|
1
|
Degasperi E, Anolli MP, Jachs M, Reiberger T, De Ledinghen V, Metivier S, D'Offizi G, di Maria F, Schramm C, Schmidt H, Zöllner C, Tacke F, Dietz-Fricke C, Wedemeyer H, Papatheodoridi M, Papatheodoridis G, Carey I, Agarwal K, Van Bömmel F, Brunetto MR, Cardoso M, Verucchi G, Ciancio A, Zoulim F, Aleman S, Semmo N, Mangia A, Hilleret MN, Merle U, Santantonio TA, Coppola N, Pellicelli A, Roche B, Causse X, D'Alteroche L, Dumortier J, Ganne N, Heluwaert F, Ollivier I, Roulot D, Viganò M, Loglio A, Federico A, Pileri F, Maracci M, Tonnini M, Arpurt JP, Barange K, Billaud E, Pol S, Gervais A, Minello A, Rosa I, Puoti M, Lampertico P. Real-world effectiveness and safety of bulevirtide monotherapy for up to 96 weeks in patients with HDV-related cirrhosis. J Hepatol 2025:S0168-8278(25)00001-7. [PMID: 39793613 DOI: 10.1016/j.jhep.2024.12.044] [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: 07/20/2024] [Revised: 12/04/2024] [Accepted: 12/17/2024] [Indexed: 01/13/2025]
Abstract
BACKGROUND & AIMS Bulevirtide (BLV) 2 mg/day is EMA approved for the treatment of compensated chronic HDV infection; however, real-world data in large cohorts of patients with cirrhosis are lacking. METHODS Consecutive HDV-infected patients with cirrhosis starting BLV 2 mg/day from September 2019 were included in a European retrospective multicenter real-world study (SAVE-D). Patient characteristics before and during BLV treatment were collected. Virological, biochemical, combined responses, adverse events and liver-related events (hepatocellular carcinoma [HCC], decompensation, liver transplant) were assessed. RESULTS A total of 244 patients with HDV-related cirrhosis receiving BLV monotherapy for a median of 92 (IQR 71-96) weeks were included: at BLV start, median (IQR) age was 49 (40-58) years and 61% were men; median ALT, LSM and platelet count were 80 (55-130) U/L, 18.3 (13.0-26.3) kPa, and 94 (67-145) x103/mm3, respectively; 54% had esophageal varices, 95% Child-Pugh A cirrhosis, and 10% HIV coinfection; 92% were on nucleos(t)ide analogues; median HDV RNA and HBsAg were 5.4 (4.1-6.5) log10 IU/ml and 3.8 (3.4-4.1) log10 IU/ml, respectively. At weeks 48 and 96, virological, biochemical and combined responses were observed in 65% and 79%, 61% and 64%, 44% and 54% of patients, respectively. AST, GGT, albumin, IgG and LSM values significantly improved throughout treatment. Serum bile acid levels increased in most patients, but only 10% reported mild and transient pruritus, which was independent of bile acid levels. The week 96 cumulative risks of de novo HCC and decompensation were 3.0% (95% CI 2-6%) and 2.8% (95% CI 1-5%), respectively. Thirteen (5%) patients underwent liver transplantation (n = 11 for HCC, n = 2 for decompensation). CONCLUSION BLV 2 mg/day monotherapy for up to 96 weeks was safe and effective in patients with HDV-related cirrhosis. Virological and clinical responses increased over time, while the incidence of liver-related complications was low. IMPACT AND IMPLICATIONS Bulevirtide 2 mg/day is EMA approved for the treatment of compensated chronic hepatitis delta; however, real-world data in large cohorts of patients with cirrhosis are lacking. Bulevirtide 2 mg/day monotherapy for up to 96 weeks was safe and effective (week 96: 79% virological, 64% biochemical and 54% combined response) in a large real-world cohort of patients with HDV-related cirrhosis, including patients with clinically significant portal hypertension. Liver function tests and liver stiffness improved, suggesting a potential clinical benefit in patients with advanced liver disease, while the incidence of de novo liver-related events (hepatocellular carcinoma and decompensation) was low during the 96-week study period.
Collapse
Affiliation(s)
- Elisabetta Degasperi
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Maria Paola Anolli
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Mathias Jachs
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | | | | | - Gianpiero D'Offizi
- Division of Infectious Diseases - Hepatology, Department of Transplantation and General Surgery, Istituto Nazionale per le Malattie Infettive "L. Spallanzani" IRCCS, Rome Italy
| | - Francesco di Maria
- Division of Infectious Diseases - Hepatology, Department of Transplantation and General Surgery, Istituto Nazionale per le Malattie Infettive "L. Spallanzani" IRCCS, Rome Italy
| | - Christoph Schramm
- Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Essen, Germany
| | - Hartmut Schmidt
- Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Essen, Germany
| | - Caroline Zöllner
- Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Frank Tacke
- Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Christopher Dietz-Fricke
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Margarita Papatheodoridi
- Department of Gastroenterology, General Hospital of Athens "Laiko", Medical School of National & Kapodistrian University of Athens, Greece
| | - George Papatheodoridis
- Department of Gastroenterology, General Hospital of Athens "Laiko", Medical School of National & Kapodistrian University of Athens, Greece
| | - Ivana Carey
- Institute of Liver Studies, King's College Hospital, London, UK
| | - Kosh Agarwal
- Institute of Liver Studies, King's College Hospital, London, UK
| | - Florian Van Bömmel
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Laboratory for Clinical and Experimental Hepatology, Leipzig, Germany
| | - Maurizia R Brunetto
- Department of Clinical and Experimental Medicine, University of Pisa and Hepatology Unit, University Hospital of Pisa, Pisa, Italy
| | - Mariana Cardoso
- Gastroenterology Department, Hospital Prof. Doutor Fernando Fonseca, Amadora, Portugal
| | - Gabriella Verucchi
- Department of Medical and Surgical Sciences, Unit of Infectious Diseases, "Alma Mater Studiorum" University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy
| | - Alessia Ciancio
- Department of Medical Sciences, University of Turin, Gastroenterology Division of Città della Salute e della Scienza of Turin, University Hospital, Turin, Italy
| | - Fabien Zoulim
- Lyon Hepatology Institute, Université Claude Bernard Lyon 1, Hospices Civils de Lyon, INSERM Unit 1052 - CRCL, Lyon, France
| | - Soo Aleman
- Department of Infectious Diseases, Karolinska University Hospital, and Karolinska Institutet, Stockholm, Sweden
| | - Nasser Semmo
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland
| | - Alessandra Mangia
- Liver Unit, Fondazione IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy
| | | | - Uta Merle
- Department of Internal Medicine IV, Gastroenterology & Hepatology, Medical University of Heidelberg, Heidelberg, Germany
| | - Teresa A Santantonio
- Department of Medical and Surgical Sciences, Infectious Diseases Unit, University of Foggia, Foggia, Italy
| | - Nicola Coppola
- Department of Mental Health and Public Medicine - Infectious Diseases Unit, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Adriano Pellicelli
- Liver Unit, San Camillo Hospital, Department of Transplantation and General Surgery, Rome, Italy
| | - Bruno Roche
- Hepato-Biliary Center, AP-HP Hôpital Universitaire Paul Brousse, Paris-Saclay University, Research INSERM-Paris Saclay Unit 1193, Villejuif, France
| | | | | | - Jérome Dumortier
- Department of Digestive Diseases, Hospices Civils de Lyon, Edouard Herriot hospital, France; Claude Bernard Lyon 1 University, France
| | - Nathalie Ganne
- AP-HP, Avicenne Hospital, Hepatology Department, F-93000 Bobigny, France
| | | | - Isabelle Ollivier
- Department of Hepatogastroenterology, CHU de Caen Normandie, Caen, France
| | - Dominique Roulot
- AP-HP, Avicenne hospital, Liver Unit, Sorbonne Paris Nord University, Bobigny, France
| | - Mauro Viganò
- Division of Hepatology, Ospedale San Giuseppe, Italy
| | - Alessandro Loglio
- Gastroenterology, Hepatology and Transplantation Division, ASST Papa Giovanni XXIII, Bergamo, Italy
| | - Alessandro Federico
- Division of Hepatogastroenterology, Department of Precision Medicine, Università della Campania "Luigi Vanvitelli", Naples, Italy
| | - Francesca Pileri
- Division of Internal Medicine and Center for Hemochromatosis, University of Modena and Reggio Emilia, Modena, Italy
| | - Monia Maracci
- Institute of Infectious Diseases and Public Health, Università Politecnica delle Marche, Ancona, Italy
| | - Matteo Tonnini
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | | | - Karl Barange
- Department of Gastroenterology, Toulouse University Hospital, Toulouse, France
| | - Eric Billaud
- Université de Nantes, INSERM UIC 1413, Department of Infectious Diseases, CHU Hôtel Dieu, Nantes, France
| | - Stanislas Pol
- Université Paris Cité, Assistance Publique des Hôpitaux de Paris, Hôpital Cochin, Hepatology/Addictology department, Paris, France
| | - Anne Gervais
- Assistance Publique des Hôpitaux de Paris, Hôpital Bichat Claude Bernard, Service des Maladies Infectieuses et Tropicales, Paris, France
| | - Anne Minello
- CHU Dijon, Service d'Hépato-gastroentérologie et oncologie digestive, INSERM EPICAD LNC-UMR1231, Université de Bourgogne-Franche Comté, Dijon, France
| | - Isabelle Rosa
- Service d'hépatogastroentérologie, Centre Hospitalier Intercommunal, Créteil, France
| | - Massimo Puoti
- School of Medicine and Surgery University of Milano Bicocca, Italy
| | - Pietro Lampertico
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; CRC "A. M. and A. Migliavacca" Center for Liver Disease, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy; D-SOLVE consortium, Germany(†).
| |
Collapse
|
|
2
|
Wranke A, Lobato C, Ceausu E, Dalekos GN, Rizzetto M, Turcanu A, Niro GA, Keskin O, Gherlan G, Abbas M, Ingiliz P, Muche M, Buti M, Jachs M, Vanwolleghem T, Cornberg M, Abbas Z, Yurdaydin C, Dörge P, Wedemeyer H. Long-term outcome of hepatitis delta in different regions world-wide: Results of the Hepatitis Delta International Network. Liver Int 2024; 44:2442-2457. [PMID: 38888267 DOI: 10.1111/liv.16006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Revised: 04/23/2024] [Accepted: 05/23/2024] [Indexed: 06/20/2024]
Abstract
BACKGROUND AND AIMS Chronic hepatitis delta represents a major global health burden. Clinical features of hepatitis D virus (HDV) infection vary largely between different regions worldwide. Treatment approaches are dependent on the approval status of distinct drugs and financial resources. METHODS The Hepatitis Delta International Network (HDIN) registry involves researchers from all continents (Wranke, Liver International 2018). We here report long-term follow-up data of 648 hepatitis D patients recruited by 14 centres in 11 countries. Liver-related clinical endpoints were defined as hepatic decompensation (ascites, encephalopathy and variceal bleeding), liver transplantation, hepatocellular carcinoma or liver-related death. RESULTS Patient data were available from all continents but Africa: 22% from Eastern Mediterranean, 32% from Eastern Europe and Central Asia, 13% from Central and Southern Europe, 14% from South Asia (mainly Pakistan) and 19% from South America (mainly Brazil). The mean follow-up was 6.4 (.6-28) years. During follow-up, 195 patients (32%) developed a liver-related clinical event after 3.5 (±3.3) years. Liver cirrhosis at baseline and a detectable HDV RNA test during follow-up were associated with a worse clinical outcome in multivariate regression analysis while patients receiving interferon alfa-based therapies developed clinical endpoints less frequently. Patients from South Asia developed endpoints earlier and had the highest mortality. CONCLUSIONS The HDIN registry confirms the severity of hepatitis D and provides further evidence for HDV viraemia as a main risk factor for disease progression. Hepatitis D seems to take a particularly severe course in patients born in Pakistan. There is an urgent need to extend access to antiviral therapies and to provide appropriate education about HDV infection.
Collapse
Affiliation(s)
- Anika Wranke
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
- German Centre for Infection Research (DZIF), HepNet Study-House/German Liver Foundation, Hannover, Germany
| | - Cirley Lobato
- Centro de Ciências de Saúde e do Desporto, Universidade Federal do Acre, Rio Branco, Brazil
| | - Emanoil Ceausu
- Infectious Diseases, Dr. Victor Babes Clinical Hospital for Infectious and Tropical Diseases, Bucharest, Romania
| | - George N Dalekos
- Department of Medicine and Research Laboratory of Internal Medicine, Medical School, University of Thessaly, Larissa, Greece
| | - Mario Rizzetto
- Department of Internal Medicine-Gastroenterology, University of Torino, Torino, Italy
| | - Adela Turcanu
- Department of Gastroenterology, State University of Medicine "Nicolae Testemitanu", Chisinau, Republic of Moldova
| | - Grazia A Niro
- Division of Gastroenterology, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
| | - Onur Keskin
- Medical Faculty, Ankara University, Ankara, Turkey
| | - George Gherlan
- Infectious Diseases, Dr. Victor Babes Clinical Hospital for Infectious and Tropical Diseases, Bucharest, Romania
| | - Minaam Abbas
- Department of Hepatogastroenterology and Liver Transplantation, Ziauddin University Hospital Karachi, Karachi, Pakistan
| | | | - Marion Muche
- Department of Gastroenterology, Infectious Diseases and Rheumatology (including Clinical Nutrition), Charité, Berlin, Germany
| | - Maria Buti
- Liver Unit, Valle d'Hebron University Hospital and Ciberhed del Instituto CarlosIII, Barcelona, Spain
| | - Mathias Jachs
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Thomas Vanwolleghem
- Faculty of Medicine and Health Sciences, Laboratory of Experimental Medicine and Pediatrics, Viral Hepatitis Research group, University of Antwerp, Antwerp, Belgium
- European Reference Network RARE-LIVER
| | - Markus Cornberg
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
- German Centre for Infection Research (DZIF), HepNet Study-House/German Liver Foundation, Hannover, Germany
- D-SOLVE: EU-Funded Network on Individualized Management of Hepatitis D
- Centre for Individualized Infection Medicine (CiiM), c/o CRC, Hannover, Germany
| | - Zaigham Abbas
- Department of Hepatogastroenterology and Liver Transplantation, Ziauddin University Hospital Karachi, Karachi, Pakistan
| | - Cihan Yurdaydin
- Medical Faculty, Ankara University, Ankara, Turkey
- Department of Gastroenterology & Hepatology, Koc University Medical School, Istanbul, Turkey
| | - Petra Dörge
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
- German Centre for Infection Research (DZIF), HepNet Study-House/German Liver Foundation, Hannover, Germany
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
- German Centre for Infection Research (DZIF), HepNet Study-House/German Liver Foundation, Hannover, Germany
- D-SOLVE: EU-Funded Network on Individualized Management of Hepatitis D
- Centre for Individualized Infection Medicine (CiiM), c/o CRC, Hannover, Germany
- Hannover Medical School, Excellence Cluster RESIST, Hannover, Germany
| |
Collapse
|
|
3
|
Crobu MG, Ravanini P, Impaloni C, Martello C, Bargiacchi O, Di Domenico C, Faolotto G, Macaluso P, Mercandino A, Riggi M, Quaglia V, Andreoni S, Pirisi M, Smirne C. Hepatitis C Virus as a Possible Helper Virus in Human Hepatitis Delta Virus Infection. Viruses 2024; 16:992. [PMID: 38932284 PMCID: PMC11209499 DOI: 10.3390/v16060992] [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: 05/16/2024] [Revised: 06/13/2024] [Accepted: 06/19/2024] [Indexed: 06/28/2024] Open
Abstract
Previous studies reported that the hepatitis C virus (HCV) could help disseminate the hepatitis D virus (HDV) in vivo through hepatitis B virus (HBV)-unrelated ways, but with essentially inconclusive results. To try to shed light on this still-debated topic, 146 anti-HCV-positive subjects (of whom 91 HCV/HIV co-infected, and 43 with prior HCV eradication) were screened for anti-HDV antibodies (anti-HD), after careful selection for negativity to any serologic or virologic marker of current or past HBV infection. One single HCV/HIV co-infected patient (0.7%) tested highly positive for anti-HD, but with no positive HDV-RNA. Her husband, in turn, was a HCV/HIV co-infected subject with a previous contact with HBV. While conducting a thorough review of the relevant literature, the authors attempted to exhaustively describe the medical history of both the anti-HD-positive patient and her partner, believing it to be the key to dissecting the possible complex mechanisms of HDV transmission from one subject to another, and speculating that in the present case, it may have been HCV itself that behaved as an HDV helper virus. In conclusion, this preliminary research, while needing further validation in large prospective studies, provided some further evidence of a role of HCV in HDV dissemination in humans.
Collapse
Affiliation(s)
- Maria Grazia Crobu
- Laboratory of Molecular Virology, Maggiore della Carità Hospital, 28100 Novara, Italy; (M.G.C.); (P.R.); (C.I.); (C.M.); (C.D.D.); (G.F.); (P.M.); (A.M.); (M.R.); (V.Q.); (S.A.)
- Clinical Biochemistry Laboratory, Department of Laboratory Medicine, AOU Città della Salute e della Scienza di Torino, 10126 Turin, Italy
| | - Paolo Ravanini
- Laboratory of Molecular Virology, Maggiore della Carità Hospital, 28100 Novara, Italy; (M.G.C.); (P.R.); (C.I.); (C.M.); (C.D.D.); (G.F.); (P.M.); (A.M.); (M.R.); (V.Q.); (S.A.)
| | - Clotilde Impaloni
- Laboratory of Molecular Virology, Maggiore della Carità Hospital, 28100 Novara, Italy; (M.G.C.); (P.R.); (C.I.); (C.M.); (C.D.D.); (G.F.); (P.M.); (A.M.); (M.R.); (V.Q.); (S.A.)
| | - Claudia Martello
- Laboratory of Molecular Virology, Maggiore della Carità Hospital, 28100 Novara, Italy; (M.G.C.); (P.R.); (C.I.); (C.M.); (C.D.D.); (G.F.); (P.M.); (A.M.); (M.R.); (V.Q.); (S.A.)
| | - Olivia Bargiacchi
- Unit of Infectious Diseases, Maggiore della Carità Hospital, 28100 Novara, Italy;
| | - Christian Di Domenico
- Laboratory of Molecular Virology, Maggiore della Carità Hospital, 28100 Novara, Italy; (M.G.C.); (P.R.); (C.I.); (C.M.); (C.D.D.); (G.F.); (P.M.); (A.M.); (M.R.); (V.Q.); (S.A.)
| | - Giulia Faolotto
- Laboratory of Molecular Virology, Maggiore della Carità Hospital, 28100 Novara, Italy; (M.G.C.); (P.R.); (C.I.); (C.M.); (C.D.D.); (G.F.); (P.M.); (A.M.); (M.R.); (V.Q.); (S.A.)
| | - Paola Macaluso
- Laboratory of Molecular Virology, Maggiore della Carità Hospital, 28100 Novara, Italy; (M.G.C.); (P.R.); (C.I.); (C.M.); (C.D.D.); (G.F.); (P.M.); (A.M.); (M.R.); (V.Q.); (S.A.)
| | - Alessio Mercandino
- Laboratory of Molecular Virology, Maggiore della Carità Hospital, 28100 Novara, Italy; (M.G.C.); (P.R.); (C.I.); (C.M.); (C.D.D.); (G.F.); (P.M.); (A.M.); (M.R.); (V.Q.); (S.A.)
| | - Miriam Riggi
- Laboratory of Molecular Virology, Maggiore della Carità Hospital, 28100 Novara, Italy; (M.G.C.); (P.R.); (C.I.); (C.M.); (C.D.D.); (G.F.); (P.M.); (A.M.); (M.R.); (V.Q.); (S.A.)
| | - Vittorio Quaglia
- Laboratory of Molecular Virology, Maggiore della Carità Hospital, 28100 Novara, Italy; (M.G.C.); (P.R.); (C.I.); (C.M.); (C.D.D.); (G.F.); (P.M.); (A.M.); (M.R.); (V.Q.); (S.A.)
| | - Stefano Andreoni
- Laboratory of Molecular Virology, Maggiore della Carità Hospital, 28100 Novara, Italy; (M.G.C.); (P.R.); (C.I.); (C.M.); (C.D.D.); (G.F.); (P.M.); (A.M.); (M.R.); (V.Q.); (S.A.)
| | - Mario Pirisi
- Internal Medicine Unit, Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy;
| | - Carlo Smirne
- Internal Medicine Unit, Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy;
| |
Collapse
|
|
4
|
Soriano V, Moreno-Torres V, Treviño A, de Jesús F, Corral O, de Mendoza C. Prospects for Controlling Hepatitis B Globally. Pathogens 2024; 13:291. [PMID: 38668246 PMCID: PMC11054959 DOI: 10.3390/pathogens13040291] [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: 03/09/2024] [Revised: 03/28/2024] [Accepted: 03/29/2024] [Indexed: 04/29/2024] Open
Abstract
Infection with the hepatitis B virus (HBV) is highly prevalent globally. Over 250 million people suffer from chronic hepatitis B, and more than 800,000 patients die each year due to hepatitis B complications, including liver cancer. Although protective HBV vaccines are recommended for all newborns, global coverage is suboptimal. In adults, sexual transmission is by far the most frequent route of contagion. The WHO estimates that 1.5 million new HBV infections occur annually. Oral nucleos(t)ide analogues entecavir and tenofovir are the most frequent antivirals prescribed as HBV therapy. Almost all patients adherent to the medication achieve undetectable plasma viremia beyond 6 months of monotherapy. However, less than 5% achieve anti-HBs seroconversion, and viral rebound occurs following drug discontinuation. Therefore, nucleos(t)ide analogues need to be lifelong. New long-acting formulations of tenofovir and entecavir are being developed that will maximize treatment benefit and overcome adherence barriers. Furthermore, new antiviral agents are in development, including entry inhibitors, capside assembly modulators, and RNA interference molecules. The use of combination therapy pursues a functional HBV cure, meaning it is negative for both circulating HBV-DNA and HBsAg. Even when this goal is achieved, the cccDNA reservoir within infected hepatocytes remains a signal of past infection, and HBV can reactivate under immune suppression. Therefore, new gene therapies, including gene editing, are eagerly being pursued to silence or definitively disrupt HBV genomes within infected hepatocytes and, in this way, ultimately cure hepatitis B. At this time, three actions can be taken to push HBV eradication globally: (1) expand universal newborn HBV vaccination; (2) perform once-in-life testing of all adults to identify susceptible HBV persons that could be vaccinated (or re-vaccinated) and unveil asymptomatic carriers that could benefit from treatment; and (3) provide earlier antiviral therapy to chronic HBV carriers, as being aviremic reduces the risk of both clinical progression and transmission.
Collapse
Affiliation(s)
- Vicente Soriano
- UNIR Health Sciences School & Medical Center, 28010 Madrid, Spain
| | - Víctor Moreno-Torres
- UNIR Health Sciences School & Medical Center, 28010 Madrid, Spain
- Department of Internal Medicine, Puerta de Hierro University Hospital, Majadahonda, 28222 Madrid, Spain
| | - Ana Treviño
- UNIR Health Sciences School & Medical Center, 28010 Madrid, Spain
| | | | - Octavio Corral
- UNIR Health Sciences School & Medical Center, 28010 Madrid, Spain
| | - Carmen de Mendoza
- Department of Internal Medicine, Puerta de Hierro University Hospital, Majadahonda, 28222 Madrid, Spain
| |
Collapse
|
|
5
|
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
|
|
6
|
Ferrante ND, Kallan MJ, Sukkestad S, Kodani M, Kitahata MM, Cachay ER, Bhattacharya D, Heath S, Napravnik S, Moore RD, Yendewa G, Mayer KH, Reddy KR, Hayden T, Kamili S, Martin JN, Kim HN, Lo Re V. Prevalence and determinants of hepatitis delta virus infection among HIV/hepatitis B-coinfected adults in care in the United States. J Viral Hepat 2023; 30:879-888. [PMID: 37488783 PMCID: PMC10592429 DOI: 10.1111/jvh.13874] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Accepted: 07/07/2023] [Indexed: 07/26/2023]
Abstract
Hepatitis delta virus (HDV) infection increases the risk of liver complications compared to hepatitis B virus (HBV) alone, particularly among persons with human immunodeficiency virus (HIV). However, no studies have evaluated the prevalence or determinants of HDV infection among people with HIV/HBV in the US. We performed a cross-sectional study among adults with HIV/HBV coinfection receiving care at eight sites within the Center for AIDS Research Network of Integrated Clinical Systems (CNICS) between 1996 and 2019. Among patients with available serum/plasma specimens, we selected the first specimen on or after their initial HBV qualifying test. All samples were tested for HDV IgG antibody and HDV RNA. Multivariable log-binomial generalized linear models were used to estimate prevalence ratios (PRs) with 95% CIs of HDV IgG antibody-positivity associated with determinants of interest (age, injection drug use [IDU], high-risk sexual behaviour). Among 597 adults with HIV/HBV coinfection in CNICS and available serum/plasma samples (median age, 43 years; 89.9% male; 52.8% Black; 42.4% White), 24/597 (4.0%; 95% CI, 2.4%-5.6%) were HDV IgG antibody-positive, and 10/596 (1.7%; 95% CI, 0.6%-2.7%) had detectable HDV RNA. In multivariable analysis, IDU was associated with exposure to HDV infection (adjusted PR = 2.50; 95% CI, 1.09-5.74). In conclusion, among a sample of adults with HIV/HBV coinfection in care in the US, 4.0% were HDV IgG antibody-positive, among whom 41.7% had detectable HDV RNA. History of IDU was associated with exposure to HDV infection. These findings emphasize the importance of HDV testing among persons with HIV/HBV coinfection, especially those with a history of IDU.
Collapse
Affiliation(s)
- Nicole D. Ferrante
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
- Department of Biostatistics, Epidemiology, and Informatics, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA
| | - Michael J. Kallan
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Sophia Sukkestad
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA
| | - Maja Kodani
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA
| | - Mari M. Kitahata
- Division of Allergy and Infectious Disease, Department of Medicine, University of Washington School of Medicine, Seattle, WA
| | - Edward R. Cachay
- Department of Medicine, Division of Infectious Diseases and Global Public Health University of California, San Diego, CA
| | - Debika Bhattacharya
- Department of Medicine, Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, CA
| | - Sonya Heath
- Division of Infectious Disease, Department of Medicine, University of Alabama, Birmingham, AL
| | - Sonia Napravnik
- Department of Medicine, University of North Carolina, Chapel Hill, NC
| | - Richard D. Moore
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins University, Baltimore, MD
| | - George Yendewa
- Department of Medicine, Case Western Reserve University, Cleveland, OH
| | - Kenneth H. Mayer
- The Fenway Institute, Fenway Health, Boston, MA; Department of Medicine, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA
| | - K. Rajender Reddy
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Tonya Hayden
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA
| | - Saleem Kamili
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA
| | - Jeffrey N. Martin
- Department of Epidemiology and Biostatistics, University of California, San Francisco, CA
| | - H. Nina Kim
- Division of Allergy and Infectious Disease, Department of Medicine, University of Washington School of Medicine, Seattle, WA
| | - Vincent Lo Re
- Department of Biostatistics, Epidemiology, and Informatics, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA
- Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| |
Collapse
|
|
7
|
Abstract
Hepatitis delta virus (HDV) only infects patients with hepatitis B virus (HBV) due to its reliance on HBV surface proteins to form its envelope. With shared routes of transmission, HDV coinfection is estimated to occur in 15% of patients with HIV and HBV. However, HDV is often underdiagnosed and may be missed particularly in people living with HIV (PLWH) who are already on antiretroviral therapy with anti-HBV activity and coincidental HBV suppression. At the same time, HDV causes the most severe form of chronic viral hepatitis and leads to faster progression of liver disease and hepatocellular carcinoma. Thus, increased recognition and effective treatment are paramount, and as novel treatment options approach global markets, the study of their efficacy in PLWH should be pursued.
Collapse
Affiliation(s)
- Debra W Yen
- Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
| | - Vicente Soriano
- Health Sciences School & Medical Center, Universidad Internacional La Rioja (UNIR), Madrid, Spain
| | - Pablo Barreiro
- Public Health Regional Laboratory, Hospital Isabel Zendal, Universidad Rey Juan Carlos, Madrid, Spain
| | - Kenneth E Sherman
- Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
| |
Collapse
|
|
8
|
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
|
|
9
|
Kamal H, Aleman S. Natural history of untreated HDV patients: Always a progressive disease? Liver Int 2023; 43 Suppl 1:5-21. [PMID: 36308026 DOI: 10.1111/liv.15467] [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: 02/07/2022] [Revised: 10/20/2022] [Accepted: 10/25/2022] [Indexed: 02/13/2023]
Abstract
A severe course has been described in early studies on chronic hepatitis D (CHD), with faster pace towards liver cirrhosis with subsequent high liver-related morbidity and mortality in the majority of patients. Earlier studies have included risk groups as people using intravenous drugs (PWID) or those with multiple co-morbidities. During the last decade, the epidemiological landscape of CHD has changed with domestic cases decreasing while increasing cases of CHD consisting of younger persons immigrating from endemic regions to low-endemic regions. Recently, further insights into the spectrum of the disease with an indolent disease course in a substantial proportion of persons with CHD have been gained. At diagnosis, ≥30%-50% had already established liver cirrhosis. Older age, liver cirrhosis, co-infection with HIV and lack of interferon (IFN) therapy are the main predictors of worse clinical outcome. The newly introduced and upcoming antivirals against CHD are highly anticipated, considering the historically low virological response rates to antiviral therapy. Further knowledge is needed to fully comprehend the natural course and the spectrum of this severe form of viral hepatitis. This is also to be able to evaluate the long-term effects of the new antivirals on disease progression.
Collapse
Affiliation(s)
- Habiba Kamal
- Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden
- Department of Medicine Huddinge, Infectious Diseases, Karolinska Institute, Stockholm, Sweden
| | - Soo Aleman
- Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden
- Department of Medicine Huddinge, Infectious Diseases, Karolinska Institute, Stockholm, Sweden
| |
Collapse
|
|
10
|
Valente C. [Hepatitis Delta in HIV/HBV Infected Individuals: Why does this Issue Matter?]. ACTA MEDICA PORT 2023. [PMID: 37171618 DOI: 10.20344/amp.19527] [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: 12/22/2022] [Accepted: 03/15/2023] [Indexed: 05/13/2023]
Affiliation(s)
- Cristina Valente
- Serviço de Doenças Infecciosas. Centro Hospitalar e Universitário de Coimbra. Coimbra. Portugal
| |
Collapse
|
|
11
|
Béguelin C, Atkinson A, Boyd A, Falconer K, Kirkby N, Suter-Riniker F, Günthard HF, Rockstroh JK, Mocroft A, Rauch A, Peters L, Wandeler G. Hepatitis delta infection among persons living with HIV in Europe. Liver Int 2023; 43:819-828. [PMID: 36625770 DOI: 10.1111/liv.15519] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Revised: 11/20/2022] [Accepted: 01/04/2023] [Indexed: 01/11/2023]
Abstract
BACKGROUND AND AIMS A high prevalence of hepatitis delta virus (HDV) infection, the most severe form of viral hepatitis, has been reported among persons living with HIV (PLWH) in Europe. We analysed data from a large HIV cohort collaboration to characterize HDV epidemiological trends across Europe, as well as its impact on clinical outcomes. METHODS All PLWH with a positive hepatitis B surface antigen (HBsAg) in the Swiss HIV Cohort Study and EuroSIDA between 1988 and 2019 were tested for anti-HDV antibodies and, if positive, for HDV RNA. Demographic and clinical characteristics at initiation of antiretroviral therapy were compared between HDV-positive and HDV-negative individuals using descriptive statistics. The associations between HDV infection and overall mortality, liver-related mortality as well as hepatocellular carcinoma (HCC) were assessed using cumulative incidence plots and cause-specific multivariable Cox regression. RESULTS Of 2793 HBsAg-positive participants, 1556 (56%) had stored serum available and were included. The prevalence of HDV coinfection was 15.2% (237/1556, 95% confidence interval [CI]: 13.5%-17.1%) and 66% (132/200) of HDV-positive individuals had active HDV replication. Among persons who inject drugs (PWID), the prevalence of HDV coinfection was 50.5% (182/360, 95% CI: 45.3%-55.7%), with similar estimates across Europe, compared to 4.7% (52/1109, 95% CI: 3.5%-5.9%) among other participants. During a median follow-up of 10.8 years (interquartile range 5.6-17.8), 82 (34.6%) HDV-positive and 265 (20.1%) HDV-negative individuals died. 41.5% (34/82) of deaths were liver-related in HDV-positive individuals compared to 17.7% (47/265) in HDV-negative individuals. HDV infection was associated with overall mortality (adjusted hazard ratio 1.6; 95% CI 1.2-2.1), liver-related death (2.9, 1.6-5.0) and HCC (6.3, 2.5-16.0). CONCLUSION We found a very high prevalence of hepatitis delta among PWID across Europe. Among PLWH who do not inject drugs, the prevalence was similar to that reported from populations without HIV. HDV coinfection was associated with liver-related mortality and HCC incidence.
Collapse
Affiliation(s)
- Charles Béguelin
- Department of Infectious Diseases, Bern University Hospital, Inselspital, University of Bern, Bern, Switzerland
| | - Andrew Atkinson
- Department of Infectious Diseases, Bern University Hospital, Inselspital, University of Bern, Bern, Switzerland
| | - Anders Boyd
- Stichting HIV Monitoring, Department of Infectious Diseases, Public Health Service of Amsterdam, Amsterdam, the Netherlands
| | - Karolin Falconer
- Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - Nikolai Kirkby
- Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark
| | - Franziska Suter-Riniker
- Institute for Infectious Diseases, Faculty of Medicine, University of Bern, Bern, Switzerland
| | - Huldrych F Günthard
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland
- Institute of Medical Virology, University of Zurich, Zurich, Switzerland
| | | | - Amanda Mocroft
- Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, UCL, London, UK
- Rigshospitalet, University of Copenhagen, Centre of Excellence for Health, Immunity and Infections (CHIP), Copenhagen, Denmark
| | - Andri Rauch
- Department of Infectious Diseases, Bern University Hospital, Inselspital, University of Bern, Bern, Switzerland
| | - Lars Peters
- Rigshospitalet, University of Copenhagen, Centre of Excellence for Health, Immunity and Infections (CHIP), Copenhagen, Denmark
| | - Gilles Wandeler
- Department of Infectious Diseases, Bern University Hospital, Inselspital, University of Bern, Bern, Switzerland
- Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
| | | |
Collapse
|
|
12
|
Brancaccio G, Shanyinde M, Puoti M, Gaeta GB, Monforte AD, Vergori A, Rusconi S, Mazzarelli A, Castagna A, Antinori A, Cozzi-Lepri A. Hepatitis delta coinfection in persons with HIV: misdiagnosis and disease burden in Italy. Pathog Glob Health 2023; 117:181-189. [PMID: 35249472 PMCID: PMC9970224 DOI: 10.1080/20477724.2022.2047551] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022] Open
Abstract
Hepatitis Delta virus (HDV) causes severe liver disease. Due to similarities in transmission routes, persons living with HIV (PLWH) are at risk of HDV infection. This analysis investigates the prevalence and the long-term clinical outcome of people with HDV in a large cohort of PLWH. We retrieved HBsAg ± anti-HDV positive PLWH enrolled from 1997 to 2015 in the multicentre, prospective ICONA study. The primary endpoint was a composite clinical outcome (CCO = having experienced ≥1 of the following: Fib4 score >3.25; diagnosis of cirrhosis; decompensation; hepatocellular carcinoma or liver-related death). Kaplan-Meier curves and unweighted and weighted Cox regression models were used for data analysis. Less than half of HBsAg positive patients had been tested for anti-HDV in clinical practice. After testing stored sera, among 617 HBV/HIV cases, 115 (19%) were anti-HDV positive; 405 (65%) HBV monoinfected; 99 (16%) undeterminate. The prevalence declined over the observation period. HDV patients were more often males, intravenous drug users, HCV coinfected. After a median of 26 months, 55/115 (48%) developed CCO among HDV+; 98/403 (24%) among HBV monoinfected; 18/99 (18%) in HDV unknown (p < 0.001). After controlling for geographical region, alcohol consumption, CD4 count, anti-HCV status and IFN-based therapies, the association with HDV retained statistical significance [HR = 1.67 (1.15, 2.95; p = 0.025)]. HDV infection among PLWH is underdiagnosed, although HDV entails an high risk of liver disease progression. Because effective drugs to treat HDV are now available, it is even more crucial to identify PLWH at an early stage of liver disease.
Collapse
Affiliation(s)
| | - Milensu Shanyinde
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Massimo Puoti
- Infectious Diseases, Hospital Niguarda, Milan, Italy
| | - Giovanni B Gaeta
- Department of Mental and Physical Health and Preventive Medicine, University L. Vanvitelli, Naples, Italy
| | | | - Alessandra Vergori
- Infectious Diseases, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy
| | - Stefano Rusconi
- UOC Malattie Infettive, Ospedale Civile di Legnano, ASST Ovest Milanese, Legnano, Italy
| | - Antonio Mazzarelli
- Infectious Diseases, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy
| | | | - Andrea Antinori
- Infectious Diseases, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy
| | | | | |
Collapse
|
|
13
|
Chen S, Ren F, Huang X, Xu L, Gao Y, Zhang X, Cao Y, Fan Z, Tian Y, Liu M. Underestimated Prevalence of HIV, Hepatitis B Virus (HBV), and Hepatitis D Virus (HDV) Triple Infection Globally: Systematic Review and Meta-analysis. JMIR Public Health Surveill 2022; 8:e37016. [PMID: 36445732 PMCID: PMC9748799 DOI: 10.2196/37016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 06/19/2022] [Accepted: 10/11/2022] [Indexed: 11/06/2022] Open
Abstract
BACKGROUND Hepatitis delta virus (HDV) is a satellite RNA virus that relies on hepatitis B virus (HBV) for transmission. HIV/HBV/HDV coinfection or triple infection is common and has a worse prognosis than monoinfection. OBJECTIVE We aimed to reveal the epidemiological characteristics of HIV/HBV/HDV triple infection in the global population. METHODS A systematic literature search in PubMed, Embase, and the Cochrane Library was performed for studies of the prevalence of HIV/HBV/HDV triple infection published from January 1, 1990, to May 31, 2021. The Der Simonian-Laird random effects model was used to calculate the pooled prevalence. RESULTS We included 14 studies with 11,852 participants. The pooled triple infection rate in the global population was 7.4% (877/11,852; 95% CI 0.73%-29.59%). The results of the subgroup analysis showed that the prevalence of triple infection was significantly higher in the Asian population (214/986, 21.4%; 95% CI 7.1%-35.8%), in men (212/5579, 3.8%; 95% CI 2.5%-5.2%), and in men who have sex with men (216/2734, 7.9%; 95% CI 4.3%-11.4%). In addition, compared with people living with HIV, the HIV/HBV/HDV triple infection rate was higher in people with hepatitis B. CONCLUSIONS This meta-analysis suggests that the prevalence of HIV/HBV/HDV triple infection in the global population is underestimated, and we should focus more effort on the prevention and control of HIV/HBV/HDV triple infection. TRIAL REGISTRATION PROSPERO CRD42021273949; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=273949.
Collapse
Affiliation(s)
- Sisi Chen
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
- Department of Oncology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Feng Ren
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Xiaojie Huang
- Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Ling Xu
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Yao Gao
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Xiangying Zhang
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Yaling Cao
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Zihao Fan
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Yuan Tian
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Mei Liu
- Department of Oncology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| |
Collapse
|
|
14
|
Abstract
PURPOSE OF REVIEW The epidemiology of liver disease in people living with HIV has evolved since the arrival of effective hepatitis C virus (HCV) treatment. Nonalcoholic fatty liver disease (NAFLD) in HIV patients is highly prevalent while hepatitis D, hepatitis E, and occult hepatitis B remain underappreciated. We discuss mechanisms of fibrosis in HIV and review clinical outcomes of HIV-associated liver diseases. RECENT FINDINGS HIV-HCV co-infection is receding as a cause of progressive liver disease, but fibrosis biomarkers after HCV treatment remain elevated. Antiretroviral therapy (ART) with anti-hepatitis B virus (HBV) activity promotes stable liver disease, but oversimplifying ART regimens in unrecognized suppressed HBV may lead to activation of HBV. A high prevalence of fibrosis and rapid progression of fibrosis are seen in HIV-associated NAFLD, with visceral fat as a major risk factor. Newer ART such as integrase strand inhibitors may have limited intrinsic hepatoxicity but do increase weight, which may secondarily lead to hepatic steatosis. Promising therapies for HIV-associated NAFLD include tesamorelin and CCR5 blockade agents. SUMMARY Our understanding of the natural history and pathogenesis of liver diseases in HIV has advanced and adapted to the changing landscape of liver disease in this population. Future research should evaluate long-term clinical and histological outcomes, prevention strategies, and treatment options to improve morbidity and mortality in HIV-related liver diseases.
Collapse
|
|
15
|
Begré L, Béguelin C, Boyd A, Peters L, Rockstroh J, Günthard HF, Bernasconi E, Cavassini M, Lacombe K, Mocroft A, Wandeler G, Rauch A. Long-term trends of alanine aminotransferase levels among persons living with human immunodeficiency virus/hepatitis B virus with and without hepatitis delta coinfection. Front Med (Lausanne) 2022; 9:988356. [PMID: 36186807 PMCID: PMC9522477 DOI: 10.3389/fmed.2022.988356] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Accepted: 08/26/2022] [Indexed: 11/13/2022] Open
Abstract
BackgroundHepatitis delta virus (HDV) infection accelerates the progression of liver disease in persons living with HIV and hepatitis B virus (HBV) coinfection. We explored the association between HDV infection and alanine aminotransferase (ALT) elevation during tenofovir-containing antiretroviral treatment among persons living with HIV/HBV.Materials and methodsWe included persons living with HIV/HBV with and without HDV starting tenofovir-containing antiretroviral therapy (ART) in three European cohorts with at least 18 months of follow-up. We defined HDV infection as a positive anti-HDV antibody test. We assessed risk factors for ALT elevation ≥ 1.25x upper limit of normal after 5 years of tenofovir-treatment using multivariate logistic regression models. The difference in ALT trends between individuals with and without HDV was evaluated using linear mixed effects models.Results61/518 (11.8%) participants had an HDV infection. Among individuals with HDV, 63.9% had ALT elevation after 2 years and 55.6% after 5 years of tenofovir, whereas the estimates were 34.1% after two and 27.0% after 5 years in those without HDV. HDV coinfection (adjusted odds ratio 2.8, 95% confidence interval 1.4–5.8) and obesity at baseline (adjusted odds ratio 3.2, 95% confidence interval 1.2–8.0) were associated with ALT elevation after 5 years of tenofovir therapy. Mean ALT levels were consistently higher during follow-up in participants with HDV compared to those without HDV.ConclusionPersistent ALT elevation is common in persons living with HIV/HBV in Europe despite adequate HBV therapy. HDV coinfection and obesity are independent risk factors for persistent ALT elevation during long-term tenofovir treatment.
Collapse
Affiliation(s)
- Lorin Begré
- Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Graduate School for Health Sciences, University of Bern, Bern, Switzerland
- *Correspondence: Lorin Begré,
| | - Charles Béguelin
- Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Anders Boyd
- Department of Infectious Diseases, Research and Prevention, Public Health Service of Amsterdam, Stichting HIV Monitoring, Amsterdam, Netherlands
| | - Lars Peters
- CHIP, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Jürgen Rockstroh
- HIV Clinic, Department of Medicine, University Hospital Bonn, Bonn, Germany
| | - Huldrych F. Günthard
- Department of Infectious Diseases, University Hospital Zurich, Zurich, Switzerland
- Institute of Medical Virology, University of Zurich, Zurich, Switzerland
| | - Enos Bernasconi
- Division of Infectious Diseases, Regional Hospital Lugano EOC, University of Geneva and University of Southern Switzerland, Lugano, Switzerland
| | - Matthias Cavassini
- Division of Infectious Diseases, University Hospital Lausanne, University of Lausanne, Lausanne, Switzerland
| | - Karine Lacombe
- INSERM IPLESP, St Antoine Hospital, AP-HP, Sorbonne Université, Paris, France
| | - Amanda Mocroft
- CHIP, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
- Center for Clinical Research, Epidemiology, Modeling, and Evaluation, Institute for Global Health, University College London, London, United Kingdom
| | - Gilles Wandeler
- Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Andri Rauch
- Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| |
Collapse
|
|
16
|
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
|
|
17
|
Hamady A, Cooke GS, Garvey LJ. Identification of hepatitis delta superinfection when investigating transaminitis in HIV/hepatitis B virus co-infection. AIDS 2021; 35:1704-1706. [PMID: 33973877 DOI: 10.1097/qad.0000000000002940] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Hepatitis delta virus (HDV) is a highly pathogenic virus which can cause rapidly progressive liver disease in individuals with chronic hepatitis B virus and for which treatment options are limited. The incidence of sexually transmitted HDV infection is unknown. Here we report the case of a HDV seronegative man with pre-existent HIV/hepatitis B virus, taking effective tenofovir-containing antiretroviral therapy, who experienced a significant acute transaminitis with HDV antibody seroconversion and viraemia and no other identifiable cause.
Collapse
Affiliation(s)
| | - Graham S Cooke
- Division of Medicine, Imperial College
- Division of Medicine, Imperial College Healthcare NHS Trust, London, UK
| | - Lucy J Garvey
- Division of Medicine, Imperial College Healthcare NHS Trust, London, UK
| |
Collapse
|
|
18
|
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
|
|
19
|
Shen DT, Han PC, Ji DZ, Chen HY, Cao WD, Goyal H, Xu HG. Epidemiology estimates of hepatitis D in individuals co-infected with human immunodeficiency virus and hepatitis B virus, 2002-2018: A systematic review and meta-analysis. J Viral Hepat 2021; 28:1057-1067. [PMID: 33877742 DOI: 10.1111/jvh.13512] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Revised: 03/09/2021] [Accepted: 03/28/2021] [Indexed: 01/05/2023]
Abstract
Hepatitis delta virus (HDV) is an obligate satellite of hepatitis B virus (HBV). HIV/HDV co-infection is associated with a high rate of hepatic decompensation events and death. We aimed to characterize the epidemiology of HDV infection in HIV/HBV co-infected individuals. We systematically searched PubMed, Embase, Cochrane Library, Web of Science, CINAHL and Scopus for studies published from 1 Jan 2002 to 7 May 2018 measuring prevalence of HDV among the HIV population. Pooled seroprevalence was calculated with the DerSimonian-Laird random-effects model. Our search returned 4624 records, 38 of which met the inclusion and exclusion criteria. These studies included data for 63 cohorts from 18 countries and regions. The overall HDV seroprevalence of HIV-infected individuals was 1.03% (95% CI 0.43-1.85) in 2002-2018 globally. Moreover, the estimated pooled HDV seroprevalence among the general population was 1.07% (95% CI 0.65-1.59) in 2002-2018, which was not significantly different from the HDV seroprevalence of individuals living with HIV (p = 0.951). The overall HDV seroprevalence of the HBsAg positive population was 12.15% (95% CI 10.22-14.20), p = 0.434 when compared with the corresponding data of HIV/HBV co-infected individuals. This meta-analysis suggested that there was no difference between the HDV seroprevalence in HIV-infected individuals and the general population.
Collapse
Affiliation(s)
- Dan-Ting Shen
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Department of Laboratory Medicine, HUA DONG Sanatorium, Wuxi, China
| | - Pei-Chun Han
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Dong-Ze Ji
- Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Hai-Yan Chen
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Wei-Dong Cao
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Hemant Goyal
- Department of Internal Medicine, Mercer University School of Medicine, Macon, GA, USA
| | - Hua-Guo Xu
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| |
Collapse
|
|
20
|
de Mattos ÂZ, Debes JD, Boonstra A, Yang JD, Balderramo DC, Sartori GDP, de Mattos AA. Current impact of viral hepatitis on liver cancer development: The challenge remains. World J Gastroenterol 2021; 27:3556-3567. [PMID: 34239269 PMCID: PMC8240060 DOI: 10.3748/wjg.v27.i24.3556] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 03/11/2021] [Accepted: 04/21/2021] [Indexed: 02/06/2023] Open
Abstract
Chronic infections due to hepatitis B and hepatitis C viruses are responsible for most cases of hepatocellular carcinoma (HCC) worldwide, and this association is likely to remain during the next decade. Moreover, viral hepatitis-related HCC imposes an important burden on public health in terms of disability-adjusted life years. In order to reduce such a burden, some major challenges must be faced. Universal vaccination against hepatitis B virus, especially in the neonatal period, is probably the most relevant primary preventive measure against the development of HCC. Moreover, considering the large adult population already infected with hepatitis B and C viruses, it is also imperative to identify these individuals to ensure their access to treatment. Both hepatitis B and C currently have highly effective therapies, which are able to diminish the risk of development of liver cancer. Finally, it is essential for individuals at high-risk of HCC to be included in surveillance programs, so that tumors are detected at an early stage. Patients with hepatitis B or C and advanced liver fibrosis or cirrhosis benefit from being followed in a surveillance program. As hepatitis B virus is oncogenic and capable of leading to liver cancer even in individuals with early stages of liver fibrosis, other high-risk groups of patients with hepatitis B are also candidates for surveillance. Considerable effort is required concerning these strategies in order to decrease the incidence and the mortality of viral hepatitis-related HCC.
Collapse
MESH Headings
- Adult
- Carcinoma, Hepatocellular/epidemiology
- Carcinoma, Hepatocellular/etiology
- Carcinoma, Hepatocellular/prevention & control
- Hepatitis B/complications
- Hepatitis B/epidemiology
- Hepatitis B/prevention & control
- Hepatitis B virus
- Hepatitis B, Chronic/complications
- Hepatitis B, Chronic/epidemiology
- Hepatitis, Viral, Human/complications
- Hepatitis, Viral, Human/epidemiology
- Humans
- Infant, Newborn
- Liver Neoplasms/epidemiology
- Liver Neoplasms/prevention & control
- Risk Factors
Collapse
Affiliation(s)
- Ângelo Zambam de Mattos
- Department of Gastroenterology and Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90020-090, Brazil
- Gastroenterology and Hepatology Unit, Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90050-170, Brazil
| | - Jose D Debes
- Department of Medicine, Division of Gastroenterology and Infectious Diseases, University of Minnesota, Minneapolis, MN 55455, United States
- Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam NL-3015, Netherlands
| | - Andre Boonstra
- Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam NL-3015, Netherlands
| | - Ju-Dong Yang
- Division of Digestive and Liver Diseases, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
| | - Domingo C Balderramo
- Department of Gastroenterology, Hospital Privado Universitario de Córdoba, Córdoba 5016, Argentina
- Department of Medicine, Instituto Universitario de Ciencias Biomédicas de Córdoba, Córdoba 5016, Argentina
| | - Giovana D P Sartori
- Department of Internal Medicine, Hospital Nossa Senhora da Conceição, Porto Alegre 91350-200, Brazil
| | - Angelo Alves de Mattos
- Department of Gastroenterology and Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90020-090, Brazil
- Gastroenterology and Hepatology Unit, Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90050-170, Brazil
| |
Collapse
|
|
21
|
Rizzetto M, Hamid S, Negro F. The changing context of hepatitis D. J Hepatol 2021; 74:1200-1211. [PMID: 33484770 DOI: 10.1016/j.jhep.2021.01.014] [Citation(s) in RCA: 113] [Impact Index Per Article: 28.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 01/04/2021] [Accepted: 01/09/2021] [Indexed: 12/18/2022]
Abstract
The global epidemiology of hepatitis D is changing with the widespread implementation of vaccination against hepatitis B. In high-income countries that achieved optimal control of HBV, the epidemiology of hepatitis D is dual, consisting of an ageing cohort of domestic patients with advanced liver fibrosis who represent the end stage of the natural history of HDV, and of a younger generation of immigrants from endemic countries who account for the majority of new infections. As observed in Europe in the 1980s, the distinctive clinical characteristic of chronic hepatitis D in endemic countries is the accelerated progression to cirrhosis and hepatocellular carcinoma. Despite some recent progress, the therapeutic management of HDV remains unsatisfactory, as most patients are not cured of HDV with currently available medicines. This review article describes the current epidemiology and clinical features of chronic hepatitis D, based on the literature published in the last 10 years.
Collapse
Affiliation(s)
- Mario Rizzetto
- Department of Medical Sciences, University of Turin, Turin, Italy.
| | - Saeed Hamid
- Department of Medicine, The Aga Khan University, Karachi, Pakistan
| | - Franco Negro
- Division of Gastroenterology and Hepatology, Geneva University Hospitals, Geneva, Switzerland; Division of Clinical Pathology, Geneva University Hospitals, Geneva, Switzerland
| |
Collapse
|
|
22
|
HDV Pathogenesis: Unravelling Ariadne's Thread. Viruses 2021; 13:v13050778. [PMID: 33924806 PMCID: PMC8145675 DOI: 10.3390/v13050778] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 04/22/2021] [Accepted: 04/23/2021] [Indexed: 12/22/2022] Open
Abstract
Hepatitis Delta virus (HDV) lies in between satellite viruses and viroids, as its unique molecular characteristics and life cycle cannot categorize it according to the standard taxonomy norms for viruses. Being a satellite virus of hepatitis B virus (HBV), HDV requires HBV envelope glycoproteins for its infection cycle and its transmission. HDV pathogenesis varies and depends on the mode of HDV and HBV infection; a simultaneous HDV and HBV infection will lead to an acute hepatitis that will resolve spontaneously in the majority of patients, whereas an HDV super-infection of a chronic HBV carrier will mainly result in the establishment of a chronic HDV infection that may progress towards cirrhosis, liver decompensation, and hepatocellular carcinoma (HCC). With this review, we aim to unravel Ariadne’s thread into the labyrinth of acute and chronic HDV infection pathogenesis and will provide insights into the complexity of this exciting topic by detailing the different players and mechanisms that shape the clinical outcome.
Collapse
|
|
23
|
Attiku K, Bonney J, Agbosu E, Bonney E, Puplampu P, Ganu V, Odoom J, Aboagye J, Mensah J, Agyemang S, Awuku-Larbi Y, Arjarquah A, Mawuli G, Quaye O. Circulation of hepatitis delta virus and occult hepatitis B virus infection amongst HIV/HBV co-infected patients in Korle-Bu, Ghana. PLoS One 2021; 16:e0244507. [PMID: 33411715 PMCID: PMC7790253 DOI: 10.1371/journal.pone.0244507] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Accepted: 12/10/2020] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Within HIV/HBV infected patients, an increase in HDV infection has been observed; there is inadequate information on HDV prevalence as well as virologic profile in Ghana. This study sought to determine the presence of HDV in HIV/HBV co-infected patients in Ghana. METHODS This was a longitudinal purposive study which enrolled 113 HIV/HBV co-infected patients attending clinic at Korle-Bu Teaching Hospital (KBTH) in Accra, Ghana. After consenting, 5 mL whole blood was collected at two-time points (baseline and 4-6 months afterwards). The sera obtained were tested to confirm the presence of HIV, HBV antibodies and/or antigens, and HBV DNA. Antibodies and viral RNA were also determined for HDV. Amplified HBV DNA and HDV RNA were sequenced and phylogenetic analysis carried out with reference sequences from the GenBank to establish the genotypes. RESULTS Of the 113 samples tested 63 (55.7%) were females and 50 (44.25%) were males with a median age of 45 years. A total of 100 (88.5%) samples had detectable HBV surface antigen (HBsAg), and 32 out of the 113 had detectable HBV DNA. Nucleotide sequences were obtained for 15 and 2 samples of HBV and HDV, respectively. Phylogenetic analysis was predominantly genotype E for the HBVs and genotype 1 for the HDVs. Of the 13 samples that were HBsAg unreactive, 4 (30.8%) had detectable HBV DNA suggesting the incidence of occult HBV infections. The percentage occurrence of HDV in this study was observed to be 3.54. CONCLUSION Our data suggest the presence and circulation of HDV and incidence of occult HBV infection in HIV/HBV co-infected patients in Ghana. This informs health staff and makes it imperative to look out for the presence of HDV and occult HBV in HIV/HBV co-infected patients presenting with potential risk of liver cancers and HBV transmission through haemodialysis and blood transfusions.
Collapse
Affiliation(s)
- Keren Attiku
- West African Centre for Cell Biology of Infectious Pathogens, Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Accra, Ghana
- Department of Virology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana
| | - Joseph Bonney
- West African Centre for Cell Biology of Infectious Pathogens, Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Accra, Ghana
- Department of Virology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana
| | - Esinam Agbosu
- West African Centre for Cell Biology of Infectious Pathogens, Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Accra, Ghana
- Department of Virology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana
| | - Evelyn Bonney
- West African Centre for Cell Biology of Infectious Pathogens, Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Accra, Ghana
- Department of Virology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana
| | | | - Vincent Ganu
- Fevers Unit, Korle-Bu Teaching Hospital, Accra, Ghana
| | - John Odoom
- West African Centre for Cell Biology of Infectious Pathogens, Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Accra, Ghana
- Department of Virology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana
| | - James Aboagye
- Department of Virology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana
| | - John Mensah
- Fevers Unit, Korle-Bu Teaching Hospital, Accra, Ghana
| | - Seth Agyemang
- West African Centre for Cell Biology of Infectious Pathogens, Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Accra, Ghana
- Fevers Unit, Korle-Bu Teaching Hospital, Accra, Ghana
| | - Yaw Awuku-Larbi
- School of Public Health, University of Witwatersrand, Johannesburg, South Africa
| | - Augustina Arjarquah
- West African Centre for Cell Biology of Infectious Pathogens, Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Accra, Ghana
- Department of Virology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana
| | - Gifty Mawuli
- Department of Virology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana
| | - Osbourne Quaye
- West African Centre for Cell Biology of Infectious Pathogens, Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Accra, Ghana
| |
Collapse
|
|
24
|
Ferrante ND, Lo Re V. Epidemiology, Natural History, and Treatment of Hepatitis Delta Virus Infection in HIV/Hepatitis B Virus Coinfection. Curr HIV/AIDS Rep 2020; 17:405-414. [PMID: 32607773 DOI: 10.1007/s11904-020-00508-z] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
PURPOSE OF REVIEW Limited data exist on the prevalence, determinants, and outcomes of hepatitis delta virus (HDV) infection among HIV/hepatitis B virus (HBV)-coinfected persons. This review provides current evidence on the epidemiology, natural history, and treatment of HDV infection in patients with HIV/HBV coinfection and highlights future research needs. RECENT FINDINGS Cross-sectional studies in Europe, Africa, South America, and Asia show that the prevalence of HDV among HIV/HBV-coinfected patients ranges from 1.2 to 25%. No studies have evaluated the prevalence of HDV infection among HIV/HBV-coinfected patients in the USA. HDV infection increases the risk of hepatic decompensation and hepatocellular carcinoma among HIV/HBV-coinfected patients. HDV treatment remains limited to pegylated interferon-alpha, which results in sustained virologic response in fewer than 25%. Data on the epidemiology, natural history, and treatment of HDV among HIV/HBV-coinfected persons remain limited. More research is needed to address these knowledge gaps in order to better manage HDV coinfection in HIV/HBV-coinfected patients.
Collapse
Affiliation(s)
- Nicole D Ferrante
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Department of Biostatistics, Epidemiology, and Informatics, Center for Clinical Epidemiology and Biostatistics, Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine, University of Pennsylvania, 836 Blockley Hall, 423 Guardian Drive, Philadelphia, PA, 19104-6021, USA
| | - Vincent Lo Re
- Department of Biostatistics, Epidemiology, and Informatics, Center for Clinical Epidemiology and Biostatistics, Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine, University of Pennsylvania, 836 Blockley Hall, 423 Guardian Drive, Philadelphia, PA, 19104-6021, USA.
- Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine University of Pennsylvania, Philadelphia, PA, USA.
- Center for AIDS Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
| |
Collapse
|
|
25
|
Hercun J, Koh C, Heller T. Hepatitis Delta: Prevalence, Natural History, and Treatment Options. Gastroenterol Clin North Am 2020; 49:239-252. [PMID: 32389361 DOI: 10.1016/j.gtc.2020.01.004] [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] [Indexed: 02/16/2023]
Abstract
Half a century after its discovery, hepatitis delta remains a pertinent global health issue with a major clinical impact in endemic regions and an underestimated prevalence worldwide. Hepatitis delta virus infection follows a challenging clinical course and is responsible for significant liver-related morbidity. Although the only currently available treatment (pegylated interferon) does not provide consistent results, emerging therapeutic options are promising. This article explores the epidemiology, natural history, as well as current and potential therapeutic options for hepatitis delta virus infection.
Collapse
Affiliation(s)
- Julian Hercun
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10 Center Drive, Room 4-5722, Bethesda, MD 20892, USA.
| | - Christopher Koh
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10 Center Drive, Room 4-5722, Bethesda, MD 20892, USA
| | - Theo Heller
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10 Center Drive, Room 4-5722, Bethesda, MD 20892, USA
| |
Collapse
|
|
26
|
Farid Y, Martin C, Delforge M, De Wit S. Epidemiology and clinical management of HIV-HBV coinfected patients in a large AIDS Reference Center in Belgium. Acta Clin Belg 2019; 74:424-429. [PMID: 30513065 DOI: 10.1080/17843286.2018.1554292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Objectives: Human immunodeficiency virus (HIV) and hepatitis B virus (HBV) are both worldwide health concerns with similar routes of transmission and no curative treatment to date. Coinfection is associated with increased morbidity and mortality. We aim to provide epidemiological data about HIV-HBV coinfected patients and asses if management of patients following European recommendation (EACS) was achieved in a large AIDS Reference Center in Belgium. Methods: Retrospective review of the HIV database of Saint-Pierre University Hospital in Brussels (Belgium) focusing on HIV-HBV coinfected patients in active follow-up. We classified patients in six serological profiles: (A) patients with active chronic HBV infection (HBsAg positive and HBeAg positive), (B) patients with persistent chronic HBV infection (HBsAg positive and HBeAg negative), (C) patients with isolated core antibody (isolated anti-HBc positive), (D) patients with resolved HBV infection (anti-HBc positive and anti-HBs positive), (E) vaccinated patients (anti-HBs positive), and (F) patients with all above markers negative. Chronic HBV infection (cHBV) was defined by two positive hepatitis B surface antigens (AgHBs positive) with at least 6-month intervals and chronic HBeAg positive group by a positive AgHBe (Ag HBe positive). We reviewed individual files of HIV-HBV chronically coinfected patients to assess if European recommendations in terms of HBV coinfection management were adequately followed in our center. Results: Among 2601 HIV-infected patients in active follow-up, 98 (3.8%) were chronically infected with HBV. Median age of chronically coinfected patients was 46 years with male predominance and heterosexual Africans representing the majority. Among the chronically coinfected patients, 33.7% were HBeAg positive carriers. Mean HBV DNA and ALT/AST were significantly higher in the chronic HBeAg positive (cHBeAg positive) patients compared to chronic HBeAg negative patients (cHBeAg negative). Nearly 95% of the cHBV patients were treated with two anti-HBV drugs (99% for the cHBeAg positive group), with 79% having Tenofovir (TDF) in their antiretroviral treatment history. 8% were screened for hepatitis D virus (HDV) antibodies. Liver fibrosis, upper endoscopy and alpha-foetoprotein were assessed at least once in the last 5 years in 32%, 31% and 32% of cHBV patients respectively. cHBeAg positive patients were not significantly monitored closer except for liver fibrosis assessment in 52% (p < 0.0017). Conclusion: The prevalence of cHBV coinfection in the Saint-Pierre HIV cohort is lower than in neighboring European countries. Hepatic monitoring should be reinforced in our cHBV and cHBeAg positive patients because of higher risk of progression to cirrhosis progression and hepatocellular carcinoma.
Collapse
Affiliation(s)
- Yasser Farid
- Department of Surgery, Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Charlotte Martin
- Department of Infectious Diseases, Saint-Pierre University Hospital, Brussels,
Belgium
| | - Marc Delforge
- Department of Infectious Diseases, Saint-Pierre University Hospital, Brussels,
Belgium
| | - Stephane De Wit
- Department of Infectious Diseases, Saint-Pierre University Hospital, Brussels,
Belgium
| |
Collapse
|
|
27
|
Laut K, Kirk O, Rockstroh J, Phillips A, Ledergerber B, Gatell J, Gazzard B, Horban A, Karpov I, Losso M, d'Arminio Monforte A, Pedersen C, Ristola M, Reiss P, Scherrer AU, de Wit S, Aho I, Rasmussen LD, Svedhem V, Wandeler G, Pradier C, Chkhartishvili N, Matulionyte R, Oprea C, Kowalska JD, Begovac J, Miró JM, Guaraldi G, Paredes R, Raben D, Podlekareva D, Peters L, Lundgren JD, Mocroft A. The EuroSIDA study: 25 years of scientific achievements. HIV Med 2019; 21:71-83. [PMID: 31647187 DOI: 10.1111/hiv.12810] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Revised: 09/11/2019] [Accepted: 09/17/2019] [Indexed: 01/19/2023]
Abstract
The EuroSIDA study was initiated in 1994 and follows adult people living with HIV (PLHIV) in 100 collaborating clinics across 35 countries covering all European regions, Israel and Argentina. The study aims to study the long-term virological, immunological and clinical outcomes of PLHIV and to monitor temporal changes and regional differences in outcomes across Europe. Annually collected data include basic demographic characteristics, information on AIDS- and non-AIDS-related clinical events, and details about antiretroviral therapy (ART), hepatitis C treatment and other medications, in addition to a range of laboratory values. The summer 2016 data set held data from a total of 23 071 individuals contributing 174 481 person-years of follow-up, while EuroSIDA's unique plasma repository held over 160 000 samples. Over the past 25 years, close to 300 articles have been published in peer-reviewed journals (h-index 52), covering a range of scientific focus areas, including monitoring of clinical and virological outcomes, ART uptake, efficacy and adverse events, the influence of hepatitis virus coinfection, variation in the quality of HIV care and management across settings and regions, and biomarker research. Recognizing that there remain unresolved issues in the clinical care and management of PLHIV in Europe, EuroSIDA was one of the cohorts to found The International Cohort Consortium of Infectious Disease (RESPOND) cohort consortium on infectious diseases in 2017. In celebration of the EuroSIDA study's 25th anniversary, this article aims to summarize key scientific findings and outline current and future scientific focus areas.
