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Kondili LA, Brancaccio G, Tosti ME, Coco B, Quaranta MG, Messina V, Ciancio A, Morisco F, Cossiga V, Claar E, Rosato V, Ciarallo M, Cacciola I, Ponziani FR, Cerrito L, Coppola R, Longobardi F, Biliotti E, Rianda A, Barbaro F, Coppola N, Stanzione M, Barchiesi F, Fagiuoli S, Viganò M, Massari M, Russo FP, Ferrarese A, Laccabue D, Di Marco V, Blanc P, Marrone A, Morsica G, Federico A, Ieluzzi D, Rocco A, Foschi FG, Soria A, Maida I, Chessa L, Milella M, Rosselli Del Turco E, Madonia S, Chemello L, Gentile I, Toniutto P, Bassetti M, Surace L, Baiocchi L, Pellicelli A, De Santis A, Puoti M, Degasperi E, Niro GA, Zignego AL, Craxi A, Raimondo G, Santantonio TA, Brunetto MR, Gaeta GB. A holistic evaluation of patients with chronic Hepatitis D virus (HDV) infection enrolled in the Italian PITER-B and delta cohort. Int J Infect Dis 2024; 146:107115. [PMID: 38801968 DOI: 10.1016/j.ijid.2024.107115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Revised: 05/21/2024] [Accepted: 05/23/2024] [Indexed: 05/29/2024] Open
Abstract
BACKGROUND AND AIMS We aimed to characterize the epidemiologic and comorbidities profiles of patients with chronic Hepatitis D (CHD) followed in clinical practice in Italy and explored their interferon (IFN) eligibility. METHODS This was a cross-sectional study of the PITER cohort consisting of consecutive HBsAg-positive patients from 59 centers over the period 2019-2023. Multivariable analysis was performed by logistic regression model. RESULTS Of 5492 HBsAg-positive enrolled patients, 4152 (75.6%) were screened for HDV, 422 (10.2%) were anti-HDV positive. Compared with HBsAg mono-infected, anti-HDV positive patients were more often younger, non-Italians, with a history of drug use, had elevated alanine transaminase (ALT), cirrhosis, or hepatocellular carcinoma (HCC). Compared with Italians, anti-HDV positive non-Italians were younger (42.2% age ≤ 40 years vs. 2.1%; P < 0.001), more often females (males 43.0% vs. 68.6%; P < 0.001) with less frequent cirrhosis and HCC. HDV-RNA was detected in 63.2% of anti-HDV-positive patients, who were more likely to have elevated ALT, cirrhosis, and HCC. Extrahepatic comorbidities were present in 47.4% of anti-HDV positive patients and could affect the eligibility of IFN-containing therapies in at least 53.0% of patients in care. CONCLUSIONS CHD affects young, foreign-born patients and older Italians, of whom two-thirds had cirrhosis or HCC. Comorbidities were frequent in both Italians and non-Italians and impacted eligibility for IFN.
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Affiliation(s)
- Loreta A Kondili
- Center for Global Health, Istituto Superiore di Sanità, Rome, Italy; UniCamillus-Saint Camillus International University of Health Sciences, Rome, Italy.
| | - Giuseppina Brancaccio
- Department of Molecular Medicine, Infectious Diseases, University of Padua, Padua, Italy
| | | | - Barbara Coco
- Hepatology Unit, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | | | - Vincenzo Messina
- Department of Infectious Diseases, Sant'Anna Hospital, Caserta, Italy
| | - Alessia Ciancio
- Gastroenterology Unit, Città della Salute e della Scienza of Turin, University Hospital, Turin, Italy
| | - Filomena Morisco
- Liver and Biliary System Unit, Department of Clinical Medicine and Surgery, University of Naples, Naples, Italy
| | - Valentina Cossiga
- Liver and Biliary System Unit, Department of Clinical Medicine and Surgery, University of Naples, Naples, Italy
| | | | | | | | - Irene Cacciola
- Department of Internal Medicine, University Hospital of Messina, Messina, Italy
| | - Francesca Romana Ponziani
- Liver Unit, Digestive Disease Center, CEMAD Division of Internal Medicine and Gastroenterology, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Lucia Cerrito
- Liver Unit, Digestive Disease Center, CEMAD Division of Internal Medicine and Gastroenterology, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Roberta Coppola
- Department of Hepatology, Gragnano Hospital, Gragnano (NA), Italy
| | | | - Elisa Biliotti
- National Institute for Infectious Diseases, Lazzaro Spallanzani-IRCCS, Rome, Italy
| | - Alessia Rianda
- National Institute for Infectious Diseases, Lazzaro Spallanzani-IRCCS, Rome, Italy
| | - Francesco Barbaro
- Department of Medicine, Infectious Diseases Unit, University Hospital of Padua, Padua, Italy
| | - Nicola Coppola
- Infectious Diseases Unit, Department of Mental Health and Public Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Maria Stanzione
- Infectious Diseases Unit, Department of Mental Health and Public Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Francesco Barchiesi
- Clinical Infectious Diseases, Polytechnic University of Marche, Ancona, Italy
| | - Stefano Fagiuoli
- Department of Medicine, University of Milan Bicocca & Gastroenterology Hepatology and Transplantation, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Mauro Viganò
- Department of Medicine, University of Milan Bicocca & Gastroenterology Hepatology and Transplantation, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Marco Massari
- Malattie Infettive, Azienda Unità Sanitaria Locale, IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Francesco Paolo Russo
- Department of Surgery, Oncology and Gastroenterology, Gastroenterology Unit, University of Padua, Padua, Italy
| | - Alberto Ferrarese
- Gastroenterology Unit, University Hospital Borgo Trento, Verona, Italy
| | - Diletta Laccabue
- Department of Medicine and Surgery, Università degli Studi di Parma, Parma, Italy
| | - Vito Di Marco
- Biomedical Department of Internal and Specialistic Medicine University of Palermo, Unit of Gastroenterology and Hepatology, Palermo, Italy
| | - Pierluigi Blanc
- Infectious Disease Unit, Santa Maria Annunziata Hospital, Florence, Italy
| | - Aldo Marrone
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Giulia Morsica
- Unit of Infectious Diseases, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Alessandro Federico
- Hepato-Gastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples, Italy
| | | | - Alba Rocco
- Department of Clinical Medicine and Surgery, Hepato-Gastroenterology Unit, University of Naples Federico II, Naples, Italy
| | | | - Alessandro Soria
- Clinic of Infectious Diseases, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
| | - Ivana Maida
- Infectious and Tropical Diseases Unit, Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy
| | - Luchino Chessa
- Liver Unit, University Hospital, Monserrato, Cagliari, Italy
| | - Michele Milella
- Clinic of Infectious Diseases, University of Bari, University Hospital Policlinico, Bari, Italy
| | - Elena Rosselli Del Turco
- Infectious Diseases Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Salvatore Madonia
- Department of Internal Medicine Villa Sofia-Cervello Hospital, Palermo, Italy
| | - Liliana Chemello
- Department of Medicine-DIMED, Padua University, University Hospital, Padua, Italy
| | - Ivan Gentile
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Pierluigi Toniutto
- Hepatology and Liver Transplant Unit, Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy
| | - Matteo Bassetti
- Clinica Malattie Infettive, Università degli Studi di Genova, Policlinico S. Martino IRCCS, Genova, Italy
| | - Lorenzo Surace
- Ambulatorio di Epatologia e Infettivologia, Azienda Sanitaria Provinciale CZ-Distretto del Lametino, Lamezia Terme (CZ), Italy
| | | | | | - Adriano De Santis
- Department of Internal Medicine, Policlinico Umberto I Hospital, Sapienza University of Rome, Rome, Italy
| | - Massimo Puoti
- Infectious Disease Unit, Niguarda Hospital, Milan, Italy
| | | | - Grazia Anna Niro
- Division of Gastroenterology and Endoscopy, Fondazione IRCCS 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, Foggia, Italy
| | - Anna Linda Zignego
- Department of Experimental and Clinical Medicine, Interdepartmental Centre MASVE, University of Florence, Italy
| | - Antonio Craxi
- Gastroenterology and Hepatology Unit, PROMISE, University of Palermo, Palermo, Italy
| | - Giovanni Raimondo
- Department of Internal Medicine, University Hospital of Messina, Messina, Italy
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Demirel A, Uraz S, Deniz Z, Daglilar E, Basar O, Tahan V, Ozaras R. Epidemiology of hepatitis D virus infection in Europe: Is it vanishing? J Viral Hepat 2024; 31:120-128. [PMID: 37964693 DOI: 10.1111/jvh.13899] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2023] [Revised: 08/13/2023] [Accepted: 11/04/2023] [Indexed: 11/16/2023]
Abstract
Co-infection with hepatitis delta virus (HDV) is a challenging health care problem worldwide, estimated to occur in approximately 5%-10% of patients with chronic hepatitis B virus (HBV) infection. While HBV prevalence is decreasing globally, the prevalence of HDV infection is rising in some parts mainly due to injection drug use, sexual transmission and immigration from high endemicity areas. Eastern Europe and the Mediterranean are among the regions with high rates of endemicity for HDV and the immigration from high endemicity areas to Central and Western Europe has changed the HDV epidemiology. We aimed to review the prevalence of HDV infection in Europe. A paucity of publication appears in many European countries. Prevalence studies from some countries are old dated and some other countries did not report any prevalence studies. The studies are accumulated in few countries. Anti-HDV prevalence is high in Greenland, Norway, Romania, Sweden and Italy. Belgium, France, Germany, Spain, Switzerland, Turkey and United Kingdom reported decreasing prevalences. Among cirrhotic HBV patients, Germany, Italy and Turkey reported higher rates of HDV. The studies including centres across the Europe reported that HIV-HBV coinfected individuals have higher prevalence of HDV infection. The immigrants contribute the HDV infection burden in Greece, Italy, and Spain in an increasing rate. Previous studies revealed extremely high rates of HDV infection in Germany, Greece, Italy and Sweden. The studies report a remarkably high prevalence of hepatitis delta among HIV/HBV-coinfected individuals, individuals who inject drugs, immigrants and severe HBV infected patients across Europe. The HDV infection burden still appears to be significant. In the lack of an effective HDV therapy, prevention strategies and active screening of HBV/HDV appear as the most critical interventions for reducing the burden of liver disease related to HDV infection in Europe.
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Affiliation(s)
- Aslıhan Demirel
- Department of Infectious Diseases, School of Medicine, Demiroglu Bilim University, Istanbul, Turkey
| | - Suleyman Uraz
- Department of Gastroenterology, School of Medicine, Demiroglu Bilim University, Istanbul, Turkey
| | - Zeynep Deniz
- School of Medicine, Acıbadem Mehmet Ali Aydınlar University, Istanbul, Turkey
| | - Ebubekir Daglilar
- Department of Gastroenterology, West Virginia University-Charleston Area Medical Center, Charleston, West Virginia, USA
| | - Omer Basar
- Division of Gastroenterology, Summa Health System, Akron, Ohio, USA
| | - Veysel Tahan
- Division of Gastroenterology, Summa Health System, Akron, Ohio, USA
- Division of Gastroenterology, Northeast Ohio Medical University, Rootstown, Ohio, USA
| | - Resat Ozaras
- Department of Infectious Diseases, Medilife Hospital, Istanbul, Turkey
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Narciso-Schiavon JL, Schiavon LDL. Hepatitis B and Celiac Disease: a cause for concern? REVISTA COLOMBIANA DE GASTROENTEROLOGÍA 2023; 38:479-485. [DOI: 10.22516/25007440.1016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2025]
Abstract
Some theories suggest that the development of the immune response to clear hepatitis B triggers the intestinal tissue damage seen in celiac disease in genetically predisposed individuals. Although the role of hepatitis B virus infection in the development of autoimmune diseases has been widely discussed in the literature, it remains a controversial topic. Our objective is to review whether there is an association between hepatitis B and celiac disease and the particularities of vaccination against hepatitis B in celiac patients.
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Tsaneva-Damyanova DT, Georgieva LH. Epidemiology Pattern, Prevalent Genotype Distribution, Fighting Stigma and Control Options for Hepatitis D in Bulgaria and Other European Countries. Life (Basel) 2023; 13:life13051115. [PMID: 37240760 DOI: 10.3390/life13051115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 04/24/2023] [Accepted: 04/28/2023] [Indexed: 05/28/2023] Open
Abstract
Hepatitis D virus (HDV) is a satellite virus that causes the most aggressive form of all viral hepatitis in individuals already infected with HBV (hepatitis B virus). In recent years, there has been a negative trend towards an increase in the prevalence of chronic hepatitis D in Europe, especially among immigrant populations coming from regions endemic for the virus. The aim of this review is to analyse the current epidemiology of chronic HDV, routes of transmission, prevalent genotype, its management, prevention, fighting stigma and options for viral control in European countries, such as Bulgaria.
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Affiliation(s)
| | - Lora Hristova Georgieva
- Department of Social Medicine and Healthcare Organization, Medical University, 9000 Varna, Bulgaria
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Brancaccio G, Coco B, Nardi A, Quaranta MG, Tosti ME, Ferrigno L, Cacciola I, Messina V, Chessa L, Morisco F, Milella M, Barbaro F, Ciancio A, Russo FP, Coppola N, Blanc P, Claar E, Verucchi G, Puoti M, Zignego AL, Chemello L, Madonia S, Fagiuoli S, Marzano A, Ferrari C, Lampertico P, Di Marco V, Craxì A, Santantonio TA, Raimondo G, Brunetto MR, Gaeta GB, Kondili LA. Trends in chronic hepatitis B virus infection in Italy over a 10-year period: Clues from the nationwide PITER and MASTER cohorts toward elimination. Int J Infect Dis 2023; 129:266-273. [PMID: 36791877 DOI: 10.1016/j.ijid.2023.02.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 02/03/2023] [Accepted: 02/07/2023] [Indexed: 02/15/2023] Open
Abstract
OBJECTIVES The study measures trends in the profile of patients with chronic hepatitis B virus linked to care in Italy. METHODS A cross-sectional, multicenter, observational cohort (PITER cohort) of consecutive patients with hepatitis B surface antigen (HBsAg) over the period 2019-2021 from 46 centers was evaluated. The reference was the MASTER cohort collected over the years 2012-2015. Standard statistical methods were used. RESULTS The PITER cohort enrolled 4583 patients, of whom 21.8% were non-Italian natives. Compared with those in MASTER, the patients were older and more often female. The prevalence of hepatitis B e antigen (HBeAg) declined (7.2% vs 12.3; P <0.0001) and that of anti-hepatitis D virus (HDV) remained stable (9.3% vs 8.3%). In both cohorts, about 25% of the patients had cirrhosis, and those in the PITER cohort were older. HBeAg-positive was 5.0% vs 12.6% (P <0.0001) and anti-HDV positive 24.8% vs 17.5% (P <0.0017). In the logistic model, the variables associated with cirrhosis were anti-HDV-positive (odds ratio = 10.08; confidence interval 7.63-13.43), age, sex, and body mass index; the likelihood of cirrhosis was reduced by 40% in the PITER cohort. Among non-Italians, 12.3% were HBeAg-positive (vs 23.4% in the MASTER cohort; P <0.0001), and 12.3% were anti-HDV-positive (vs 11.1%). Overall, the adherence to the European Association for the Study of the Liver recommendations for antiviral treatment increased over time. CONCLUSION Chronic hepatitis B virus infection appears to be in the process of becoming under control in Italy; however, HDV infection is still a health concern in patients with cirrhosis and in migrants.
