Endocrine disorders associated with hepatitis C virus chronic infection Michele Colaci 1 & Lorenzo Malatino 1 & Alessandro Antonelli 2 & Poupak Fallahi 2 & Dilia Giuggioli 3 & Clodoveo Ferri 3 # Springer Science+Business Media, LLC, part of Springer Nature 2018 Abstract The term BHCV syndrome^ encompasses several organ- and systemic pathophysiological states, which often recognize autoim- munity or neoplastic evolution in their pathophysiology, as well as chronic HCV infection as trigger. The clinical features of HCV patients are heterogenous, and may include endocrine or metabolic disorders, namely autoimmune thyroiditis, type 2 diabetes mellitus, and erectile/sexual dysfunctions. In this review, we summarize current knowledge on the endocrine/metabolic diseases associated with chronic HCV infection, focusing on the main concepts emerged in the recent literature in this field. The application of this knowledge in everyday clinical practice may be relevant, in order to reinforce a holistic vision of the patient with chronic HCV infection, stimulating in turn a multi-disciplinary approach, thus increasing the probability of early diagnosis, more effective treatments, and a better prognostic outcome. Keywords Hepatitis C . HCV . Diabetes . Thyroiditis . Hypothyroidism . Erectile dysfunction 1 Introduction Hepatitis C (HCV)-infected patients frequently present with a variable combination of different organ and systemic autoim- mune or neoplastic diseases. A number of extra-hepatic man- ifestations have been reported, suggesting that HCV is respon- sible for a systemic disorder, more severe than just a liver disease itself. The term BHCV syndrome^ includes the group of hepatic and extra-hepatic disorders among which the mixed cryoglobulinemic vasculitis may be seen as the pathophysio- logical prototype [1, 2]. A few endocrine and metabolic dis- eases, such as autoimmune thyroiditis (AT), type 2 diabetes mellitus, and erectile dysfunction, may be considered part of HCV syndrome [2–7] (Table 1). In addition to the well-known tropism for hepatocytes, HCV has tropism for other cells, particularly the B lympho- cytes [8]. Therefore, HCV can stimulate complex autoimmune alterations through benign B lymphocyte expansion into tis- sues chronically infected by the virus [1, 2]. In the present paper, we reviewed recent literature data re- garding endocrine/metabolic disorders associated with HCV. 2 Thyroid diseases associated with HCV Autoimmune thyroiditis (AT) is a prototype of organ-specific autoimmune disease: it includes two main pathophysiological and clinical entities, Hashimoto’ s thyroiditis and Graves dis- ease; nonetheless, subclinical thyroid dysfunction should be considered in the disease spectrum [9]. Clinically, AT could lead to both hypo- and hyperthyroidism, more often the first one, or it can produce modest alterations of TSH levels, with- out overt manifestations. Presence of AT in the course of au- toimmune systemic diseases is very frequent. In particular, thyroid involvement is considered one of the most frequent endocrine disorders in association with chronic HCV infec- tion, in the spectrum of HCV syndrome [1–10]. A large Italian population-based study published in 2004 investigated the prevalence of AT in a series of 630 HCV patients not treated with interferon-alpha (IFN). In this survey, HCV patients were more likely than the control groups to show hypothyroidism (13%), anti-thyroglobulin antibodies (TgAb) (17%), and anti-thyroperoxidase antibodies (TPOAb) (21%) [11]. A retrospective cohort study analyzing data of more than 140,000 HCV-infected male patients of US Veterans Affairs * Michele Colaci michele.colaci@unict.it 1 Internal Medicine Unit, Cannizzaro Hospital, Department of Clinical and Experimental Medicine, University of Catania, Via Messina, 829, 95100 Catania, Italy 2 Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy 3 Rheumatology Unit, Azienda Ospedaliero-Universitaria di Modena, University of Modena and Reggio Emilia, Modena, Italy Reviews in Endocrine and Metabolic Disorders https://doi.org/10.1007/s11154-018-9475-y