Collapse
Affiliation(s)
- K Laut
- Department of Infectious Diseases, CHIP, Centre of Excellence for Health, Immunity and Infections, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - O Kirk
- Department of Infectious Diseases, CHIP, Centre of Excellence for Health, Immunity and Infections, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | | | - A Phillips
- Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global health, University College London, London, UK
| | - B Ledergerber
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - J Gatell
- Hospital Clinic - IDIBAPS, University of Barcelona, Barcelona, Spain
| | - B Gazzard
- St Stephen's Clinic, Chelsea and Westminster Hospital, London, UK
| | - A Horban
- Hospital for Infectious Diseases in Warsaw, Medical University of Warsaw, Warsaw, Poland
| | - I Karpov
- Department of Infectious Diseases, Belarus State Medical University, Minsk, Belarus
| | - M Losso
- Latin America Coordination of Academic Clinical Research, Buenos Aires, Argentina
| | - A d'Arminio Monforte
- Department of Health Sciences, Clinic of Infectious Diseases, ASST Saint Paul and Charles, University of Milan, Milan, Italy
| | - C Pedersen
- Department of Infectious Diseases, Odense University Hospital, Odense, Denmark
| | - M Ristola
- Helsinki University Hospital, Helsinki, Finland
| | - P Reiss
- Division of Infectious Diseases and Department of Global Health, Academic Medical Center, University of Amsterdam and Stichting HIV Monitoring, Amsterdam, The Netherlands
| | - A U Scherrer
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - S de Wit
- CHU Saint-Pierre, Brussels, Belgium
| | - I Aho
- Helsinki University Hospital, Helsinki, Finland
| | - L D Rasmussen
- Department of Infectious Diseases, Odense University Hospital, Odense, Denmark
| | - V Svedhem
- Unit of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institute, Stockholm, Sweden
| | - G Wandeler
- Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland
| | | | - N Chkhartishvili
- Infectious Diseases, AIDS & Clinical Immunology Research Center, Tbilisi, Georgia
| | - R Matulionyte
- Department of Infectious Diseases and Dermatovenerology, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.,Centre of Infectious Diseases, Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania
| | - C Oprea
- 'Victor Babes' Clinical Hospital for Infectious and Tropical Diseases, Bucharest, Romania.,Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - J D Kowalska
- Hospital for Infectious Diseases in Warsaw, Medical University of Warsaw, Warsaw, Poland
| | - J Begovac
- University Hospital of Infectious Diseases, Zagreb, Croatia
| | - J M Miró
- Hospital Clinic - IDIBAPS, University of Barcelona, Barcelona, Spain
| | - G Guaraldi
- Department of Medical and Surgical Sciences for Adults and Children, Clinic of Infectious Diseases, University of Modena and Reggio Emilia, Modena, Italy
| | - R Paredes
- Infectious Diseases Unit &, IrsiCaixa AIDS Research Institute, Germans Trias Hospital, Badalona, Spain
| | - D Raben
- Department of Infectious Diseases, CHIP, Centre of Excellence for Health, Immunity and Infections, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - D Podlekareva
- Department of Infectious Diseases, CHIP, Centre of Excellence for Health, Immunity and Infections, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - L Peters
- Department of Infectious Diseases, CHIP, Centre of Excellence for Health, Immunity and Infections, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - J D Lundgren
- Department of Infectious Diseases, CHIP, Centre of Excellence for Health, Immunity and Infections, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - A Mocroft
- Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global health, University College London, London, UK
| |
Collapse
|
|
28
|
Prevalence and incidence of hepatitis delta in patients with chronic hepatitis B in Spain. Eur J Gastroenterol Hepatol 2018; 30:1060-1062. [PMID: 29742524 DOI: 10.1097/meg.0000000000001163] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Hepatitis delta virus (HDV) is a defective agent that only replicates in the presence of the hepatitis B virus. Accordingly, HDV acquisition may occur as superinfection of HBsAg+ carriers or following acute dual HDV and hepatitis B virus exposure. Herein, we examined the global and incident rates of HDV infections in Spain. PATIENTS AND METHODS The presence of anti-HDV antibody and new HDV superinfections was examined in all HBsAg+ patients who attended one large tertiary outclinic in Spain since year 2000. Anti-HDV antibodies were tested repeatedly every 5 years in those previously negative. RESULTS During a median follow-up of 12 years, 478 individuals were diagnosed as HBsAg+. Overall, 64.4% were male, median age was 55 years, 88.1% were native Spaniards, 6.5% were coinfected with HIV, and 7.3% were reactive for hepatitis C virus (HCV) antibodies.A total of 19 (4%) patients had anti-HDV antibody at first diagnosis. There were no further HDV seroconversions. Most anti-HDV+ patients were male (n=12), former injection drug users (n=13), and native Spaniards (n=16). Coinfection with HIV was found in six, and 12 had HCV antibodies. Interestingly, three of seven women with delta hepatitis were foreigners (Asian or African), denied injection drug use, were younger than 40 years old, and negative for both HCV and HIV. CONCLUSION The prevalence of chronic hepatitis delta is currently very low (<5%) among chronic HBsAg+ carriers in Spain, with lower rates in recent years. Moreover, new incident HDV infections were not seen in 478 chronic hepatitis B carriers since year 2000, following drastic declines in injection drug use.
Collapse
|
|
29
|
Abstract
BACKGROUND The hepatitis delta virus (HDV) causes the most aggressive form of chronic viral hepatitis. As HDV replication requires hepatitis B virus (HBV), HDV screening is limited to HBsAg+ carriers. To date, individuals with HDV-antibodies and markers of resolved hepatitis B are considered cured. However, a subset shows elevated liver enzymes and hepatic fibrosis. Could they represent HBsAg-seronegative occult HDV infections? METHODS We tested for HDV-antibodies 406 individuals with markers of past HBV exposure. RESULTS Overall, 20 (4.9%) were reactive for HDV-antibodies. All were negative for serum HDV-RNA, including four with elevated liver enzymes. CONCLUSION These results support the current policy of screening for hepatitis delta only in HBsAg+ individuals.
Collapse
|
|
30
|
Soriano V, Ramos JM, Barreiro P, Fernandez-Montero JV. AIDS Clinical Research in Spain-Large HIV Population, Geniality of Doctors, and Missing Opportunities. Viruses 2018; 10:v10060293. [PMID: 29848987 PMCID: PMC6024378 DOI: 10.3390/v10060293] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2018] [Revised: 05/24/2018] [Accepted: 05/25/2018] [Indexed: 02/07/2023] Open
Abstract
The first cases of AIDS in Spain were reported in 1982. Since then over 85,000 persons with AIDS have been cumulated, with 60,000 deaths. Current estimates for people living with HIV are of 145,000, of whom 20% are unaware of it. This explains the still high rate of late HIV presenters. Although the HIV epidemic in Spain was originally driven mostly by injection drug users, since the year 2000 men having sex with men (MSM) account for most new incident HIV cases. Currently, MSM represent over 80% of new yearly HIV diagnoses. In the 80s, a subset of young doctors and nurses working at Internal Medicine hospital wards became deeply engaged in attending HIV-infected persons. Before the introduction of antiretrovirals in the earlier 1990s, diagnosis and treatment of opportunistic infections was their major task. A new wave of infectious diseases specialists was born. Following the wide introduction of triple combination therapy in the late 1990s, drug side effects and antiretroviral resistance led to built a core of highly devoted HIV specialists across the country. Since then, HIV medicine has improved and currently is largely conducted by multidisciplinary teams of health care providers working at hospital-based outclinics, where HIV-positive persons are generally seen every six months. Antiretroviral therapy is currently prescribed to roughly 75,000 persons, almost all attended at clinics belonging to the government health public system. Overall, the impact of HIV/AIDS publications by Spanish teams is the third most important in Europe. HIV research in Spain has classically been funded mostly by national and European public agencies along with pharma companies. Chronologically, some of the major contributions of Spanish HIV research are being in the field of tuberculosis, toxoplasmosis, leishmaniasis, HIV variants including HIV-2, drug resistance, pharmacology, antiretroviral drug-related toxicities, coinfection with viral hepatitis, design and participation in clinical trials with antiretrovirals, immunopathogenesis, ageing, and vaccine development.
Collapse
Affiliation(s)
- Vicente Soriano
- Infectious Diseases Unit, La Paz University Hospital, 28046 Madrid, Spain.
- UNIR Health Sciences School, 28040 Madrid, Spain.
| | - José M Ramos
- Department of Internal Medicine, General University Hospital, 03010 Alicante, Spain.
| | - Pablo Barreiro
- Infectious Diseases Unit, La Paz University Hospital, 28046 Madrid, Spain.
| | | |
Collapse
|
|
31
|
Safaie P, Razeghi S, Rouster SD, Privitera I, Sherman KE. Hepatitis D diagnostics:Utilization and testing in the United States. Virus Res 2018; 250:114-117. [PMID: 29596839 DOI: 10.1016/j.virusres.2018.03.013] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2018] [Revised: 03/23/2018] [Accepted: 03/25/2018] [Indexed: 12/16/2022]
Abstract
Hepatitis D virus (HDV) infection may accompany acute or chronic hepatitis B virus infection. While HDV infection in the United States is thought to be uncommon, there are limited data regarding frequency of testing, and prevalence of HDV antibody and HDV RNA. We evaluated the use of HDV antibody testing using electronic medical record (EMR) data. Among 1007 HBsAg positive patients, only 121 had been tested for HDV antibody. Testing was performed primarily by gastroenterologists/hepatologists and limited testing was performed in identifiable high risk groups including those with HBV/HIV coinfection. Overall, HDV antibody was detected in 3.3% (95% C.I. = 0.9%-8.2%) An HDV RNA assay was developed and validated and 138 HBV or HBV/HIV coinfected patients were tested. The prevalence of HDV among the HBV/HIV coinfected subjects was 2.2% (95% C.I. = 0-5.3%). In a U.S. Midwestern population of HBV infected patients, HDV testing is under-employed. Overall prevalence exceeds 2% whether testing by antibody or HDV RNA and more comprehensive HDV surveillance may be indicated.
Collapse
Affiliation(s)
- Parham Safaie
- Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH, United States
| | - Sanam Razeghi
- Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH, United States
| | - Susan D Rouster
- Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH, United States
| | - Isaac Privitera
- Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH, United States
| | - Kenneth E Sherman
- Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH, United States.
| |
Collapse
|
|
32
|
Katwesigye E, Seremba E, Semitala F, Ocama P. Low sero-prevalence of hepatitis delta antibodies in HIV/ hepatitis B co-infected patients attending an urban HIV clinic in Uganda. Afr Health Sci 2017; 17:974-978. [PMID: 29937867 PMCID: PMC5870270 DOI: 10.4314/ahs.v17i4.4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Background Co-infection with hepatitis B (HBV) and hepatitis D (HDV) is common among human immunodeficiency virus (HIV) infected individuals in developing countries and it aggressively accelerates progression of liver disease to cirrhosis and other complications. There is scarcity of data on HDV in sub-Saharan Africa .We investigated the sero-prevalence and factors associated with HDV antibody among HIV/HBV co-infected patients attending a large urban HIV clinic in Uganda. Methods We screened 189 HIV/HBV co-infected individuals for anti-HDV immunoglobulin G (IgG) and performed logistic regression to determine the associated factors. Socio-demographic, clinical data, immunological status, and liver fibrosis (as determined by the Aspartate transaminase to platelet ratio index and transient elastography) were included. Results Participants were predominately young and of sound immunologic status (median age 40 years, median CD4 440 cells/µl). 98% were on ART regimens containing anti-HBV active medications (95.2% were on TDF/3TC while 4.8% on 3TC containing regimen). Median duration on ART was 36 months (IQR 22–72). Anti-HDV was detected in 6/198, 3.2% (95% CI 1.14–6.92%), associated with male gender and a duration of more than 5 years since HIV diagnosis. Conclusions The sero-prevalence of HDV antibodies among the HIV/HBV co-infected patients is low in a Ugandan urban cohort.