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Affiliation(s)
- Giuseppina Brancaccio
- Department of Molecular Medicine, Infectious Diseases Unit, University of Padua, Padua, Italy
| | - Barbara Coco
- Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa, Italy
| | - Alessandra Nardi
- Department of Mathematics, University of Rome Tor Vergata, Rome, Italy
| | | | | | - Luigina Ferrigno
- Center for Global Health, Istituto Superiore di Sanità, Rome, Italy
| | - Irene Cacciola
- Department of Internal Medicine, University Hospital of Messina, Messina, Italy
| | - Vincenzo Messina
- Department of Infectious Diseases, Sant'Anna Hospital, Caserta, Italy
| | - Luchino Chessa
- Liver Unit, University Hospital, Monserrato, Cagliari, Italy
| | - Filomena Morisco
- Liver and Biliary System Unit, Department of Clinical Medicine and Surgery, University of Naples, Federico II, Naples, Italy
| | - Michele Milella
- Clinic of Infectious Diseases, University of Bari, University Hospital Policlinico, Bari, Italy
| | - Francesco Barbaro
- Department of Medicine, Infectious Diseases Unit, University Hospital of Padua, Padua, Italy
| | - Alessia Ciancio
- Gastroenterology Unit, Città della Salute e della Scienza of Turin, University Hospital, Turin, Italy
| | - Francesco Paolo Russo
- Department of Surgery, Oncology and Gastroenterology, Gastroenterology Unit, University of Padua, Padua, Italy
| | - Nicola Coppola
- Infectious Diseases Unit, Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Pierluigi Blanc
- Infectious Disease Unit, Santa Maria Annunziata Hospital, Florence, Italy
| | | | - Gabriella Verucchi
- Clinic of Infectious Diseases and Microbiology Unit, Alma Mater Studiorum Bologna University, Bologna, Italy
| | - Massimo Puoti
- Infectious Disease Unit, Niguarda Hospital, Milan, Italy
| | - Anna Linda Zignego
- Center for Systemic Manifestations of Hepatitis Viruses, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Liliana Chemello
- Department of Medicine, Unit of Internal Medicine & Hepatology, University of Padua, Padua, Italy
| | - Salvatore Madonia
- Department of Internal Medicine, Villa Sofia-Cervello Hospital, Palermo, Italy
| | - Stefano Fagiuoli
- Gastroenterology, Department of Medicine, University of Milan Bicocca, Milan, Italy; Gastroenterology Hepatology and Transplantation, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | | | - Carlo Ferrari
- Department of Medicine and Surgery, University of Parma, Unit of Hematology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
| | - Pietro Lampertico
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy; CRC "A. M. and A. Migliavacca" Center for Liver Disease, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Vito Di Marco
- Unit of Gastroenterology and Hepatology, Biomedical Department of Internal and Specialistic Medicine, University of Palermo, Palermo, Italy
| | - Antonio Craxì
- Gastroenterology and Hepatology Unit, PROMISE, University of Palermo, Palermo, Italy
| | | | - Giovanni Raimondo
- Department of Internal Medicine, University Hospital of Messina, Messina, Italy
| | - Maurizia R Brunetto
- Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa, Italy
| | | | - Loreta A Kondili
- Center for Global Health, Istituto Superiore di Sanità, Rome, Italy; UniCamillus-Saint Camillus International University of Health Sciences, Rome, Italy.
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Pisaturo M, Alessio L, Di Fraia A, Macera M, Minichini C, Cordua E, Onorato L, Scotto G, Di Caprio G, Calò F, Sagnelli C, Coppola N. Hepatitis D virus infection in a large cohort of immigrants in southern Italy: a multicenter, prospective study. Infection 2022; 50:1565-1572. [PMID: 36222979 PMCID: PMC9554856 DOI: 10.1007/s15010-022-01938-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Accepted: 09/30/2022] [Indexed: 11/27/2022]
Abstract
Background Since few data are available in the literature on the prevalence of anti-Delta-positive subjects in immigrant populations, the aim of the present study was to evaluate the demographic and virological characteristics of HDV infection in a large cohort of immigrants living in southern Italy. Methods Between January 2012 and February 2020 all immigrants attending one of the 5 first- level centers were enrolled and screened for HBsAg, the HBsAg-positive for anti-Delta and if positive, for HDV-RNA and HDV genotype. Results Of the 3521 immigrants observed in the study period, 3417 (97.0%) agreed to be screened; they were mainly males (61%), with a median age of 27 years (IQR 8–74) and came prevalently (58%) from sub-Saharan Africa. Of the 3417 patients enrolled, 319 (9%) subjects were HBsAg-positive, and of those, 8 (2.5%) were anti-Delta-positive. No difference in the demographic and epidemiological characteristics was observed between the anti-Delta-negative vs -positive. Of the 8 anti-Delta-positive subjects, only one was HDV-RNA-positive (viral load: 7050 IU/mL), genotype 1, with clinical signs of cirrhosis. Conclusions the present study showed a prevalence of HDV of 2.5% in a large cohort of asymptomatic immigrants, suggesting the need for screening campaigns for viral infections including delta hepatitis in this population. Supplementary Information The online version contains supplementary material available at 10.1007/s15010-022-01938-0.
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Affiliation(s)
- Mariantonietta Pisaturo
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
- Medical Center, Centro Sociale ex Canapificio, Caserta, Italy
| | - Loredana Alessio
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
- Medical Center, Centro di Accoglienza "La Tenda di Abramo", Caserta, Italy
| | - Alessandra Di Fraia
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
| | - Margherita Macera
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
- Medical Center, Centro per la Tutela Della Salute Degli Immigrati, Naples, Italy
| | - Carmine Minichini
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
| | - Emanuele Cordua
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
| | - Lorenzo Onorato
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
- Medical Center, Centro Suore Missionarie Della Carità, Naples, Italy
| | - Gaetano Scotto
- Medical Center, Centro Borgoroma, Foggia, Italy
- Infectious Diseases Unit, Foggia, Italy
| | - Giovanni Di Caprio
- Medical Center, Centro Sociale ex Canapificio, Caserta, Italy
- Infectious Diseases Unit, AORN Sant'Anna e San Sebastiano, Caserta, Italy
| | - Federica Calò
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
- Medical Center, Centro per la Tutela Della Salute Degli Immigrati, Naples, Italy
| | - Caterina Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
- Medical Center, Centro Suore Missionarie Della Carità, Naples, Italy
| | - Nicola Coppola
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy.
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Sagnelli C, Sagnelli E, Russo A, Pisaturo M, Occhiello L, Coppola N. HBV/HDV Co-Infection: Epidemiological and Clinical Changes, Recent Knowledge and Future Challenges. Life (Basel) 2021; 11:life11020169. [PMID: 33671730 PMCID: PMC7926847 DOI: 10.3390/life11020169] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 02/18/2021] [Accepted: 02/18/2021] [Indexed: 02/06/2023] Open
Abstract
Several investigations have been published on Hepatitis Delta Virus (HDV) infection in recent years, from which we have drawn the salient data to provide readers with useful information to improve their knowledge on the subject. HDV genotypes 5–8 have been recently imported to Western countries from central Africa, whose clinical relevance deserves further investigation. Ongoing HDV replication has been identified as an independent predictor of progression to cirrhosis and HCC for patients with HDV chronic hepatitis (HDV-CH). Long-term treatments of HDV-CH with standard or pegylated interferon alfa (peg-IFN-α) have all been unsatisfactory, leading to a sustained virological response (SVR) only in 20–30% of patients treated, faced with a poor tolerability and frequent serious adverse reactions; the addition of HBV nucleo(s)tide analogues to peg-IFN- α did not improve the rate of SVR. The improved knowledge of the HDV life cycle has allowed the development of direct acting agents towards key-points of the HDV life cycle, namely bulevirtide, lonafarnib and nucleic acid polymers. Preliminary data have shown that these drugs are more effective than interferon-based therapies, but adverse reactions are also common, which however seem toned down in combination therapy with other antivirals.
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Tan M, Bhadoria AS, Cui F, Tan A, Van Holten J, Easterbrook P, Ford N, Han Q, Lu Y, Bulterys M, Hutin Y. Estimating the proportion of people with chronic hepatitis B virus infection eligible for hepatitis B antiviral treatment worldwide: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol 2020; 6:106-119. [PMID: 33197397 PMCID: PMC7801814 DOI: 10.1016/s2468-1253(20)30307-1] [Citation(s) in RCA: 96] [Impact Index Per Article: 19.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 09/08/2020] [Accepted: 09/17/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND In 2016, of the estimated 257 million people living with chronic hepatitis B virus (HBV) infection worldwide, only a small proportion was diagnosed and treated. The insufficiency of information on the proportion of people infected with HBV who are eligible for treatment limits the interpretation of global treatment coverage. We aimed to estimate the proportion of people with chronic HBV infection who were eligible for antiviral treatment worldwide, based on the WHO 2015 guidelines. METHODS In this systematic review and meta-analysis, we searched Medline, EMBASE, and the Cochrane databases from Jan 1, 2007, to Jan 31, 2018, for studies describing HBsAg-positive people in the population or health-care facilities. We extracted information from published studies using a standardised form to estimate the frequency of cirrhosis, abnormal alanine aminotransferase (ALT), HBV DNA exceeding 2000 IU/mL or 20 000 IU/mL, presence of HBeAg, and eligibility for treatment as per WHO and other guidelines as reported in the studies. We pooled proportions through meta-analysis with random effects. The study was registered with PROSPERO, CRD42020132345. FINDINGS Of the 13 497 studies, 162 were eligible and included in our analysis. These studies included 145 789 participants. The pooled estimate of the proportion of cirrhosis was 9% (95% CI 8-10), ranging from 6% (4-8) in community settings to 10% (9-11) in clinic settings. Examining the proportion of participants who had characteristics used to determine eligibility in the WHO guidelines, 1750 (10·1%) of 17 394 had HBV DNA exceeding 20 000 IU/mL, and 20 425 (30·8%) of 66 235 had ALT above the upper limit of normal. 32 studies reported eligibility for treatment according to WHO or any other guidelines, with a pooled estimate of eligibility at 19% (95% CI 18-20), ranging from 12% (6-18) for studies in community settings to 25% (19-30) in clinic settings. INTERPRETATION Many studies described people with HBV infection, but few reported information in a way that allowed assessment of eligibility for treatment. Although about one in ten of the 257 million people with HBV infection (26 million) might be in urgent need of treatment because of cirrhosis, a larger proportion (12-25%) is eligible for treatment in accordance with different guidelines. Future studies describing people with HBV infection should report on treatment eligibility, according to broadly agreed definitions. FUNDING WHO and US Centers for Disease Control and Prevention.
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Affiliation(s)
- Mingjuan Tan
- Department of HIV/AIDS and Global Hepatitis Programme, WHO, Geneva, Switzerland; Department of Medicine, National University Health System, Singapore
| | - Ajeet S Bhadoria
- All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
| | - Fuqiang Cui
- Department of HIV/AIDS and Global Hepatitis Programme, WHO, Geneva, Switzerland
| | | | - Judith Van Holten
- Department of HIV/AIDS and Global Hepatitis Programme, WHO, Geneva, Switzerland
| | | | - Nathan Ford
- Department of HIV/AIDS and Global Hepatitis Programme, WHO, Geneva, Switzerland
| | - Qin Han
- Department of HIV/AIDS and Global Hepatitis Programme, WHO, Geneva, Switzerland
| | - Ying Lu
- Department of HIV/AIDS and Global Hepatitis Programme, WHO, Geneva, Switzerland
| | - Marc Bulterys
- Department of HIV/AIDS and Global Hepatitis Programme, WHO, Geneva, Switzerland
| | - Yvan Hutin
- Department of HIV/AIDS and Global Hepatitis Programme, WHO, Geneva, Switzerland.
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9
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Chronic hepatitis B virus infection in Italy during the twenty-first century: an updated survey in 2019. Eur J Clin Microbiol Infect Dis 2020; 40:607-614. [PMID: 33029767 DOI: 10.1007/s10096-020-04065-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Accepted: 10/01/2020] [Indexed: 12/15/2022]
Abstract
The aim of this study is to provide updates on the characteristics of chronic HBsAg carriers in Italy before the advent of new drugs eliminating or functionally inactivating the genome HBV reservoirs. HBV endemicity has greatly decreased in Italy over the past decades. A not negligible number of chronic HBsAg carriers are still alive in the country. Chronic HBsAg carriers consecutively referring to 9 units in Italy were prospectively enrolled for a 6-month period in 2019. Multiple logistic regression analysis was performed to identify independent predictors of treatment. A total of 894 cases was recruited (sex ratio 1.6; mean age 53.7 ± 13.5 years). The proportion of subjects born abroad was 19.0%; only 1% of cases reported current heavy alcohol intake (> 4 units/day). Chronic HBV infection, chronic HBV hepatitis, and subjects with liver cirrhosis and/or HCC represented 24.8%, 55%, and 19.3% of cases, respectively. After exclusion of the 222 subjects with chronic HBV infection, the proportion of subjects under therapy was as high as 89.3%. A more severe liver disease (OR 2.52; 95% CI = 1.25-5.14) resulted an independent predictor of the likelihood of treatment; male sex was marginally associated (OR 1.67; 95% CI = 1.02-2.76) to the chance of treatment. People born abroad had same chance than Italians native to be treated (OR 2.12; 95% CI = 0.9-4.97). The high proportion of subjects under treatment and the absence of gender and ethnic barrier against treatment sound good news. These updated figures may represent reference data for evaluating the potential impact of forthcoming new therapy against HBV-related disease.
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10
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Coppola N, Alessio L, Onorato L, Sagnelli C, Sagnelli E, Pisaturo M. HDV infection in immigrant populations. J Med Virol 2019; 91:2049-2058. [PMID: 31429940 DOI: 10.1002/jmv.25570] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Accepted: 08/10/2019] [Indexed: 12/16/2022]
Abstract
AIMS Little data have been published so far on the epidemiological aspects of hepatitis D virus (HDV) infection in immigrant populations and even poorer is the information on the virological, phylogenetic, and clinical aspects of this infection in these populations. This review article, aimed primarily at physicians caring for immigrants, summarizes the information available on HDV infection and analyzes data on this topic concerning the immigrant populations. METHODS AND RESULTS The prevalence of HDV infection in HBsAg-positive immigrants varies according to the country of origin. For example, in immigrants from sub-Saharan Africa, this prevalence is higher in those born in Equatorial Guinea (24.4%) than those from other African countries (10.3%). The epidemiological impact of HDV infection linked to migratory flows is a function of the different endemicity between countries of origin and countries in which a new existence has been established. This impact is high when immigrants from areas endemic to HDV infection (eg, Equatorial Guinea) settle in areas of low endemicity (eg, Germany or England, with a prevalence of around 4%), while the impact is lesser or nonexistent if the migratory flows are directed toward countries with intermediate endemicity (eg, Italy and Greece, with a prevalence of around 10%). CONCLUSION This impact of immigration on HDV epidemiology can be strong when HDV endemicity is high in the country of origin and low in the host country and slight when immigrants move to high or medium endemic countries.
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Affiliation(s)
- Nicola Coppola
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples, Italy.,Infectious Disease Unit, AORN Caserta, Caserta, Italy
| | | | - Lorenzo Onorato
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Caterina Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples, Italy.,Infectious Disease Unit, AORN Caserta, Caserta, Italy
| | - Evangelista Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Mariantonietta Pisaturo
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples, Italy
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11
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Milana M, Angelico M. The evolving scenario of HBV infection and disease: A never-ending story. Dig Liver Dis 2019; 51:443-444. [PMID: 30470554 DOI: 10.1016/j.dld.2018.10.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2018] [Revised: 10/21/2018] [Accepted: 10/24/2018] [Indexed: 12/11/2022]
Affiliation(s)
- Martina Milana
- Hepatology and Liver Transplant Unit, Tor Vergata University, Fondazione Policlinico Tor Vergata, Rome, Italy
| | - Mario Angelico
- Hepatology and Liver Transplant Unit, Tor Vergata University, Fondazione Policlinico Tor Vergata, Rome, Italy.
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12
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Brancaccio G, Nardi A, Madonia S, Fasano M, Verucchi G, Massari M, Maimone S, Contini C, Levantesi F, Alfieri A, Gavrila C, Andreone P, Milella M, Gaeta GB. The present profile of chronic hepatitis B virus infection highlights future challenges: An analysis of the Multicenter Italian MASTER-B cohort. Dig Liver Dis 2019; 51:438-442. [PMID: 30314950 DOI: 10.1016/j.dld.2018.09.008] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2018] [Revised: 07/31/2018] [Accepted: 09/10/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND Chronic hepatitis B virus (HBV) infection remains a primary cause of morbidity and mortality worldwide. AIM The study is aimed at updating the clinical and epidemiological profile of chronic HBV infection in Italy. METHODS A cross-sectional multicenter prospective study enrolled consecutive HBsAg positive patients seen in 73 Italian centers in the period 2012-2015. Individual patient data were collected using an electronic platform and analyzed using standard statistical methods. RESULTS Among 2877 HBsAg positive individuals (median age 49.8 years, 68% males), 27% were non-Italian natives (NINs); 20% had chronic infection, 58.5% chronic hepatitis and 21.5% cirrhosis. Among NINs, age was younger, male gender was less prevalent and liver disease less advanced than in Italians (all p < 0.0001). HBeAg positive cases were 23.6% among NINs vs 8.2% in Italians (p < 0.0001); HDV coinfections 11.1% vs 7.3% (p = 0.006) and HCV coinfections 2.3% vs 4.2% (p = 0.017), respectively. Anti-HDV or anti-HCV antibodies were detected more frequently in patients with cirrhosis. Fifty percent of NINs with cirrhosis were aged below 45 years. CONCLUSION The study offers an insight into the evolving burden of chronic hepatitis B virus infection in the near future and highlights new territories for public health interventions.
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Affiliation(s)
- Giuseppina Brancaccio
- Department of Molecular Medicine, Infectious Diseases, University of Padua, Italy; Infectious Diseases, Campania University "Luigi Vanvitelli", Naples, Italy.
| | - Alessandra Nardi
- Department of Mathematics, University of Rome Tor Vergata, Rome, Italy
| | | | - Massimo Fasano
- Infectious Diseases, University of Foggia, Foggia, Italy; Infectious Diseases, Fallacara Hospital, Triggiano, Italy
| | | | - Marco Massari
- Infectious Diseases, Azienda Ospedaliera, Reggio Emilia, Italy
| | - Sergio Maimone
- Division of Clinical and Molecular Hepatology, University Hospital of Messina, Messina, Italy
| | - Carlo Contini
- Infectious Diseases, University Hospital, Ferrara, Italy
| | | | | | | | - Pietro Andreone
- Research Center for the Study of Hepatitis, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | | | - Giovanni B Gaeta
- Infectious Diseases, Campania University "Luigi Vanvitelli", Naples, Italy
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13
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14
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Francisci D, Falcinelli F, Schiaroli E, Capponi M, Belfiori B, Cecchini E, Baldelli F. Reactivation of Hepatitis B Virus Replication Due to Cytotoxic Therapy: A Five-Year Prospective Study. TUMORI JOURNAL 2018; 98:220-4. [DOI: 10.1177/030089161209800207] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
Background and aims In hepatitis B virus (HBV) carriers receiving chemotherapy, the risk of reactivation is high, particularly if rituximab is given alone or in combination with steroids. The aim of this study was to assess the incidence, prevalence, and clinical course of HBV infection in a cohort of patients with hematological malignancies receiving cytotoxic therapy as well as to propose a strategy for managing HBV reactivation. Methods This is a prospective observational study. All consecutive patients with hematological malignancies receiving intravenous cytotoxic chemotherapy between October 2005 and June 2010 and followed up for at least six months were enrolled in the study. Viral hepatitis markers and liver function indexes were monitored prospectively. Results We enrolled 478 patients, including 263 males (55%) and 465 (97.3%) Italians. Non-Hodgkin's lymphoma was the most frequent diagnosis (66%). At least one HBV marker was positive in 96 patients (20%): 21 (4.4%) patients were HBsAg positive, 17 (3.5%) were anti-HBc positive, and 58 (12.1%) were anti-HBc/anti-HBs positive. All but one HBsAg-positive patient received therapy with nucleoside/nucleotide analogs prior to chemotherapy. All but three reached complete virological suppression at six months from the start of treatment. Of the 17 HBsAg-negative/anti-HBc-positive patients, three (18%) had reactivation with seroreversion. All three obtained viral suppression with adefovir. Regarding the 58 anti-HBc/anti-HBs-positive patients, two (3.4%) experienced seroreversion and were treated successfully with nucleoside analogs; both were taking rituximab. No severe ALT flares were observed during or after antiviral therapy. Conclusion Our data suggest that pre-treatment screening of patients at risk of viral reactivation yields benefit and therefore should be practiced by clinicians treating patients with malignancies.
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Affiliation(s)
- Daniela Francisci
- Section of Infectious Diseases, Department of Experimental Medicine and Biochemical Sciences, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy
| | - Flavio Falcinelli
- Section of Hematology and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy
| | - Elisabetta Schiaroli
- Section of Infectious Diseases, Department of Experimental Medicine and Biochemical Sciences, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy
| | - Monia Capponi
- Section of Hematology and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy
| | - Barbara Belfiori
- Section of Infectious Diseases, Department of Experimental Medicine and Biochemical Sciences, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy
| | - Enisia Cecchini
- Section of Infectious Diseases, Department of Experimental Medicine and Biochemical Sciences, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy
| | - Franco Baldelli
- Section of Infectious Diseases, Department of Experimental Medicine and Biochemical Sciences, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy
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15
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Bazinet M, Pântea V, Cebotarescu V, Cojuhari L, Jimbei P, Albrecht J, Schmid P, Le Gal F, Gordien E, Krawczyk A, Mijočević H, Karimzadeh H, Roggendorf M, Vaillant A. Safety and efficacy of REP 2139 and pegylated interferon alfa-2a for treatment-naive patients with chronic hepatitis B virus and hepatitis D virus co-infection (REP 301 and REP 301-LTF): a non-randomised, open-label, phase 2 trial. Lancet Gastroenterol Hepatol 2017; 2:877-889. [PMID: 28964701 DOI: 10.1016/s2468-1253(17)30288-1] [Citation(s) in RCA: 181] [Impact Index Per Article: 22.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2017] [Revised: 08/11/2017] [Accepted: 08/11/2017] [Indexed: 02/06/2023]
Affiliation(s)
| | - Victor Pântea
- Department of Infectious Diseases, State University of Medicine and Pharmacy 'Nicolae Testemitanu', Chișinău, Moldova
| | - Valentin Cebotarescu
- Department of Infectious Diseases, State University of Medicine and Pharmacy 'Nicolae Testemitanu', Chișinău, Moldova
| | - Lilia Cojuhari
- Department of Infectious Diseases, State University of Medicine and Pharmacy 'Nicolae Testemitanu', Chișinău, Moldova
| | - Pavlina Jimbei
- Toma Ciorbă Hospital of Infectious Diseases, Chișinău, Moldova
| | | | - Peter Schmid
- National Genetics Institute, Los Angeles, CA, USA
| | - Frédéric Le Gal
- Laboratoire de Microbiologie Clinique, Centre National de référence des hépatites B, C et Delta, Hôpitaux Universitaires de Paris Seine-Saint-Denis, Université Sorbonne Paris Cité, Paris, France
| | - Emmanuel Gordien
- Laboratoire de Microbiologie Clinique, Centre National de référence des hépatites B, C et Delta, Hôpitaux Universitaires de Paris Seine-Saint-Denis, Université Sorbonne Paris Cité, Paris, France
| | - Adalbert Krawczyk
- Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Hrvoje Mijočević
- Institute for Virology, Technical University of Munich, Munich, Germany
| | - Hadi Karimzadeh
- Institute for Virology, Technical University of Munich, Munich, Germany
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16
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Sagnelli E, Stroffolini T, Sagnelli C, Morisco F, Coppola N, Smedile A, Pisaturo M, Colloredo G, Babudieri S, Licata A, Brancaccio G, Andriulli A, Almasio PL, Gaeta GB. Influence of universal HBV vaccination on chronic HBV infection in Italy: Results of a cross-sectional multicenter study. J Med Virol 2017; 89:2138-2143. [PMID: 28608566 DOI: 10.1002/jmv.24873] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2017] [Accepted: 05/25/2017] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND AIM The universal hepatitis B vaccination for infants and 12-year-old adolescents (the latter limited to the first 12 years of application) was launched in Italy in 1991. Twenty-three years later we evaluated the impact of the vaccination campaign on the burden of HBsAg-positive chronic liver diseases (CLD). MATERIAL AND METHODS A total of 513 HBsAg-positive chronic carriers referring to 16 Italian liver units were investigated and compared with HBsAg carriers enrolled in previous surveys. RESULTS The proportion of inactive carriers decreased from 20.0% in 2001 to 3.3% in 2014, while that of cirrhotic patients increased from 22.6% to 33.2%. Regarding the age class 0-33 (fully covered by HBV vaccination in 2014), the rate of inactive carriers decreased from the 21.7% in 2001 to 5.9% in 2014, that of chronic hepatitis from 17.5% to 5.2% and that of cirrhosis cases from 26.4% to 4.1%. Instead, in the over-60 age group the rate of inactive carriers increased from 22.8% to 41.2% and that of chronic hepatitis from 16.8% to 46%; the rate of patients with cirrhosis ranged from 5% to 8% in different studies. CONCLUSION Twenty-three years after the introduction universal HBV vaccination in Italy, the clinical presentation of CLD had shown a shift toward older ages and more severe diseases.
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Affiliation(s)
- Evangelista Sagnelli
- Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy
| | - Tommaso Stroffolini
- Department of Tropical and Infectious Diseases, Policlinico Umberto Primo, Rome, Italy
| | - Caterina Sagnelli
- Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy
| | - Filomena Morisco
- Department of Clinical Medicine and Surgery, Gastroenterology Unit, University of Naples "Federico II", via Sergio Pansini, Naples, Italy
| | - Nicola Coppola
- Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy
| | - Antonina Smedile
- Department of Medical Sciences, University of Turin, Turin, Italy
| | | | - Guido Colloredo
- Department of Internal Medicine, San Pietro Hospital, Ponte San Pietro, Italy
| | - Sergio Babudieri
- Clinic of Infectious Diseases, University of Sassari, Sassari, Italy
| | - Anna Licata
- Gastroenterology and Hepatology Unit, Di.Bi.MI.S. University of Palermo, Palermo, Italy
| | - Giuseppina Brancaccio
- Infectious Diseases, Department of Mental and Physical Health and Preventive Medicine, Second University of Naples, Caserta, Italy
| | - Angelo Andriulli
- Gastroenterology Unit, Fondazione "Casa Sollievo della Sofferenza" IRCCS Hospital, San Giovanni Rotondo, Foggia, Italy
| | - Piero L Almasio
- Gastroenterology and Hepatology Unit, Di.Bi.MI.S. University of Palermo, Palermo, Italy
| | - Giovani B Gaeta
- Infectious Diseases, Department of Mental and Physical Health and Preventive Medicine, Second University of Naples, Caserta, Italy
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17
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Chao M, Wang TC, Lin CC, Yung-Liang Wang R, Lin WB, Lee SE, Cheng YY, Yeh CT, Iang SB. Analyses of a whole-genome inter-clade recombination map of hepatitis delta virus suggest a host polymerase-driven and viral RNA structure-promoted template-switching mechanism for viral RNA recombination. Oncotarget 2017; 8:60841-60859. [PMID: 28977829 PMCID: PMC5617389 DOI: 10.18632/oncotarget.18339] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2016] [Accepted: 05/22/2017] [Indexed: 01/05/2023] Open
Abstract
The genome of hepatitis delta virus (HDV) is a 1.7-kb single-stranded circular RNA that folds into an unbranched rod-like structure and has ribozyme activity. HDV redirects host RNA polymerase(s) (RNAP) to perform viral RNA-directed RNA transcription. RNA recombination is known to contribute to the genetic heterogeneity of HDV, but its molecular mechanism is poorly understood. Here, we established a whole-genome HDV-1/HDV-4 recombination map using two cloned sequences coexisting in cultured cells. Our functional analyses of the resulting chimeric delta antigens (the only viral-encoded protein) and recombinant genomes provide insights into how recombination promotes the genotypic and phenotypic diversity of HDV. Our examination of crossover distribution and subsequent mutagenesis analyses demonstrated that ribozyme activity on HDV genome, which is required for viral replication, also contributes to the generation of an inter-clade junction. These data provide circumstantial evidence supporting our contention that HDV RNA recombination occurs via a replication-dependent mechanism. Furthermore, we identify an intrinsic asymmetric bulge on the HDV genome, which appears to promote recombination events in the vicinity. We therefore propose a mammalian RNAP-driven and viral-RNA-structure-promoted template-switching mechanism for HDV genetic recombination. The present findings improve our understanding of the capacities of the host RNAP beyond typical DNA-directed transcription.
