *** 1-4 Social functioning 1.84 (1.1) 2.56 (1.4) ** 1.89 (1.2) 3.27 (1.3) *** 1-5 Bodily pain 2.39 (1.4) 3.43 (1.5) *** 2.71 (1.3) 4.19 (1.4) *** 1-6 Mental health 2.34 (1.1) 2.54 (1.1) 2.25 (1.1) 2.85 (1.0) * 1-5 Vitality 2.74 (1.1) 3.48 (1.5) *** 3.07 (1.2) 3.92 (0.9) ** 1-5 HUI-Mark 2 Overall 0.85 (0.2) 0.72 (0.2) *** 0.82 (0.1) 0.61 (0.2) *** 0-1 Cognition 0.94 (0.1) 0.91 (0.1) 0.97 (0.1) 0.86 (0.1) *** 0-1 Emotion 0.92 (0.1) 0.87 (0.2) * 0.88 (0.2) 0.85 (0.1) 0-1 Mobility 0.99 (0.0) 0.92 (0.2) ** 0.99 (0.0) 0.85 (0.2) ** 0-1 Pain 0.92 (0.2) 0.86 (0.2) 0.94 (0.1) 0.77 (0.3) ** 0-1 Self-care 0.99 (0.1) 0.93 (0.2) * 1.00 (0.0) 0.85 (0.3) * 0-1 Sensation 0.88 (0.1) 0.78 (0.2) ** 0.82 (0.2) 0.74 (0.3) 0-1 Abbreviation: HUI, Health Utility Index. Higher scores reflect better health. Higher scores reflect poorer health. utility scores and whether patients with cirrhosis differed in their utility scores compared to patients who did not have cirrhosis. Pearson s correlations were used to examine the relationship between utility scales and age. Female patients experienced poorer health status as measured by all SF-6D subscales (P 0.05), the overall SF-6D health status measure (P 0.05), and the cognition and mobility HUI subscales. Older age was only modestly associated with many of these subscales, particularly physical functioning and sensation. Compared to patients without cirrhosis, patients with cirrhosis had poorer health status as measured by the SF-6D summary score (P 0.05), all SF-6D subscales (P 0.05), and the overall HUI score and 4 of the HUI subscales (emotion, mobility, self-care, and sensation) (P 0.05). Mean scores for patients with cirrhosis and patients without cirrhosis are presented in Table 3. As a more detailed analysis about the effect of cirrhosis on health status, we compared patients with Child-Turcotte-Pugh class A (20% of patients), B (12%), C (6%), and patients without cirrhosis using one-way ANOVA. Mean scores for patients who had Child-Turcotte-Pugh A cirrhosis compared to patients with Child-Turcotte- Pugh B or C are also listed in Table 3. Results indicated that patients without cirrhosis had the least impairment in health status on all the scales, followed by patients with Child-Turcotte-Pugh class A (P 0.05). Patients with Child-Turcotte-Pugh cirrhosis B and C had the lowest levels of HRQL as measured by all scales (P 0.05). Two ordinary least squares regression models were run to test the simultaneous effects of age, gender, diagnosis (HBV was the reference group) in the multivariate model, and having cirrhosis on the overall SF-6D and HUI scales. The results are presented in Table 4. For the SF-6D utility score model, gender and having HCV (compared to patients with HBV) were statistically significantly predictive of SF-6D utility scores (P 0.05). Patients with cholestatic liver disease and other liver diseases did not differ from patients with HBV in SF-6D scores (P 0.05). Age and cirrhosis were not predictive of SF-6D scores in the multivariate model (P 0.05). In the multivariate model to predict HUI-2 scores, only cirrhosis affected health status (P 0.05). Diagnosis, age, and gender were not statistically significant predictors of HUI sores (P 0.05). We examined the strength of the relationship between the overall HUI and SF-6D utility scales using Pearson s correlation. The correlation value was 0.715, indicating that the 2 overall health utility scores are highly correlated. DISCUSSION This is the first known study to examine the health utility scores of liver disease patients using the SF-6D and to compare scores by the type of liver disease. Our findings document that patients with HBV have the highest health status of the 4 patient groups studied, followed, almost equally, by patients with cholestatic liver disease and HCV. Those with other liver diseases, including nonalcoholic steatohepatitis and cryptogenic cirrhosis, have significantly poorer health status

5 CHRONIC LIVER DISEASE AND HEALTH UTILITIES 325 TABLE 4. OLS Regression Results: Predictors of Overall SF-6D and HUI Scores Unstandardized (Standardized) Coefficients Overall SF-6D Overall HUI-2 HCV 0.08 ( 0.24) * 0.08 ( 0.19) Cholestatic liver disease 0.03 ( 0.09) 0.00 ( 0.01) Other liver disease 0.10 ( 0.19) 0.07 ( 0.11) Age 0.00 ( 0.04) 0.00 ( 0.07) Female 0.08 ( 0.25) ** 0.03 ( 0.08) Cirrhosis 0.05 ( 0.16) 0.10 ( 0.23) * MR Abbreviations: HCV, hepatitis C virus; HUI, Health Utility Index; OLS, ordinary least squares; MR2, multiple regression coefficient squared. Hepatitis B virus was the reference category. scores, as measured by both the SF-6D and HUI-2. Multivariate analyses, however, indicate that once the presence of cirrhosis is controlled, only HCV patients have statistically significantly different HRQL scores compared to HBV patients; and differences between HBV patients, cholestatic liver disease and other liver disease were no longer statistically significant. A comparison of SF-6D scores among a representative sample of the U.S. adult population to the 4 patient groups 9 (data not presented) indicated that the patients utility scores are significantly lower than in the general population norms. Looking more carefully at the effects of cirrhosis, patients with Child-Turcotte-Pugh cirrhosis B and C had comparatively poorer health status compared to patients with Child-Turcotte-Pugh class A cirrhosis and patients who did not have cirrhosis. This is consistent with previous HRQL research using generic and disease-specific HRQL instruments We find that HUI-2 and SF-6D scores