Comorbid Illness Is an Important Determinant of Health-Related Quality of Life in Patients With Chronic Hepatitis C Khozema B. Hussain, M.D., Robert J. Fontana, M.D., Cheryl A. Moyer, M.S., Grace L. Su, M.D., Naomi Sneed-Pee, B.S., and Anna S. F. Lok, M.D. Division of Gastroenterology and Consortium for Health Outcomes Innovations and Cost-effectiveness Studies (CHOICES), University of Michigan Health System, Ann Arbor, Michigan OBJECTIVES: Chronic hepatitis C (CHC) patients selected for entry into treatment trials have been reported to have impaired health-related quality of life (HRQOL). However, these trials have an inherent selection bias, and HRQOL in CHC patients may have been underestimated because of the exclusion of patients with comorbid illness. The aim of this study was to assess HRQOL in an unselected group of CHC patients and to identify factors associated with impairment in HRQOL. METHODS: A total of 220 consecutive eligible CHC patients were enrolled from a hepatology clinic. HRQOL was as- sessed by the short form 36 (SF-36) and comorbid illnesses were assessed by an interview. RESULTS: CHC patients had significantly lower SF-36 scores in all subscales and in the summary scales when compared to those of the healthy general population in the United States (p  0.001). Compared to CHC patients entering treatment trials, our patients had lower SF-36 scores on five subscales (p  0.001). The presence of comorbid illness was the most important predictor of HRQOL in CHC patients. However, CHC alone resulted in significantly lower SF-36 scores in all subscales and sum- mary scales (p  0.003) compared to those of the healthy U.S. population. There was no correlation between SF-36 scores and history of i.v. drug use or dependence, alcohol dependence, and serum aminotransferase levels. CONCLUSIONS: We conclude that unselected CHC patients presenting for medical evaluation have a reduced HRQOL, which is lower than that reported for CHC patients entering treatment trials. CHC alone is associated with significant impairment in HRQOL, but the presence of comorbid illness leads to further diminution in HRQOL. (Am J Gastroenterol 2001;96:2737–2744. © 2001 by Am. Coll. of Gastroenter- ology) INTRODUCTION Approximately 1–2% of the U.S. population, or an esti- mated 4 million Americans, are chronically infected with hepatitis C (1). Although most chronic hepatitis C (CHC) patients have few or no symptoms during the early stages of their illness, several studies have reported impairment in health-related quality of life (HRQOL) compared to healthy individuals (2–7). Most studies have used an instrument based on the short-form 36 (2– 6) developed by the Medical Outcomes Trust (8, 9). All but one of the published studies on HRQOL in CHC patients have focused on patients se- lected for enrollment into treatment trials (2, 4 – 6). In one study, HRQOL was assessed in 642 treatment-naive CHC patients who participated in a multicenter treatment trial. Before treatment, the CHC patients had markedly impaired quality of life compared to that of the healthy U.S. popula- tion (2). During posttreatment follow-up, significant im- provement in HRQOL was observed among the sustained responders but not in the nonresponders or relapsers, sup- porting a causal relation between viral replication and im- pairment in HRQOL. However, sustained responders con- tinued to have impaired HRQOL compared to healthy individuals, suggesting that residual liver disease or factors besides hepatitis C may be responsible for the persistent impairment in HRQOL in these patients. These studies clearly demonstrate a consistent and marked reduction in HRQOL among CHC patients. However, the magnitude of reduction in HRQOL associated with CHC may have been underestimated because of selection bias, because patients with psychiatric illness, polysubstance abuse or multiple comorbid medical illnesses are usually excluded from treat- ment trials. Serum aminotransferase (ALT) level (2– 6), presence of cirrhosis on liver biopsy (3, 6, 10), and viral factors (2, 6) have not been shown to correlate with HRQOL in CHC patients. Among the published studies on HRQOL in CHC pa- tients, only one was conducted outside the context of a treatment trial (3). This study found that CHC patients had not only lower HRQOL scores than those of healthy con- trols, but also lower scores than those of chronic hepatitis B patients (N = 30) with similar severity of liver disease. We hypothesize that unselected CHC patients have more marked impairment in HRQOL than that reported in patients THE AMERICAN JOURNAL OF GASTROENTEROLOGY Vol. 96, No. 9, 2001 © 2001 by Am. Coll. of Gastroenterology ISSN 0002-9270/01/$20.00 Published by Elsevier Science Inc. PII S0002-9270(01)02695-8