title: International diagnostic guidelines for patients with HCV-related extrahepatic manifestations. A multidisciplinary expert statement.
abstract: Hepatitis C virus (HCV) infection is responsible for both hepatic and extra-hepatic disorders (HCV-EHDs); these latter are correlated on one hand clearly with HCV lymphotropism causing immune-system dysregulation as well as with viral oncogenic potential, and on the other hand probably with chronic inflammatory status causing cardio-metabolic complications as well as neurocognitive disturbances. The spectrum of HCV-EHDs ranges from mild or moderate manifestations, such as arthralgia, sicca syndrome, peripheral neuropathy, to severe, life-threatening complications, mainly vasculitis and neoplastic conditions. Given the clinical heterogeneity of HCV-EHDs, HCV-infected individuals are inevitably referred to different specialists according to the presenting/prevalent symptom(s); therefore, the availability of comprehensive diagnostic guidelines is necessary for a patient's whole assessment that is decisive for early diagnosis and correct therapeutic approach of various hepatic and HCV-EHDs, regardless of the specific competencies of different physicians or referral centers. In this respect, a multidisciplinary network of experts, the International Study Group of Extrahepatic Manifestations Related to Hepatitis C Virus Infection (ISG-EHCV), was organized with the intention to formulate diagnostic guidelines for the work-up of possible HCV-EHDs. There was a broad consensus among ISG-EHCV members on the proposed guidelines, which essentially are based on two main levels of patient's assessment. At the referral stage, it is proposed that all patients with HCV infection should be invariably examined by means of first-line diagnostic procedures including virological and hepatic parameter evaluation, as well as the detection of clinical findings that may suggest one or more HCV-EHDs. This preliminary assessment should reveal specific HCV-EHDs, which will be deeper analyzed by means of second-line, targeted investigations. The proposed multidisciplinary expert statement represents the first attempt to draw comprehensive diagnostic guidelines for HCV-infected individuals encompassing the entire spectrum of HCV-related disorders, namely typical hepatic manifestations along with less common, often unpredictable HCV-EHDs. The HCV-EHDs may compromise to a substantial degree the overall disease outcome in a significant number of HCV-infected individuals that renders their timely identification and treatment an imperative. In conclusion, the application of standardized but thorough diagnostic guidelines of HCV-EHDs is advisable at the referral stage as well as during the follow-up period of HCV infected patients. It is envisioned that the proposed strategy will result in improvement of clinical outcomes in such patients.
authors.affiliation: Chair and Rheumatology Unit, Medical School, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico di Modena, 41124 Modena, Italy. Electronic address: clodoveoferri@unimo.it.
authors.forename: Clodoveo
authors.initials: C
authors.lastname: Ferri
authors.affiliation: Department of Autoimmune Diseases, ICMiD Josep Font Autoimmune Lab, CELLEX-IDIBAPS, Hospital Clinic, Barcelona, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Ramos-Casals
authors.affiliation: Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Anna Linda
authors.initials: AL
authors.lastname: Zignego
authors.affiliation: Department of Molecular Medicine, University of Pavia, Italy; Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Arcaini
authors.affiliation: Center of Research of Immunopathology and Rare Diseases, and Nephrology and Dialysis Unit, San G. Bosco Hospital and University of Turin, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Roccatello
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, Pisa 56126, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Antonelli
authors.affiliation: Sorbonne University, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR S 959, Paris, France; CNRS, FRE3632 Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Saadoun
authors.affiliation: Sorbonne University, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR S 959, Paris, France; CNRS, FRE3632 Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France.
authors.forename: Anne Claire
authors.initials: AC
authors.lastname: Desbois
authors.affiliation: Chair and Rheumatology Unit, Medical School, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico di Modena, 41124 Modena, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Sebastiani
authors.affiliation: Department of Clinical Medicine, Sapienza University of Rome, Viale dell'Università 37, 00185 Rome, Italy. Electronic address: milvia.casato@uniroma1.it.
authors.forename: Milvia
authors.initials: M
authors.lastname: Casato
authors.affiliation: Department of Rheumatology & Vasculitis Center, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany. Electronic address: peter.lamprecht@uksh.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Lamprecht
authors.affiliation: Liver Unit, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy. Electronic address: a.mangia@tin.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mangia
authors.affiliation: Department of Pathophysiology, School of Medicine, University of Athens, 75 M. Asias st, Building 16, Room 32, 11527 Athens, Greece. Electronic address: agtzi@med.uoa.gr.
authors.forename: Athanasios G
authors.initials: AG
authors.lastname: Tzioufas
authors.affiliation: Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital; Beatty Liver and Obesity Program, Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA.
authors.forename: Zobair M
authors.initials: ZM
authors.lastname: Younossi
authors.affiliation: Sorbonne University, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR S 959, Paris, France; CNRS, FRE3632 Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Cacoub
mesh_terms: D006287:Health Planning Guidelines; D016174:Hepacivirus / Q000378:metabolism*; D006526:Hepatitis C / Q000150:complications*; D006801:Humans
keywords: Arthritis; Autoimmunity; Diabetes; Diagnostic guidelines; Extrahepatic disorders; HCV; Hepatitis; Hepatitis C virus; Lymphoma; Mixed cryoglobulinemia; Neuropathy; Porphyria; Sicca syndrome; Sjögren's syndrome; Thyroid; Vasculitis