The Impact of Chronic Hepatitis C and Comorbid Psychiatric Illnesses on Health-related Quality of Life Joseph K. Lim, MD,* Ruth Cronkite, PhD,w Mary K. Goldstein, MD MSc,z and Ramsey C. Cheung, MD* Goals: To determine the relative impact of chronic hepatitis C (CHC) and comorbid psychiatric illness on the health-related quality of life (HRQoL). Background: Psychiatric conditions are more common among patients with CHC but their relative influence on HRQoL is not well understood. Study: We identified 864 veterans who had previously completed a veteran-specific HRQoL questionnaire (SF-36V) as part of the 1999 VA Large Health Survey with known HCV antibody (anti- HCV) status before the survey. For 201 anti-HCV(+) and 663 anti-HCV(  ) patients, we compared the HRQoL status and the prevalence of 6 major psychiatric diagnoses. We conducted multiple regression analyses to measure the effect of anti-HCV status and psychiatric comorbidity. Results: Compared with the anti-HCV(  ) group, anti-HCV(+) veterans were more likely to have alcohol dependence (P <0.001), depression (P = 0.01), or posttraumatic stress disorder (PTSD) (P <0.004). The anti-HCV(+) group also reported lower HRQoL on 4 of the 8 SF-36V subscales (P <0.01) and the mental component summary scale (P <0.001). Even after adjusting for demographic variables and comorbid psychiatric illness, anti-HCV(+) patients re- ported a significantly lower mental component summary score (P <0.01) than did anti-HCV(  ) patients. Multiple regression analysis found that depression and PTSD predicted lower HRQoL scores for all 8 HRQoL subscales (P <0.01) and both the physical (P <0.001) and mental component (P <0.03) summary scales independent of anti-HCV status. Conclusions: The HRQoL is significantly impaired in veterans with CHC, particularly the mental health components of HRQoL. In contrast, comorbid depression and PTSD are associated with both lower physical and mental components of HRQol, independent of CHC. Key Words: hepatitis C, quality of life, psychiatric disorders, veterans (J Clin Gastroenterol 2006;40:528–534) C hronic hepatitis C (CHC) is an important public health problem, affecting over 2.7 million individuals in the United States and over 170 million worldwide. 1,2 CHC accounts for 8000 to 10,000 deaths annually and is the leading indication for liver transplantation. 3 It has been projected that between 2010 and 2019, 165,000 hepatitis C virus (HCV)-related deaths will result from chronic liver disease, including 27,200 from hepatocellu- lar carcinoma at a cost of $10.7 billion in direct medical expenditures. 4 Since the initial discovery of HCV in 1989, 5 significant advances have been made in our understanding of the disease and therapy. Clinical symptoms of CHC tend to be mild and nonspecific (eg, fatigue, malaise, abdominal pain). Pa- tients with CHC have a lower health-related quality of life (HRQoL), 6–15 which improves after achieving sustained virologic response to antiviral therapy or undergoing liver transplantation. 6–9,16–20 These impairments are not asso- ciated with age, sex, mode of transmission, substance use, serum ALT levels, or social support. 21,22 Although previous studies have shown that psychiatric illnesses are common in patients with CHC, 6,23 their relative impact on HRQoL is poorly understood. Drug and alcohol use, depression, post traumatic stress disorder (PTSD), anxiety, and CHC are more common among veterans than in the general popula- tion. 24–28 Veterans who receive care from the Veterans Health Affairs (VHA) facilities are more likely to have greater disability with more complex medical and mental health problems than veterans using other facilities or the general population. 15,29 Not surprisingly, HRQoL is significantly lower across multiple domains in veterans than in the general population. 30–32 We hypothesize that HRQoL is significantly impaired among veterans with CHC compared with those who are anti-HCV negative, and that comorbid psychiatric illnesses con- tribute significantly to these changes independent of HCV status. Copyright r 2006 by Lippincott Williams & Wilkins Received for publication September 22, 2005; accepted February 06 2006. From the *Division of Gastroenterology and Hepatology, Department of Internal Medicine; wCenter for Health Care Evaluation; and zGeriatric Research, Education and Clinical Center, VA Palo Alto Health Care System, Palo Alto, California and Stanford University, Stanford, CA. Supported by funding from the Department of Veterans Affairs Health Services and Research Development Service Grant No. LIP 62-096. Reprints: Ramsey C. Cheung, MD, Division of Gastroenterology and Hepatology, VAPAHCS (154C), 3801 Miranda Avenue, Palo Alto, CA 94304 (e-mail: rcheung@stanford.edu). LIVER,PANCREAS AND BILIARY TRACT:CLINICAL RESEARCH 528 J Clin Gastroenterol  Volume 40, Number 6, July 2006