Hepatitis C Virus Infection Is Systemic: Meeting Additional Goals.

Chronic hepatitis C virus (HCV) infection is a major public health concern in the United States. HCV infection is the leading cause of cirrhosis and the most common indication for liver transplantation [1]. There is growing appreciation that HCV infection is a systemic infection and does not only cause liver disease. For instance, health-related quality of life (HRQL)may be notably diminished, even in the absence of overt complications of liver dysfunction. Patient-reported outcomes (PROs) represent a systematic attempt to quantify the subjective experience of illness. Self-perceptions of health predict mortality andmorbidity, as well as enhance the patient-provider relationship [2, 3]. Research involving patients coinfected with HCV and human immunodeficiency virus (HIV) represents a major unmet healthcare need in the United States. Approximately 30% of patients with HIV infection are coinfected with HCV, and their sustained virologic response (SVR) rates of HCV have until recently trailed behind HCV-monoinfected patients [4–6]. Hepatitis C causes progressive liver disease at a faster rate in HIV/HCV-coinfected patients, compared with HCV-monoinfected patients [7]. Equally important, there have been few major studies assessing the impact of HCV on PROs in HIV infected patients. In this issue of The Journal of Infectious Diseases, Younossi et al elegantly address the relationship between HCV and HIV infection and PROs [8]. Subjects used in the analysis were obtained from studies using interferon-free regimens consisting of sofosbuvir and weight-based ribavirin. The HIV/HCV-coinfected patients were drawn from 2 large studies, PHOTON-1 and PHOTON-2 [9, 10]. In these studies, HIV-infected patients were either untreated and had a CD4 T-cell count of >500 cells/μL or received antiretroviral therapy and had a CD4 T-cell count of >200 cells/μL and an HCV RNA load of <50 copies/mL [9, 10]. All patients were naive to treatment for HCV infection. In contrast, the studies of HCV-monoinfected patients (FUSION and VALENCE) included treatmentexperienced patients, and the distribution of HCV genotypes among them was restricted to genotypes 2 and 3 [11, 12]. HIV/HCV-coinfected individuals were matched with HCV-monoinfected controls according to HCV treatment history, age, sex, body mass index, presence of cirrhosis, baseline HCV load, anxiety, depression, insomnia, clinically overt fatigue, and the presence of type 2 diabetes. Four PRO questionnaires were administered before, during, and after treatment: the Short-Form 36 (SF-36) questionnaire, the Functional Assessment of Chronic Illness Therapy-Fatigue questionnaire, the Chronic Liver Disease Questionnaire– Hepatitis C Virus questionnaire, and the Work Productivity and Activity–Specific Health Problem questionnaire. The results of this study are important. Baseline PROs were lower in coinfected patients, compared withmonoinfected patients, and this trend continued throughout treatment. The authors found that most PROs improved for coinfected patients who achieved a SVR. In contrast, no improvement was seen in coinfected patients who did not achieve an SVR. The results of their multivariate analysis indicate that HIV/HCV coinfection was an independent predictor of PRO scores at baseline (P < .02) but not during or after treatment (P > .05 for both). The presence of cirrhosis was associated with lower PRO scores at baseline. However, all changes that emerged during treatment and in patients with a SVR for 12 weeks after treatment cessation were similar in HIV/ HCV-coinfected patients with cirrhosis, compared with patients without cirrhosis (P > .05), with the exception of the General Health domain of SF-36 (P = .0002). Equally important, PROs can help predict the likelihood of achieving a SVR. Patients who were cured had less fatigue, fewer Received 31 December 2014; accepted 2 January 2015; electronically published 12 January 2015. Correspondence: Sammy Saab, MD, MPH, Pfleger Liver Institute, UCLA Medical Center, 200 Medical Plz, Ste 214, Los Angeles, CA 90095 ([email protected]). The Journal of Infectious Diseases 2015;212:343–4 © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. [email protected]. DOI: 10.1093/infdis/jiv006