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Affiliation(s)
- Mei Chao
- Department of Microbiology and Immunology, Chang Gung University, Guishan, Taoyang, Taiwan.,Division of Microbiology, Graduate Institute of Biomedical Sciences, Chang Gung University, Guishan, Taoyang, Taiwan.,Department of Hepato-Gastroenterology, Liver Research Center, Chang Gung Memorial Hospital, Guishan, Taoyang, Taiwan
| | - Tzu-Chi Wang
- Division of Microbiology, Graduate Institute of Biomedical Sciences, Chang Gung University, Guishan, Taoyang, Taiwan
| | - Chia-Chi Lin
- Division of Microbiology, Graduate Institute of Biomedical Sciences, Chang Gung University, Guishan, Taoyang, Taiwan
| | - Robert Yung-Liang Wang
- Division of Microbiology, Graduate Institute of Biomedical Sciences, Chang Gung University, Guishan, Taoyang, Taiwan.,Department of Biomedical Sciences, Chang Gung University, Guishan, Taoyang, Taiwan
| | - Wen-Bin Lin
- Division of Microbiology, Graduate Institute of Biomedical Sciences, Chang Gung University, Guishan, Taoyang, Taiwan
| | - Shang-En Lee
- Division of Microbiology, Graduate Institute of Biomedical Sciences, Chang Gung University, Guishan, Taoyang, Taiwan
| | - Ying-Yu Cheng
- Division of Microbiology, Graduate Institute of Biomedical Sciences, Chang Gung University, Guishan, Taoyang, Taiwan
| | - Chau-Ting Yeh
- Department of Hepato-Gastroenterology, Liver Research Center, Chang Gung Memorial Hospital, Guishan, Taoyang, Taiwan
| | - Shan-Bei Iang
- Division of Microbiology, Graduate Institute of Biomedical Sciences, Chang Gung University, Guishan, Taoyang, Taiwan
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18
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Prevalence and epidemiology of hepatitis D among patients with chronic hepatitis B virus infection: a report from Northern Spain. Eur J Gastroenterol Hepatol 2017; 29:277-283. [PMID: 27902514 DOI: 10.1097/meg.0000000000000795] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND The incidence of hepatitis delta virus (HDV) infection has decreased during the last decades. However, an increasing trend has been reported recently. PATIENTS AND METHODS We carried out a case-control study to analyze changes in its prevalence in 1215 chronic hepatitis B virus (HBV) patients, diagnosed consecutively in a tertiary center, between 1983 and 2012. According to the year of diagnosis, patients were distributed into two groups: A [1983-1997 (n=786)] and B [1998-2012 (n=429)]. RESULTS The prevalence of anti-HDV was 8.2% (9.4% in group A and 6.1% in group B) (P=0.04). Multivariate regression revealed that intravenous drug use [odds ratio (OR) 261.0; 95% confidence interval (CI), 28.7-2368.5; P<0.001], blood transfusion (OR 28.0; 95% CI, 2.7-295.9; P=0.03), anti-HIV(+) (OR 4.8; 95% CI, 1.6-14.5; P=0.004), and high alanine aminotransferase (OR 14.4; 95% CI, 3.4-60.6; P<0.001) were associated independently with the presence of anti-HDV in group A, whereas in group B, it was associated with immigration (OR 20.0; 95% CI, 4.7-84.9; P<0.001), intravenous drug use (OR 683.5; 95% CI, 52.7-8855.7; P<0.001), promiscuous sexual activity (OR 22.6; 95% CI, 2.2-228.5; P=0.008), and high alanine aminotransferase (OR 3.4; 95% CI, 1.1-10.0; P=0.02). CONCLUSION Although a significant decrease in the prevalence of HDV infection has been observed, it is still above 5%. Immigration and sexual transmission have emerged as new risk factors for HDV infection.
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19
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Federico A, Brancaccio G, Dallio M, Iodice P, Fabozzi A, Del Prete S, Ciardiello F, Loguercio C, Gaeta GB. Reactivation of hepatitis B virus in cancer patients treated with chemotherapy for solid tumors. Is the prophylaxis really required? Dig Liver Dis 2017; 49:197-201. [PMID: 27899262 DOI: 10.1016/j.dld.2016.11.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2016] [Revised: 11/05/2016] [Accepted: 11/08/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND Reactivation of hepatitis B virus during cancer chemotherapy for non-hematological tumors is not fully clear. AIM To evaluate the risk of hepatitis B virus reactivation in carriers of hepatitis B virus cancer patients treated with chemotherapy for solid tumors. METHODS Two hundred sixty-seven patients with solid tumors were consecutively enrolled: 13 (4.8%) were hepatitis B s-antigen positive, of whom 6 were documented inactive carriers and 7 had chronic liver disease. Thirty-two patients (12%) were hepatitis B s-antigen negative/hepatitis B c-antibody positive. Hepatitis B virus inactive carriers were followed every 3 months by alanine aminotransferases, hepatitis B virus-DNA; whereas hepatitis B virus occult carriers were followed every 3 months by alanine aminotransferases and hepatitis B s-antigen. RESULTS None of the 38 total patients with inactive or occult B infection who did not receive prophylaxis presented hepatitis B virus reactivation during the follow-up period. CONCLUSION This study suggests that, in hepatitis B s-antigen negative patients who undergo chemotherapy for solid tumors, hepatitis B and c-antibody screening results are not relevant to clinical decision and can be avoided. Larger studies are needed to establish whether the risk of reactivation of HBV during chemotherapy is negligible in this subset of patients and they could not be monitored for HBV reactivation.
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Affiliation(s)
- Alessandro Federico
- Division of Hepatogastroenterology, Second University of Naples, Naples, Italy.
| | | | - Marcello Dallio
- Division of Hepatogastroenterology, Second University of Naples, Naples, Italy
| | - Patrizia Iodice
- Division of Oncology, S. Giovanni di Dio Hospital, Frattamaggiore, Italy
| | - Alessio Fabozzi
- Division of Oncology, Second University of Naples, Naples, Italy
| | | | | | - Carmela Loguercio
- Division of Hepatogastroenterology, Second University of Naples, Naples, Italy
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Carbone M, Nardi A, Marianelli T, Martin K, Hudson A, Collett D, Romagnoli R, Pinna A, Gimson A, Neuberger JM, Angelico M. International comparison of liver transplant programmes: differences in indications, donor and recipient selection and outcome between Italy and UK. Liver Int 2016; 36:1481-9. [PMID: 27028510 DOI: 10.1111/liv.13132] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2015] [Accepted: 03/23/2016] [Indexed: 12/19/2022]
Abstract
BACKGROUND & AIMS Comparing liver transplant (LT) programmes internationally can improve outcomes by stimulating cross-national learning. Yet, comparison of crude outcomes, by using registry data, is limited by missing data, not allowing proper risk-adjustment for donor- and recipient-related factors. The objective of this study was to compare two European LT programmes based on high-quality national longitudinal databases prospectively collected in Italy and UK respectively. METHODS We undertook a multicentre, international cohort study including all adults who underwent a first single organ LT in Italy (N = 1480) and the UK (N = 1003) between June 2007 and May 2009. RESULTS Italian donors were much older compared to the UK ones. Hepatitis C virus infection and hepatocellular carcinoma had higher prevalence in the Italian cohort compared to the UK one (47.5% vs. 23.1%, and 47.2% vs. 17.1% respectively). Centres' volume differed significantly, with five centres out of seven in UK vs. only two out of 20 in Italy performing >60 transplants per year. No national strategies to drive the donor-recipient matching were identified in both countries. After appropriate adjustment, a higher risk of early transplant loss was identified in the Italian cohort, whereas no differences were found in the 3-year survival rates. CONCLUSIONS International comparison of LT programmes provides the opportunity for benchmarking between heterogeneous healthcare systems and should ideally become a vital part of national quality assurance programmes. This requires the implementation of a standardized methodology for data collection to appropriately weigh each country's patient case-mix and donor and recipients risk factors.
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Affiliation(s)
- Marco Carbone
- Liver Match Study, Associazione Italiana Studio Fegato (AISF), Rome, Italy.,National Health Service Blood and Transplant (NHSBT), Bristol, UK
| | - Alessandra Nardi
- Liver Match Study, Associazione Italiana Studio Fegato (AISF), Rome, Italy
| | - Tania Marianelli
- Liver Match Study, Associazione Italiana Studio Fegato (AISF), Rome, Italy
| | - Kate Martin
- National Health Service Blood and Transplant (NHSBT), Bristol, UK
| | - Alex Hudson
- National Health Service Blood and Transplant (NHSBT), Bristol, UK
| | - David Collett
- National Health Service Blood and Transplant (NHSBT), Bristol, UK
| | - Renato Romagnoli
- Liver Match Study, Associazione Italiana Studio Fegato (AISF), Rome, Italy
| | - Antonio Pinna
- Liver Match Study, Associazione Italiana Studio Fegato (AISF), Rome, Italy
| | - Alexander Gimson
- National Health Service Blood and Transplant (NHSBT), Bristol, UK
| | | | - Mario Angelico
- Liver Match Study, Associazione Italiana Studio Fegato (AISF), Rome, Italy.
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21
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Sagnelli E, Stroffolini T, Sagnelli C, Smedile A, Morisco F, Furlan C, Babudieri S, Brancaccio G, Coppola N, Gaeta GB, Almasio PL. Epidemiological and clinical scenario of chronic liver diseases in Italy: Data from a multicenter nationwide survey. Dig Liver Dis 2016; 48:1066-71. [PMID: 27291331 DOI: 10.1016/j.dld.2016.05.014] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2016] [Revised: 05/03/2016] [Accepted: 05/16/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND The last Italian prevalence survey on chronic liver diseases (CLD) was performed in 2001. The present study evaluated the changes occurring over thirteen years. METHODS We enrolled 2,557 CLD consecutive patients in 16 Italian liver units in 2014. RESULTS HBV etiology accounted for 513 (20.2%) cases, alone in 439 and associated with HCV and/or alcohol abuse in 74. Of these 513, 11.9% were anti-HDV-positive and 7.2% HBeAg-positive. HCV alone was responsible for 50.3% of CLD and with alcohol abuse for 5.9%. HCV RNA was detected in 64.0% of the anti-HCV-positive patients tested. HCV genotyping, performed for 899 patients, showed genotype-1a, 1b, 2, 3, 4 and 5 respectively in 16.5%, 45.5%, 15.4%, 8.2%, 15.1% and 0.2%. Alcohol abuse alone was responsible for 6.4% of cases and NAFLD/NASH for 6.3%. Liver cirrhosis (p<0.001) and HCC (p<0.001) were more frequent in alcoholic than viral etiologies. HCV and alcohol etiologies were more frequent in 2001 than 2014 (from 69.9% to 59.9% and from 23.0% to 12.3%, respectively). HBV showed a similar impact. In all etiologies, the 2001 CLD cases were 10 years younger and with a significantly lower rate of cirrhosis than the 2014 cases. CONCLUSION The changes in HCV, HBV and alcohol etiologies may help apply more appropriate healthcare strategies.
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Affiliation(s)
- Evangelista Sagnelli
- Department of Mental Health and Public Medicine, Second University of Naples, Italy.
| | - Tommaso Stroffolini
- Department of Tropical and Infectious Diseases, Policlinico Umberto Primo, Rome, Italy
| | - Caterina Sagnelli
- Department of Clinical and Experimental Medicine and Surgery, Second University of Naples, Napoli, Italy
| | - Antonina Smedile
- Department of Medical Sciences, University of Turin, Turin, Italy
| | - Filomena Morisco
- Department of Clinical Medicine and Surgery, Gastroenterology Unit, University of Naples "Federico II", Napoli, Italy
| | - Caterina Furlan
- Department of Tropical and Infectious Diseases, Policlinico Umberto Primo, Rome, Italy
| | - Sergio Babudieri
- Clinic of Infectious Diseases, University of Sassari, Sassari, Italy
| | - Giuseppina Brancaccio
- Department of Clinical and Experimental Medicine and Surgery, Viral Hepatitis Unit, University of Naples, Napoli, Italy
| | - Nicola Coppola
- Department of Mental Health and Public Medicine, Second University of Naples, Italy
| | - Giovanni Battista Gaeta
- Department of Clinical and Experimental Medicine and Surgery, Viral Hepatitis Unit, University of Naples, Napoli, Italy
| | - Piero Luigi Almasio
- Gastroenterology & Hepatology Unit, Di.Bi.MI.S. University of Palermo, Palermo, Italy
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Coppola N, De Pascalis S, Onorato L, Calò F, Sagnelli C, Sagnelli E. Hepatitis B virus and hepatitis C virus infection in healthcare workers. World J Hepatol 2016; 8:273-281. [PMID: 26925201 PMCID: PMC4757650 DOI: 10.4254/wjh.v8.i5.273] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2015] [Revised: 10/25/2015] [Accepted: 01/11/2016] [Indexed: 02/06/2023] Open
Abstract
Approximately 3 million healthcare workers per year receive an injury with an occupational instrument, with around 2000000 exposures to hepatitis B virus (HBV) and 1000000 to hepatitis C virus (HCV). Although an effective HBV vaccine has been available since the early eighties, and despite the worldwide application of universal vaccination programs started in the early nineties, HBV still remains a prominent agent of morbidity and mortality. There is no vaccine to limit the diffusion of HCV infection, which progresses to chronicity in the majority of cases and is a major cause of morbidity and mortality worldwide due to a chronic liver disease. Healthcare workers are frequently exposed by a mucosal-cutaneous or percutaneous route to accidental contact with human blood and other potentially infectious biological materials while carrying out their occupational duties. Mucosal-cutaneous exposure occurs when the biological material of a potentially infected patient accidentally comes in contact with the mucous membranes of the eyes or mouth or with the skin of a healthcare worker. Percutaneous exposure occurs when an operator accidentally injures himself with a sharp contaminated object, like a needle, blade or other sharp medical instrument. About 75% of the total occupational exposure is percutaneous and 25% mucosal-cutaneous, the risk of infecting a healthcare worker being higher in percutaneous than in mucosal-cutaneous exposure. All healthcare workers should be considered for HBV vaccination and should meticulously apply the universal prophylactic measures to prevent exposure to HBV and HCV.
