Retrospective Cohort Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. May 27, 2018; 10(5): 409-416
Published online May 27, 2018. doi: 10.4254/wjh.v10.i5.409
Clinical epidemiology of chronic viral hepatitis B: A Tuscany real-world large-scale cohort study
Cristina Stasi, Caterina Silvestri, Roberto Berni, Maurizia Rossana Brunetto, Anna Linda Zignego, Cristina Orsini, Stefano Milani, Liana Ricciardi, Andrea De Luca, Pierluigi Blanc, Cesira Nencioni, Donatella Aquilini, Alessandro Bartoloni, Giampaolo Bresci, Santino Marchi, Franco Filipponi, Piero Colombatto, Paolo Forte, Andrea Galli, Sauro Luchi, Silvia Chigiotti, Alessandro Nerli, Giampaolo Corti, Rodolfo Sacco, Paola Carrai, Angelo Ricchiuti, Massimo Giusti, Paolo Almi, Andrea Cozzi, Silvia Carloppi, Giacomo Laffi, Fabio Voller, Francesco Cipriani
Cristina Stasi, Caterina Silvestri, Fabio Voller, Observatory of Epidemiology, Regional Health Agency of Tuscany, Florence 50141, Italy
Cristina Stasi, Anna Linda Zignego, Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Internal Medicine and Liver Unit, Department of Experimental and Clinical Medicine, Careggi University Hospital, Florence 50134, Italy
Roberto Berni, Cristina Orsini, Web Solutions, Data Visualization and Scientific Documentation, Regional Health Agency of Tuscany, Florence 50141, Italy
Maurizia Rossana Brunetto, Piero Colombatto, Hepatology Unit, Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa 56100, Italy
Stefano Milani, Paolo Forte, Andrea Galli, Andrea Cozzi, Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, Careggi University Hospital, Florence 50134, Italy
Liana Ricciardi, Sauro Luchi, Infectious Disease Unit, Hospital of Lucca, Lucca 55100, Italy
Andrea De Luca, Infectious Diseases Unit, Department of Medical Biotechnologies, Siena University Hospital, Siena 53100, Italy
Pierluigi Blanc, Infectious Disease Unit, “S. Maria Annunziata” Hospital, Ponte a Niccheri 50012, Italy
Cesira Nencioni, Silvia Chigiotti, Infectious Disease Unit, Hospital of Grosseto, Grosseto 58100, Italy
Donatella Aquilini, Alessandro Nerli, Infectious Disease Unit, Hospital of Prato, Prato 59100, Italy
Alessandro Bartoloni, Giampaolo Corti, Infectious and Tropical Diseases Unit, Department of Experimental and Clinical Medicine, Careggi University Hospital, Florence 50134, Italy
Giampaolo Bresci, Rodolfo Sacco, Gastroenterology and Metabolic Disorders, Department of Surgery, Cisanello University Hospital, Pisa 56100, Italy
Santino Marchi, Angelo Ricchiuti, Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, Cisanello University Hospital of Pisa, Pisa 56100, Italy
Franco Filipponi, Paola Carrai, Liver Surgery and Transplantation Unit, Department of Surgical Pathology, Medicine, Molecular and Critical Area, Cisanello University Hospital, Pisa 56100, Italy
Massimo Giusti, Internal Medicine Unit, “San Jacopo” Hospital, Pistoia 51100, Italy
Paolo Almi, Infectious Diseases and Hepatology Unit, Department of Internal and Specialized Medicine, University Hospital of Siena, Siena 53100, Italy
Silvia Carloppi, Gastroenterology Unit, San Giuseppe Hospital, Empoli 50053, Italy
Giacomo Laffi, Internal Medicine and Liver Unit, Department of Experimental and Clinical Medicine, Careggi University Hospital, Florence 50135, Italy
Francesco Cipriani, Department of Prevention, Central Tuscany Local Unit, Florence 50100, Italy
Author contributions: Stasi C designed the study, wrote the paper, participated in acquisition, interpretation and analysis of the data and revised the article; Silvestri C participated in the study design and acquisition and analysis of the data and revised the article; Berni R and Orsini C designed and developed the software for data registration and revised statistical analysis; Brunetto MR, Zignego AL, Milani S, Ricciardi L, De Luca A, Blanc P, Nencioni C, Quilini D, Bartoloni A, Bresci G, Marchi S, Filipponi F, Colombatto P, Forte P, Galli A, Luchi S, Chigiotti S, Nerli A, Corti G, Sacco R, Carrai P, Ricchiuti A, Giusti M, Almi P, Cozzi A, Carloppi S and Laffi G participated in study design and acquisition of data and revised the article critically for important intellectual content; Voller F and Cipriani F participated in study design, were the guarantors of methods used, and revised the article critically for important intellectual content; all authors have reviewed and approved the final manuscript.
Institutional review board statement: This study was reviewed and approved by the Institutional Review Board.
Informed consent statement: The demographic data of the study were appropriately encrypted in the database and the exported file (containing the “anonymized” data) was sent from the system to the Regional Health Agency of Tuscany via a secure channel.
Conflict-of-interest statement: Professor Brunetto MR reports grants and personal fees from BMS, personal fees from Gilead, outside the submitted work; Professor De Luca A reports grants from ViiV Healthcare, grants from Gilead, personal fees from ViiV Healthcare, personal fees from Gilead, personal fees from Merck Sharp and Dohme, personal fees from Janssen Cilag, outside the submitted work. No other authors have relevant conflicts of interests to disclose.
STROBE statement: The guidelines of the STROBE Statement have been adopted.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Cristina Stasi, MD, PhD, Consultant Gastroenterologist, Observatory of Epidemiology, Regional Health Agency of Tuscany, Via P. Dazzi 1, Florence 50141, Italy.
Telephone: +39-55-4624385
Received: February 20, 2018
Peer-review started: February 21, 2018
First decision: March 15, 2018
Revised: March 20, 2018
Accepted: April 15, 2018
Article in press: April 16, 2018
Published online: May 27, 2018

To build a regional database of chronic patients to define the clinical epidemiology of hepatitis B virus (HBV)-infected patients in the Tuscan public health care system.


This study used a cross-sectional cohort design. We evaluated chronic viral hepatitis patients with HBV referred to the outpatient services of 16 hospital units. Information in the case report forms included main demographic data, blood chemistry data, viral hepatitis markers, instrumental evaluations, and eligibility for treatment or ongoing therapy and liver transplantation.


Of 4015 chronic viral hepatitis patients, 1096 (27.3%) were HBV infected. The case report form was correctly completed for only 833 patients (64% males, 36% females; mean age 50.1 ± 15.4). Of these HBV-infected patients, 73% were Caucasian, 21% Asian, 4% Central African, 1% North African and 1% American. Stratifying patients by age and nationality, we found that 21.7% of HBV-infected patients were aged < 34 years (only 2.8% were Italian). The most represented routes of transmission were nosocomial/dental procedures (23%), mother-to-child (17%) and sexual transmission (12%). The most represented HBV genotypes were D (72%) and A (14%). Of the patients, 24.7% of patients were HBeAg positive, and 75.3% were HBeAg negative. Of the HBV patients 7% were anti-HDV positive. In the whole cohort, 26.9% were cirrhotic (35.8% aged < 45 years), and 47% were eligible for or currently undergoing treatment, of whom 41.9 % were cirrhotic.


Only 27.3% of chronic viral hepatitis patients were HBV infected. Our results provide evidence of HBV infection in people aged < 34 years, especially in the foreign population not protected by vaccination. In our cohort of patients, liver cirrhosis was also found in young adults.

Keywords: Hepatitis B virus infection, Liver fibrosis, Cirrhosis, Public health, Epidemiology

Core tip: Although the introduction of a vaccine against hepatitis B virus (HBV) has been highly effective in reducing the incidence and prevalence of HBV infection in many countries, an estimated 257 million people worldwide are chronically infected. In 2015, WHO published the guidelines for prevention, care and treatment of HBV infected people promoting treatment based on noninvasive assessment. This real-world large-scale cohort study provides appropriate planning for public health programs, as well as the specific characteristics of patients, thus contributing to the successful, efficient translation of new knowledge to management and treatment of HBV patients to eradicate HBV.