High levels of circulating N-terminal pro-brain natriuretic peptide in patients with hepatitis C A. Antonelli, 1 C. Ferri, 2 S. M. Ferrari, 1 M. Colaci, 2 M. Sebastiani, 2 A. L. Zignego, 3 E. Ghiri, 1 F. Goglia 4 and P. Fallahi 1 1 Department of Internal Medicine, University of Pisa School of Medicine, Pisa; 2 Department of Internal Medicine, Rheumatology Unit, University of Modena and Reggio Emilia School of Medicine, Modena; 3 Center for Systemic Manifestations of Hepatitis Viruses, University of Florence, Florence; and 4 Department of Biological and Environmental Sciences, University of Sannio, Benevento, Italy Received August 2009; accepted for publication October 2009 SUMMARY. Many patients chronically infected by hepatitis C virus (HCV) experience symptoms like fatigue, dyspnea and reduced physical activity. However, in many patients, these symptoms are not proportional to the liver involvement and could resemble symptoms of chronic heart failure. To our knowledge, no study evaluated serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) in a large series of patients with HCV chronic infection (HCV+). Serum NT- proBNP was assayed in 50 patients HCV+ and in 50 sex- and age-matched controls. HCV+ patients showed sig- nificantly higher mean NT-proBNP level than controls (P = 0.001). By defining high NT-proBNP level as a value higher than 125 pg/mL (the single cut-off point for patient under 75 years of age), 34% HCV+ and 6% controls had high NT- proBNP (Fisher exact test; P < 0.001). With a cut-off point of 300 pg/mL (used to rule out chronic heart failure in patients under 75 years of age) 10% HCV+ and 0 controls had high NT-proBNP (Fisher exact test; P = 0.056). With a cut-off point of 900 pg/mL (used for ruling in chronic heart failure in patients with age 50–75) 8% HCV+ patients and 0 con- trols had high NT-proBNP (Fisher exact test; P = 0.12). The study demonstrates high levels of circulating NT-proBNP in HCV+ patients compared to healthy controls. The increase of NT-proBNP may indicate the presence of a sub-clinical cardiac dysfunction. Further prospective studies quantifying these symptoms in correlation with echocardiography are needed to confirm this association. Keywords: fatigue, hepatitis C, hepatitis C virus, N-terminal pro-brain natriuretic peptide. INTRODUCTION Many patients with hepatitis C virus (HCV) positive experience symptoms like fatigue, dyspnoea and reduced physical activity. Yet, the exact pathophysiology of these clinical manifestations has not been clarified. Indeed, the relation between the fatigue and the degree of liver fibrosis is controversial; although an association between asthenia and extent of fibrosis was demonstrated [1], some authors have hypothesized a brain involvement in patients with HCV infection and an alteration in neuroaminergic and serotonergic neurotransmission as an important cause of fatigue [2]. Furthermore, some authors have suggested that HCV infection is frequently associated with dilated cardiomyopathy and that HCV replicates in myocardial tissue of patients with myocarditis [3]. Several studies have shown that plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) are reliable diagnostic and prognostic markers for cardiac disease; furthermore, they correlate with symptoms of heart failure and with the severity of systolic and diastolic dysfunction [4]. The aim of this study was to evaluate preliminarily the serum levels of NT-proBNP in a series of patients with chronical infection of HCV, and to correlate this parameter with the clinical features of the disease. METHODS Patients Fifty patients with HCV positive (34 women and 16 men; mean age 56 ± 10SD years), consecutively referred to our internal medicine unit between 2001 and 2006, were recruited for the study. They were extracted from a larger cohort of 491 chronic hepatitis referrals, excluding Abbreviations: HCV, hepatitis C virus; NT-proBNP, N-terminal pro-brain natriuretic peptide. Correspondence: Michele Colaci, MD, Rheumatology Unit, University of Modena and Reggio Emilia, Via del Pozzo, 71 – 41100 Modena, Italy. E-mail: michelecolaci@virgilio.it Journal of Viral Hepatitis, 2010, 17, 851–853 doi:10.1111/j.1365-2893.2009.01237.x Ó 2009 Blackwell Publishing Ltd