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23
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Lampertico P, Invernizzi F, Viganò M, Loglio A, Mangia G, Facchetti F, Primignani M, Jovani M, Iavarone M, Fraquelli M, Casazza G, de Franchis R, Colombo M. The long-term benefits of nucleos(t)ide analogs in compensated HBV cirrhotic patients with no or small esophageal varices: A 12-year prospective cohort study. J Hepatol 2015; 63:1118-25. [PMID: 26100495 DOI: 10.1016/j.jhep.2015.06.006] [Citation(s) in RCA: 69] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2014] [Revised: 05/14/2015] [Accepted: 06/08/2015] [Indexed: 12/16/2022]
Abstract
BACKGROUND & AIMS Esophageal varices (EV) are a marker of disease severity in compensated cirrhosis due to hepatitis B virus (HBV) which predicts also the risk of hepatocellular carcinoma (HCC), clinical decompensation and anticipated liver related death. The dynamics and prognostic significance of EV in patients under long-term HBV suppression by nucleos(t)ide analogs (NUC), are poorly known. METHODS A standardized protocol (Baveno) including 414 upper gastrointestinal (GI) endoscopies was applied to 107 HBeAg-negative compensated cirrhotic patients (93% Child-Pugh A) during a median of 12 (range 2 to 17) years of NUC therapy. Patients who initially started on lamivudine (LMV) and then developed resistance (LMV-R), were rescued by early administration of adefovir, or were switched to tenofovir. Surveillance included serum HBV DNA every three months and abdominal ultrasound every six months. RESULTS Twenty-seven patients had baseline F1 EV which regressed in 18, remained unchanged in eight and progressed in one patient; the 12-year cumulative incidence of EV regression was 83% (95% CI: 52-92%). De novo F1/F2 EV developed in 6/80 patients with a 12-year cumulative incidence of 10% (95% CI: 5-20%). Six of seven patients with de novo varices or progression of pre-existing varices had either a clinical breakthrough due to LMV-R and/or developed a HCC. No bleedings from ruptured EV occurred, 12 patients died (9 HCC) and 15 were transplanted (13 HCC): the 12-year cumulative incidence of HCC and overall survival was 33% (95% CI: 24-42%) and 76% (95% CI: 67-83%), respectively. CONCLUSIONS Long-term pharmacological suppression of HBV in HBeAg-seronegative patients with compensated cirrhosis leads to a significant regression of pre-existing EV accompanied by a negligible risk of developing de novo EV.
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Affiliation(s)
- Pietro Lampertico
- "A.M. and A. Migliavacca" Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Federica Invernizzi
- "A.M. and A. Migliavacca" Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Mauro Viganò
- Division of Hepatology, Ospedale San Giuseppe, Università degli Studi di Milano, Italy
| | - Alessandro Loglio
- "A.M. and A. Migliavacca" Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Giampaolo Mangia
- "A.M. and A. Migliavacca" Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Floriana Facchetti
- "A.M. and A. Migliavacca" Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Massimo Primignani
- "A.M. and A. Migliavacca" Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Manol Jovani
- "A.M. and A. Migliavacca" Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Massimo Iavarone
- "A.M. and A. Migliavacca" Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Mirella Fraquelli
- Division of Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Giovanni Casazza
- Department of Biomedical and Clinical Sciences, Ospedale Luigi Sacco, Università degli Studi di Milano, Milan, Italy
| | - Roberto de Franchis
- Division of Gastroenterology, Ospedale Luigi Sacco, Università degli Studi di Milano, Milan, Italy
| | - Massimo Colombo
- "A.M. and A. Migliavacca" Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
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Alfaiate D, Dény P, Durantel D. Hepatitis delta virus: From biological and medical aspects to current and investigational therapeutic options. Antiviral Res 2015; 122:112-29. [PMID: 26275800 DOI: 10.1016/j.antiviral.2015.08.009] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2015] [Revised: 08/10/2015] [Accepted: 08/11/2015] [Indexed: 12/14/2022]
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Abstract
Hepatitis D is caused by the hepatitis D virus (HDV), a unique RNA pathogen that requires the hepatitis B surface antigen (HBsAg) to infect. Hepatitis D is transmitted by the parenteral route. The main susceptible group is patients with chronic HBsAg infection who become superinfected with the virus. Hepatitis D occurs throughout the globe, but control of hepatitis B virus (HBV) in the last two decades has consistently diminished the circulation of HDV in industrialized countries. However, hepatitis D remains a medical issue for injecting drug users (IDUs), as well as immigrants from endemic HDV areas, who are reintroducing the infection in Europe.
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Affiliation(s)
- Mario Rizzetto
- Division of Gastroenterology, University of Torino, 10126 Torino, Italy
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26
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Stroffolini T, Esvan R, Biliotti E, Sagnelli E, Gaeta GB, Almasio PL. Gender differences in chronic HBsAg carriers in Italy: Evidence for the independent role of male sex in severity of liver disease. J Med Virol 2015; 87:1899-903. [PMID: 26037919 DOI: 10.1002/jmv.24243] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/15/2015] [Indexed: 01/05/2023]
Abstract
It has been shown that sexual hormones have an opposite effect on hepatic fibrosis progression and hepatocellular carcinoma development. Sex differences among 2,762 chronic HBsAg carriers consecutively referring Italian hospitals in 2001 and in 2007 have been evaluated, particularly focusing on the role of gender on severity of liver disease. The overall sex ratio (males/females) was 2.6. Females were more likely born abroad and new diagnosis cases; but less likely HIV coinfected. No sex difference was observed regarding coinfection with other hepatitis viruses. The sex ratio linearly increased with increasing severity of liver disease, being 1.3 in normal ALT, 2.8 in chronic hepatitis, 3.6 in liver cirrhosis, and 6.8 in hepatocellular carcinoma. Adjustment by multiple logistic regression analysis for the confounding effect of age, alcohol intake, HDV infection, HCV infection, and BMI shows that male gender is an independent predictor of the likelihood of more severe liver disease (O.R. 1.7; C.I. 95% = 1.3-2.1). HBV-DNA levels resulted not associated with the outcome of chronic HBV infection. Despite some potential risk factors associated with liver disease, such as HBV genotype or mutations, not having been controlled for due to lack of availability, the observed sex disparity in the outcome of chronic HBV infection may support biological observation that HBV infection could be considered a sex hormone-responsive virus.
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Affiliation(s)
| | - Rozenn Esvan
- Department of Tropical and Infectious Diseases, University of Rome, Italy
| | - Elisa Biliotti
- Department of Tropical and Infectious Diseases, University of Rome, Italy
| | - Evangelista Sagnelli
- Department of Public Medicine, Infectious Diseases Unit, Second University of Naples, Caserta CE, Italy
| | - Giovanni Battista Gaeta
- Department of Internal and Specialized Medicine, Second University of Naples, Caserta CE, Italy
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Papatheodoridis GV, Tsochatzis E, Hardtke S, Wedemeyer H. Barriers to care and treatment for patients with chronic viral hepatitis in Europe: a systematic review. Liver Int 2014; 34:1452-63. [PMID: 24750532 DOI: 10.1111/liv.12565] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2014] [Accepted: 04/17/2014] [Indexed: 12/17/2022]
Abstract
BACKGROUND & AIMS Despite the availability of effective therapies for hepatitis B (HBV) and C virus (HCV), only a minority of these patients receive treatment. We systematically reviewed published data on barriers to management for chronic HBV/HCV patients in Europe. METHODS Literature search to identify studies including adult patients with chronic HBV/HCV infection from European countries and data on barriers to treatment. RESULTS Twenty-five studies including 6253 chronic HBV and 19,014 HCV patients were identified, of which only two were from Eastern Europe. The mean rate of no treatment in HBV patients was 42% being higher in North-Western European countries than Italy (56% vs. 39%, P < 0.001). Immigrants represented the most common barrier to HBV treatment. The mean rate of no treatment in HCV RNA-positive patients was 57%, being highest in Romania (89%), intermediate in France (79%) and lower though still high in other European countries (52%, P < 0.001). The predominant barriers to HCV treatment were lack of financial resources in Romania and direct/indirect limitations of interferon-alfa and/or parenteral drug and alcohol abuse in other countries. The mean rate of no treatment was highest in HCV RNA-positive parenteral drug users (72%) and intermediate in those with HCV-HIV co-infection (64%). CONCLUSIONS A substantial proportion of diagnosed chronic HBV and the majority of diagnosed HCV patients remain untreated. The rates and most importantly the reasons of barriers to treatment in chronic HBV/HCV patients vary widely among European countries supporting the need for country-specific national strategies, resource allocation and implementation of global management policies.
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Affiliation(s)
- George V Papatheodoridis
- Department of Gastroenterology, Athens University Medical School, Laiko General Hospital of Athens, Athens, Greece
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28
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Onali S, Figorilli F, Balestrieri C, Serra G, Conti M, Scioscia R, Barca L, Lai ME, Chessa L. Can antiretroviral therapy modify the clinical course of HDV infection in HIV-positive patients? Antivir Ther 2014; 20:671-9. [PMID: 25345373 DOI: 10.3851/imp2911] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/01/2014] [Indexed: 10/24/2022]
Abstract
BACKGROUND Infection with hepatitis delta virus (HDV) affects approximately 6-14.5% of patients coinfected with HIV-1 and HBV, showing a more aggressive clinical course compared with an HIV-negative population. There is no universally approved treatment for chronic hepatitis D (CHD) in HIV-infected patients. Antiretroviral therapy (ART) containing tenofovir has been recently associated with HDV suppression. Our aim was to evaluate whether the outcome of CHD in HIV-infected patients can be favourably influenced by ART including reverse transcriptase inhibitors. METHODS The clinical course of four HBV/HDV/HIV-coinfected patients receiving ART were retrospectively examined. RESULTS HDV RNA became undetectable in all patients after a variable period of ART along with the disappearance of hepatitis B surface antigen in two of them, and an increase in CD4(+) T-cell count. In all patients, virological changes were associated with improved liver function tests and clinical features. CONCLUSIONS We suggest that ART regimens including drugs active against HBV could have beneficial effects on the clinical course of CHD in patients with HIV-1 by favouring immunological reconstitution.
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Affiliation(s)
- Simona Onali
- Center for the Study of Liver Diseases, Department of Medical Sciences 'Mario Aresu', University of Cagliari, Cagliari, Italy
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Nyan DC, Ulitzky LE, Cehan N, Williamson P, Winkelman V, Rios M, Taylor DR. Rapid detection of hepatitis B virus in blood plasma by a specific and sensitive loop-mediated isothermal amplification assay. Clin Infect Dis 2014; 59:16-23. [PMID: 24704724 PMCID: PMC4305128 DOI: 10.1093/cid/ciu210] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2013] [Accepted: 03/25/2014] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Hepatitis B virus (HBV) is an important blood-borne pathogen that causes hepatic inflammation and can lead to liver cirrhosis and hepatocellular carcinoma. Conventional methods of HBV detection are time consuming and require highly trained personnel and elaborate equipment. This report describes the development of a rapid, simple, specific, and sensitive loop-mediated isothermal amplification assay (LAMP) for detection of HBV genotypes A, B, C, D, E, and F in blood samples. METHODS HBV standard plasma panels and clinical donor plasma specimens were used for the development and validation of the LAMP assay. Amplification was performed at 60°C for 60 minutes using extracted DNA or heat-treated plasma specimens without DNA extraction. The assay was evaluated for its ability to detect various HBV genotypes and for its sensitivity, specificity, and time-point of detection. RESULTS The LAMP assay detected HBV genotypes A-F and demonstrated a sensitivity of 10-100 IU per reaction of HBV DNA. The assay also detected 69 of 75 (92%) HBV-positive donor plasma specimens tested and demonstrated a specificity of 100%. CONCLUSIONS These results demonstrate that our HBV-LAMP assay is rapid, sensitive and specific, and capable of detecting the major HBV genotypes. This assay could be used in clinical point-of-care settings, mainly in endemic and resource-limited environments for HBV diagnostics, donor screening, epidemiological studies, and therapeutic monitoring of patients undergoing antiviral treatment.
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Affiliation(s)
- Dougbeh-Chris Nyan
- Laboratory of Emerging Pathogens, Office of Blood Research and Review, Division of Emerging and Transfusion-Transmitted Diseases, Center for Biologics Evaluation and Research, US Food and Drug Administration, Bethesda, Maryland
| | - Laura E. Ulitzky
- Laboratory of Emerging Pathogens, Office of Blood Research and Review, Division of Emerging and Transfusion-Transmitted Diseases, Center for Biologics Evaluation and Research, US Food and Drug Administration, Bethesda, Maryland
| | - Nicoleta Cehan
- Laboratory of Emerging Pathogens, Office of Blood Research and Review, Division of Emerging and Transfusion-Transmitted Diseases, Center for Biologics Evaluation and Research, US Food and Drug Administration, Bethesda, Maryland
| | | | | | - Maria Rios
- Laboratory of Emerging Pathogens, Office of Blood Research and Review, Division of Emerging and Transfusion-Transmitted Diseases, Center for Biologics Evaluation and Research, US Food and Drug Administration, Bethesda, Maryland
| | - Deborah R. Taylor
- Laboratory of Emerging Pathogens, Office of Blood Research and Review, Division of Emerging and Transfusion-Transmitted Diseases, Center for Biologics Evaluation and Research, US Food and Drug Administration, Bethesda, Maryland
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Sagnelli E, Sagnelli C, Pisaturo M, Macera M, Coppola N. Epidemiology of acute and chronic hepatitis B and delta over the last 5 decades in Italy. World J Gastroenterol 2014; 20:7635-7643. [PMID: 24976701 PMCID: PMC4069292 DOI: 10.3748/wjg.v20.i24.7635] [Citation(s) in RCA: 85] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2013] [Revised: 01/28/2014] [Accepted: 04/09/2014] [Indexed: 02/06/2023] Open
Abstract
The spread of hepatitis B virus (HBV) infection has gradually decreased in Italy in the last 5 decades as shown by the steady reduction in the incidence rates of acute hepatitis B, from 10/100000 inhabitants in 1984 to 0.85/100000 in 2012, and by the reduced prevalence of hepatitis B surface antigen (HBsAg)-positive cases among chronic hepatitis patients with different etiologies, from 60% in 1975 to about 10% in 2001. The prevalence of HBsAg chronic carriers in the general population also decreased from nearly 3% in the 1980s to 1% in 2010. Linked to HBV by its characteristics of defective virus, the hepatitis delta virus (HDV) has shown a similar epidemiological impact on the Italian population over time. The incidence of acute HDV infection decreased from 3.2/100000 inhabitants in 1987 to 0.8/100000 in 2010 and the prevalence of HDV infection in HBsAg chronic carriers decreased from 24% in 1990 to 8.5% in 2006. Before the beneficial effects of HBV mass vaccination introduced in 1991, the decreased endemicity of HBV and HDV infection in Italy paralleled the improvement in screening blood donations, the higher standard of living and impressive reduction in the birth rate associated with a marked reduction in the family size. A further contribution to the decline in HBV and HDV infections most probably came from the media campaigns to prevent the spread of human immunodeficiency virus infection by focusing the attention of the general population on the same routes of transmission of viral infections such as unsafe sexual intercourse and parenteral exposures of different kinds.
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Noureddin M, Gish R. Hepatitis delta: epidemiology, diagnosis and management 36 years after discovery. Curr Gastroenterol Rep 2014; 16:365. [PMID: 24293018 PMCID: PMC3918112 DOI: 10.1007/s11894-013-0365-x] [Citation(s) in RCA: 69] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/02/2023]
Abstract
With recent studies showing increased prevalence of hepatitis delta (HDV) even in the US, Australia, and some countries in Europe, and very high prevalence in endemic regions, HDV infection is far from being a disappearing disease. Although immigrants from endemic countries have been shown to have increased risk, studies have clearly shown that the disease is not solely appearing in traditional high-risk groups. Recent studies provide increasing evidence that sexual transmission may be an important factor in HDV infection spread. Based on the totality of evidence showing increased disease progression and substantially increased risk of cirrhosis in HDV-infected CHB patients, and the current studies showing higher than expected prevalence, it is time to call for HDV screening of all CHB patients. HDV viral load detection and measurement should be considered in all patients whether or not they are anti-HDV-positive. With universal screening of CHB patients for HDV, earlier diagnosis and consideration of treatment would be possible. Current treatment of HDV is IFN-based therapy with or without HBV antivirals, but current research indicates the possibility that prenylation inhibitors, entry inhibitors, HBsAg release inhibitors, or other therapies currently in the pipeline may provide more effective therapy in the future. In addition, universal screening would serve the important public health goal of allowing patients to be educated on their status and on the need for HDV-negative patients to protect themselves against superinfection and for HDV-infected patients to protect against transmission to others. Further studies and global awareness of HDV infection are needed.
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Affiliation(s)
- Mazen Noureddin
- Division of Gastroenterology and Hepatology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, HMR 101, Los Angeles, CA 90033 USA
| | - Robert Gish
- Robert G. Gish Consultants, LLC, San Diego, CA USA
- St. Joseph’s Hospital and Medical Center, Phoenix, AZ USA
- University of Nevada, Las Vegas, 6022 La Jolla Mesa Drive, San Diego, CA 92037 USA
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Stornaiuolo G, Cuniato V, Cuomo G, Nocera E, Brancaccio G, De Rosa M, Pontarelli A, Grasso G, Danzi G, Grossi A, Natale RF, Gaeta GB. Active recruitment strategy in disadvantaged immigrant populations improves the identification of human immunodeficiency but not of hepatitis B or C virus infections. Dig Liver Dis 2014; 46:62-6. [PMID: 24148806 DOI: 10.1016/j.dld.2013.08.126] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2013] [Revised: 07/26/2013] [Accepted: 08/03/2013] [Indexed: 12/11/2022]
Abstract
BACKGROUND Barriers to access medical screening and care may underestimate the number of diseased subjects among immigrant populations. AIMS To evaluate the prevalence of human immunodeficiency virus, hepatitis B virus and hepatitis C virus infections among immigrants recruited in a disadvantaged area. METHODS The study enrolled all subjects seen between 1999 and 2009 at an on-site health and family counselling centre for immigrants. During the first 6 years of the study a pro-active recruitment was performed using a mobile unit. RESULTS Overall 2681 subjects were enrolled (median age: 31 years; 52.8% males; 82.3% from Sub-Saharan Africa; 13.9% of the women were sex workers). A total of 206 subjects (7.6%) were hepatitis B surface antigen-positive, 84 (3.6%) were anti-hepatitis C virus-positive, 129 (5%) were anti-human immunodeficiency virus-positive, 84 (3.1%) were drug users, and 436 (16.3%) were alcohol abusers. The prevalence of hepatitis B surface antigen and anti-hepatitis C virus remained consistent throughout the study period, while the prevalence of human immunodeficiency virus significantly decreased. At multivariate analysis, hepatitis B virus infection was associated with male gender, hepatitis C virus infection with drug addiction, and human immunodeficiency virus infection was associated with female gender, drug addiction, and active recruitment. CONCLUSIONS An active recruitment strategy should be considered to reach disadvantaged populations at high risk of human immunodeficiency virus infection.
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Affiliation(s)
| | - Vincenzo Cuniato
- Social Medical Voluntary Association "Jerry Essan Masslo", Castelvolturno, Caserta, Italy
| | - Gianluca Cuomo
- Viral Hepatitis Unit, Department of Internal Medicine, Second University, Naples, Italy
| | - Espedito Nocera
- Social Medical Voluntary Association "Jerry Essan Masslo", Castelvolturno, Caserta, Italy
| | - Giuseppina Brancaccio
- Viral Hepatitis Unit, Department of Internal Medicine, Second University, Naples, Italy
| | - Maddalena De Rosa
- Social Medical Voluntary Association "Jerry Essan Masslo", Castelvolturno, Caserta, Italy
| | - Agostina Pontarelli
- Viral Hepatitis Unit, Department of Internal Medicine, Second University, Naples, Italy
| | - Giovanni Grasso
- Social Medical Voluntary Association "Jerry Essan Masslo", Castelvolturno, Caserta, Italy
| | - Gaetano Danzi
- Unit of Pathology, G. Moscati Hospital, Aversa, Italy
| | - Alessandra Grossi
- Faculty of Communication Sciences, Institute for Public Communication-ICP, Swiss Italian University, Lugano, Switzerland
| | - Renato F Natale
- Social Medical Voluntary Association "Jerry Essan Masslo", Castelvolturno, Caserta, Italy
| | - Giovanni B Gaeta
- Viral Hepatitis Unit, Department of Internal Medicine, Second University, Naples, Italy.
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Abstract
Immigration is fuelling a new reservoir of hepatitis D virus (HDV) in Europe, and hepatitis D still represents an important medical problem in the USA. The disease continues to be a major medical scourge in the developing world, in particular in countries such as Pakistan, Mongolia and Mauritania. New therapeutic strategies are being developed to disrupt interactions between HDV and its viral partner HBV, or with the host. Blocking or modifying the hepatitis B surface antigen (HBsAg) might interfere with the uptake or release of the hepatitis D virion; interference with host-mediated post-translational changes of proteins that are crucial to the HDV life cycle, such as prenylation, is another potential therapeutic option. At present, however, the only realistic option is to optimize IFN-α therapy. As eradication of HBsAg is the ultimate end point of therapy, long-term interferon administration might be required, raising an issue of tolerance in patients. Treatment with IFN-λ is a potential alternative approach to IFN-α; treatment of hepatitis C with this cytokine seems to cause fewer adverse effects than IFN-α and, therefore, might be more suitable for long-term treatment of HDV.
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Servant-Delmas A, Le Gal F, Gallian P, Gordien E, Laperche S. Increasing prevalence of HDV/HBV infection over 15 years in France. J Clin Virol 2013; 59:126-8. [PMID: 24365475 DOI: 10.1016/j.jcv.2013.11.016] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2013] [Revised: 11/25/2013] [Accepted: 11/30/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND In France, there are no consistent data estimating hepatitis delta virus (HDV) prevalence in the general population. OBJECTIVES To better characterize HDV/HBV infection and its trends over a 15-years period from 1997 to 2011, we used data retrieved from the National Epidemiological Donors database including viral and demographic characteristics of all French HBV infected blood donors. STUDY DESIGN Of the 39,911,011 donations collected over the 15 year-study-period, 6214 (1.56 in 10(4) donations) were confirmed positive for HBV from which 72.3% were tested for HDV antibodies (Ab). HDV viral load was performed using a real-time PCR assay on positive HDV Ab samples and HDV genotype determined for each positive viremic sample. RESULTS Among the 4492 HBV donations, 89 (1.98%) were HDV Ab positive. After being stable around 1.1% from 1997 to 2005, this rate has continuously increased to reach 6.5% in 2010, before declining to 0.85% in 2011. Of the 61 investigated HDV Ab positive individuals, 22.9% were viremic with a viral load ranging from 10(4) to 9.8 × 10(7) copies mL(-1). Genotyping revealed 12 HDV-1, 1 HDV-6 and 1 HDV-7 in accordance with the geographical origin of individuals. CONCLUSION Such a study gives unexpected features of HBV-HDV infection in the population of blood donors which is a priori, a healthy population. The increase of HDV prevalence mainly linked to migration of population from endemic countries, demonstrates that there is still no complete control of HBV infection and must encourage HBV vaccination campaigns and systematic screening for HDV in HBV-infected.
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Affiliation(s)
- Annabelle Servant-Delmas
- Laboratoire d'expertise en Virologie, Centre National de Référence des hépatites virales B et C et du VIH en Transfusion, Institut National de la Transfusion Sanguine, Paris, France.
| | - Frédéric Le Gal
- Laboratoire de Bactériologie-Virologie-Hygiène, associé Centre National de Référence des hépatites virales B et C et Delta, Hôpital Avicenne, Bobigny, France
| | - Pierre Gallian
- Etablissement Français du Sang, Direction médicale, Saint Denis, France
| | - Emmanuel Gordien
- Laboratoire de Bactériologie-Virologie-Hygiène, associé Centre National de Référence des hépatites virales B et C et Delta, Hôpital Avicenne, Bobigny, France
| | - Syria Laperche
- Laboratoire d'expertise en Virologie, Centre National de Référence des hépatites virales B et C et du VIH en Transfusion, Institut National de la Transfusion Sanguine, Paris, France
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Manesis EK, Vourli G, Dalekos G, Vasiliadis T, Manolaki N, Hounta A, Koutsounas S, Vafiadis I, Nikolopoulou G, Giannoulis G, Germanidis G, Papatheodoridis G, Touloumi G. Prevalence and clinical course of hepatitis delta infection in Greece: a 13-year prospective study. J Hepatol 2013; 59:949-56. [PMID: 23850875 DOI: 10.1016/j.jhep.2013.07.005] [Citation(s) in RCA: 91] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2012] [Revised: 07/02/2013] [Accepted: 07/03/2013] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS Hepatitis D virus (HDV) has decreased in Europe, but recent reports indicate a rising trend. We report the epidemiological changes, clinical progress, and effect of treatment on the natural course of HDV infection in Greece during the last 13 years. METHODS Prospective data were extracted from the HepNet.Greece Cohort-Study. RESULTS Since 1997, 4673 chronic HBV (CHB) cases (4527 adults, 146 children) have been followed prospectively. Two thousand one hundred thirty-seven patients were tested for anti-HDV [101 (4.7%) positive]. Anti-HDV testing in Greece decreased significantly (57.0% before 2003, 35.3% thereafter; p<0.001). Anti-HDV prevalence among HBsAg-positives was 4.2%; lower in native Greeks (2.8%) than in immigrants (7.5%) or in children (15.3%; p<0.001). Within 2.3 years of follow-up, HDV occurred in 11/2047 HBsAg-positive patients (2.2 new delta-infected adults and 8.7 children per 1000 HBsAg-positive annually). HDV-positive compared to CHB adults were younger (p=0.035) and had more active and advanced disease at baseline, as indicated by laboratory indices and the higher prevalence of cirrhosis at younger age. During a 4.2-year median observation, significantly more anti-HDV-positive than CHB adults developed a liver-related first event (20.0% vs. 8.5%, p Log-rank=0.014).Treatment was received by 46/90 (51.1%) patients, 40 of them interferon-based. In multivariable analysis, interferon significantly decreased disease progression in HDV-positive patients [HR=0.14 (95% CI: 0.02-0.86; p=0.033)]. CONCLUSIONS In Greece, HDV serology is currently tested in only one-third of HBsAg-positive patients. HDV prevalence is lower in native Greeks compared to immigrants, who may contribute >50% of the HDV infection burden in Greece. Data show that HDV infection is a rapidly progressive disease, but interferon-based treatment may alter its course.
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Affiliation(s)
- Emanuel K Manesis
- Division of Internal Medicine, Athens University Medical School, Greece.
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Sy BT, Ratsch BA, Toan NL, Song LH, Wollboldt C, Bryniok A, Nguyen HM, Luong HV, Velavan TP, Wedemeyer H, Kremsner PG, Bock CT. High prevalence and significance of hepatitis D virus infection among treatment-naïve HBsAg-positive patients in Northern Vietnam. PLoS One 2013; 8:e78094. [PMID: 24205106 PMCID: PMC3799775 DOI: 10.1371/journal.pone.0078094] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2013] [Accepted: 09/07/2013] [Indexed: 02/07/2023] Open
Abstract
Background Hepatitis D virus (HDV) infection is considered to cause more severe hepatitis than hepatitis B virus (HBV) monoinfection. With more than 9.5 million HBV-infected people, Vietnam will face an enormous health burden. The prevalence of HDV in Vietnamese HBsAg-positive patients is speculative. Therefore, we assessed the prevalence of HDV in Vietnamese patients, determined the HDV-genotype distribution and compared the findings with the clinical outcome. Methods 266 sera of well-characterized HBsAg-positive patients in Northern Vietnam were analysed for the presence of HDV using newly developed HDV-specific RT-PCRs. Sequencing and phylogenetic analysis were performed for HDV-genotyping. Results The HDV-genome prevalence observed in the Vietnamese HBsAg-positive patients was high with 15.4% while patients with acute hepatitis showed 43.3%. Phylogenetic analysis demonstrated a predominance of HDV-genotype 1 clustering in an Asian clade while HDV-genotype 2 could be also detected. The serum aminotransferase levels (AST, ALT) as well as total and direct bilirubin were significantly elevated in HDV-positive individuals (p<0.05). HDV loads were mainly low (<300 to 4.108 HDV-copies/ml). Of note, higher HDV loads were mainly found in HBV-genotype mix samples in contrast to single HBV-infections. In HBV/HDV-coinfections, HBV loads were significantly higher in HBV-genotype C in comparison to HBV-genotype A samples (p<0.05). Conclusion HDV prevalence is high in Vietnamese individuals, especially in patients with acute hepatitis B. HDV replication activity showed a HBV-genotype dependency and could be associated with elevated liver parameters. Besides serological assays molecular tests are recommended for diagnosis of HDV. Finally, the high prevalence of HBV and HDV prompts the urgent need for HBV-vaccination coverage.
