359 JOURNAL OF INTERFERON & CYTOKINE RESEARCH Volume 30, Number 5, 2010 © Mary Ann Liebert, Inc. DOI: 10.1089/jir.2009.0059 Many patients with hepatitis C chronic infection (HCV+ patients) experience symptoms (fatigue, dyspnea) not proportional to the liver involvement and resemble symptoms of heart failure (HF). To our knowledge, no study evaluated at the same time serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and tumor necrosis factor α (TNF-α) in HCV+ patients. Circulating NT-proBNP and TNF-α were assayed in 60 HCV+ patients, and in 60 sex- and age-matched controls. HCV+ patients showed significantly higher mean NT-proBNP and TNF-α levels than controls ( P < 0.003). By defining high NT-proBNP level as a value higher than 125 pg/mL (the single cutoff point for outpatients under 75 years of age), 28% of HCV+ and 7% controls had high NT-proBNP (chi-square; P < 0.002). With a cutoff point of 900 pg/mL (that should be used for ruling in HF in patients age 50–75; such as the patients in our study), 3% HCV+ and 0 controls had high NT-proBNP. In conclusion, the study demonstrates high levels of circulating NT-proBNP and TNF-α in HCV+ patients. The increase of NT-proBNP may indicate the presence of a subclinical cardiac dysfunction. Further prospective studies quantifying symp- toms and correlating these with echocardiographic parameters are needed to confirm this association. Introduction M any patients with “chronic hepatitis C” (HCV+) expe- rience symptoms like fatigue, dyspnea, and reduced physical activity. However, in many patients, these symp- toms are not proportional to the liver involvement and may resemble symptoms of heart failure (HF). Furthermore, several studies have suggested that hepa- titis C virus (HCV) infection is frequently found in patients with dilated cardiomyopathy and that HCV is an important causal agent in the pathogenesis of the disease (Matsumori and others 1995; Matsumori and Sasayama 1996). Moreover, it has been suggested that HCV replicated in myocardial tissue of patients with myocarditis; thus, HCV infection may contribute to the development of this unusual form of myocarditis (Okabe and others 1997; Frustaci and others 2002, 2003, 2006; Matsumori and others 2006). In a retrospective study, it has been shown that N-terminal pro-brain natriuretic peptide (NT-proBNP) is a sensitive marker of myocardial injury in patients with HF from HCV myocarditis (Matsumori and others 2006). Elevated levels of NT-proBNP during and after interfer- on-based antiviral therapy of chronic hepatitis C have been found, suggesting the presence of cardiac dysfunction, which may contribute to the clinical symptoms observed in these patients during interferon therapy. However, no conclusion could be made from this study about baseline NT-proBNP levels in HCV+ patients lacking an internal control (Bojunga and others 2006). Several studies have shown that plasma levels of brain natriuretic peptide (BNP) and NT-proBNP are reliable diag- nostic and prognostic markers for cardiac disease (Clerico and Emdin 2004; Doust and others 2004) that correlate with symptoms of HF and the severity of systolic and diastolic dysfunction (Koglin and others 2001). Some authors have recently stated that NT-proBNP appears superior to BNP for the evaluation of suspected N-Terminal Pro-Brain Natriuretic Peptide and Tumor Necrosis Factor- α Both Are Increased in Patients with Hepatitis C Alessandro Antonelli, 1 Clodoveo Ferri, 2 Silvia Martina Ferrari, 1 Santino Marchi, 1 Nicola De Bortoli, 1 Domenico Sansonno, 3 Chiara Chiavacci, 1 Ele Ferrannini, 1 and Poupak Fallahi 1 1 Department of Internal Medicine, University of Pisa School of Medicine, Pisa, Italy. 2 Department of Internal Medicine, Rheumatology Unit, University of Modena and Reggio E. School of Medicine, Modena, Italy. 3 Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy.