|
1
|
Cabezas J, Aguilera A, García F, Domínguez-Hernández R, Casado-Gómez A, Espinoza-Cámac N, Casado MÁ, Crespo J, Task Force Spanish Group for Comprehensive Hepatitis Diagnosis. Comprehensive Diagnosis of Viral Hepatitis in Spain: Bases for Implementation. Viruses 2025; 17:667. [PMID: 40431679 DOI: 10.3390/v17050667] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2025] [Accepted: 04/30/2025] [Indexed: 05/29/2025] Open
Abstract
In 2022, scientific societies agreed on a document with recommendations for a comprehensive diagnosis of viral hepatitis (B, C, and D). The aim was to evaluate the situation in Spain regarding the comprehensive diagnosis of viral hepatitis in a single blood draw before it is recommended. A panel of experts prepared a structured survey directed at hospitals (public or private with teaching accreditation) with ≥200 beds (sent 20 October 2022, closed 1 December 2022). The response rate was 61% (79/129; 52 hospitals with >500 beds). Among the participating hospitals, all could perform tests for HBsAg, anti-HCV, and HIV serology; 94% could perform PCR testing for HCV, 63% could test for anti-HDV, and 28% could test for HDV-RNA (67% [53/79] outsourced this testing). Point-of-care (POC) testing availability was low (24%), with 84% of these tests being supervised by the reference microbiological laboratory and the results being registered in the patients' medical history. Ninety percent of the centers carried out the diagnosis in a single step (99% HCV, 70% HBV, 48% HDV, and 44% HBV-HDV). In addition, 77% used some communication strategy when an active infection was encountered (100% HCV, 49% HBV, and 31% HDV). Only 20% had an automated system for scheduling a specialist physician appointment. Most hospitals had the means for a comprehensive diagnosis of viral hepatitis in a single sample, but <50% could test for HBV/HDV. Alerts for continuity of care were available for HCV, but not HBV or HDV. POC device implementation is important for decentralized testing.
Collapse
Affiliation(s)
- Joaquin Cabezas
- Gastroenterology and Hepatology Service, Marqués de Valdecilla University Hospital, 39008 Santander, Spain
- Clinical and Translational Research Group in Digestive Diseases, Valdecilla Research Institute (IDIVAL), 39011 Santander, Spain
| | - Antonio Aguilera
- Microbiology Service and Instituto de Investigación Sanitaria de Santiago (IDIS), University Clinical Hospital of Santiago de Compostela, 15706 A Coruña, Spain
- Microbiology Department, University of Santiago de Compostela, 15705 A Coruña, Spain
| | - Federico García
- Microbiology Service, San Cecilio Clinical University Hospital, 18007 Granada, Spain
- Instituto de Investigación Biosanitaria Ibs.GRANADA, 18012 Granada, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), 28029 Madrid, Spain
| | | | | | | | | | - Javier Crespo
- Gastroenterology and Hepatology Service, Marqués de Valdecilla University Hospital, 39008 Santander, Spain
- Clinical and Translational Research Group in Digestive Diseases, Valdecilla Research Institute (IDIVAL), 39011 Santander, Spain
- Faculty of Medicine, University of Cantabria, 39011 Santander, Spain
| | | |
Collapse
|
|
2
|
Ortega González E, Ocete Mochón MD, Martínez-Roma M, Gimeno Cardona C, Gómez Muñoz N, Diago Madrid M, Carrodeguas A, González-Sánchez JL, de la Torre MP, García Deltoro M. Current prevalence of hepatitis delta diagnosis in Valencia, Spain. Sci Rep 2025; 15:7584. [PMID: 40038382 PMCID: PMC11880328 DOI: 10.1038/s41598-025-91765-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2024] [Accepted: 02/24/2025] [Indexed: 03/06/2025] Open
Abstract
Hepatitis delta virus (HDV) is the most aggressive form of chronic viral hepatitis, yet substantial knowledge gaps exist regarding its epidemiology and optimal diagnostic workflows. From February 2019 to March 2022, an HBV screening project was conducted across various healthcare settings in Valencia, Spain. This included twenty-six primary care centers, six sexual and reproductive health centers, three mental health centers, three addiction treatment centers, selected hospital departments, outpatient clinics, and a penitentiary center. A retrospective analysis of HDV diagnostic and prevalence (2007-2020) was followed by prospective HDV screening using reflex testing from April to October 2022. Of 31,995 patients screened, 141 were HBsAg-positive (0.44% seroprevalence). Previously unknown HBV infection prevalence was 0.36%. Among HBsAg-positive patients, 5.15% had HDV IgG/IgM antibodies, and 2% had HDV RNA. Reflex single-step HDV testing increased HDV diagnosis coverage from 24 to 99.4%. This study highlights the effectiveness of reflex HDV testing, which significantly increased diagnostic coverage and simplified the screening process. Reflex testing provides a cost-effective and efficient approach, particularly benefiting high-risk populations such as migrants, who accounted for 77.8% of HBsAg-positive cases. Its implementation is crucial for improving patient outcomes and addressing gaps in HDV diagnosis and management.
Collapse
Affiliation(s)
| | - María Dolores Ocete Mochón
- Servicio de Microbiología, Consorcio Hospital General Universitario, Valencia, Spain
- Universidad Católica de Valencia San Vicente Mártir, Valencia, Spain
| | - María Martínez-Roma
- Fundació Investigació Hospital General Universitari de Valencia, Valencia, Spain
| | - Concepción Gimeno Cardona
- Servicio de Microbiología, Consorcio Hospital General Universitario, Valencia, Spain
- Universitad de Valencia, Valencia, Spain
| | - Neus Gómez Muñoz
- Fundació Investigació Hospital General Universitari de Valencia, Valencia, Spain
| | - Moisés Diago Madrid
- Universitad de Valencia, Valencia, Spain
- Servicio de Digestivo. Sección de Hepatología, Consorcio Hospital General Universitario, Valencia, Spain
| | | | | | | | - Miguel García Deltoro
- Universitad de Valencia, Valencia, Spain.
- Servicio de Enfermedades Infecciosas, Consorcio Hospital General Universitario, Valencia, Spain.
| |
Collapse
|
|
3
|
Buti M, Calleja JL, Rodríguez MÁ, Domínguez-Hernández R, Cantero H, Espinoza-Cámac N, Casado MÁ. Clinical and economic value of bulevirtide in the treatment of chronic hepatitis D. GASTROENTEROLOGIA Y HEPATOLOGIA 2025; 48:502241. [PMID: 39251019 DOI: 10.1016/j.gastrohep.2024.502241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 08/12/2024] [Accepted: 09/02/2024] [Indexed: 09/11/2024]
Abstract
BACKGROUND/AIMS Bulevirtide (Hepcludex®) is the first drug approved for the treatment of chronic hepatitis D (CHD), unlike the current off-label treatment (PEG-IFN-α), limited in clinical practice and associated with post-treatment relapses. In a hypothetical cohort of CHD patients in Spain, the study aim was to compare the efficiency of bulevirtide with PEG-IFN-α in terms of clinical events avoided and associated cost savings. METHODS A validated economic model reflecting the natural history of the disease was used to project lifetime liver complications and costs for two hypothetical cohorts treated with bulevirtide or PEG-IFN-α. The model considered progression to complications such as decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC), liver transplantation (LT), and death. The efficacy rates used at 24 and 48 weeks were defined as the combined response rate for bulevirtide and undetectable HDV RNA to PEG-IFN-α. The numbers of clinic events and associated costs were evaluated from the perspective of the National Healthcare System. RESULTS In a hypothetical cohort of 3882 patients, bulevirtide reduced the numbers of complications events in comparison to PEG-IFN-α (152 DCC, 113 HCC, 11 LT, and 321 deaths over a lifetime). This was associated with a reduction of event-related costs of €11,837,044 (DCC €1,138,059; HCC €1,503,583; LT €7,834,291; and death €1,361,111). CONCLUSION In patients with CHD, bulevirtide could prevent a significant number of clinical events compared to PEG-IFN-α and contribute to cost savings through these reduction in liver complications. Further testing for hepatitis D virus is needed so that more patients can benefit from bulevirtide.
Collapse
Affiliation(s)
- María Buti
- Hospital Universitario Vall d'Hebron, CIBERehd, Barcelona, Spain
| | | | | | | | | | | | | |
Collapse
|
|
4
|
Rodríguez-Tajes S, Palom A, Giráldez-Gallego Á, Moreno A, Urquijo JJ, Rodríguez M, Alvarez-Argüelles M, Diago M, García-Eliz M, Fuentes J, Martínez-Sapiña AM, Castillo P, Casado M, Pérez-Campos E, Muñoz R, Hernández-Conde M, Morillas RM, Granados R, Miquel M, Morillas MJ, García-Retortillo M, Carrión JA, Moreno JM, Montón C, González-Santiago JM, Lorente S, Cabezas J, Mateos B, Vázquez-Rodríguez S, Díaz-Fontenla F, Pinazo JM, Delgado M, Pérez-Palacios D, Horta D, Fernández-Marcos C, López C, Calleja JL, Fernández I, García-Samaniego J, Forns X, Buti M, Lens S. Characterizing Hepatitis Delta in Spain and the gaps in its management. GASTROENTEROLOGIA Y HEPATOLOGIA 2025; 48:502222. [PMID: 38908682 DOI: 10.1016/j.gastrohep.2024.502222] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Accepted: 06/18/2024] [Indexed: 06/24/2024]
Abstract
BACKGROUND AND AIMS Chronic hepatitis D (CHD) is a severe form of chronic viral hepatitis. The estimated hepatitis delta prevalence in Spain is around 5% of patients with hepatitis B. Reimbursement of new antiviral therapies (Bulevirtide, BLV) was delayed in our country until February 2024. We aimed to characterize the clinical profile of patients with HDV/HBV infection in Spain and current barriers in their management at the time of BLV approval. METHOD Multicenter registry including patients with positive anti-HDV serology actively monitored in 30 Spanish centers. Epidemiological, clinical and virological variables were recorded at the start of follow-up and at the last visit. RESULTS We identified 329 anti-HDV patients, 41% were female with median age 51 years. The most common geographical origin was Spain (53%) and East Europe (24%). Patients from Spain were older and had HCV and HIV coinfection probably associated to past drug injection (p<0.01). HDV-RNA was positive in 138 of 221 assessed (62%). Liver cirrhosis was present at diagnosis in 33% and it was more frequent among viremic patients (58% vs 25%, p<0.01). After a median follow-up of 6 (3-12) years, 44 (16%) resolved infection (18 spontaneously and 26 after Peg-INF). An additional 10% of patients developed cirrhosis (n=137) during follow-up (45% had portal hypertension and 14% liver decompensation). Liver disease progression was associated to persisting viremia. CONCLUSION One-third of the patients with CHD already have cirrhosis at diagnosis. Persistence of positive viremia is associated to rapid liver disease progression. Importantly, barriers to locally determine/quantify HDV-RNA were present.
Collapse
Affiliation(s)
| | - Adriana Palom
- Hospital Universitari Vall d'Hebron, CIBEREHD, Barcelona, Spain
| | | | | | | | | | | | | | | | | | | | | | - Marta Casado
- Hospital Universitario Torrecárdenas, Almería, Spain
| | | | | | | | | | | | | | | | | | | | | | | | | | - Sara Lorente
- Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain
| | - Joaquín Cabezas
- Hospital Universitario Marqués de Valdecilla, Santander, Spain
| | | | | | | | | | - Mercè Delgado
- Hospital de Mataró Consorci Sanitari del Maresme, Mataró, Spain
| | | | | | | | | | | | | | | | - Xavier Forns
- Hospital Clínic, Universitat de Barcelona, IDIBAPS, CIBEREHD, Barcelona, Spain
| | - María Buti
- Hospital Universitari Vall d'Hebron, CIBEREHD, Barcelona, Spain
| | - Sabela Lens
- Hospital Clínic, Universitat de Barcelona, IDIBAPS, CIBEREHD, Barcelona, Spain.
| |
Collapse
|
|
5
|
Redondo Betancor G, Hernández Febles M, Zaragozá González R, Granados Monzón R, Quiñones Morales I, de Salazar A, García García F, Pena López MJ. Prevalencia y características clínico-epidemiológicas de la hepatitis crónica por el virus de la hepatitis delta en la isla de Gran Canaria. Enferm Infecc Microbiol Clin 2024; 42:507-511. [DOI: 10.1016/j.eimc.2024.06.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
|
|
6
|
Redondo Betancor G, Hernández Febles M, Zaragozá González R, Granados Monzón R, Quiñones Morales I, de Salazar A, García García F, Pena López MJ. Prevalence and clinical-epidemiological characteristics of chronic hepatitis due to hepatitis delta virus on Gran Canaria Island. ENFERMEDADES INFECCIOSAS Y MICROBIOLOGIA CLINICA (ENGLISH ED.) 2024; 42:507-511. [PMID: 39389798 DOI: 10.1016/j.eimce.2024.09.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Revised: 06/11/2024] [Accepted: 06/13/2024] [Indexed: 10/12/2024]
Abstract
OBJECTIVE The objective of this study was to know the prevalence and clinical-epidemiological characteristics of patients with chronic infection due to hepatitis D virus (HDV). PATIENTS AND METHODS A retrospective descriptive study was carried out on patients with HDV infection under follow-up in a hospital in 2023. All patients carrying HBsAg were tested for antibodies against HDV. HDV RNA detection was performed in all antibody-positive samples. The medical records were reviewed. RESULTS Of the 340 patients carrying HBsAg, 24 (7.1%) had anti-HDV antibodies, and 6 (25%) had detectable HDV RNA (chronic infection). The prevalence of chronic hepatitis in HBsAg carriers was 1.8%. All patients had a genotype 1 infection. Half of the patients were of African origin and 29.2% were Spanish. Of the 6 patients with chronic infection, 5 (83.3%) had cirrhosis and 2 (33.3%) had hepatocellular carcinoma. Half of the patients had some exacerbation of the disease during follow-up. Of the 18 patients without viremia, 2 (11.1%) presented cirrhosis (one recently diagnosed). The mean follow-up time of patients without viremia was 13.5 years. CONCLUSIONS The prevalence of chronic HDV hepatitis in our area is low and in all cases it presents as an advanced disease, with exacerbations during follow-up. Patients without viremia have probably resolved the infection, as viremia was not detected in any moment.
Collapse
Affiliation(s)
- Goretti Redondo Betancor
- Servicio de Microbiología, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain
| | - Melisa Hernández Febles
- Servicio de Microbiología, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain
| | - Raquel Zaragozá González
- Servicio de Microbiología, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain
| | - Rafael Granados Monzón
- Unidad de Enfermedades Infecciosas, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain
| | - Ildefonso Quiñones Morales
- Servicio de Digestivo, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain
| | - Adolfo de Salazar
- Servicio de Microbiología, Hospital Universitario Clínico San Cecilio, Granada, Spain
| | | | - María José Pena López
- Servicio de Microbiología, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain.
| |
Collapse
|
|
7
|
Weichselbaum L, Njimi H, van den Wijngaert S, Dahma H, Nkuize M, Van Gossum M, Eisendrath P, Mulkay J, Sersté T. A regular screening for hepatitis delta virus among chronic hepatitis B carriers improves the diagnostic of this infection and of subsequent cirrhosis development. United European Gastroenterol J 2024; 12:516-525. [PMID: 38520063 PMCID: PMC11091775 DOI: 10.1002/ueg2.12564] [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: 08/02/2023] [Accepted: 02/26/2024] [Indexed: 03/25/2024] Open
Abstract
BACKGROUND AND OBJECTIVE The prevalence of Hepatitis Delta Virus (HDV) is underestimated and the assessment of fibrosis is recommended for this infection. We tested the diagnostic impact of an annual screening for HDV serology in Hepatitis B Surface Antigen (HBs Ag) chronic carriers and followed the progression of fibrosis in these patients. METHODS Between January 2014 and October 2021, we annually tested all chronic HBs Ag-positive patients for HDV antibody (HDV Ab). Each HDV Ab positive patient underwent annually repeated elastometry. Patients with detectable HDV RNA levels (group 1) were compared to those with undetectable HDV RNA (group 2). RESULTS We identified 610 chronic HBs Ag-positive patients, and repeated screening for HDV Ab was performed in 534 patients. Sixty (11%) patients were HDV Ab positive at baseline and were considered as "coinfected". Seven cases of HDV superinfection were diagnosed through repeated screening. In co-infected patients, cirrhosis was initially diagnosed in 12/60 patients and developed in six patients during follow-up. HDV RNA PCR was performed in 57/67 patients and 27 had detectable levels (group 1). Cumulative incidence of cirrhosis at 7 years was 13.8% (95% CI 0-30) in group 1 and 0 (95% CI 0-0) in group 2 (p = 0.026). CONCLUSION A systematic screening for HDV in chronic HB Ag carriers revealed a high prevalence of HDV Ab. Repeated serological screening enables the diagnosis of superinfections in asymptomatic patients. Regular assessment of fibrosis using elastometry leads to the identification of incidental cirrhosis in patients with detectable HDV RNA.
Collapse
Affiliation(s)
- Laura Weichselbaum
- Department of Gastroenterology and HepatologyCHU Saint‐PierreBrusselsBelgium
- Department of Gastroenterology and HepatologyCUB ErasmeBrusselsBelgium
| | - Hassane Njimi
- Department of Intensive CareCUB ErasmeBrusselsBelgium
| | | | - Hafid Dahma
- Department of MicrobiologyLHUB‐ULB site Porte de HalBrusselsBelgium
| | - Marcel Nkuize
- Department of Gastroenterology and HepatologyCHU Saint‐PierreBrusselsBelgium
| | - Marc Van Gossum
- Department of Gastroenterology and HepatologyCHU Saint‐PierreBrusselsBelgium
| | - Pierre Eisendrath
- Department of Gastroenterology and HepatologyCHU Saint‐PierreBrusselsBelgium
- Department of Gastroenterology and HepatologyCUB ErasmeBrusselsBelgium
| | - Jean‐Pierre Mulkay
- Department of Gastroenterology and HepatologyCHU Saint‐PierreBrusselsBelgium
| | - Thomas Sersté
- Department of Gastroenterology and HepatologyCHU Saint‐PierreBrusselsBelgium
- Department of Gastroenterology and HepatologyCUB ErasmeBrusselsBelgium
| |
Collapse
|
|
8
|
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.
Collapse
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
| |
Collapse
|
|
9
|
Soriano V, de Mendoza C, Treviño A, Ramos-Rincón JM, Moreno-Torres V, Corral O, Barreiro P. Treatment of hepatitis delta and HIV infection. Liver Int 2023; 43 Suppl 1:108-115. [PMID: 35748639 DOI: 10.1111/liv.15345] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Accepted: 06/20/2022] [Indexed: 01/18/2023]
Abstract
Hepatitis delta virus (HDV) is a defective agent that only infects individuals with hepatitis B virus (HBV). Around 5-10% of chronic hepatitis B patients worldwide are superinfected with HDV, which means 15-25 million people. Hepatitis delta is the most severe of all chronic viral hepatitis, leading to cirrhosis, liver cancer and/or transplantation in most patients. Despite it, many HDV patients remain undiagnosed. The only treatment available until recently was peginterferon alfa, with poor results and significant side effects. The recent approval of bulevirtide, a lipopeptide that blocks HBV/HDV entry, has revolutionized the field. Another drug, lonafarnib, already approved to treat progeria, is expected to be available soon as HDV therapy. Since there is no cell reservoir for the HDV RNA genome, hypothetically viral clearance could be achieved if complete blocking of viral replication occurs for a minimum time frame. This is what happens in hepatitis C using direct-acting antivirals, with the achievement of cure in nearly all treated patients. We envision the cure of hepatitis delta using combination antiviral therapy. Given that sexual and parenteral transmission routes are the most frequent for the acquisition of HBV and HDV, shared with HIV infection and HBV/HDV and HIV coinfection. The clinical outcome of hepatitis delta is worst in the HIV setting, with more frequent liver complications. Since most persons infected with HIV are on regular health care follow-up, we propose that HIV-HDV patients should be prioritized for moving forward new and potentially curative treatments for hepatitis delta.
Collapse
Affiliation(s)
| | - Carmen de Mendoza
- Department of Internal Medicine, Puerta de Hierro Research Institute & University Hospital, Madrid, Spain
| | - Ana Treviño
- UNIR Health Sciences School & Medical Center, Madrid, Spain
| | - José Manuel Ramos-Rincón
- Medicine Department, Alicante University Hospital & Alicante Institute of Health and Biomedical Research (ISABIAL), Alicante, Spain
| | - Víctor Moreno-Torres
- Department of Internal Medicine, Puerta de Hierro Research Institute & University Hospital, Madrid, Spain
| | - Octavio Corral
- UNIR Health Sciences School & Medical Center, Madrid, Spain
| | - Pablo Barreiro
- Public Health Regional Laboratory, Hospital Isabel Zendal, Madrid, Spain
| |
Collapse
|
|
10
|
Ruo commercial real-time PCR kit offers rapid and reliable results for hepatitis delta virus. JOURNAL OF CLINICAL VIROLOGY PLUS 2022. [DOI: 10.1016/j.jcvp.2022.100092] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
|
|
11
|
Ramos-Rincon JM, Pinargote-Celorio H, de Mendoza C, Ramos-Belinchón C, Barreiro P, Treviño A, Corral O, Soriano V. Liver cancer and hepatic decompensation events in patients hospitalized with viral hepatitis in Spain. Hepatol Int 2022; 16:1161-1169. [PMID: 35666390 DOI: 10.1007/s12072-022-10365-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Accepted: 05/07/2022] [Indexed: 11/30/2022]
Abstract
BACKGROUND Chronic viral hepatitis B, C, and D are the main causes of decompensated cirrhosis and liver cancer worldwide. Newborn HBV vaccination was implemented more than 2 decades ago in most EU countries. Furthermore, potent oral antivirals have been available to treat HBV for 15 years and to cure HCV since 2014. The real-life clinical benefits of these interventions at country level have not been assessed, especially regarding major hepatic outcomes such as cirrhotic decompensation events and hepatocellular carcinoma (HCC). METHODS Retrospective study of all hospitalizations in Spain having HBV, HCV, and HDV as diagnosis using the Spanish National Registry of Hospital Discharges. Information was retrieved from 1997 up to 2017. RESULTS From a total of 73,939,642 hospital admissions during the study period, a diagnosis of HBV, HCV, and HDV was made in 124,915 (1.7‰), 981,985 (13.3‰), and 4850 (0.07‰) patients, respectively. The median age of patients hospitalized within each group was 53.2, 55.9, and 47.0 years, respectively. Significant increases in mean age at hospitalization occurred in all groups (0.6 years older per calendar year on average). The overall rate of hepatic decompensation events for HBV, HCV, and HDV was 12.1%, 14.1%, and 18.8%, respectively. For HCC hospitalizations, these figures were 6.7%, 8.0%, and 7.8%, respectively. Whereas, the rate of decompensation events declined in recent years for HBV, and more recently for HCV, it continued rising up for HDV. Likewise, liver cancer rates recently plateaued for HBV and HCV, but kept growing for HDV. CONCLUSION The rate of hepatic decompensation events and liver cancer has declined and/or plateaued in recent years for patients hospitalized with HBV and HCV infections, following the widespread use of oral antiviral therapies for these viruses. In contrast, the rate of decompensated cirrhotic events and HCC has kept rising up for patients with hepatitis delta, for which effective antiviral treatment does not exist yet.
Collapse
Affiliation(s)
- José-Manuel Ramos-Rincon
- Internal Medicine Department, General University Hospital of Alicante-ISABIAL and Miguel Hernández University of Elche, Alicante, Spain
| | - Héctor Pinargote-Celorio
- Internal Medicine Department, General University Hospital of Alicante-ISABIAL and Miguel Hernández University of Elche, Alicante, Spain
| | - Carmen de Mendoza
- Laboratory of Internal Medicine, Puerta de Hierro Research Institute and University Hospital, Majadahonda, Madrid, Spain
| | | | - Pablo Barreiro
- Regional Public Health Laboratory, Hospital Isabel Zendal, Madrid, Spain
| | - Ana Treviño
- UNIR Health Sciences School and Medical Center, Calle Almansa 101, 28040, Madrid, Spain
| | - Octavio Corral
- UNIR Health Sciences School and Medical Center, Calle Almansa 101, 28040, Madrid, Spain
| | - Vicente Soriano
- UNIR Health Sciences School and Medical Center, Calle Almansa 101, 28040, Madrid, Spain.
| |
Collapse
|
|
12
|
Ezquerra-Durán A, Gutiérrez-Cobos A, García-Buey L. Healing of chronic hepatitis delta relapsing to pegylated interferon with tenofovir. Med Clin (Barc) 2022; 159:e32. [PMID: 35659423 DOI: 10.1016/j.medcli.2022.02.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 02/17/2022] [Accepted: 02/23/2022] [Indexed: 10/18/2022]
Affiliation(s)
| | | | - Luisa García-Buey
- Servicio de Aparato Digestivo, Hospital Universitario de La Princesa, Madrid, España; Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (UAM), Madrid, España
| |
Collapse
|
|
13
|
Ramos-Rincon JM, Pinargote H, Ramos-Belinchón C, de Mendoza C, Aguilera A, Soriano V. Hepatitis delta in patients hospitalized in Spain (1997-2018). AIDS 2021; 35:2311-2318. [PMID: 34261094 DOI: 10.1097/qad.0000000000003024] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND Hepatitis delta is the most aggressive form of chronic viral hepatitis. We examined the clinical burden, epidemiological features and time trends for hepatitis delta patients hospitalized in Spain during the last two decades. METHODS Retrospective, observational study using the Spanish National Registry of Hospital Discharges. Information was retrieved since 1997 to 2018. RESULTS From a total of 79 647 783 nationwide hospital admissions recorded during the study period, 5179 included hepatitis delta as diagnosis. The overall hospitalization rate because of hepatitis delta was 6.5/105, without significant yearly changes. In-hospital death occurred in 335 (6.6%) patients. Acute hepatitis and cirrhosis were recorded in 46.5 and 33.5% of hepatitis delta hospitalizations, respectively. Acute hepatitis delta predominated until 2007 (55.9%) whereas cirrhosis increased since then (39.4%). Hepatic decompensation events and liver cancer accounted on average for 16 and 8% of hospitalizations, increasing significantly over time. Coinfection with HIV and hepatitis C virus (HCV) were recognized in 24 and 31.2% of hepatitis delta patients, respectively. All hepatitis C, HIV and injection drug use declined significantly since 2008. CONCLUSION The rate of hepatitis delta in patients hospitalized in Spain is low and has remained stable over two decades. However, hepatitis delta-related decompensation events and liver cancer are on the rise. The association of hepatitis delta with injection drug use, HIV and HCV has declined among recently hospitalized hepatitis delta patients.
Collapse
Affiliation(s)
- José-Manuel Ramos-Rincon
- Internal Medicine Department, General University Hospital of Alicante & Miguel Hernandez University of Elche, Alicante
| | - Héctor Pinargote
- Internal Medicine Department, General University Hospital of Alicante & Miguel Hernandez University of Elche, Alicante
| | | | - Carmen de Mendoza
- Laboratory of Internal Medicine, Puerta de Hierro Research Institute & University Hospital, Majadahonda, Madrid
| | - Antonio Aguilera
- Microbiology Department, Complexo Hospitalario Universitario Santiago (CHUS) & University of Santiago, Santiago de Compostela
| | | |
Collapse
|
|
14
|
Pérez-Latorre L, Berenguer J, Micán R, Montero M, Cifuentes C, Puig T, Sanz J, Ferrero OL, De La Fuente B, Rodríguez C, Reus S, Hernández-Quero J, Gaspar G, Pérez-Martínez L, García C, Force L, Veloso S, De Miguel M, Jarrín I, González-García J. HIV/HBV coinfection: temporal trends and patient characteristics, Spain, 2002 to 2018. ACTA ACUST UNITED AC 2021; 26. [PMID: 34169818 PMCID: PMC8229377 DOI: 10.2807/1560-7917.es.2021.26.25.2000236] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Background Recent and reliable estimates on the prevalence of coinfection with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) in Europe are lacking. Aim Leveraged on a study designed to assess HIV/HCV coinfection prevalence, we assessed the prevalence of HIV/HBV coinfection in Spain in 2018 and compared the results with five similar studies performed since 2002. Methods This cross-sectional prevalence study was carried out in 43 centres, and patients were selected using simple random sampling. The reference population comprised 40,322 patients and the sample size were 1,690 patients. Results The prevalence of HIV/HBV coinfection in Spain at the end of 2018 was 3.2%. The prevalence in 2002, 2009, 2015, 2016 and 2017 was 4.9%, 3.4%, 3%, 3.9% and 3%, respectively. Among the HIV/HBV-coinfected patients identified in 2018, 16.7% had cirrhosis according to transient elastography and 26.3% tested positive for antibodies against hepatitis D virus. All HIV/HBV-coinfected patients were receiving drugs with activity against HBV, and 97% of those tested for HBV DNA had an HBV DNA load < 80 IU/mL. Conclusions The prevalence of HIV/HBV coinfection in Spain remained stable at around 3% for a decade. Our data could facilitate the design of national programmes to control HBV infection and help identify areas of patient management that need improvement.
Collapse
Affiliation(s)
| | - Juan Berenguer
- Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | | | | | | | - Teresa Puig
- Hospital Universitari Arnau de Vilanova, Lleida, Spain
| | - José Sanz
- Hospital Príncipe de Asturias, Alcalá de Henares, Spain
| | | | | | | | - Sergio Reus
- Hospital General Universitario de Alicante, Alicante, Spain
| | | | | | | | - Coral García
- Hospital Universitario Virgen de las Nieves, Granada, Spain
| | | | | | | | | | | | -
- The members of the GeSIDA 8514 Study Group have been listed under Investigators
| |
Collapse
|
|
15
|
Aguilera A, Trastoy R, Rodríguez-Frias F, Muñoz-Bellido JL, Melón S, Suárez A, Orduña A, Viciana I, Bernal S, García-Bujalance S, Montiel N, Molina JM, Basaras M, Fernández-Cuenca F, García-Arata I, Reina G, Ocete MD, Fuentes A, Navarro-de la Cruz D, Nieto L, Blazquez de Castro A, Buti M, Álvarez M, García F. GEHEP 010 study: Prevalence and distribution of hepatitis B virus genotypes in Spain (2000-2016). J Infect 2020; 81:600-606. [PMID: 32711039 DOI: 10.1016/j.jinf.2020.07.019] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 06/29/2020] [Accepted: 07/17/2020] [Indexed: 02/06/2023]
Abstract
OBJECTIVE To study the prevalence and distribution of HBV genotypes in Spain for the period 2000-2016. METHODS Retrospective study recruiting 2559 patients from 17 hospitals. Distribution of HBV genotypes, as well as sex, age, geographical origin, mode of transmission, HDV-, HIV- and/or HCV-coinfection, and treatment were recorded. RESULTS 1924 chronically HBV native Spanish patients have been recruited. Median age was 54 years (IQR: 41-62), 69.6% male, 6.3% HIV-coinfected, 3.1% were HCV-coinfected, 1.7% HDV-co/superinfected. Genotype distribution was: 55.9% D, 33.5% A, 5.6% F, 0.8% G, and 1.9% other genotypes (E, B, H and C). HBV genotype A was closely associated with male sex, sexual transmission, and HIV-coinfection. In contrast, HBV genotype D was associated with female sex and vertical transmission. Different patterns of genotype distribution and diversity were found between different geographical regions. In addition, HBV epidemiological patterns are evolving in Spain, mainly because of immigration. Finally, similar overall rates of treatment success across all HBV genotypes were found. CONCLUSIONS We present here the most recent data on molecular epidemiology of HBV in Spain (GEHEP010 Study). This study confirms that the HBV genotype distribution in Spain varies based on age, sex, origin, HIV-coinfection, geographical regions and epidemiological groups.
Collapse
Affiliation(s)
- Antonio Aguilera
- Complexo Hospitalario Universitario de Santiago, Santiago de Compostela, Instituto de Investigación Sanitaria de Santiago IDIS, Spain
| | - Rocío Trastoy
- Hospital Universitario Vall d'Hebrón, Barcelona, Spain
| | | | | | - Santiago Melón
- Hospital Universitario Central de Asturias, Oviedo, Spain
| | - Avelina Suárez
- Hospital Clínico Universitario San Carlos, Madrid, Spain
| | - Antonio Orduña
- Hospital Clínico Universitario de Valladolid, Valladolid, Spain
| | - Isabel Viciana
- Hospital Universitario Virgen de la Victoria, Málaga, Spain
| | - Samuel Bernal
- Hospital Universitario Virgen de Valme, Sevilla, Spain
| | | | | | | | | | | | | | | | | | - Ana Fuentes
- Hospital Universitario San Cecilio, Instituto de Investigación Biosanitaria Ibs, Av. de la Innovación S/N, 18016 Granada, Spain
| | | | | | | | - María Buti
- Hospital Universitario Vall d'Hebrón, Barcelona, Spain
| | - Marta Álvarez
- Hospital Universitario San Cecilio, Instituto de Investigación Biosanitaria Ibs, Av. de la Innovación S/N, 18016 Granada, Spain
| | - Federico García
- Hospital Universitario San Cecilio, Instituto de Investigación Biosanitaria Ibs, Av. de la Innovación S/N, 18016 Granada, Spain.
| |
Collapse
|
|
16
|
Sperle I, Steffen G, Leendertz SA, Sarma N, Beermann S, Thamm R, Simeonova Y, Cornberg M, Wedemeyer H, Bremer V, Zimmermann R, Dudareva S. Prevalence of Hepatitis B, C, and D in Germany: Results From a Scoping Review. Front Public Health 2020; 8:424. [PMID: 33014960 PMCID: PMC7493659 DOI: 10.3389/fpubh.2020.00424] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Accepted: 07/14/2020] [Indexed: 12/11/2022] Open
Abstract
Background: One of the five strategic directions in the World Health Organization global health sector strategy on viral hepatitis 2016-2021 is to generate strong strategic information for focused action to understand the viral hepatitis epidemic and focus the response. Knowledge of national prevalence is a cornerstone of strategic information. Germany is considered to be a low prevalence country for viral hepatitis B, C, and D, however the prevalence is likely to be higher among at-risk groups. Methods: The aim of this work was to give a detailed overview of the prevalence of viral hepatitis B (HBsAg, anti-HBc), C (anti-HCV, HCV RNA), and D (anti-HDV, HDV RNA) in different population groups in Germany. Therefore, we analyzed the results of a comprehensive literature search on various aspects of the epidemiological situation of hepatitis B, C, and D in Germany. Eligible publications including information on hepatitis B, C, and D prevalence were extracted from the overall spreadsheet table and summarized and analyzed based on virus and different population groups. A quality appraisal was performed using a checklist developed by Hoy et al. to assess risk of bias in prevalence studies. Results: Overall, 51 publications were identified through the literature search. The overall prevalence of HBsAg in the general (and proxy) population ranged from 0.3 to 1.6%. Among at-risk groups, including clinical populations and health care workers, the HBsAg prevalence ranged from 0.2% (among rheumatic patients) to 4.5% among HIV positive patients. The overall prevalence of anti-HCV in the general (and proxy) population ranged from 0.2 to 1.9%. Among at-risk groups, including clinical populations and health care workers, the anti-HCV prevalence ranged from 0.04% (among health care workers) to 68.0% among people who inject drugs. Conclusions: The hepatitis B and C prevalence in the general population in Germany is low. Prevalence is high to very high among at-risk populations, however for some groups evidence was incomplete or missing completely. To reach the elimination goals in Germany and implement a targeted response, more research among at-risk groups is needed.
Collapse
Affiliation(s)
- Ida Sperle
- Department of Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany
- Charité—Universitätsmedizin, Berlin, Germany
| | - Gyde Steffen
- Department of Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany
- Department of Infectious Disease Epidemiology, Translational Infrastructure Epidemiology of the German Centre for Infection Research, Robert Koch Institute, Berlin, Germany
| | - Siv Aina Leendertz
- Department of Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany
- Department of Infectious Disease Epidemiology, Translational Infrastructure Epidemiology of the German Centre for Infection Research, Robert Koch Institute, Berlin, Germany
| | - Navina Sarma
- Department of Epidemiology and Health Monitoring, Robert Koch Institute, Berlin, Germany
| | - Sandra Beermann
- Department of Infectious Disease Epidemiology, Translational Infrastructure Epidemiology of the German Centre for Infection Research, Robert Koch Institute, Berlin, Germany
- Centre for International Health Protection, Robert Koch Institute, Berlin, Germany
| | - Roma Thamm
- Department of Infectious Disease Epidemiology, Translational Infrastructure Epidemiology of the German Centre for Infection Research, Robert Koch Institute, Berlin, Germany
- Department of Epidemiology and Health Monitoring, Robert Koch Institute, Berlin, Germany
| | - Yanita Simeonova
- Department of Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany
| | - Markus Cornberg
- Department of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Hanover, Germany
- Thematic Translational Unit Hepatitis of the German Centre for Infection Research, Hanover, Germany
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Hanover, Germany
| | - Viviane Bremer
- Department of Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany
| | - Ruth Zimmermann
- Department of Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany
| | - Sandra Dudareva
- Department of Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany
| |
Collapse
|
|
17
|
Hernàndez-Èvole H, Briz-Redón Á, Berenguer M. Changing delta hepatitis patient profile: A single center experience in Valencia region, Spain. World J Hepatol 2020; 12:277-287. [PMID: 32742570 PMCID: PMC7364323 DOI: 10.4254/wjh.v12.i6.277] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2020] [Revised: 04/07/2020] [Accepted: 05/05/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Delta hepatitis is a rare infection with an aggressive disease course. For almost three decades, however, there have been no epidemiological studies in our traditionally endemic area.
AIM To investigate the prevalence of delta hepatitis in a sample of patients with chronic hepatitis B virus (HBV) infection followed at a Hepatology Unit in Valencia, Spain.
METHODS Retrospective evaluation of anti-hepatitis D virus-immunoglobulin G seroprevalence among patients with chronic HBV infection (n = 605) followed at a reference Hepatology Unit in Spain.
RESULTS The prevalence of anti-hepatitis D virus-immunoglobulin G among HBV-infected patients was 11.5%: Male (63%) and median age of 52 years. The majority were born in Spain (67%) and primarily infected through intravenous drug use. However, a significant percent (24.5%), particularly those diagnosed in more recent years, were migrants presumably nosocomially infected. Comorbidities such as diabetes (8.5%), obesity/overweight (55%), and alcohol consumption (34%) were frequent. A high proportion of patients developed liver complications such as cirrhosis (77%), liver decompensation (81%), hepatocellular carcinoma (HCC) (16.5%), or required liver transplantation (LT) (59.5%). Diabetes was associated with progression to cirrhosis, LT, and death. Male sex, increasing age, and alcohol were associated with LT and HCC. Compared to HBV mono-infected patients, delta individuals developed cirrhosis and liver decompensation more frequently, with no differences in HCC rates.
CONCLUSION Patients infected in the 1980’s were mostly locals infected through intravenous drug use, whereas those diagnosed recently are frequently non-Spanish natives from endemic areas. Regardless of their origin, patients are predominantly male with significant comorbidities, which potentially play a major role in disease progression. We confirm a high rate of subsequent liver complications.
Collapse
Affiliation(s)
| | | | - Marina Berenguer
- Departament de Medicina, University of València, Valencia 46010, Spain
- Liver Transplantation and Hepatology Unit, Hospital Universitari I Politècnic La Fe, Valencia 46026, Spain
- CIBERehd, Instituto de Salud Carlos III, Madrid 28029, Spain
- ISS La Fe, Valencia 46026, Spain
| |
Collapse
|
|
18
|
Daw MA, Daw AM, Sifennasr NEM, Draha A, Daw A, Daw A, Ahmed M, Mokhtar E, El-Bouzedi A, Daw I, Adam S, Warrag S. The epidemiological characterization and geographic distribution of hepatitis D virus infection in Libya. Pan Afr Med J 2020; 35:120. [PMID: 32637018 PMCID: PMC7320781 DOI: 10.11604/pamj.2020.35.120.20055] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Accepted: 03/03/2020] [Indexed: 12/20/2022] Open
Abstract
Introduction North Africa is known to be endemic for hepatitis D virus. However, data one the prevalence of this virus in Libya are scanty. This study aimed to determine the prevalence of hepatitis D virus infection in Libya and analyze the demographic factors associated with the infection, and also to assess the variations across the regions and districts. Methods A total of 1873 samples collected from all over the country were tested for antibodies against hepatitis B surface antigen and the results were correlated with demographic and geographic variables. Results The overall prevalence of hepatitis D virus infection was 1.7%. The prevalence rate was significantly high among those aged over 40 years (P < 0.001) and it was associated with intravenous drug use and coinfection with human immunodeficiency virus and/or hepatitis C virus infection (P < 0.001). The prevalence rates varied with geographic location and differed markedly within the regions the country. The highest rate reported was in the central region of Libya, followed by the western and eastern regions. Conclusion Hepatitis D virus infection rate in Libya is considered to be low but is of some concern in some districts. This has been propagated by population displacement and African immigrants, indicating that a continuous epidemiological surveillance program should be implemented.
Collapse
Affiliation(s)
- Mohamed Ali Daw
- Department of Medical Microbiology & Immunology, Faculty of Medicine, University of Tripoli, CC 82668, Tripoli, Libya
| | - Amina Mohamed Daw
- Department of General Medicine, Faculty of Medicine, University of Tripoli, CC 82668, Tripoli, Libya
| | | | - Aisha Draha
- Department of Pharmacology, Faculty of Medicine, University of Tripoli, CC 82668, Tripoli, Libya
| | - Ahmed Daw
- Tripoli Medical Centre, Faculty of Medicine, Tripoli, CC 82668, Tripoli, Libya
| | - Ali Daw
- Tripoli Medical Centre, Faculty of Medicine, Tripoli, CC 82668, Tripoli, Libya
| | - Mohamed Ahmed
- Department of Microbiology & Parasitology, Faculty of Veterinary Medicine, University of Tripoli, CC 82668, Tripoli, Libya
| | - Ebtisam Mokhtar
- Department of Medical Microbiology & Immunology, Faculty of Medicine, University of Tripoli, CC 82668, Tripoli, Libya
| | - Abdallah El-Bouzedi
- Department of Laboratory Medicine, Faculty of Biotechnology, Tripoli University, CC 82668, Tripoli, Libya
| | - Ibrahem Daw
- Department of Electric Engineering, Faculty of Engineering, University of Tripoli, CC 82668Libya
| | - Samia Adam
- Department of Medical Microbiology & Immunology, Faculty of Medicine, University of Tripoli, CC 82668, Tripoli, Libya
| | - Saed Warrag
- Department of Laboratory Medicine, Faculty of Biotechnology, Aljabel-Agarbi University, Nalot, Libya
| |
Collapse
|
|
19
|
Patients with suboptimal hepatitis B virus diagnostic characterization are at risk of liver fibrosis progression. Eur J Gastroenterol Hepatol 2020; 32:426-432. [PMID: 31490418 DOI: 10.1097/meg.0000000000001527] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Many patients with chronic hepatitis B virus infection remain infradiagnosed and untreated. In a national health system with unrestricted access to treatment, our aims were to assess the level of compliance with clinical guidelines and the characteristics and risk of fibrosis progression in patients with suboptimal diagnosis. METHODS In a cohort of patients with positive hepatitis B surface antigen from January 2011 to December 2013, data were registered to assess characteristics and compliance with guidelines. For assessing the risk of liver fibrosis, positive hepatitis B surface antigen patients from January 2008 to December 2013 were grouped depending on DNA request. Liver fibrosis was estimated by serological scores. RESULTS Of 41 158 subjects with hepatitis B surface antigen request, 351 (0.9%) tested positive, and DNA was not available from 110 patients (66.4% male, mean 42.4 ± 14.5 years) after a median of 25.6 months (range 12.0-43.5). Most of these patients (76%) were assessed by primary care. Half of the patients (47.2%) showed hypertransaminasemia, at least significant fibrosis, or both conditions. After long follow-up (mean 90.1 ± 45.2 months), these patients had a higher risk of achieving at least significant fibrosis during follow-up (log-rank 8.73; P = 0.003). CONCLUSION In more than one-third of patients with positive hepatitis B surface antigen, DNA was not requested despite showing hypertransaminasemia and significant fibrosis. Patients without DNA request are at high risk of liver fibrosis progression. Thus, educational measures and other strategies are necessary, especially targeting primary care, to improve access to treatment.
Collapse
|
|
20
|
Palom A, Rodríguez-Tajes S, Navascués CA, García-Samaniego J, Riveiro-Barciela M, Lens S, Rodríguez M, Esteban R, Buti M. Long-term clinical outcomes in patients with chronic hepatitis delta: the role of persistent viraemia. Aliment Pharmacol Ther 2020; 51:158-166. [PMID: 31721254 DOI: 10.1111/apt.15521] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2019] [Revised: 07/14/2019] [Accepted: 09/09/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND Chronic hepatitis delta is a severe liver disease with rapid progression to cirrhosis. The impact of hepatitis delta virus (HDV)-RNA on disease progression and interferon treatment in a real-world cohort has been barely explored. AIM To assess the development of clinical events in a cohort of chronic hepatitis delta patients according to the presence or absence of HDV-RNA METHODS: Multicentre study at four academic hospitals in Spain included anti-HDV-positive patients with compensated liver disease with a follow-up ≥12 months. RESULTS Among 2888 HBsAg-positive subjects, 151 (5.2%) tested positive for anti-HDV, and 118 were included (58% men; median age, 49 years; 73% detectable HDV-RNA and 30% cirrhosis, most often in subjects with HDV-RNA). After a median follow-up of 8 years, subjects with initially detectable HDV-RNA were more prone to developing cirrhosis (31% vs 0%, P = .002) and/or liver decompensation (28% vs 3%, P = .019). Mortality rate was 0.44 per 1000 person-months. The probability of a clinical event was 6%, 25%, and 80% according to initial baseline-event-anticipation score. HDV-RNA became undetectable in 21 (24%) subjects either due to interferon or spontaneously (48% vs 52%, P = .29). Liver decompensation was reduced in interferon-treated patients (13% vs 38%, P = .026). CONCLUSIONS Subjects with persistently positive HDV-RNA had a worse prognosis in terms of clinical events. Baseline-event-anticipation score is useful in predicting the risk of developing liver decompensation and hepatocellular carcinoma. Interferon was beneficial in reducing liver decompensation, even in the absence of virological response.