Collapse
Affiliation(s)
- Elizabeth Katwesigye
- Department of Medicine, Mulago Hospital and Makerere University College of Health Sciences, Kampala, Uganda
| | | | - Fred Semitala
- Department of Medicine, Mulago Hospital and Makerere University College of Health Sciences, Kampala, Uganda
| | - Ponsiano Ocama
- Department of Medicine, Mulago Hospital and Makerere University College of Health Sciences, Kampala, Uganda
| |
Collapse
|
|
33
|
Belyhun Y, Liebert UG, Maier M. Clade homogeneity and low rate of delta virus despite hyperendemicity of hepatitis B virus in Ethiopia. Virol J 2017; 14:176. [PMID: 28899424 PMCID: PMC5596854 DOI: 10.1186/s12985-017-0844-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2017] [Accepted: 09/05/2017] [Indexed: 12/14/2022] Open
Abstract
Background Although hepatitis B virus (HBV) is hyperendemic and heterogeneous in its genetic diversity in Ethiopia, little is known about hepatitis D virus (HDV) circulating genotypes and molecular diversity. Methods A total of 321 hepatitis B surface antigen (HBsAg) positives (125 HIV co-infected, 102 liver disease patients and 94 blood donors) were screened for anti-HDV antibody. The anti-HDV positive sera were subjected to Real time PCR for HDV-RNA confirmation. The non coding genome region (spanning from 467 to 834 nucleotides) commonly used for HDV genotyping as well as complete HDV genome were sequenced for genotyping and molecular analysis. Results The anti-HDV antibody was found to be 3.2% (3) in blood donors, 8.0% (10) in HIV co-infected individuals and 12.7% (13) in liver disease patients. None of the HIV co-infected patients who revealed HBV lamivudine (3TC) resistance at tyrosine-methionine/isoleucine-aspartate-aspartate (YM(I)DD) reverse transcriptase (RT) motif with concomitant vaccine escape gene mutants was positive for anti-HDV antibody. The HDV viremia rate was 33.3%, 30.0% and 23.1% in respect to the above study groups. All the six isolates sequenced were phylogenetically classified as HDV genotype 1 (HDV-1) and grouped into two monophyletic clusters. Amino acid (aa) residues analysis of clathrin heavy chain (CHC) domain and the isoprenylation signal site (Py) at 19 carboxyl (C)-terminal amino acids (aa 196–214) and the HDV RNA binding domain (aa 79–107) were highly conserved and showed a very little nucleotide variations. All the sequenced isolates showed serine at amino acid position 202. The RNA editing targets of the anti-genomic HDV RNA (nt1012) and its corresponding genomic RNA (nt 580) showed nucleotides A and C, respectively. Conclusions The low seroprevalence and viraemic rates of HDV in particular during HIV-confection might be highly affected by HBV drug resistance selected HBsAg mutant variants in this setting, although HDV-1 sequences analysis revealed clade homogeneity and highly conserved structural and functional domains. Thus, the potential role of HBV drug resistance associated polymerase mutations and concomitant HBsAg protein variability on HDV viral assembly, secretion and infectivity needs further investigation.
Collapse
Affiliation(s)
- Yeshambel Belyhun
- Institute of Virology, Medical Faculty, Leipzig University, Johannisallee 30, 04103, Leipzig, Germany. .,School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia.
| | - Uwe Gerd Liebert
- Institute of Virology, Medical Faculty, Leipzig University, Johannisallee 30, 04103, Leipzig, Germany
| | - Melanie Maier
- Institute of Virology, Medical Faculty, Leipzig University, Johannisallee 30, 04103, Leipzig, Germany
| |
Collapse
|
|
34
|
Alcohol use, viral hepatitis and liver fibrosis among HIV-positive persons in West Africa: a cross-sectional study. J Int AIDS Soc 2017; 19:21424. [PMID: 28362065 PMCID: PMC5467604 DOI: 10.7448/ias.20.1.21424] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Introduction: Liver fibrosis is often the first stage of liver disease in people living with HIV (PLWHIV) in industrialized countries. However, little is known about liver fibrosis and its correlates among PLWHIV in sub-Saharan Africa. Methods: The study was undertaken in three HIV referral clinics in Côte d’Ivoire, Senegal and Togo. Enrolled PLWHIV underwent a non-invasive assessment of liver fibrosis combining liver stiffness measure (LSM) with transient elastography and the aspartate aminotransferase-to-platelet ratio index (APRI). Significant liver fibrosis was defined as LSM ≥7.1 kPa. Patients were screened for alcohol use (alcohol use disorder identification test (AUDIT)-C questionnaire), hepatitis B virus (HBV) antigen, hepatitis Delta virus (HDV) antibody and anti-hepatitis C (HCV) antibody. A logistic regression model was used to identify the factors associated with significant liver fibrosis. Results: A total of 807 PLWHIV were screened at a median age of 43 years (interquartile range (IQR): 36–50). Their median CD4 count was 393 cells/mm3 (IQR: 234–563) and 682 (84.5%) were on antiretroviral therapy (ART). The prevalence of significant fibrosis was 5.3% (3.8–6.7). Infections with HBV and HCV were identified in 74 (9.2%) and nine (1.1%) participants. Main factors associated with liver fibrosis were alcohol use (AUDIT-C >6): (odds ratio (OR) = 4.0, confidence interval (CI): 1.2–14.0), (Ref. AUDIT-C <4) and HBV infection (OR = 2.9, CI: 1.2–7.2). Of the 74 patients positively screened for HBV, 50.0% were on a tenofovir-based ART regimen. Overall, 10% of HIV/HBV coinfected patients were detected with a positive HDV antibody with a higher prevalence in patients with a significant liver fibrosis (43.0%) compared to others (6.3%) (p = 0.01). Conclusions: Considering the WHO recommendations to screen for HBV infection and treat co-infected patients with tenofovir-based ART, screening of alcohol use and brief interventions to prevent alcohol abuse should be implemented in West Africa, especially in HBV/HIV co-infected patients.
Collapse
|
|
35
|
Chronic Hepatitis B, C, and D. Microbiol Spectr 2017; 4. [PMID: 27726758 DOI: 10.1128/microbiolspec.dmih2-0025-2015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Chronic hepatitis B, C, and D virus infections contribute significantly to the morbidity and mortality of immunocompromised individuals. To contextualize discussion of these infections in immunocompromised patients, this paper provides an overview of aspects of infection in normal hosts. It then describes differences in disease, diagnostic testing, and therapeutic management observed in immunocompromised patients.
Collapse
|
|
36
|
Abstract
Viral liver diseases are frequent comorbidities and major contributors to death in HIV-positive individuals on antiretroviral therapy. Although cure of hepatitis C and control of hepatitis B with antivirals avert liver disease progression in most HIV-coinfected patients, the lack of satisfactory treatment for hepatitis delta virus (HDV) infection remains a major threat for developing cirrhosis and liver cancer in this population. In the European Union (EU) and North America, sexual contact has replaced injection drug use that has been the major transmission route for HDV in HIV-positive persons. PegIFNα is the only approved HDV therapy; however, sustained HDV-RNA clearance is achieved by less than 25%. The recent discovery of sodium taurocholate cotransporting polypeptide as the key hepatitis B virus (HBV) and HDV cell entry receptor has opened the door to a new therapeutic era. Indeed, promising results have been released using Myrcludex-B, a sodium taurocholate cotransporting polypeptide inhibitor. More encouraging are data with new classes of HDV blockers, such as prenylation inhibitors (i.e. lonafarnib) and nucleic acid polymers. At this time, sustained suppression of HDV replication is the primary goal of HDV therapy, as it is associated with normalization of liver enzymes and histological improvement. Of note, the use of specific antivirals for HDV must be given along with anti-HBV agents to prevent HBV rebounds following removal of viral interference. The lack of persistent forms of HDV-RNA could provide a unique opportunity for curing hepatitis delta, even without eliminating HBV circular covalently closed DNA. Ultimately, suppression of HDV replication along with hepatitis B surface antigen clearance once drugs are off would be the best reflect of hepatitis delta cure.
Collapse
|
|
37
|
Alfaiate D, Miaglia C, Zoulim F. Hépatite delta : aspects cliniques et perspectives thérapeutiques. Presse Med 2017; 46:271-281. [DOI: 10.1016/j.lpm.2016.10.013] [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: 09/22/2016] [Accepted: 10/10/2016] [Indexed: 10/20/2022] Open
|
|
38
|
Béguelin C, Moradpour D, Sahli R, Suter-Riniker F, Lüthi A, Cavassini M, Günthard HF, Battegay M, Bernasconi E, Schmid P, Calmy A, Braun DL, Furrer H, Rauch A, Wandeler G. Hepatitis delta-associated mortality in HIV/HBV-coinfected patients. J Hepatol 2017; 66:297-303. [PMID: 27746337 DOI: 10.1016/j.jhep.2016.10.007] [Citation(s) in RCA: 91] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2016] [Revised: 09/28/2016] [Accepted: 10/03/2016] [Indexed: 12/16/2022]
Abstract
BACKGROUND & AIMS Hepatitis delta virus (HDV) infection accelerates the progression of hepatitis B virus (HBV)-related liver disease. We assessed the epidemiological characteristics of HDV infection in the nationwide Swiss HIV Cohort Study and evaluated its impact on clinical outcomes. METHODS All HIV-infected patients with a positive hepatitis B surface antigen test were considered and tested for anti-HDV antibodies. HDV amplification and sequencing were performed in anti-HDV-positive patients. Demographic and clinical characteristics at initiation of antiretroviral therapy, as well as causes of death were compared between HDV-positive and HDV-negative individuals using descriptive statistics. Kaplan-Meier and multivariable Cox regression analyses were used to evaluate the association between HDV infection and overall mortality, liver-related mortality as well as incidence of hepatocellular carcinoma (HCC). RESULTS Of 818 patients with a positive hepatitis B surface antigen tests, 771 (94%) had a stored serum sample available and were included. The prevalence of HDV infection was 15.4% (119/771, 95% CI: 12.9-18.0) and the proportion of HDV-positive patients with HDV replication 62.9% (73/116). HDV-infected patients were more likely to be persons who inject drugs (60.6% vs. 9.1%) and to have a positive hepatitis C virus (HCV) serology (73.1% vs. 17.8%) compared to HDV-uninfected ones. HDV infection was strongly associated with overall death (adjusted hazard ratio 2.33, 95% CI 1.41-3.84), liver-related death (7.71, 3.13-18.97) and with the occurrence of HCC (9.30, 3.03-28.61). Results were similar when persons who inject drugs or HCV-coinfected patients were excluded from the analyses. CONCLUSIONS The prevalence of HDV in hepatitis B surface antigen-positive patients in the Swiss HIV Cohort Study (SHCS) is high and HDV infection is independently associated with mortality and liver-related events, including HCC. LAY SUMMARY Hepatitis delta virus (HDV) infection accelerates the progression of hepatitis B virus (HBV)-related liver disease. In a nationwide cohort of HIV-infected individuals in Switzerland, 15% of HBV-coinfected patients had antibodies to HDV infection, of which a majority had active HDV replication. HDV-infected individuals were 2.5 times more likely to die, eight times more likely to die from a liver-related cause and nine times more likely to develop liver cancer compared to HDV-uninfected ones. Our results emphasize the need for prevention programs (including HBV vaccination), the systematic screening of at risk populations as well as close monitoring, and underline the importance of developing new treatments for chronic HDV infection.
Collapse
Affiliation(s)
- Charles Béguelin
- Department of Infectious Diseases, Bern University Hospital, University of Bern, Switzerland
| | - Darius Moradpour
- Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Switzerland
| | - Roland Sahli
- Institute of Microbiology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Switzerland
| | | | - Alexander Lüthi
- Institute for Infectious Diseases, Faculty of Medicine, University of Bern, Switzerland
| | - Matthias Cavassini
- Division of Infectious Diseases, University Hospital Lausanne, University of Lausanne, Switzerland
| | - Huldrych F Günthard
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Switzerland; Institute of Medical Virology, University of Zurich, Switzerland
| | - Manuel Battegay
- Division of Infectious Diseases & Hospital Hygiene, University Hospital Basel, Switzerland
| | - Enos Bernasconi
- Division of Infectious Diseases, Regional Hospital Lugano, Switzerland
| | - Patrick Schmid
- Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St.Gallen, Switzerland
| | - Alexandra Calmy
- Division of Infectious Diseases, University Hospital Geneva, University of Geneva, Switzerland
| | - Dominique L Braun
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Switzerland; Institute of Medical Virology, University of Zurich, Switzerland
| | - Hansjakob Furrer
- Department of Infectious Diseases, Bern University Hospital, University of Bern, Switzerland
| | - Andri Rauch
- Department of Infectious Diseases, Bern University Hospital, University of Bern, Switzerland
| | - Gilles Wandeler
- Department of Infectious Diseases, Bern University Hospital, University of Bern, Switzerland; Institute of Social and Preventive Medicine, University of Bern, Switzerland.
| | | |
Collapse
|
|
39
|
Aguilera A, Trastoy R, Barreiro P, Costa JJ, de Mendoza C, Peña JM, Soriano V. Decline and changing profile of hepatitis delta among injection drug users in Spain. Antivir Ther 2017; 23:87-90. [PMID: 28353446 DOI: 10.3851/imp3161] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/27/2017] [Indexed: 10/19/2022]
|
|
40
|
Katwesigye E, Seremba E, Semitala F, Ocama P. Low sero-prevalence of hepatitis delta antibodies in HIV/ hepatitis B co-infected patients attending an urban HIV clinic in Uganda. Afr Health Sci 2016; 16:1089-1093. [PMID: 28479902 DOI: 10.4314/ahs.v16i4.26] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND Co-infection with hepatitis B (HBV) and hepatitis D (HDV) is common among human immunodeficiency virus (HIV) infected individuals in developing countries and it aggressively accelerates progression of liver disease to cirrhosis and other complications. There is scarcity of data on HDV in sub-Saharan Africa .We investigated the sero-prevalence and factors associated with HDV antibody among HIV/HBV co-infected patients attending a large urban HIV clinic in Uganda. METHODS We screened 189 HIV/HBV co-infected individuals for anti-HDV immunoglobulin G (IgG) and performed logistic regression to determine the associated factors. Socio-demographic, clinical data, immunological status, and liver fibrosis (as determined by the Aspartate transaminase to platelet ratio index and transient elastography) were included. RESULTS Participants were predominately young and of sound immunologic status (median age 40 years, median CD4 440 cells/µl). 98% were on ART regimens containing anti-HBV active medications (95.2% were on TDF/3TC while 4.8% on 3TC containing regimen). Median duration on ART was 36 months (IQR 22-72). Anti-HDV was detected in 6/198, 3.2% (95% CI 1.14-6.92%), associated with male gender and a duration of more than 5 years since HIV diagnosis. CONCLUSIONS The sero-prevalence of HDV antibodies among the HIV/HBV co-infected patients is low in a Ugandan urban cohort.
Collapse
Affiliation(s)
- Elizabeth Katwesigye
- Department of Medicine, Mulago Hospital and Makerere University College of Health Sciences, Kampala, Uganda
| | | | - Fred Semitala
- Department of Medicine, Mulago Hospital and Makerere University College of Health Sciences, Kampala, Uganda
| | - Ponsiano Ocama
- Department of Medicine, Mulago Hospital and Makerere University College of Health Sciences, Kampala, Uganda
| |
Collapse
|
|
41
|
Performance Characteristics of a New Consensus Commercial Kit for Hepatitis D Virus RNA Viral Load Quantification. J Clin Microbiol 2016; 55:431-441. [PMID: 27881614 DOI: 10.1128/jcm.02027-16] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2016] [Accepted: 11/07/2016] [Indexed: 12/16/2022] Open
Abstract
Hepatitis D virus (HDV) is responsible for fulminant hepatitis and liver failure and accelerates evolution toward cirrhosis and hepatocellular carcinoma in hepatitis B virus (HBV)-infected patients. To date, treatment relies upon long-term administration of pegylated alpha-interferon with a sustained virological response in 30% of the patients. Very recently, new, promising anti-HDV therapies have been developed and are already being used in clinical trials. HDV RNA viral load (HDVL) monitoring must be an integral part of the management of the infected patients. However, HDV genus is characterized by a high genetic variability into eight genotypes (HDV-1 to -8), and most available in-house or commercial assays are useful for only a limited subset of genotypes. Results of a comparison of the performance of a new kit for HDVL quantification with the consensus in-house assay of the French National Reference Laboratory for HDV developed in 2005 are reported here. A total of 611 clinical samples of all HDV genotypes with various HDVL values, including several consecutive samples over several years from 36 patients, were studied. A specificity, sensitivity, and reproducibility evaluation was conducted using HDV-positive clinical samples, hepatitis A, B, C and E (HAV, HBV, HCV, and HEV, respectively) and HIV mono-infected samples, and the WHO HDV RNA international standard. Overall results were strictly comparable between the two assays (median difference, 0.07 log IU/ml), with high diagnosis precision and capacity. In summary, this new kit showed high performance in detection/quantification of HDVL, regardless of the genotype of the infecting strain used, and seems to be a suitable tool for patient management.
Collapse
|
|
42
|
Hsieh MH, Wang SC, Hsieh MY, Huang CF, Yeh ML, Yang JF, Chang K, Lin WR, Lin CY, Chen TC, Huang JF, Dai CY, Tsai JJ, Chuang WL, Yu ML. Hepatitis D virus infections among injecting drug users with and without human immunodeficiency virus infection in Taiwan. Kaohsiung J Med Sci 2016; 32:526-530. [PMID: 27742037 DOI: 10.1016/j.kjms.2016.08.004] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2016] [Revised: 08/01/2016] [Accepted: 07/27/2016] [Indexed: 11/19/2022] Open
Abstract
In Taiwan, injecting drug use has been the main route of human immunodeficiency virus (HIV) transmission since 2005, with hepatitis B virus (HBV) and hepatitis D virus (HDV) also having similar transmission routes. This has now become an important public health issue. The aim of this study is to explore the conditions of HDV infections between injecting drug users (IDUs) with and without HIV infection in Southern Taiwan. In this study, 87 IDUs were enrolled, including 27 anti-HDV seronegative IDUs and 60 anti-HDV seropositive IDUs, and the results of their liver function tests, CD4 cell counts, and anti-HIV and HIV RNA levels were analyzed. The prevalence of anti-HDV seropositivity among hepatitis B surface antigen (HBsAg) seropositive IDUs in this study was 68.9% (60/87). The prevalence rate of anti-HDV seropositive IDUs among anti-HIV seronegative and anti-HIV seropositive cases was 40.0% (12/30) and 84.2% (48/57), respectively. Anti-HIV seropositivity was related to anti-HDV seropositivity (odds ratio = 9.34, 95% confidence interval = 2.67-31.59, p < 0.001). Among IDUs with HIV infection, there was no significant difference in CD4 cell counts and HIV RNA viral load between HBsAg-positive patients with anti-HDV seronegativity and those with anti-HDV seropositivity. In conclusion, the prevalence of HDV infection among IDUs is higher among IDUs with HIV infection. Because anti-HIV seropositivity is significantly related to anti-HDV seropositivity, HDV infection among IDUs is still important. We suggest that for IDUs, HBsAg and anti-HDV should be monitored closely.
Collapse
Affiliation(s)
- Meng-Hsuan Hsieh
- Health Management Center, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung City, Taiwan; School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan
| | - Shu-Chi Wang
- Hepatitis Center and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung City, Taiwan
| | - Ming-Yen Hsieh
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung City, Taiwan
| | - Chung-Feng Huang
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan; Department of Occupational Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung City, Taiwan
| | - Ming-Lun Yeh
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung City, Taiwan
| | - Jeng-Fu Yang
- Health Management Center, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung City, Taiwan
| | - Ko Chang
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan; Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung City, Taiwan
| | - Wei-Ru Lin
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung City, Taiwan
| | - Chun-Yu Lin
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan; Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung City, Taiwan
| | - Tun-Chieh Chen
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan; Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung City, Taiwan
| | - Jee-Fu Huang
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan; Hepatitis Center and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung City, Taiwan
| | - Chia-Yen Dai
- Health Management Center, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung City, Taiwan; School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan; Hepatitis Center and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung City, Taiwan
| | - Jih-Jin Tsai
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan; Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung City, Taiwan; Tropical Medicine Center, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung City, Taiwan.
| | - Wan-Long Chuang
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan; Hepatitis Center and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung City, Taiwan
| | - Ming-Lung Yu
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan; Hepatitis Center and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung City, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan
| |
Collapse
|
|
43
|
Affiliation(s)
- Vincent Soriano
- Infectious Diseases Unit, IdiPAZ & La Paz University Hospital, Madrid, Spain
| | - Pablo Barreiro
- Infectious Diseases Unit, IdiPAZ & La Paz University Hospital, Madrid, Spain
| | - Carmen de Mendoza
- Puerta de Hierro Research Institute & University Hospital, Majadahonda, Spain
| |
Collapse
|
|
44
|
Rizzetto M, Smedile A, Ciancio A. Hepatitis D. CLINICAL VIROLOGY 2016:1409-1423. [DOI: 10.1128/9781555819439.ch58] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
|
|
45
|
Soriano V, Labarga P, de Mendoza C, Fernández-Montero JV, Treviño A, Benítez-Gutiérrez L, Peña JM, Barreiro P. Delta hepatitis: new approaches to therapy. Future Virol 2016. [DOI: 10.2217/fvl-2015-0009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Hepatitis delta virus (HDV) infection is a neglected disease despite causing the most severe form of viral hepatitis. Over 15 million people are infected worldwide. IFN-α is largely inefficient and poorly tolerated. The discovery of sodium taurocholate cotransporting polypeptide as the cell receptor for HBV (and consequently for HDV) has allowed development of viral entry inhibitors (i.e., myrcludex-B). More recently, prenylation inhibitors (i.e., lonafarnib) that disrupt virion assembly are being tested. At this time, sustained suppression of HDV replication is the primary goal of hepatitis delta treatment, being associated with normalization of liver enzymes and histological improvement. The lack of persistent forms of HDV-RNA could provide unique opportunities for hepatitis delta cure using specific antivirals, even in the face of persistent HBV cccDNA.
Collapse
Affiliation(s)
- Vincent Soriano
- Infectious Diseases Unit, La Paz University Hospital, Madrid, Spain
| | - Pablo Labarga
- Department of Internal Medicine, La Luz Clinic, Madrid, Spain
| | - Carmen de Mendoza
- Department of Internal Medicine, Puerta de Hierro Research Institute & University Hospital, Majadahonda, Spain
| | | | - Ana Treviño
- Infectious Diseases Unit, La Paz University Hospital, Madrid, Spain
| | - Laura Benítez-Gutiérrez
- Department of Internal Medicine, Puerta de Hierro Research Institute & University Hospital, Majadahonda, Spain
| | - José M Peña
- Infectious Diseases Unit, La Paz University Hospital, Madrid, Spain
| | - Pablo Barreiro
- Infectious Diseases Unit, La Paz University Hospital, Madrid, Spain
| |
Collapse
|
|
46
|
Uncontrolled hepatitis delta virus infection after initial suppression on tenofovir in a HIV/HBV-coinfected patient. AIDS 2016; 30:530-2. [PMID: 26760236 DOI: 10.1097/qad.0000000000000972] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
|
|
47
|
Wranke A, Heidrich B, Hardtke S, Wedemeyer H. Current Management of HBV/HDV Coinfection and Future Perspectives. ACTA ACUST UNITED AC 2015. [DOI: 10.1007/s11901-015-0280-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
|
|
48
|
Epidemiology of sexually transmitted viral hepatitis in human immunodeficiency virus-positive men who have sex with men in Asia. J Formos Med Assoc 2015; 114:1154-61. [PMID: 26375778 DOI: 10.1016/j.jfma.2015.08.008] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2015] [Revised: 07/02/2015] [Accepted: 08/11/2015] [Indexed: 01/10/2023] Open
Abstract
Both human immunodeficiency virus (HIV) and viral hepatitis constitute major disease burden globally. As with other parts of the world, the HIV epidemic in Asia impacts mainly on men who have sex with men, one of the at-risk populations for sexually transmitted viral hepatitis. With the increasing availability of effective antiretroviral therapy, HIV-related mortality of people living with HIV has markedly reduced. Liver disease has become an important cause of mortality and morbidity in the HIV-infected population. With the improvement of socioeconomic conditions and availability of healthcare in Asian countries in recent years, the epidemiology of sexually transmitted viral hepatitis among HIV-positive men who have sex with men has also evolved. This review updates the epidemiology of different types of sexually transmitted viral hepatitis in this defined population in Asia.
Collapse
|
|
49
|
Motamedifar M, Taheri M, Lankarani KB, Gholami M, Lari MA, Faramarzi H, Sarvari J. The Prevalence and Risk Factors of Hepatitis Delta Virus in HIV/HBV Co-Infected Patients in Shiraz, Iran, 2012. IRANIAN JOURNAL OF MEDICAL SCIENCES 2015; 40:448-53. [PMID: 26379352 PMCID: PMC4567605] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/06/2014] [Revised: 06/23/2014] [Accepted: 07/13/2014] [Indexed: 11/13/2022]
Abstract
Evidence has shown that liver disease caused by hepatitis viruses can be more aggressive and severe in HIV infected subjects. Therefore, the present cross-sectional study aimed to evaluate the seroprevalence of HDV infection among HIV/HBV co-infected clients in Shiraz, southwest Iran. In this study, 178 patients co-infected with HBV and HIV individuals were enrolled. The diagnosis of HIV infection was documented based on serological assays. The demographic and complementary data were collected by a questionnaire. HBsAg and HDV Ab were detected by commercial quantitative enzyme linked immunosorbent assay kits according to the manufacturer's instructions. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also measured. The mean age of the participants was 37.4±7.4 years (range 22-63). 175 (98.4 %) patients were male and 3 (1.6 %) were female. Among 178 patients co-infected with HIV/HBV, 35 cases (19.7%, 95% CI: 14%-25%) were anti-HDV positive and 143 (80.3%) were negative for anti-HDV. HDV exposure in HIV/HBV co-infected patients was associated with blood transfusion (P=0.002, OR: 14.3) and prison history (P=0.01, OR: 2.31) but not with age, marital status, unsafe sex contact, and injection drug abuse. Our data showed a relatively high prevalence of HDV infection in HIV infected population in Shiraz, Iran. The high frequency of HDV Ab in patients with blood transfusion and prison history reveals that HDV transmission occurs more frequently in the parental route than sexual contacts; therefore, blood screening for HDV diagnosis in the high-risk group is recommended.
Collapse
Affiliation(s)
- Mohammad Motamedifar
- Shiraz HIV/AIDS Research Center (SHARC), Shiraz University of Medical Sciences, Shiraz, Iran,Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammad Taheri
- Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Kamran Bagheri Lankarani
- Health Policy Research Center (HPRC), School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mina Gholami
- Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mahmood Amini Lari
- Shiraz HIV/AIDS Research Center (SHARC), Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hossein Faramarzi
- Shiraz HIV/AIDS Research Center (SHARC), Shiraz University of Medical Sciences, Shiraz, Iran
| | - Jamal Sarvari
- Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran,Correspondence: Jamal Sarvari, PhD; Assistant Professor of Virology, Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, P.O. Box: 71348- 45794, Shiraz, Iran Tel/Fax: +98 71 32304356
| |
Collapse
|
|
50
|
|