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Affiliation(s)
- Bui Tien Sy
- Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany
- Department of Pathophysiology, Vietnam Military Medical University, Ha Noi, Ha Dong, Viet Nam
| | - Boris A. Ratsch
- Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany
| | - Nguyen Linh Toan
- Department of Pathophysiology, Vietnam Military Medical University, Ha Noi, Ha Dong, Viet Nam
| | - Le Huu Song
- 108 Institute of Clinical Medical and Pharmaceutical Sciences Tran Hung Dao Hospital, Ha Noi, Viet Nam
| | | | - Agnes Bryniok
- Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany
| | - Hung Minh Nguyen
- Center of Research and Development, Duy Tan University, da Nang, Viet Nam
| | - Hoang Van Luong
- Department of Pathophysiology, Vietnam Military Medical University, Ha Noi, Ha Dong, Viet Nam
| | | | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Peter G. Kremsner
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
| | - C.-Thomas Bock
- Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany
- Department of Molecular Pathology, University of Tübingen, Tübingen, Germany
- * E-mail:
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Rosenberg GK, Lattimore S, Brailsford SR, Hewitt PE, Tettmar KI, Kitchen AD, Ijaz S, Tedder RS. The diversity of chronic hepatitis B virus infections within blood donors in England and North Wales 2005 through 2010. Transfusion 2013; 53:2467-76. [DOI: 10.1111/trf.12003] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2012] [Revised: 10/08/2012] [Accepted: 10/11/2012] [Indexed: 12/14/2022]
Affiliation(s)
- Gillian K. Rosenberg
- National Transfusion Microbiology Laboratories; NHS Blood and Transplant/Health Protection Agency Epidemiology Unit; Clinical Transfusion Microbiology; National Transfusion Microbiology Reference Laboratory; NHS Blood and Transplant
- Blood Borne Virus Unit; Viral Reference Department; Microbiology Services; Health Protection Agency; Colindale London UK
| | - Sam Lattimore
- National Transfusion Microbiology Laboratories; NHS Blood and Transplant/Health Protection Agency Epidemiology Unit; Clinical Transfusion Microbiology; National Transfusion Microbiology Reference Laboratory; NHS Blood and Transplant
- Blood Borne Virus Unit; Viral Reference Department; Microbiology Services; Health Protection Agency; Colindale London UK
| | - Susan R. Brailsford
- National Transfusion Microbiology Laboratories; NHS Blood and Transplant/Health Protection Agency Epidemiology Unit; Clinical Transfusion Microbiology; National Transfusion Microbiology Reference Laboratory; NHS Blood and Transplant
- Blood Borne Virus Unit; Viral Reference Department; Microbiology Services; Health Protection Agency; Colindale London UK
| | - Patricia E. Hewitt
- National Transfusion Microbiology Laboratories; NHS Blood and Transplant/Health Protection Agency Epidemiology Unit; Clinical Transfusion Microbiology; National Transfusion Microbiology Reference Laboratory; NHS Blood and Transplant
- Blood Borne Virus Unit; Viral Reference Department; Microbiology Services; Health Protection Agency; Colindale London UK
| | - Kate I. Tettmar
- National Transfusion Microbiology Laboratories; NHS Blood and Transplant/Health Protection Agency Epidemiology Unit; Clinical Transfusion Microbiology; National Transfusion Microbiology Reference Laboratory; NHS Blood and Transplant
- Blood Borne Virus Unit; Viral Reference Department; Microbiology Services; Health Protection Agency; Colindale London UK
| | - Alan D. Kitchen
- National Transfusion Microbiology Laboratories; NHS Blood and Transplant/Health Protection Agency Epidemiology Unit; Clinical Transfusion Microbiology; National Transfusion Microbiology Reference Laboratory; NHS Blood and Transplant
- Blood Borne Virus Unit; Viral Reference Department; Microbiology Services; Health Protection Agency; Colindale London UK
| | - Samreen Ijaz
- National Transfusion Microbiology Laboratories; NHS Blood and Transplant/Health Protection Agency Epidemiology Unit; Clinical Transfusion Microbiology; National Transfusion Microbiology Reference Laboratory; NHS Blood and Transplant
- Blood Borne Virus Unit; Viral Reference Department; Microbiology Services; Health Protection Agency; Colindale London UK
| | - Richard S. Tedder
- National Transfusion Microbiology Laboratories; NHS Blood and Transplant/Health Protection Agency Epidemiology Unit; Clinical Transfusion Microbiology; National Transfusion Microbiology Reference Laboratory; NHS Blood and Transplant
- Blood Borne Virus Unit; Viral Reference Department; Microbiology Services; Health Protection Agency; Colindale London UK
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Abstract
Hepatitis D is returning to western Europe through immigration. The clinical presentation recapitulates the typical features of a florid hepatitis D. Hepatitis D is also being rediscovered in the developing world and in the United States. Hepatitis D virus (HDV) remains endemic in many countries and efforts are underway to map the infection at local levels and improve the medical alert to hepatitis D. In the United States it is generally thought that HDV has gone and hepatitis D is no longer a problem. Awareness of hepatitis D in the country has recently been revived.
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Affiliation(s)
- Mario Rizzetto
- Division of Gastroenterology, University of Torino, Molinette, c.so Bramante 88, Torino 10126, Italy.
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Wedemeyer H, Hardtke S, Manns MP. Epidemiology and Natural History. VIRAL HEPATITIS 2013:403-409. [DOI: 10.1002/9781118637272.ch28] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Boccalini S, Taddei C, Ceccherini V, Bechini A, Levi M, Bartolozzi D, Bonanni P. Economic analysis of the first 20 years of universal hepatitis B vaccination program in Italy: an a posteriori evaluation and forecast of future benefits. Hum Vaccin Immunother 2013; 9:1119-28. [PMID: 23376840 DOI: 10.4161/hv.23827] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
Italy was one of the first countries in the world to introduce a routine vaccination program against HBV for newborns and 12-y-old children. From a clinical point of view, such strategy was clearly successful. The objective of our study was to verify whether, at 20 y from its implementation, hepatitis B universal vaccination had positive effects also from an economic point of view. An a posteriori analysis evaluated the impact that the hepatitis B immunization program had up to the present day. The implementation of vaccination brought an extensive reduction of the burden of hepatitis B-related diseases in the Italian population. As a consequence, the past and future savings due to clinical costs avoided are particularly high. We obtained a return on investment nearly equal to 1 from the National Health Service perspective, and a benefit-to-cost ratio slightly less than 1 for the Societal perspective, considering only the first 20 y from the start of the program. In the longer-time horizon, ROI and BCR values were positive (2.78 and 2.46, respectively). The break-even point was already achieved few years ago for the NHS and for the Society, and since then more and more money is progressively saved. The implementation of universal hepatitis B vaccination was very favorable during the first 20 y of adoption, and further benefits will be increasingly evident in the future. The hepatitis B vaccination program in Italy is a clear example of the great impact that universal immunization is able to provide in the medium-long-term when health care authorities are so wise as to invest in prevention.
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Affiliation(s)
- Sara Boccalini
- Department of Health Sciences; University of Florence; Florence, Italy
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Fasano M, Saracino A, Carosi G, Mazzotta F, Marino N, Sagnelli E, Gaeta GB, Angarano G, Verucchi G, Bellissima P, Angeletti C, Santantonio T. Hepatitis B and immigrants: a SIMIT multicenter cross-sectional study. Infection 2013. [PMID: 23264094 DOI: 10.1007/s15010-012-0384-9]] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
BACKGROUND The continuing migration of individuals from geographic areas with high/medium endemicity has determined the arrival of new chronic hepatitis B virus (HBV) carriers in Italy. The magnitude of this phenomenon and clinical/virological features of HBsAg-positive migrants remain not very well defined. AIMS To evaluate the proportion of HBsAg-positive immigrants enrolled in this multicenter Società Italiana di Malattie Infettive e Tropicali (SIMIT) cross-sectional study and to compare the characteristics of chronic hepatitis B infection in migrants to those of Italian carriers. METHODS From February 1 to July 31 2008, anonymous data were obtained from all HBsAg-positive patients aged ≥ 18 years observed at 74 Italian centers of infectious diseases. RESULTS Of the 3,760 HBsAg-positive subjects enrolled, 932 (24.8 %) were immigrants, with a prevalent distribution in central to northern Italy. The areas of origin were: Far East (37.1 %), Eastern Europe (35.4 %), Sub-Saharan Africa (17.5 %), North Africa (5.5 %), and 4.5 % from various other sites. Compared to Italian carriers, migrants were significantly younger (median age 34 vs. 52 years), predominantly female (57.5 vs. 31 %), and most often at first observation (incident cases 34.2 vs. 13.3 %). HBeAg-positives were more frequent among migrants (27.5 vs. 14 %). Genotype D, found in 87.8 % of Italian carriers, was present in only 40 % of migrants, who were more frequently inactive HBV carriers, with a lower prevalence of chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Only 27.1 % of migrants received antiviral treatment compared to 50.3 % of Italians. CONCLUSIONS Twenty-five percent of all HBV carriers examined at Italian centers was composed of immigrants with demographic, serological, and virological characteristics that differed from those of natives and appeared to have an inferior access to treatment.
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Affiliation(s)
- M Fasano
- Clinic of Infectious Diseases, University of Bari, Bari, Italy
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Chen P, Yu C, Wu W, Wang J, Ruan B, Ren J, Yang S, Xu K, Yu L, Li L. Serolological Profile Among HBsAg-Positive Infections in Southeast China: A Community-Based Study. HEPATITIS MONTHLY 2013; 13:e7604. [PMID: 23483608 PMCID: PMC3589882 DOI: 10.5812/hepatmon.7604] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/11/2012] [Revised: 11/27/2012] [Accepted: 12/24/2012] [Indexed: 12/11/2022]
Abstract
BACKGROUND Hepatitis B virus (HBV) infection has remained a significant public health problem. Generating a large-scale, community-based profile of HBV infection in China is essential to prevention of the disease. OBJECTIVES The current study was designed to investigate HBV-infected individuals at the community level and determine the age distribution, hepatitis B e antigen (HBeAg) positivity and its related risk factors, relationship among serological markers. PATIENTS AND METHODS A cross-sectional, community-based survey was carried out without age restriction, in 12 communities of two counties. The study population was selected by random multistage cluster sampling. Serological samples and demographic information were collected from 8439 HB surface antigen (HBsAg)-positive individuals. RESULTS The constituent ratio of individuals with HBsAg-positive infections was lowest among persons aged < 20 years (0.4%) and the highest among persons aged 40-49 years (33.2%). The HBeAg-positive rate among infected individuals was 18.5%, and the constituent ratio decreased with increasing of age. The HBeAg-positive rate in males (21.9%) was significantly higher than in females (14.7%), and was higher among coastland inhabitants (22.9%) than among plains inhabitants (12.9%). Among the 1561 HBeAg-positive individuals, 91.0% were HBV DNA-positive. However, of the 6878 HBeAg-negative individuals, only 45.4% were HBV DNA-positive, and the HBeAg-positive rate was significantly different at different levels of HBV DNA expression. The proportion of detectable HBV DNA levels was significantly higher in individuals with elevated ALT, compared to those with normal ALT, regardless of HBeAg-positivity. CONCLUSIONS The HBV prevalence remained high in the > 20 age group. The positivity of HBeAg was related to age, region, and sex. Testing HBeAg and serum ALT levels were effective ways to assess HBV infectiousness in community-level hospitals in China.
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Affiliation(s)
- Ping Chen
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Chengbo Yu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Wei Wu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Jinghua Wang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Bing Ruan
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Jingjing Ren
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Shigui Yang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Kaijin Xu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Liang Yu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Corresponding author: Lanjuan Li, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qing-Chun Road, 310003, Hangzhou, China. Tel.: +86-57187236458, Fax: +86-57187236459, E-mail:
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Fasano M, Saracino A, Carosi G, Mazzotta F, Marino N, Sagnelli E, Gaeta GB, Angarano G, Verucchi G, Bellissima P, Angeletti C, Santantonio T. Hepatitis B and immigrants: a SIMIT multicenter cross-sectional study. Infection 2012; 41:53-9. [PMID: 23264094 DOI: 10.1007/s15010-012-0384-9] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2012] [Accepted: 12/07/2012] [Indexed: 12/17/2022]
Abstract
BACKGROUND The continuing migration of individuals from geographic areas with high/medium endemicity has determined the arrival of new chronic hepatitis B virus (HBV) carriers in Italy. The magnitude of this phenomenon and clinical/virological features of HBsAg-positive migrants remain not very well defined. AIMS To evaluate the proportion of HBsAg-positive immigrants enrolled in this multicenter Società Italiana di Malattie Infettive e Tropicali (SIMIT) cross-sectional study and to compare the characteristics of chronic hepatitis B infection in migrants to those of Italian carriers. METHODS From February 1 to July 31 2008, anonymous data were obtained from all HBsAg-positive patients aged ≥ 18 years observed at 74 Italian centers of infectious diseases. RESULTS Of the 3,760 HBsAg-positive subjects enrolled, 932 (24.8 %) were immigrants, with a prevalent distribution in central to northern Italy. The areas of origin were: Far East (37.1 %), Eastern Europe (35.4 %), Sub-Saharan Africa (17.5 %), North Africa (5.5 %), and 4.5 % from various other sites. Compared to Italian carriers, migrants were significantly younger (median age 34 vs. 52 years), predominantly female (57.5 vs. 31 %), and most often at first observation (incident cases 34.2 vs. 13.3 %). HBeAg-positives were more frequent among migrants (27.5 vs. 14 %). Genotype D, found in 87.8 % of Italian carriers, was present in only 40 % of migrants, who were more frequently inactive HBV carriers, with a lower prevalence of chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Only 27.1 % of migrants received antiviral treatment compared to 50.3 % of Italians. CONCLUSIONS Twenty-five percent of all HBV carriers examined at Italian centers was composed of immigrants with demographic, serological, and virological characteristics that differed from those of natives and appeared to have an inferior access to treatment.
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Affiliation(s)
- M Fasano
- Clinic of Infectious Diseases, University of Bari, Bari, Italy
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Antonucci G, Mazzotta F, Puoti M, Angeletti C, Girardi E, Santantonio T, Ambu S, Gaeta GB, Colucci M, Angarano G, Marino N, Rinaldi R, Bellissima P, Armignacco O, Carosi G, Sagnelli E. Factors associated with access to antiviral treatment in a multicentre cross-sectional study of patients with chronic hepatitis B in Italy. J Viral Hepat 2012; 19:881-9. [PMID: 23121367 DOI: 10.1111/j.1365-2893.2012.01615.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
A multicentre cross-sectional survey was performed to provide an accurate picture of patients with chronic hepatitis B (CHB) cared for by Italian Infectious Diseases Centers (IDCs). This analysis describes factors associated with access to the treatment of CHB in a country where barriers to treatment are not expected to exist because of comprehensive coverage under the National Health System (NHS). The study was performed in 74 IDCs. The analysis focused on 3305 patients with CHB of 3760 HBsAg-positive patients enrolled from March to September, 2008. To account for missing values, a Multiple Imputation method was used. Treatment was reported in 2091 (63.3%) patients. In the multivariate analysis, an increased chance of getting treatment was independently associated with 10 years increase of age at diagnosis (adjusted odds ratio [aOR] 1.2, 95% confidence interval [CI] 1.1-1.3, P < 0.001), HBeAg positivity (aOR 1.8, 95% CI 1.1-2.8, P < 0.001), cirrhosis (aOR 3.6, 95% CI 2-6.3, P = 0.012), HDV (aOR 1.6, 95% CI 1.02-2.5, P = 0.042) and HIV positivity (aOR 6.5, 95% CI 4-10.8, P < 0.001). Conversely, a decreased chance was associated with female gender (aOR 0.6, 95% CI 0.5-0.7, P < 0.001), immigration (aOR 0.6, 95% CI 0.5-0.9, P = 0.009), alcohol consumption (aOR 0.7, 95% CI 0.5-0.98, P = 0.04) and HCV positivity (aOR 0.5, 95% CI 0.3-0.8, P = 0.005). Our study shows that Italian IDCs treat a high percentage of patients with CHB. Nevertheless, disparities exist which are not related to the severity of disease limiting access to antiviral therapy of CHB, even in a country with a universal healthcare system.
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Affiliation(s)
- G Antonucci
- National Institute for Infectious Diseases L. Spallanzani, Rome, Italy.
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Stroffolini T, Rapicetta M, Lombardo F, Chionne P, Madonna E, Candido A, Taffon S, Rinaldi R, Ermg E, Bortolotti F. Historical study of acute hepatitis B in subjects with or without hepatitis C infection. Eur J Intern Med 2012; 23:e146-9. [PMID: 22863440 DOI: 10.1016/j.ejim.2012.03.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2012] [Revised: 02/29/2012] [Accepted: 03/05/2012] [Indexed: 12/18/2022]
Abstract
BACKGROUND The epidemiological pattern of hepatitis B virus infection in Italy has greatly changed over the past decades. The aim of the study was to evaluate during time the epidemiological features of acute hepatitis B cases referred to an Infectious Disease Unit in North-East of Italy between 1978 and 1995. PATIENTS AND METHODS Stored sera of 183 cases were tested for HBV markers, HBV genotypes, anti-Delta and anti-HCV. RESULTS Anti-HBcIgM was positive in all cases. Mean age increased from 30.2 years in 1978 to 37.5 in 1995 (P<0.01). Significant increase was observed in proportion of cases reporting intravenous drug use from 11.5% to 29.6% (P<0.03). Chronicity rate was as low as 1.1%. Mean days of hospitalization significantly decreased. HBV genotype determination showed that majority of cases was infected by genotype D, but its prevalence decreased from 88.2% in 1978 to 75.0% in 1995. Delta coinfection was present in 8.2%. The prevalence of HCV in patients with acute HBV was 35.0%; it fluctuated from 26.2% to 44.2%, mostly related (53.1%) to intravenous drug use. Dual infection did not lead to a more severe course of disease. CONCLUSIONS From this retrospective study, remarkable fluctuations in the prevalence of dual HBV-HCV infection before the implementation of HBV vaccination were observed. Presence of anti-HCV did not affect the course of acute HBV.
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Piccolo P, Lenci I, di Paolo D, Demelia L, Sorbello O, Nosotti L, Angelico M. A randomized controlled trial of sequential pegylated interferon-α and telbivudine or vice versa for 48 weeks in hepatitis B e antigen-negative chronic hepatitis B. Antivir Ther 2012; 18:57-64. [PMID: 22872648 DOI: 10.3851/imp2281] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/06/2012] [Indexed: 12/20/2022]
Abstract
BACKGROUND Short-term treatment for hepatitis B e antigen (HBeAg)-negative chronic hepatitis B remains unsatisfactory. The aim of our study was to compare the efficacy and safety of two sequential regimens of pegylated interferon (PEG-IFN)-α and telbivudine (LdT). METHODS Adult patients with biopsy-proven HBeAg-negative chronic hepatitis B, elevated alanine aminotransferase (ALT) and serum HBV DNA ≥ 2,000 IU/ml were randomized 1:1 at baseline to receive PEG-IFN 180 μg/week for 24 weeks followed by LdT 600 mg/day for 24 weeks (PEG-IFN first), or vice versa (LdT first), plus 24-week follow-up; individuals with HCV, HDV or HIV coinfections and lamivudine resistance were excluded. Primary end points were serum HBV DNA<2,000 IU/ml and normal ALT at week 72. RESULTS A total of 30 patients (86% male, median age 48 years) were enrolled: mean ±sd baseline serum HBV DNA was 5.56 ± 1.4 log IU/ml and ALT was 2.9 ± 2.5× upper limit of normal. At end of follow-up (week 72), HBV DNA<2,000 IU/ml was achieved in 13.3% of participants in the PEG-IFN first group versus 46.7% of those in the LdT first group (P=0.046). Mean ±sd ALT levels were significantly lower in the LdT first group (1.3 ± 0.9 versus 3.2 ± 2.7× upper limit of normal; P=0.03). PEG-IFN dose was reduced in 2 (7%) patients and 1 (7%) patient dropped out due to myalgia. CONCLUSIONS Sequential treatment with 24 weeks PEG-IFN followed or preceded by 24 weeks of LdT is safe. Virological response rate at week 72 was significantly higher in patients treated with LdT followed by PEG-IFN than vice versa. A sequential antiviral regimen of LdT followed by PEG-IFN, if confirmed in larger series, could improve response rates compared with standard PEG-IFN monotherapy.
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Affiliation(s)
- Paola Piccolo
- Hepatology Unit, Tor Vergata University, Rome, Italy.
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Epidemiology of hepatitis D virus (HDV) infection in an urban area of northern Italy. Infection 2012; 40:485-91. [PMID: 22367777 DOI: 10.1007/s15010-012-0247-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2011] [Accepted: 02/04/2012] [Indexed: 02/06/2023]
Abstract
OBJECTIVES The introduction of vaccination against hepatitis B initially reduced the number of HBV (hepatitis B virus) and HDV (hepatitis delta virus) infections, but the decreasing trend of HDV infection seems to have stopped. The aim of this study was to assess the prevalence of HDV infection in the general population living in the catchment area of Legnano Hospital in northern Italy. METHODS Of the 22,758 subjects tested in 2007-2008, the 488 who were HBsAg (hepatitis B surface antigen)-positive [including 107 (21.9%) of non-Italian origin] were subsequently tested for anti-HDV antibodies. RESULTS Of the 488 subjects who tested positive for HBsAg, 24 (4.9%) were anti-HDV positive, all aged between 30 and 60 years. The difference in prevalence between males (7.1%) and females (1.9%) was statistically significant (p < 0.05), but not that between Italian (5.0%) and non-Italian patients (4.7%). The differences in anti-HDV seropositivity between the patients with acute (0%) and chronic infections (6.3%), and between the incident (2.5%) and prevalent cases (7.4%), were not statistically significant, but there was a significant difference (p < 0.01) between those with asymptomatic (2.1%) and clinically symptomatic infections (10.3%). Intravenous drug abuse was the main source of infection. CONCLUSIONS In the catchment area of our hospital, the prevalence of HDV infection does not seem to be due to patients of non-Italian origin, but to Italian patients who are not vaccinated against HBV and who survived the HDV epidemic of the 1970s and 1980s. Nevertheless, the increase in the number of immigrants from non-EU countries in recent years is soon likely to lead to a change in the epidemiology of HDV.
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Le Gal F, Badur S, Hawajri NA, Akyüz F, Kaymakoglu S, Brichler S, Zoulim F, Gordien E, Gault E, Dény P. Current hepatitis delta virus type 1 (HDV1) infections in central and eastern Turkey indicate a wide genetic diversity that is probably linked to different HDV1 origins. Arch Virol 2012; 157:647-59. [PMID: 22241621 DOI: 10.1007/s00705-011-1212-8] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2011] [Accepted: 11/28/2011] [Indexed: 02/07/2023]
Abstract
Hepatitis delta virus (HDV) is a subviral pathogen of humans, a satellite of hepatitis B virus (HBV) that induces severe acute and chronic liver diseases. The genus Deltavirus consists of eight clades or genotypes, with HDV1 being ubiquitous and frequently characterized. In Turkey, HDV1 infection is highly endemic among HBsAg carriers, especially in the southeastern region. In this study, we analyzed 34 samples from patients who were chronically infected with HBV/HDV, originating from 22 cities of rural regions in the central and eastern parts of Turkey, in order to determine the levels of viral replication and genetic diversity. HDV RNA levels ranged between 3.02 and 8.75 Log copies/mL, and HBV DNA was detected in 25 samples (73.5%), with values ranging from 2.53 to 5.30 Log copies/mL. Analysis of nucleotides 900-1280 of HDV genomes (n = 34) and full-length (n = 17) sequences indicated that all of the strains belonged to genotype HDV1. However, a high genetic diversity was observed among the isolates, with a mean full-length dissimilarity score of 13.05%. HDV sequences clustered with sequences from Western Europe (n = 11), Eastern Europe and Asia (n = 19) or Africa (n = 4). HDV1 isolates related to strains of African origin had a serine residue instead of an alanine at position 202 of the large delta protein. HBV preS1 sequences obtained for 34 isolates indicated an HBV/D genotype in all cases. Taken together, our results indicate that in Turkey, where HBV-HDV dual infection is highly endemic, both viruses have high levels of replication, and HDV strains exhibit wide genetic diversity, which might reflect ancient evolution and/or successive outbreaks.
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Affiliation(s)
- Frédéric Le Gal
- Service de Bactériologie, Virologie-Hygiène, Hôpital Avicenne, Assistance Publique, Hôpitaux de Paris, Laboratoire associé au Centre National de Référence des Hépatites B, C et delta, Université Paris 13, Bobigny, France
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Almasio PL, Babudieri S, Barbarini G, Brunetto M, Conte D, Dentico P, Gaeta GB, Leonardi C, Levrero M, Mazzotta F, Morrone A, Nosotti L, Prati D, Rapicetta M, Sagnelli E, Scotto G, Starnini G. Recommendations for the prevention, diagnosis, and treatment of chronic hepatitis B and C in special population groups (migrants, intravenous drug users and prison inmates). Dig Liver Dis 2011; 43:589-95. [PMID: 21256097 DOI: 10.1016/j.dld.2010.12.004] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2010] [Accepted: 12/04/2010] [Indexed: 02/06/2023]
Abstract
The global spread of hepatitis B virus (HBV) and hepatitis C virus (HCV), their high chronicity rates and their progression to cirrhosis and hepatocellular carcinoma, are major public health problems. Research and intervention programmes for special population groups are needed in order to assess their infection risk and set up suitable prevention and control strategies. Aim of this paper is to give health care professionals information on HBV and HCV infections amongst migrants, drug users and prison inmates. The manuscript is an official Position Paper on behalf of the following Scientific Societies: Italian Association for the Study of the Liver (A.I.S.F.), Italian Society of Infectious and Tropical Diseases (S.I.M.I.T.), Italian Federation Department's Operators and Addiction Services (FederSerD), Italian Prison Medicine and Healthcare Society (S.I.M.S.Pe.). The considered population groups, having a high prevalence HBV and HCV infections, require specific interventions. In this context, the expression "special population" refers to specific vulnerable groups at risk of social exclusion, such as migrants, prison inmates, and intravenous drug users. When dealing with special population groups, social, environmental and clinical factors should be considered when selecting candidates for therapy as indicated by national and international guidelines.
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Affiliation(s)
- Piero L Almasio
- Gastroenterology and Hepatology Unit, University of Palermo, Palermo, Italy
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Ippolito AM, Niro GA, Fontana R, Lotti G, Gioffreda D, Valvano MR, Iacobellis A, Di Mauro L, Stroffolini T, Andriulli A. Unawareness of HBV infection among inpatients in a Southern Italian hospital. J Viral Hepat 2011; 18:e206-11. [PMID: 21692934 DOI: 10.1111/j.1365-2893.2010.01432.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Hepatitis B virus (HBV) infection may run undetected. Unawareness of an ongoing infection delays the diagnosis of HBV-related liver disease and favours the spread of the virus. We have evaluated among hepatitis B surface antigen-positive (HBsAg) inpatients admitted to a Southern Italian hospital the proportion of those aware of their carrier status and correlated the status to signs of liver disease. All patients admitted to the San Giovanni Rotondo Hospital from March 2008 to July 2009 were tested for HBV and hepatitis C virus (HCV) markers, and those positive for HBsAg were interviewed and underwent examinations for liver function and abdominal ultrasound. Overall, of 25,000 patients admitted during the observation period 311 (1.2%) were positive for HBsAg, most of them (98%) being anti-HBe positive. HCV and HDV co-infections were ascertained in 2.9% and 0.6% of cases, respectively. Two hundred and fifty-three subjects (81%) agreed to undergo further investigation, 132 of them (52%) were HBV-DNA positive. One hundred and two patients (40.3%) were unaware of their infection; this was encountered among 29% of HBV-DNA-positive and 52% of HBV-DNA-negative subjects (P < 0.01). Subjects already aware of their infection were more likely to present with abnormal alanine aminotransferase (ALT) levels (27%vs 15%), serological presence of HBV-DNA (63.6% vs. 36%) and liver cirrhosis (30%vs. 13%). A high proportion of HBsAg-positive patients (40.3%) were unaware of their infection, which had evolved to the stage of liver cirrhosis in a consistent percentage of them.
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Affiliation(s)
- A M Ippolito
- Division of Gastroenterology Blood Bank, Casa Sollievo Sofferenza Hospital, IRCCS, S. Giovanni Rotondo, Italy
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