Collapse
Affiliation(s)
- Adriana Palom
- Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Sergio Rodríguez-Tajes
- Liver Unit, Hospital Clinic Barcelona, IDIBAPS, Universitat de Barcelona, Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Carmen A Navascués
- Liver Unit, Division of Gastroenterology & Hepatology, Hospital Universitario Central de Asturias, Oviedo, Spain
| | - Javier García-Samaniego
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.,Hepatology Unit, Hospital Universitario La Paz, IdiPAZ, Madrid, Spain
| | - Mar Riveiro-Barciela
- Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Sabela Lens
- Liver Unit, Hospital Clinic Barcelona, IDIBAPS, Universitat de Barcelona, Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Manuel Rodríguez
- Liver Unit, Division of Gastroenterology & Hepatology, Hospital Universitario Central de Asturias, Oviedo, Spain
| | - Rafael Esteban
- Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Maria Buti
- Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| |
Collapse
|
|
21
|
Gilman C, Heller T, Koh C. Chronic hepatitis delta: A state-of-the-art review and new therapies. World J Gastroenterol 2019; 25:4580-4597. [PMID: 31528088 PMCID: PMC6718034 DOI: 10.3748/wjg.v25.i32.4580] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Revised: 07/03/2019] [Accepted: 07/19/2019] [Indexed: 02/06/2023] Open
Abstract
Chronic delta hepatitis is the most severe form of viral hepatitis affecting nearly 65 million people worldwide. Individuals with this devastating illness are at higher risk for developing cirrhosis and hepatocellular carcinoma. Delta virus is a defective RNA virus that requires hepatitis B surface antigen for propagation in humans. Infection can occur in the form of a co-infection with hepatitis B, which can be self-limiting, vs superinfection in a patient with established hepatitis B infection, which often leads to chronicity in majority of cases. Current noninvasive tools to assess for advanced liver disease have limited utility in delta hepatitis. Guidelines recommend treatment with pegylated interferon, but this is limited to patients with compensated disease and is efficacious in about 30% of those treated. Due to limited treatment options, novel agents are being investigated and include entry, assembly and export inhibitors of viral particles in addition to stimulators of the host immune response. Future clinical trials should take into consideration the interaction of hepatitis B and hepatitis D as suppression of one virus can lead to the activation of the other. Also, surrogate markers of treatment efficacy have been proposed.
Collapse
MESH Headings
- Antiviral Agents/pharmacology
- Antiviral Agents/therapeutic use
- Coinfection/drug therapy
- Coinfection/epidemiology
- Coinfection/virology
- Drug Therapy, Combination/methods
- Global Burden of Disease
- Hepatitis B Surface Antigens/immunology
- Hepatitis B Surface Antigens/metabolism
- Hepatitis B virus/immunology
- Hepatitis B virus/pathogenicity
- Hepatitis B, Chronic/drug therapy
- Hepatitis B, Chronic/epidemiology
- Hepatitis B, Chronic/virology
- Hepatitis D, Chronic/drug therapy
- Hepatitis D, Chronic/epidemiology
- Hepatitis D, Chronic/virology
- Hepatitis Delta Virus/immunology
- Hepatitis Delta Virus/pathogenicity
- Humans
- Interferon-alpha/pharmacology
- Interferon-alpha/therapeutic use
- Lipopeptides/pharmacology
- Lipopeptides/therapeutic use
- Organic Anion Transporters, Sodium-Dependent/antagonists & inhibitors
- Organic Anion Transporters, Sodium-Dependent/metabolism
- Piperidines/pharmacology
- Piperidines/therapeutic use
- Pyridines/pharmacology
- Pyridines/therapeutic use
- Randomized Controlled Trials as Topic
- Review Literature as Topic
- Superinfection/drug therapy
- Superinfection/epidemiology
- Superinfection/virology
- Symporters/antagonists & inhibitors
- Symporters/metabolism
- Therapies, Investigational/methods
- Treatment Outcome
- Virus Assembly/drug effects
- Virus Internalization/drug effects
Collapse
Affiliation(s)
- Christy Gilman
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, United States
| | - Theo Heller
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, United States
| | - Christopher Koh
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, United States
| |
Collapse
|
|
22
|
Mentha N, Clément S, Negro F, Alfaiate D. A review on hepatitis D: From virology to new therapies. J Adv Res 2019; 17:3-15. [PMID: 31193285 PMCID: PMC6526199 DOI: 10.1016/j.jare.2019.03.009] [Citation(s) in RCA: 65] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2019] [Revised: 03/21/2019] [Accepted: 03/22/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatitis delta virus (HDV) is a defective virus that requires the hepatitis B virus (HBV) to complete its life cycle in human hepatocytes. HDV virions contain an envelope incorporating HBV surface antigen protein and a ribonucleoprotein containing the viral circular single-stranded RNA genome associated with both forms of hepatitis delta antigen, the only viral encoded protein. Replication is mediated by the host cell DNA-dependent RNA polymerases. HDV infects up to72 million people worldwide and is associated with an increased risk of severe and rapidly progressive liver disease. Pegylated interferon-alpha is still the only available treatment for chronic hepatitis D, with poor tolerance and dismal success rate. Although the development of antivirals inhibiting the viral replication is challenging, as HDV does not possess its own polymerase, several antiviral molecules targeting other steps of the viral life cycle are currently under clinical development: Myrcludex B, which blocks HDV entry into hepatocytes, lonafarnib, a prenylation inhibitor that prevents virion assembly, and finally REP 2139, which is thought to inhibit HBsAg release from hepatocytes and interact with hepatitis delta antigen. This review updates the epidemiology, virology and management of HDV infection.
Collapse
Affiliation(s)
- Nathalie Mentha
- Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland
| | - Sophie Clément
- Division of Clinical Pathology, Geneva University Hospitals, 1211 Geneva, Switzerland
| | - Francesco Negro
- Division of Clinical Pathology, Geneva University Hospitals, 1211 Geneva, Switzerland
- Division of Gastroenterology and Hepatology, Geneva University Hospitals, 1205 Geneva, Switzerland
| | - Dulce Alfaiate
- Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland
| |
Collapse
|