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Hermanussen L, Lampalzer S, Bockmann JH, Ziegler AE, Piecha F, Dandri M, Pischke S, Haag F, Lohse AW, Lütgehetmann M, Weiler-Normann C, zur Wiesch JS. Non-organ-specific autoantibodies with unspecific patterns are a frequent para-infectious feature of chronic hepatitis D. Front Med (Lausanne) 2023; 10:1169096. [PMID: 37387781 PMCID: PMC10300640 DOI: 10.3389/fmed.2023.1169096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2023] [Accepted: 05/18/2023] [Indexed: 07/01/2023] Open
Abstract
Infections with hepatotropic viruses are associated with various immune phenomena. Hepatitis D virus (HDV) causes the most severe form of viral hepatitis. However, few recent data are available on non-disease-specific and non-organ-specific antibody (NOSA) titers and immunoglobulin G (IgG) levels in chronic hepatitis D (CHD) patients. Here, we examined the NOSA titers and IgG levels of 40 patients with CHD and different disease courses and compared them to 70 patients with chronic hepatitis B (CHB) infection. 43% of CHD patients had previously undergone treatment with pegylated interferon-α (IFN-α). The antibody display of 46 untreated patients diagnosed with autoimmune hepatitis (AIH) was used as a reference. The frequency of elevated NOSA titers (CHD 69% vs. CHB 43%, p < 0.01), and the median IgG levels (CHD 16.9 g/L vs. CHB 12.7 g/L, p < 0.01) were significantly higher in CHD patients than in patients with CHB, and highest in patients with AIH (96%, 19.5 g/L). Also, the antinuclear antibody pattern was homogeneous in many patients with AIH and unspecific in patients with viral hepatitis. Additionally, f-actin autoantibodies were only detectable in patients with AIH (39% of SMA). In CHD patients, IgG levels correlated with higher HDV viral loads, transaminases, and liver stiffness values. IgG levels and NOSA were similar in CHD patients irrespective of a previous IFN-α treatment. In summary, autoantibodies with an unspecific pattern are frequently detected in CHD patients with unclear clinical relevance.
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Affiliation(s)
- Lennart Hermanussen
- Department of Medicine (Gastroenterology, Hepatology, Infectious diseases, and Tropical Medicine), University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany
| | - Sibylle Lampalzer
- Department of Medicine (Gastroenterology, Hepatology, Infectious diseases, and Tropical Medicine), University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany
| | - Jan-Hendrik Bockmann
- Department of Medicine (Gastroenterology, Hepatology, Infectious diseases, and Tropical Medicine), University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany
- German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel-Riems Site, Hamburg, Germany
| | - Annerose E. Ziegler
- Department of Medicine (Gastroenterology, Hepatology, Infectious diseases, and Tropical Medicine), University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany
| | - Felix Piecha
- Department of Medicine (Gastroenterology, Hepatology, Infectious diseases, and Tropical Medicine), University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany
- German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel-Riems Site, Hamburg, Germany
| | - Maura Dandri
- Department of Medicine (Gastroenterology, Hepatology, Infectious diseases, and Tropical Medicine), University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany
- German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel-Riems Site, Hamburg, Germany
| | - Sven Pischke
- Department of Medicine (Gastroenterology, Hepatology, Infectious diseases, and Tropical Medicine), University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany
- German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel-Riems Site, Hamburg, Germany
| | - Friedrich Haag
- Institute of Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Ansgar W. Lohse
- Department of Medicine (Gastroenterology, Hepatology, Infectious diseases, and Tropical Medicine), University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany
- German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel-Riems Site, Hamburg, Germany
| | - Marc Lütgehetmann
- German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel-Riems Site, Hamburg, Germany
- Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany
| | - Christina Weiler-Normann
- Department of Medicine (Gastroenterology, Hepatology, Infectious diseases, and Tropical Medicine), University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany
- Department of Medicine and Martin Zeitz Centre for Rare Diseases, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - Julian Schulze zur Wiesch
- Department of Medicine (Gastroenterology, Hepatology, Infectious diseases, and Tropical Medicine), University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany
- German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel-Riems Site, Hamburg, Germany
- Institute of Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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Abstract
INTRODUCTION Treatment of chronic hepatitis D still relies on Interferon. To improve efficacy, new therapeutic strategies are in development which aim to deprive the Hepatitis D Virus (HDV) of functions of the Hepatitis B Virus and of the host required for its life-cycle. Areas covered: The therapeutic options are; 1) The inhibition of the farnesylation of the large HD-protein permissive of virion assembly with Lonafarnib, 2) The blocking of HBsAg entry into cells with Myrcludex B via the inhibition of the Sodium Taurocholate Cotransporting Receptor, to prevent the spreading of HDV to uninfected hepatocytes, 3) The reduction of subviral HBsAg particles by REP 2139, leading to diminished virion morphogenesis . Expert opinion: Lonafarnib and Myrcludex reduced serum HVD-RNA; neither diminished serum HBsAg. NAP REP-2139 diminished both HDV-RNA and HBsAg in serum; a full report is awaited. In combination with Peg-Interferon, these new drugs may provide additional efficacy.
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Affiliation(s)
- Mario Rizzetto
- a Department of Medicine , University of Torino , Torino , Italy
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Niro GA, Smedile A, Fontana R, Olivero A, Ciancio A, Valvano MR, Pittaluga F, Coppola N, Wedemeyer H, Zachou K, Marrone A, Fasano M, Lotti G, Andreone P, Iacobellis A, Andriulli A, Rizzetto M. HBsAg kinetics in chronic hepatitis D during interferon therapy: on-treatment prediction of response. Aliment Pharmacol Ther 2016; 44:620-8. [PMID: 27443972 DOI: 10.1111/apt.13734] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2016] [Revised: 05/10/2016] [Accepted: 06/27/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND Therapy of chronic hepatitis D with Interferon is successful when testing for HDV-RNA turns negative. This end-point is disputed. AIM To assess the role of serum hepatitis B surface antigen (HBsAg) in the clearance of HDV-RNA in pegylated interferon (Peg-IFN)-treated chronic hepatitis D (CHD). METHODS Sixty-two patients with CHD, treated with Peg-IFN, were considered. The patients belonged to three groups: 14 patients cleared the HBsAg and HDV-RNA (responders, R), 12 cleared the HDV-RNA remaining positive for HBsAg (partial responders, PR) and 36 cleared neither the HBsAg nor the HDV-RNA (nonresponders, NR). RESULTS In responders, at baseline the median value (mv) of HBsAg and HDV-RNA was 1187 and 188 663 IU/mL. By month 6 of therapy, HBsAg declined to less than 1000 IU/mL and HDV-RNA was undetectable in 12 patients. In NR, the pre-therapy median value of HBsAg and HDV viremia was 6577 and 676 319 IU/mL. There was no significant reduction of antigen at month 6; after a decline, HDV-RNA rebounded to baseline levels. In PR, the median value of baseline HBsAg was 7031 IU/mL; it declined at month 6 in the majority. HDV-RNA progressively declined from an initial median value of 171 405 IU/mL. HBsAg <1000 IU/mL at month 6 discriminated responders and PR from NR (P < 0.001). By ROC curve, the threshold of 0.105 log reduction of HBsAg associated with 1.610 log reduction of HDV-RNA from baseline to month 6 predicted the clearance of this marker. CONCLUSIONS A reduction of serum HBsAg is mandatory for the definitive clearance of the HDV-RNA. Quantitative HBsAg may predict the long-term response to Peg-IFN therapy and provide a guide to prolong or stop treatment.
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Affiliation(s)
- G A Niro
- Gastroenterology Unit, IRCCS 'Casa Sollievo Sofferenza' Hospital, San Giovanni Rotondo (FG), Italy
| | - A Smedile
- Department of Medical Sciences University of Turin, Division of Gastroenterology and Hepatology, Città della Salute e della Scienza University Hospital, Turin, Italy
| | - R Fontana
- Gastroenterology Unit, IRCCS 'Casa Sollievo Sofferenza' Hospital, San Giovanni Rotondo (FG), Italy
| | - A Olivero
- Department of Medical Sciences University of Turin, Division of Gastroenterology and Hepatology, Città della Salute e della Scienza University Hospital, Turin, Italy
| | - A Ciancio
- Department of Medical Sciences University of Turin, Division of Gastroenterology and Hepatology, Città della Salute e della Scienza University Hospital, Turin, Italy
| | - M R Valvano
- Gastroenterology Unit, IRCCS 'Casa Sollievo Sofferenza' Hospital, San Giovanni Rotondo (FG), Italy
| | - F Pittaluga
- Microbiology and Virology Unit, A.O. Città della Salute e della Scienza, Molinette Hospital, University of Turin, Turin, Italy
| | - N Coppola
- Department of Mental Health and Public Medicine, Second University of Naples, Caserta, Italy
| | - H Wedemeyer
- Department for Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, German Center for Infection Research, Hannover, Germany
| | - K Zachou
- Department of Medicine and Research Laboratory of Internal Medicine, School of Medicine, University of Thessaly, Larissa, Greece
| | - A Marrone
- Internal Medicine and Hepatology, Second University of Naples, Italy
| | - M Fasano
- Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy
| | - G Lotti
- IRCCS 'Casa Sollievo Sofferenza' Hospital, Blood Bank, San Giovanni Rotondo (FG), Italy
| | - P Andreone
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - A Iacobellis
- Gastroenterology Unit, IRCCS 'Casa Sollievo Sofferenza' Hospital, San Giovanni Rotondo (FG), Italy
| | - A Andriulli
- Gastroenterology Unit, IRCCS 'Casa Sollievo Sofferenza' Hospital, San Giovanni Rotondo (FG), Italy
| | - M Rizzetto
- Department of Medical Sciences University of Turin, Division of Gastroenterology and Hepatology, Città della Salute e della Scienza University Hospital, Turin, Italy
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Dienstag JL. Antiviral Drugs against Hepatitis Viruses. MANDELL, DOUGLAS, AND BENNETT'S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES 2015:563-575.e3. [DOI: 10.1016/b978-1-4557-4801-3.00046-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Dienstag JL, Delemos AS. Viral Hepatitis. MANDELL, DOUGLAS, AND BENNETT'S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES 2015:1439-1468.e7. [DOI: 10.1016/b978-1-4557-4801-3.00119-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Soriano V, de Mendoza C, Fernández-Montero JV, Labarga P, Barreiro P. Management and treatment of chronic hepatitis B in HIV-positive patients. Ann Med 2014; 46:290-6. [PMID: 24716736 DOI: 10.3109/07853890.2014.899103] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Chronic hepatitis B virus (HBV) infection is common in HIV-positive individuals, mainly among those with sexually risky behaviors. Although HBV vaccination is mandatory in all HIV-infected persons with negative HBV markers, lower rates of protection due to abnormal immune responses are achieved. HIV accelerates the course of liver disease caused by chronic HBV infection, leading rapidly to end-stage hepatic illness and increasing the risk of hepatocellular carcinoma. Treatment of HIV including nucleos(t)ide analogues active against HBV highly improves outcomes, especially when tenofovir is part of the antiviral regimen. The use of lamivudine as the only active anti-HBV agent in HIV-HBV co-infected patients should be limited to individuals with low serum HBV-DNA levels. Otherwise, selection of drug resistance may eliminate any clinical benefit, produce cross-resistance to other antivirals, and favor the emergence of HBV vaccine escape mutants.
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Affiliation(s)
- Vincent Soriano
- Department of Infectious Diseases , Hospital Carlos III, Madrid , Spain
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Botelho-Souza LF, dos Santos ADO, Borzacov LM, Honda ER, Villalobos-Salcedo JM, Vieira DS. Development of a reverse transcription quantitative real-time PCR-based system for rapid detection and quantitation of hepatitis delta virus in the western Amazon region of Brazil. J Virol Methods 2013; 197:19-24. [PMID: 24316446 DOI: 10.1016/j.jviromet.2013.11.016] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2013] [Revised: 11/19/2013] [Accepted: 11/25/2013] [Indexed: 12/31/2022]
Abstract
The hepatitis delta virus (HDV) is a pathogen that causes a severe and rapidly progressive disease of hepatocytes. The measurement of viral load in the peripheral blood of patients with HDV infections is important for diagnosis, treatment monitoring, and support for follow-up studies of viral replication during the course of the disease. This study reports the development of an assay capable of detecting and quantifying the abundance of HDV particles in serum samples, based on reverse-transcription quantitative PCR (RT-qPCR). Two standards for calibration were produced for determining the viral load of HDV: a cDNA cloned into a linear plasmid and a transcribed RNA. For validating this assay, 140 clinical samples of sera were used, comprising 100 samples from patients who tested positive for anti-HDV and hepatitis B virus surface antigen (HBsAg) by ELISA; 30 samples from blood donors; 5 samples monoinfected with hepatitis B virus (HBV); and 5 samples monoinfected with hepatitis C virus (HCV). The HDV RT-qPCR assay performed better when calibrated using the standard based on HDV cDNA cloned into a linear plasmid, yielding an efficiency of 99.8% and a specificity of 100% in the in vitro assays. This study represents the first HDV RT-qPCR assay developed with clinical samples from Brazil and offers great potential for new clinical efficacy studies of antiviral therapeutics for use in patients with hepatitis delta in the western Amazon region.
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Affiliation(s)
- Luan Felipo Botelho-Souza
- Fundação Oswaldo Cruz Rondônia (FIOCRUZ-RO), Laboratório Plataforma Técnica, Brazil; Centro de Pesquisa em Medicina Tropical de Rondônia (CEPEM), Brazil; Universidade Federal de Rondonia (UNIR), Núcleo de Saúde, Departamento de Medicina, Programa de Pós-graduação em Biologia Experimental (PGBIOEXP), Brazil.
| | - Alcione de Oliveira dos Santos
- Fundação Oswaldo Cruz Rondônia (FIOCRUZ-RO), Laboratório Plataforma Técnica, Brazil; Centro de Pesquisa em Medicina Tropical de Rondônia (CEPEM), Brazil; Universidade Federal de Rondonia (UNIR), Núcleo de Saúde, Departamento de Medicina, Programa de Pós-graduação em Biologia Experimental (PGBIOEXP), Brazil
| | | | | | - Juan Miguel Villalobos-Salcedo
- Fundação Oswaldo Cruz Rondônia (FIOCRUZ-RO), Laboratório Plataforma Técnica, Brazil; Centro de Pesquisa em Medicina Tropical de Rondônia (CEPEM), Brazil; Universidade Federal de Rondonia (UNIR), Núcleo de Saúde, Departamento de Medicina, Programa de Pós-graduação em Biologia Experimental (PGBIOEXP), Brazil
| | - Deusilene Souza Vieira
- Fundação Oswaldo Cruz Rondônia (FIOCRUZ-RO), Laboratório Plataforma Técnica, Brazil; Centro de Pesquisa em Medicina Tropical de Rondônia (CEPEM), Brazil; Universidade Federal de Rondonia (UNIR), Núcleo de Saúde, Departamento de Medicina, Programa de Pós-graduação em Biologia Experimental (PGBIOEXP), Brazil
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Abstract
Chronic hepatitis B virus (HBV) infection is common in HIV-positive individuals. Although HBV vaccination is mandatory for HIV-positive individuals with negative-HBV markers, lower rates of protection are achieved. HIV infection accelerates the course of liver disease caused by chronic HBV infection, leading to end-stage hepatic illness and increasing the risk of hepatocellular carcinoma. Anti-HBV active agents, especially tenofovir, improve outcomes. Lamivudine alone should be limited to patients with low serum HBV-DNA levels, since selection of drug resistance often compromises long-term benefits, leads to cross-resistance with other antivirals, and favors the potential emergence of HBV-vaccine escape mutants.
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Ouzan D, Pénaranda G, Joly H, Halfon P. Optimized HBsAg titer monitoring improves interferon therapy in patients with chronic hepatitis delta. J Hepatol 2013; 58:1258-9. [PMID: 23318602 DOI: 10.1016/j.jhep.2012.12.019] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2012] [Accepted: 12/19/2012] [Indexed: 12/24/2022]
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Dusheiko G. Treatment of HBeAg positive chronic hepatitis B: interferon or nucleoside analogues. Liver Int 2013; 33 Suppl 1:137-50. [PMID: 23286858 DOI: 10.1111/liv.12078] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Interferon alpha has restricted efficacy in as much as only a proportion of patients show a response. However, in appropriately selected HBeAg-positive and HBeAg-negative patients, sustained suppression of viral replication can be achieved, and HBeAg or even HBsAg seroconversion can be attained. Thus, finite course of interferon alpha can be successful, and offer an advantage to patient. Interferon (IFN) remains a benchmark therapy for chronic hepatitis B. The main advantages of IFN-α over nucleoside analogues are the absence of resistance and the possibility of immune-mediated clearance of hepatitis B. Unfortunately, side effects preclude the use of interferon alpha in substantial proportions of patients, and prolonged maintenance therapy to suppress hepatitis B virus (HBV) is not feasible. Nucleoside analogues are given by mouth, once per day, and the safety, potency and efficacy have improved and facilitated treatment. However, maintenance of long-term suppression is required for the majority of patients. In general, treatment of chronic hepatitis B should target patients with active disease and viral replication, preferably before the signs and symptoms of cirrhosis or significant injury has occurred. Current EASL guidelines suggest that treatment be based on the evaluation of three criteria: Serum aminotransferase levels, serum HBV DNA levels and histological grade and stage. Many questions remain unanswered on the optimal treatment of patients with chronic hepatitis B with a nucleoside vs interferon alpha. Both forms of treatment have benefits and the choice should be selected and tailored. Stopping or futility rules can be implemented in patients who fail interferon. Recent data suggest the safety and efficacy of nucleoside analogues in the third trimester of pregnancy to reduce the risk of transmission from mothers to their children.
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Affiliation(s)
- Geoffrey Dusheiko
- UCL Division of Liver and Digestive Health, University College London Medical School, and Royal Free Hospital, London, UK.
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EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. J Hepatol 2012; 57:167-85. [PMID: 22436845 DOI: 10.1016/j.jhep.2012.02.010] [Citation(s) in RCA: 2385] [Impact Index Per Article: 183.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2012] [Accepted: 02/28/2012] [Indexed: 02/06/2023]
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Dastgerdi ES, Herbers U, Tacke F. Molecular and clinical aspects of hepatitis D virus infections. World J Virol 2012; 1:71-8. [PMID: 24175212 PMCID: PMC3782269 DOI: 10.5501/wjv.v1.i3.71] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2011] [Revised: 05/12/2012] [Accepted: 05/20/2012] [Indexed: 02/05/2023] Open
Abstract
Hepatitis D virus (HDV) is a defective virus with circular, single-stranded genomic RNA which needs hepatitis B virus (HBV) as a helper virus for virion assembly and infectivity. HDV virions are composed of a circular shape HDV RNA and two types of viral proteins, small and large HDAgs, surrounded by HBV surface antigen (HBsAg). The RNA polymerase II from infected hepatocytes is responsible for synthesizing RNAs with positive and negative polarities for HDV, as the virus does not code any enzyme to replicate its genome. HDV occurs as co-infection or super-infection in up to 5% of HBsAg carriers. A recent multi-center study highlighted that pegylated interferon α-2a (PEG-IFN) is currently the only treatment option for delta hepatitis. Nucleotide/nucleoside analogues, which are effective against HBV, have no relevant effects on HDV. However, additional clinical trials combining PEG-IFN and tenofovir are currently ongoing. The molecular interactions between HDV and HBV are incompletely understood. Despite fluctuating patterns of HBV viral load in the presence of HDV in patients, several observations indicate that HDV has suppressive effects on HBV replication, and even in triple infections with HDV, HBV and HCV, replication of both concomitant viruses can be reduced. Additional molecular virology studies are warranted to clarify how HDV interacts with the helper virus and which key cellular pathways are used by both viruses. Further clinical trials are underway to optimize treatment strategies for delta hepatitis.
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Affiliation(s)
- Elham Shirvani Dastgerdi
- Elham Shirvani Dastgerdi, Ulf Herbers, Frank Tacke, Department of Medicine III, RWTH-University Hospital Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany
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Abstract
UNLABELLED The guideline on the management of chronic hepatitis B (CHB) was first developed in 2004 and revised in 2007 by the Korean Association for the Study of the Liver (KASL). Since then there have been many developments, including the introduction of new antiviral agents and the publications of many novel research results from both Korea and other countries. In particular, a large amount of knowledge on antiviral resistance--which is a serious issue in Korea--has accumulated, which has led to new strategies being suggested. This prompted the new guideline discussed herein to be developed based on recent evidence and expert opinion. TARGET POPULATION The main targets of this guideline comprise patients who are newly diagnosed with CHB and those who are followed or treated for known CHB. This guideline is also intended to provide guidance for the management of patients under the following special circumstances: malignancy, transplantation, dialysis, coinfection with other viruses, pregnancy, and children.
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MESH Headings
- Acute Disease
- Adolescent
- Adult
- Aged
- Alanine Transaminase/blood
- Antiviral Agents/therapeutic use
- Asian People
- Aspartate Aminotransferases/blood
- Carcinoma, Hepatocellular/diagnosis
- Carcinoma, Hepatocellular/etiology
- Child
- Child, Preschool
- Coinfection/drug therapy
- DNA, Viral/blood
- Drug Resistance, Viral
- Drug Therapy, Combination
- Female
- Hepatitis B Surface Antigens/blood
- Hepatitis B e Antigens/blood
- Hepatitis B virus/genetics
- Hepatitis B, Chronic/complications
- Hepatitis B, Chronic/diagnosis
- Hepatitis B, Chronic/drug therapy
- Humans
- Immunosuppression Therapy
- Infectious Disease Transmission, Vertical/prevention & control
- Liver/pathology
- Liver/physiology
- Liver Cirrhosis/physiopathology
- Liver Neoplasms/diagnosis
- Liver Neoplasms/etiology
- Liver Transplantation
- Male
- Middle Aged
- Pregnancy
- Renal Dialysis
- Republic of Korea
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Treatment of Chronic Delta Hepatitis: A Nine-Year Retrospective Analysis. HEPATITIS MONTHLY 2011. [DOI: 10.5812/kowsar.1735143x.2462] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
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Riaz M, Idrees M, Kanwal H, Kabir F. An overview of triple infection with hepatitis B, C and D viruses. Virol J 2011; 8:368. [PMID: 21791115 PMCID: PMC3156777 DOI: 10.1186/1743-422x-8-368] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2011] [Accepted: 07/27/2011] [Indexed: 12/25/2022] Open
Abstract
Viral hepatitis is one of the major health problems worldwide, particularly in South East Asian countries including Pakistan where hepatitis C virus (HCV) and hepatitis B virus (HBV) infections are highly endemic. Hepatitis delta virus (HDV) is also not uncommon world-wide. HCV, HBV, and HDV share parallel routes of transmission due to which dual or triple viral infection can occur in a proportion of patients at the same time. HBV and HCV are important factors in the development of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). In addition to LC and HCC, chronic HDV infection also plays an important role in liver damage with oncogenic potential. The current article reviews the available literature about the epidemiology, pathogenesis, transmission, symptoms, diagnosis, replication, disease outcome, treatment and preventive measures of triple hepatitis infection by using key words; epidemiology of triple infection, risk factors, awareness status, treatment and replication cycle in PubMed, PakMediNet, Directory of Open Access Journals (DOAJ) and Google Scholar. Total data from 74 different studies published from 1983 to 2010 on triple hepatitis infections were reviewed and included in this study. The present article briefly describes triple infection with HCV, HBV and HDV.
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Affiliation(s)
- Mehwish Riaz
- National Centre of Excellence in Molecular Biology, University of the Punjab, 87-West Canal Bank Road Thokar Niaz Baig Lahore-53700, Pakistan
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Rapti IN, Hadziyannis SJ. Treatment of special populations with chronic hepatitis B infection. Expert Rev Gastroenterol Hepatol 2011; 5:323-39. [PMID: 21651351 DOI: 10.1586/egh.11.7] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
All therapeutic agents that are currently in use for the treatment of chronic hepatitis B have been administered to a large number of patients in clinical trials in order to be approved as efficacious and safe. Nevertheless, in these trials, many patients have been excluded either because they have decompensated cirrhosis, or they belong to groups with comorbidities that can seriously affect the underlying liver disease, or where the treatment for chronic hepatitis B virus infection can be contraindicated. Such groups of patients are those with hepatitis D virus, hepatitis C virus and HIV coinfections, patients who have undergone transplantation or are immunosuppressed due to chemotherapy or other treatment, patients with end-stage renal disease under dialysis, acute and fulminant hepatitis B and also, children and pregnant women. In this article, all of the aspects of treatment of these special categories are discussed, since for many of these patients, treatment is of a greater importance compared with the standard patient with chronic hepatitis B, and in real life they represent a great percentage of chronic hepatitis B virus infection patients.
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Affiliation(s)
- Irene N Rapti
- Department of Medicine & Liver Unit, Henry Dunant Hospital, Athens, Greece
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Abstract
Hepatitis B virus (HBV) infection is a worldwide problem and can cause acute liver failure, acute hepatitis, chronic hepatitis, liver cirrhosis, and liver cancer. In areas of high prevalence such as in Asia, Africa, southern Europe, and Latin America, the hepatitis B surface antigen positive rate ranges from 2% to 20%.In endemic areas, HBV infection occurs mainly during infancy and early childhood. Mother-to-infant transmission accounts for approximately half of the chronic HBV infections. In contrast to infection in adults, HBV infection during early childhood results in a much higher rate of persistent infection and long-term serious complications such as liver cirrhosis and HCC.Three phases of chronic hepatitis B have been identified: the immune-tolerant phase, the immune-active phase, and the inactive hepatitis B phase. These phases of infection are characterized by variations in viral replication, hepatic inflammation, spontaneous clearance, and response to antiviral therapy.The optimal goal of antiviral therapy for chronic HBV infection is to eradicate HBV and to prevent its related liver complications. However, due to the limited effect of available therapies in viral eradication, the goal of treatment is to reduce viral replication, to minimize liver injury, and to reduce infectivity. In this review the current recommendations for monitoring and treating chronic HBV infection in children are reviewed.
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Broderick A, Jonas MM. HEPATITIS B AND D VIRUSES. FEIGIN AND CHERRY'S TEXTBOOK OF PEDIATRIC INFECTIOUS DISEASES 2009:1972-1992. [DOI: 10.1016/b978-1-4160-4044-6.50174-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Abstract
Despite recent advances in the treatment of chronic viral hepatitis, therapy of chronic hepatitis D is not yet satisfactory. The only option currently available is interferon-alpha (IFN), whose efficacy is related to the dose and duration of treatment. However, the rate of sustained hepatitis D virus (HDV) clearance after a 1-year course with high doses of standard IFN is low. Better results have recently been reported with pegylated IFN both in IFN-naïve and in previous nonresponders to standard IFN, suggesting the use of pegylated IFN as a first-line therapy in chronic hepatitis D. Nucleoside analogues that inhibit hepatitis B virus (HBV) are ineffective against HDV and combination therapy with lamivudine or ribavirin has not shown significant advantages over monotherapy with either standard or pegylated IFN. Because the ultimate goal of treatment is eradication of both HDV and HBV, in responders IFN therapy should be continued as long as possible until the loss of hepatitis B surface antigen, adjusting the dose to patient tolerance. However, because side-effects are common, continuous monitoring is mandatory. Although the first results obtained with pegylated IFN have been encouraging, the rate of sustained virological response is still low and the rate of relapse high, emphasizing the need for developing novel classes of antivirals specifically interfering with the life cycle of this unique virus.
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Affiliation(s)
- P Farci
- Department of Medical Sciences, University of Cagliari, Policlinico Universitario, Monserrato, Cagliari, Italy.
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Michalak TI, Pham TNQ, Mulrooney-Cousins PM. Molecular diagnosis of occult HCV and HBV infections. Future Virol 2007. [DOI: 10.2217/17460794.2.5.451] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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Tillmann HL. Screening for and Treating Hepatitis B Virus in Patients with HIV Infection. Clin Infect Dis 2007; 45:633-6. [PMID: 17683000 DOI: 10.1086/520753] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2007] [Accepted: 06/09/2007] [Indexed: 12/13/2022] Open
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Wedemeyer H, Heidrich B, Manns MP. Hepatitis D virus infection--not a vanishing disease in Europe! Hepatology 2007; 45:1331-2; author reply 1332-3. [PMID: 17464980 DOI: 10.1002/hep.21590] [Citation(s) in RCA: 115] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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