are highly correlated among patients with liver disease. This suggests that using one or the other scale would likely lead to similar conclusions about patients health status. However, given the widespread use of SF-36 in patients with chronic liver disease, obtaining the SF-6D scores have an important advantage. Nevertheless, it is important to remember that in our study predictors of SF-6D and HUI-2 in the multivariate models were different, indicating more research is needed to better identify the sensitivity of these utility scales among patients with liver disease. The use of patient-derived utility scores, such as the SF-6D and HUI-2, are important developments in the economic assessment of treatment regimens. These scales are based on quality-adjusted life years where a patient s health is measured on a scale of death to full health. Assessments of patient s health status were previously based solely on expert panels, which do not always perfectly match patients experiences. Little research has estimated the utility scores among patients with different liver diseases. The development of the SF-6D as a preference-based measure is particularly important because the SF-36 is and has been widely used with many patient groups, including liver disease patients. Deriving SF-6D scores from patients SF-36 responses is straightforward and because of the ease of calculation and popularity of the SF-36, it is likely that the SF-6D will become more popular in the future. Because this is the first known study to explore SF-6D utility scores among patients with chronic liver disease, more research is needed. Although our sample size was sufficient to make initial tentative conclusions about how SF-6D scores differ among our 4 patient groups, future research should involve not only larger samples but also focus more in-depth on aspects of patients disease status, including other comorbidities, which might impact utility scores. Additionally, our study was retrospective, and we therefore only had a small number of patients with other chronic liver diseases. Given that this group of patients had the poorest HRQL, future research should be designed with larger number of patients with different types of liver disease to better understand the impact of type of chronic liver disease on HRQL. Evaluation of how chronic liver disease patients SF-6D utility scores compare to other established utility measures, and factors that may similarly and differentially impact utility scores, would also be valuable given that we found SF-6D and HUI-2 scores were affected by different factors. In summary, this is the first study reporting health utility scores in patients with chronic liver disease using both HUI-2 and SF-6D. This utility data can be used to perform more accurate economic analysis of patients with chronic liver disease who are undergoing treatment or liver transplantation. REFERENCES 1. Marra CA, Woolcott JC, Kopec JA, Shojania K, Offer R, Brazier JE, et al. A comparison of generic, indirect utility measures (the HUI2, HUI3, SF-6D, and the EQ-5D) and disease-specific instruments (the RAQoL and the HAQ) in rheumatoid arthritis. Soc Sci Med 2005;60:

6 326 DAN ET AL. 2. Brazier J, Usherwood T, Harper R, Thomas K. Deriving a preference-based single index from the UK SF-36 Health Survey. J Clin Epidemiol 1998;51: Brazier J, Roberts J, Deverill M. The estimation of a preference-based measure of health from the SF-36. J Health Econ 2002;21: Rasanen P, Roine E, Sintonen H, Semberg-Konttinen V, Ryynanen OP, Roine R. Use of quality-adjusted life years for the estimation of effectiveness of health care: a systematic literature review. Int J Technol Assess Health Care 2006;22: McDonough CM, Tosteson AN. Measuring preferences for cost-utility analysis: how choice of method may influence decision-making. Pharmacoeconomics 2007;25: Pickard AS, Wang Z, Walton SM, Lee TA. Are decisions using cost-utility analyses robust to choice of SF-36/ SF-12 preference-based algorithm? Health Qual Life Outcomes 2005;3: Furlong WJ, Feeny DH, Torrance GW, Barr RD. The Health Utilities Index (HUI ) System for assessing health-related quality of life in clinical studies. Ann Med 2001;33: Torrance GW, Feeny DH, Furlong WJ, Barr RD, Zhang Y, Wang Q. Multiattribute utility function for a comprehensive health status classification system: Health Utilities Index Mark 2. Med Care 1996;34: Hanmer J, Lawrence WF, Anderson JP, Kaplan RM, Fryback DG. Report of nationally representative values for the noninstitutionalized US adult population for 7 health-related quality-of-life scores. Med Decis Making 2006;26: Martin LM, Younossi ZM. Health-related quality of life (HRQL) in chronic liver disease. Dig Liver Dis 2005;37: Younossi ZM, Boparai N, Price LL, Kiwi ML, McCormick M, Guyatt G. Health-related quality of life in chronic liver disease: the impact of type and severity of disease. Am J Gastroenterol 2001;96: Younossi ZM, Boparai N, McCormick M, Price LL, Guyatt G. Assessment of utilities and health-related quality of life in patients with chronic liver disease. Am J Gastroenterol 2001;96: Dan AA, Martin LM, Crone C, Ong JP, Farmer DW, Wise T, et al. Depression, anemia and health-related quality of life in chronic hepatitis C. J Hepatol 2006;44: Martin LM, Sheridan MJ, Younossi ZM. The impact of liver disease on health-related quality of life: a review of the literature. Curr Gastroenterol Rep 2002;4: Younossi ZM, Kallman J, Kincaid J. The effects of HCV infection and management on health-related quality of life. Hepatology 2007;45: