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Article ; Online: Clostridium difficile infection in the intensive care unit

Placinta, Gheorghe / Vorojbit, Valentina / Pantea, Victor / Cojuhari, Lilia / Cebotarescu, Valentin / Placinta, Lidia / Croitoru, Dan

2020

Abstract: Department of Infectious Diseases, Department of Microbiology and Immunology Department of Infectious Diseases, Tropical and Medical Parasitology, Nicolae Testemitanu State University of Medicine and Pharmacy, Chisinau, the Republic of Moldova. The 75th ... ...

Abstract	Department of Infectious Diseases, Department of Microbiology and Immunology Department of Infectious Diseases, Tropical and Medical Parasitology, Nicolae Testemitanu State University of Medicine and Pharmacy, Chisinau, the Republic of Moldova. The 75th anniversary of Nicolae Testemitanu State University of Medicine and Pharmacy of the Republic of Moldova (1945-2020) Background: Clostridium difficile (CD) infection is widespread throughout the world, showing an increased incidence over the recent years and may cause severe forms of disease. This infection most commonly affects patients whom were administered antibiotics. An increased resistance to commonly used antibiotics is associated with Clostridium difficile infection (CDI). CD has a generally recognized infectious potential on a clinical ground. CDI is unpleasant and may sometimes cause serious bowel disorders that are usually treated with another course of antibiotics. The evolution of CD infection depends on the individual characteristics of the patient along with risk factors, associated diseases as well as the particularities of the recommended treatment. However, even under the conditions of a correct and complete treatment the risk of the disease relapse is estimated to occur depending on risk factors. Many clinical instruments that are designated for the purposes to treat non-infectious diseases can be useful in estimating the severity of an infection. This review is important for understanding the abusive and irrational prescription of various groups of antibiotics, often unjustified, including the ones used in the treatment of an infection with SARS-CoV-2. Conclusions: These infections mostly occur in people aged 65 and older that receive medical care, including antibiotics administration, people with a long-term hospital stay, people with a weakened immune system or with a previous CD infection. The following measures, in order to reduce the risk of CDI in patients, should be considered: hand hygiene, avoidance of unnecessary administration of antibiotics – the antibiotic treatment is recommended only if it is prescribed by an experienced specialist, avoidance of unnecessary administration of drugs that reduce gastric acidity, because it favors the invasion of the gastrointestinal tract with CD.
Keywords	clostridium difficile ; risk factors ; treatment options ; 616.98:579.852.13+616-083.98:614.2 ; covid19
Subject code	610
Language	English
Publisher	Moldovan Medical Journal
Publishing country	md
Document type	Article ; Online
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Article ; Online: Interaction between SARS-CoV-2 and human organism

Placinta, Gheorghe / Pantea, Victor / Cojuhari, Lilia / Cebotarescu, Valentin / Placinta, Lidia / Croitoru, Dan

2020

Abstract: Department of Infectious Diseases, Department of Infectious Diseases, Tropical and Medical Parasitology, Nicolae Testemitanu State University of Medicine and Pharmacy, Chisinau, the Republic of Moldova ... Background: COVID-19 is a part of the ... ...

Abstract	Department of Infectious Diseases, Department of Infectious Diseases, Tropical and Medical Parasitology, Nicolae Testemitanu State University of Medicine and Pharmacy, Chisinau, the Republic of Moldova Background: COVID-19 is a part of the betacoronaviridae group, sabercoviridae subgroup. At the moment we are confronting a pandemy, which has a completely new pathologic pattern for the whole world. Considering the highly contagious characteristics of the virus, which is the cause of death for many people, and also the fact that many people continue to be infected with this virus there is a stringing necesity of combating this pandemy. Because of that we need the knowledge that regards the physiopathologic mechanisms, particularities of the host-invader interactions, relevance of asymptomatic forms, explanations of the evolving divergencies, posibility of recurrent infections, clinical signs, comorbidities that harshen this pathology, pharmacologic agents that are effective to fight the infection and immune mechanisms of defense in the organism. A great importance is given for the identification of the intial criteria needed for a prognostic, to prevent the critical forms of pathology and to set the parameters for the severity indicators. Conclusions: The research in the field of SARS-CoV-2 requires the gathering of the databases that are related to the investigated persons, to establish the clinico-evolutive differences for the COVID-19 patients according to many factors that could influence the course of the disease. An important difference is the identification of early signs and prevention of the critical disease forms, by extending the laboratory investigations, establishing the parameters for severity indicators through determining the degree of the immune response.
Keywords	COVID-19 ; SARS-CoV-2 ; Coronavirus ; UDC: 616.98:578.834.1 ; covid19
Language	English
Publisher	The Moldovan Medical Journal
Publishing country	md
Document type	Article ; Online
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Article ; Online: Clostridium difficile infection in the Intensive Care Unit

Placinta, Gheorghe / Vorojbit, Valentina / Pantea, Victor / Cojuhari, Lilia / Cebotarescu, Valentin / Placinta, Lidia / Croitoru, Dan

Moldovan Medical Journal 63(6)

2020

Abstract: Background: Clostridium difficile (CD) infection is widespread throughout the world, showing an increased incidence over the recent years and may cause severe forms of disease. This infection most commonly affects patients whom were administered ... ...

Abstract	Background: Clostridium difficile (CD) infection is widespread throughout the world, showing an increased incidence over the recent years and may cause severe forms of disease. This infection most commonly affects patients whom were administered antibiotics. An increased resistance to commonly used antibiotics is associated with Clostridium difficile infection (CDI). CD has a generally recognized infectious potential on a clinical ground. CDI is unpleasant and may sometimes cause serious bowel disorders that are usually treated with another course of antibiotics. The evolution of CD infection depends on the individual characteristics of the patient along with risk factors, associated diseases as well as the particularities of the recommended treatment. However, even under the conditions of a correct and complete treatment the risk of the disease relapse is estimated to occur depending on risk factors. Many clinical instruments that are designated for the purposes to treat non-infectious diseases can be useful in estimating the severity of an infection. This review is important for understanding the abusive and irrational prescription of various groups of antibiotics, often unjustified, including the ones used in the treatment of an infection with SARS-CoV-2. Conclusions: These infections mostly occur in people aged 65 and older that receive medical care, including antibiotics administration, people with a long-term hospital stay, people with a weakened immune system or with a previous CD infection. The following measures, in order to reduce the risk of CDI in patients, should be considered: hand hygiene, avoidance of unnecessary administration of antibiotics – the antibiotic treatment is recommended only if it is prescribed by an experienced specialist, avoidance of unnecessary administration of drugs that reduce gastric acidity, because it favors the invasion of the gastrointestinal tract with CD.
Keywords	clostridium difficile ; risk factors ; treatment options ; covid19
Subject code	610
Language	English
Publishing date	2020-12-01
Publishing country	eu
Document type	Article ; Online
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Article ; Online: Interaction between SARS-CoV-2 and human organism

Placinta, Gheorghe / Pantea, Victor / Cojuhari, Lilia / Cebotarescu, Valentin / Placinta, Lidia / Croitoru, Dan

Moldovan Medical Journal 63(2) 57-62

2020

Abstract: Background: COVID-19 is a part of the betacoronaviridae group, sabercoviridae subgroup. At the moment we are confronting a pandemy, which has a completely new pathologic pattern for the whole world. Considering the highly contagious characteristics of ... ...

Abstract	Background: COVID-19 is a part of the betacoronaviridae group, sabercoviridae subgroup. At the moment we are confronting a pandemy, which has a completely new pathologic pattern for the whole world. Considering the highly contagious characteristics of the virus, which is the cause of death for many people, and also the fact that many people continue to be infected with this virus there is a stringing necesity of combating this pandemy. Because of that we need the knowledge that regards the physiopathologic mechanisms, particularities of the host-invader interactions, relevance of asymptomatic forms, explanations of the evolving divergencies, posibility of recurrent infections, the clinical signs, comorbidities that harshen this patology, pharmacologic agents that are effective to fight the infection and immune mechanisms of defense in the organism. A great importance is given for the identification of the intial criteria needed for a prognostic, to prevent the critical forms of pathology and to set the parameters for the severity indicators. Conclusions: The research in the field of SARS-CoV-2 requires the gathering of the databases that are related to the investigated persons, to establish the clinico-evolutive differences for the COVID-19 patients according to many factors that could influence the course of the disease. An important difference is the identification of early signs and prevention of the critical disease forms, by extending the laboratory investigations, establishing the parameters for severity indicators through determining the degree of the immune response.
Keywords	COVID-19 ; SARS-CoV-2 ; Coronavirus ; covid19
Language	English
Publishing date	2020-05-30
Publishing country	eu
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: HBsAg isoform dynamics during NAP-based therapy of HBeAg-negative chronic HBV and HBV/HDV infection.

Bazinet, Michel / Anderson, Mark / Pântea, Victor / Placinta, Gheorghe / Moscalu, Iurie / Cebotarescu, Valentin / Cojuhari, Lilia / Jimbei, Pavlina / Iarovoi, Liviu / Smesnoi, Valentina / Musteata, Tatina / Jucov, Alina / Dittmer, Ulf / Gersch, Jeff / Holzmayer, Vera / Kuhns, Mary / Cloherty, Gavin / Vaillant, Andrew

Hepatology communications

2022 Volume 6, Issue 8, Page(s) 1870–1880

Abstract: Nucleic acid polymers block the assembly of hepatitis B virus (HBV) subviral particles, effectively preventing hepatitis B surface antigen (HBsAg) replenishment in the circulation. Nucleic acid polymer (NAP)-based combination therapy of HBV infection or ... ...

Abstract	Nucleic acid polymers block the assembly of hepatitis B virus (HBV) subviral particles, effectively preventing hepatitis B surface antigen (HBsAg) replenishment in the circulation. Nucleic acid polymer (NAP)-based combination therapy of HBV infection or HBV/hepatitis D virus (HDV) co-infection is accompanied by HBsAg clearance and seroconversion, HDV-RNA clearance in co-infection, and persistent functional cure of HBV (HBsAg < 0.05 IU/ml, HBV-DNA target not dected, normal alanine aminotransferase) and persistent clearance of HDV RNA. An analysis of HBsAg isoform changes during quantitative HBsAg declines (qHBsAg), and subsequent treatment-free follow-up in the REP 301/REP 301-LTF (HBV/HDV) and REP 401 (HBV) studies was conducted. HBsAg isoforms were analyzed from frozen serum samples using Abbott Research Use Only assays for HBsAg isoforms (large [L], medium [M], and total [T]). The relative change over time in small HBsAg relative to the other isoforms was inferred by the change in the ratio over time of T-HBsAg to M-HBsAg. HBsAg isoform declines followed qHBsAg declines in all participants. No HBsAg isoforms were detectable in any participants with functional cure. HBsAg declines > 2 log
MeSH term(s)	Antiviral Agents/therapeutic use ; Coinfection/drug therapy ; DNA, Viral/genetics ; Hepatitis B Surface Antigens ; Hepatitis B e Antigens ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/diagnosis ; Hepatitis D, Chronic/diagnosis ; Hepatitis Delta Virus ; Humans ; Nucleic Acids ; Polymers ; Protein Isoforms ; RNA, Viral/genetics
Chemical Substances	Antiviral Agents ; DNA, Viral ; Hepatitis B Surface Antigens ; Hepatitis B e Antigens ; Nucleic Acids ; Polymers ; Protein Isoforms ; RNA, Viral
Language	English
Publishing date	2022-04-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2471-254X
ISSN (online)	2471-254X
DOI	10.1002/hep4.1951
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Article ; Online: Benefit of transaminase elevations in establishing functional cure of HBV infection during nap-based combination therapy.

Bazinet, Michel / Pântea, Victor / Placinta, Gheorghe / Moscalu, Iurie / Cebotarescu, Valentin / Cojuhari, Lilia / Jimbei, Pavlina / Iarovoi, Liviu / Smesnoi, Valentina / Musteata, Tatiana / Jucov, Alina / Dittmer, Ulf / Krawczyk, Adalbert / Vaillant, Andrew

Journal of viral hepatitis

2021 Volume 28, Issue 5, Page(s) 817–825

Abstract: Treatment of HBV infection with nucleic acid polymers and pegIFN is accompanied by transaminase elevations in 95% of participants. HBV viral rebound, partial cure (HBV DNA < 2000 IU/mL, normal ALT) or functional cure (HBV DNA target not detected, HBsAg < ... ...

Abstract	Treatment of HBV infection with nucleic acid polymers and pegIFN is accompanied by transaminase elevations in 95% of participants. HBV viral rebound, partial cure (HBV DNA < 2000 IU/mL, normal ALT) or functional cure (HBV DNA target not detected, HBsAg <LLOQ, normal ALT) occurred in 27%, 38% and 35% of participants. Correlations between ALT, AST and GGT elevations, virologic baseline, response during therapy and HBV therapeutic outcome were investigated. A retrospective analysis of all 40 participants in the REP 401 study (NCT02565719) included maxima and area under the curve for ALT, AST and GGT, baseline virology, HBsAg and anti-HBs response and HBV therapeutic outcomes. ALT, AST and GGT elevations were asymptomatic, independent of baseline virologic status and anti-HBs response but correlated with HBsAg reduction ≥3 log<br />
MeSH term(s)	Alanine Transaminase ; Antiviral Agents/therapeutic use ; DNA, Viral ; Hepatitis B Surface Antigens ; Hepatitis B virus/genetics ; Humans ; Retrospective Studies ; Transaminases
Chemical Substances	Antiviral Agents ; DNA, Viral ; Hepatitis B Surface Antigens ; Transaminases (EC 2.6.1.-) ; Alanine Transaminase (EC 2.6.1.2)
Language	English
Publishing date	2021-02-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1212497-7
ISSN	1365-2893 ; 1352-0504
ISSN (online)	1365-2893
ISSN	1352-0504
DOI	10.1111/jvh.13483
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Article ; Online: Modelling hepatitis D virus RNA and HBsAg dynamics during nucleic acid polymer monotherapy suggest rapid turnover of HBsAg.

Shekhtman, Louis / Cotler, Scott J / Hershkovich, Leeor / Uprichard, Susan L / Bazinet, Michel / Pantea, Victor / Cebotarescu, Valentin / Cojuhari, Lilia / Jimbei, Pavlina / Krawczyk, Adalbert / Dittmer, Ulf / Vaillant, Andrew / Dahari, Harel

Scientific reports

2020 Volume 10, Issue 1, Page(s) 7837

Abstract: Hepatitis D virus (HDV) requires hepatitis B surface antigen (HBsAg) for its assembly and release. Current HBV treatments are only marginally effective against HDV because they fail to inhibit HBsAg production/secretion. However, monotherapy with the ... ...

Abstract	Hepatitis D virus (HDV) requires hepatitis B surface antigen (HBsAg) for its assembly and release. Current HBV treatments are only marginally effective against HDV because they fail to inhibit HBsAg production/secretion. However, monotherapy with the nucleic acid polymer REP 2139-Ca is accompanied by rapid declines in both HBsAg and HDV RNA. We used mathematical modeling to estimate HDV-HBsAg-host parameters and to elucidate the mode of action and efficacy of REP 2139-Ca against HDV in 12 treatment-naive HBV/HDV co-infected patients. The model accurately reproduced the observed decline of HBsAg and HDV, which was simultaneous. Median serum HBsAg half-life (t
MeSH term(s)	Adult ; Antiviral Agents/pharmacology ; Female ; Hepatitis B Surface Antigens/metabolism ; Hepatitis Delta Virus/drug effects ; Hepatitis Delta Virus/genetics ; Hepatitis Delta Virus/immunology ; Hepatitis Delta Virus/physiology ; Host Microbial Interactions ; Humans ; Kinetics ; Male ; Models, Biological ; RNA, Viral/metabolism
Chemical Substances	Antiviral Agents ; Hepatitis B Surface Antigens ; RNA, Viral
Language	English
Publishing date	2020-05-12
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-64122-0
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Article ; Online: Safety and Efficacy of 48 Weeks REP 2139 or REP 2165, Tenofovir Disoproxil, and Pegylated Interferon Alfa-2a in Patients With Chronic HBV Infection Naïve to Nucleos(t)ide Therapy.

Gastroenterology

2020 Volume 158, Issue 8, Page(s) 2180–2194

Abstract: Background & aims: Nucleic acid polymers (NAPs) inhibit assembly and secretion of hepatitis B virus (HBV) subviral particles. We performed an open-label, phase 2 study of the safety and efficacy of the NAPs REP 2139 or REP 2165 combined with tenofovir ... ...

Abstract	Background & aims: Nucleic acid polymers (NAPs) inhibit assembly and secretion of hepatitis B virus (HBV) subviral particles. We performed an open-label, phase 2 study of the safety and efficacy of the NAPs REP 2139 or REP 2165 combined with tenofovir disoproxil fumarate (TDF) and pegylated interferon alfa-2a (pegIFN) in patients with chronic HBV infection who were negative for hepatitis B e antigen. Methods: Following 24 weeks TDF therapy, 40 patients were randomly assigned to groups that received 48 weeks of experimental therapy (TDF + pegIFN + REP 2139-Mg or REP 2165-Mg) or 24 weeks of control therapy (TDF + pegIFN) followed by 48 weeks of experimental therapy. Patients were then followed for a treatment-free period of 48 weeks. Primary outcomes were the safety and tolerability of REP 2139-Mg or REP 2165-Mg in combination with TDF + pegIFN compared with TDF + pegIFN alone through the first 48 weeks of therapy and subsequently throughout 48 weeks of NAP-based combination therapy (treatment weeks 24-72 in the experimental group and weeks 48-96 in the control group). Secondary outcomes were reductions in hepatitis B surface antigen (HBsAg) in control and experimental groups over the first 48 weeks of the study and throughout 48 weeks of combination therapy and virologic control (HBsAg positive, HBV DNA below 2000 IU/mL, normal level of alanine aminotransferase) or functional cure (HBsAg below 0.05 IU/mL, HBV DNA target not detected, normal level of alanine aminotransferase) after removal of all therapy. Results: Levels of HBsAg, anti-HBs, and HBV DNA did not differ significantly between the groups given REP 2139 vs REP 2165. PegIFN-induced thrombocytopenia (P = .299 vs controls) and neutropenia (P = .112 vs controls) were unaffected by NAPs (REP 2139 vs REP 2165). Increases in levels of transaminases were significantly more frequent (P < .001 vs controls) and greater (P = .002 vs controls) in the NAP groups (but did not produce symptoms), correlated with initial decrease in HBsAg, and normalized during therapy and follow-up. During the first 24 weeks of TDF and pegIFN administration, significantly higher proportions of patients in NAP groups had decreases in HBsAg to below 1 IU/mL (P < .001 vs control) and HBsAg seroconversion (P = .046 vs control). At the time patients completed the TDF + pegIFN + NAP regimen, HBsAg levels were 0.05 IU/mL or lower in 24/40 participants (all with seroconversion up to 233,055 mIU/mL). During 48 weeks of treatment-free follow-up, virologic control persisted in 13 of 40 participants (2 lost to follow-up after 24 weeks), whereas functional cure persisted in 14 of 40 participants (all completing 48 weeks of follow-up) with persistent HBsAg seroconversion. One participant had a viral rebound during follow-up with hepatic decompensation and was placed on TDF therapy. Conclusions: In a phase 2 randomized trial, we found that addition of NAPs to TDF + pegIFN did not alter tolerability and significantly increased rates of HBsAg loss and HBsAg seroconversion during therapy and functional cure after therapy. Clinicaltrials.gov no: NCT02565719.
MeSH term(s)	Adult ; Antiviral Agents/adverse effects ; Antiviral Agents/therapeutic use ; Biomarkers/blood ; DNA, Viral/blood ; Drug Therapy, Combination ; Female ; Hepatitis B Antibodies/blood ; Hepatitis B Surface Antigens/blood ; Hepatitis B, Chronic/blood ; Hepatitis B, Chronic/diagnosis ; Hepatitis B, Chronic/drug therapy ; Hepatitis B, Chronic/virology ; Humans ; Interferon-alpha/adverse effects ; Interferon-alpha/therapeutic use ; Male ; Middle Aged ; Moldova ; Nucleic Acids/adverse effects ; Nucleic Acids/therapeutic use ; Polyethylene Glycols/adverse effects ; Polyethylene Glycols/therapeutic use ; Polymers/adverse effects ; Polymers/therapeutic use ; Recombinant Proteins/adverse effects ; Recombinant Proteins/therapeutic use ; Tenofovir/adverse effects ; Tenofovir/therapeutic use ; Time Factors ; Treatment Outcome ; Viral Load ; Young Adult
Chemical Substances	Antiviral Agents ; Biomarkers ; DNA, Viral ; Hepatitis B Antibodies ; Hepatitis B Surface Antigens ; Interferon-alpha ; Nucleic Acids ; Polymers ; REP 2139 ; Recombinant Proteins ; Polyethylene Glycols (3WJQ0SDW1A) ; Tenofovir (99YXE507IL) ; peginterferon alfa-2a (Q46947FE7K)
Language	English
Publishing date	2020-03-06
Publishing country	United States
Document type	Clinical Trial, Phase II ; Comparative Study ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	80112-4
ISSN	1528-0012 ; 0016-5085
ISSN (online)	1528-0012
ISSN	0016-5085
DOI	10.1053/j.gastro.2020.02.058
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Article ; Online: Persistent Control of Hepatitis B Virus and Hepatitis Delta Virus Infection Following REP 2139-Ca and Pegylated Interferon Therapy in Chronic Hepatitis B Virus/Hepatitis Delta Virus Coinfection.

Bazinet, Michel / Pântea, Victor / Cebotarescu, Valentin / Cojuhari, Lilia / Jimbei, Pavlina / Anderson, Mark / Gersch, Jeff / Holzmayer, Vera / Elsner, Carina / Krawczyk, Adalbert / Kuhns, Mary C / Cloherty, Gavin / Dittmer, Ulf / Vaillant, Andrew

Hepatology communications

2020 Volume 5, Issue 2, Page(s) 189–202

Abstract: The nucleic acid polymer REP 2139 inhibits assembly/secretion of hepatitis B virus (HBV) subviral particles. Previously, REP 2139-Ca and pegylated interferon (pegIFN) in HBV/hepatitis delta virus (HDV) coinfection achieved high rates of HDV RNA and ... ...

Abstract	The nucleic acid polymer REP 2139 inhibits assembly/secretion of hepatitis B virus (HBV) subviral particles. Previously, REP 2139-Ca and pegylated interferon (pegIFN) in HBV/hepatitis delta virus (HDV) coinfection achieved high rates of HDV RNA and hepatitis B surface antigen (HBsAg) loss/seroconversion in the REP 301 study (NCT02233075). The REP 301-LTF study (NCT02876419) examined safety and efficacy during 3.5 years of follow-up. In the current study, participants completing therapy in the REP 301 study were followed for 3.5 years. Primary outcomes were safety and tolerability, and secondary outcomes were HDV functional cure (HDV RNA target not detected [TND], normal alanine aminotransferase [ALT]), HBV virologic control (HBV DNA ≤2,000 IU/mL, normal ALT), HBV functional cure (HBV DNA TND; HBsAg <0.05 IU/mL, normal ALT), and HBsAg seroconversion. Supplemental analysis included high-sensitivity HBsAg (Abbott ARCHITECT HBsAg NEXT), HBV pregenomic RNA (pgRNA), HBsAg/hepatitis B surface antibody (anti-HBs) immune complexes (HBsAg ICs), and hepatitis B core-related antigen (HBcrAg). Asymptomatic grade 1-2 ALT elevations occurred in 2 participants accompanying viral rebound; no other safety or tolerability issues were observed. During therapy and follow-up, HBsAg reductions to <0.05 IU/mL were also <0.005 IU/mL. HBsAg ICs declined in 7 of 11 participants during REP 2139-Ca monotherapy and in 10 of 11 participants during follow-up. HDV functional cure persisted in 7 of 11 participants; HBV virologic control persisted in 3 and functional cure (with HBsAg seroconversion) persisted in 4 of these participants. Functional cure of HBV was accompanied by HBV pgRNA TND and HBcrAg <lower limit of quantitation.<br />
MeSH term(s)	Adolescent ; Adult ; Alanine Transaminase/blood ; Antiviral Agents/adverse effects ; Antiviral Agents/therapeutic use ; Coinfection/drug therapy ; DNA, Viral/blood ; Female ; Hepatitis B Antibodies/blood ; Hepatitis B Surface Antigens/blood ; Hepatitis B, Chronic/blood ; Hepatitis B, Chronic/complications ; Hepatitis B, Chronic/drug therapy ; Hepatitis D, Chronic/blood ; Hepatitis D, Chronic/complications ; Hepatitis D, Chronic/drug therapy ; Humans ; Interferons/therapeutic use ; Male ; Middle Aged ; Moldova ; Nucleic Acids/therapeutic use ; Polyethylene Glycols/therapeutic use ; Polymers/therapeutic use ; Seroconversion ; Time Factors ; Treatment Outcome ; Young Adult
Chemical Substances	Antiviral Agents ; DNA, Viral ; Hepatitis B Antibodies ; Hepatitis B Surface Antigens ; Nucleic Acids ; Polymers ; REP 2139 ; Polyethylene Glycols (3WJQ0SDW1A) ; Interferons (9008-11-1) ; Alanine Transaminase (EC 2.6.1.2)
Language	English
Publishing date	2020-11-13
Publishing country	United States
Document type	Clinical Trial, Phase II ; Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
ISSN	2471-254X
ISSN (online)	2471-254X
DOI	10.1002/hep4.1633
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Article ; Online: Analysis of HBsAg Immunocomplexes and cccDNA Activity During and Persisting After NAP-Based Therapy.

Hepatology communications

2021 Volume 5, Issue 11, Page(s) 1873–1887

Abstract: Therapy with nucleic acid polymers (NAPs), tenofovir disoproxil fumarate (TDF), and pegylated interferon (pegIFN) achieve high rates of HBsAg loss/seroconversion and functional cure in chronic hepatitis B virus (HBV) infection. The role of hepatitis B ... ...

Abstract	Therapy with nucleic acid polymers (NAPs), tenofovir disoproxil fumarate (TDF), and pegylated interferon (pegIFN) achieve high rates of HBsAg loss/seroconversion and functional cure in chronic hepatitis B virus (HBV) infection. The role of hepatitis B surface antigen (HBsAg) seroconversion and inactivation of covalently closed circular DNA (cccDNA) in establishing functional cure were examined. Archived serum from the REP 401 study was analyzed using the Abbott ARCHITECT HBsAg NEXT assay (Chicago, IL), Abbott research use-only assays for HBsAg immune complexes (HBsAg ICs), circulating HBV RNA, and the Fujirebio assay for hepatitis B core-related antigen (HBcrAg; Malvern, PA). HBsAg became < 0.005 IU/mL in 23 participants during NAP exposure, which persisted in all participants with functional cure. HBsAg IC declined during lead-in TDF monotherapy and correlated with minor declines in HBsAg. Following the addition of NAPs and pegIFN, minor HBsAg IC increases (n = 13) or flares (n = 2) during therapy were not correlated with HBsAg decline, hepatitis B surface antibody (anti-HBs) titers, or alanine aminotransferase. HBsAg IC universally declined during follow-up in participants with virologic control or functional cure. Universal declines in HBV RNA and HBcrAg during TDF monotherapy continued with NAP + pegIFN regardless of therapeutic outcome. At the end of therapy, HBV RNA was undetectable in only 5 of 14 participants with functional cure but became undetectable after removal of therapy in all participants with functional cure. Undetectable HBV RNA at the end of therapy in 5 participants was followed by relapse to virologic control or viral rebound. Conclusion: Anti-HBs-independent mechanisms contribute to HBsAg clearance during NAP therapy. Inactivation of cccDNA does not predict functional cure following NAP-based therapy; however, functional cure is accompanied by persistent inactivation of cccDNA. Persistent HBsAg loss with functional cure may also reflect reduction/clearance of integrated HBV DNA. Clinicaltrials.org number NCT02565719.
MeSH term(s)	Adult ; Alanine Transaminase/blood ; Alanine Transaminase/drug effects ; Antiviral Agents/therapeutic use ; Cross-Over Studies ; DNA, Circular/blood ; DNA, Circular/drug effects ; Drug Therapy, Combination ; Female ; Hepatitis B Core Antigens/blood ; Hepatitis B Core Antigens/drug effects ; Hepatitis B Core Antigens/immunology ; Hepatitis B Surface Antigens/blood ; Hepatitis B Surface Antigens/immunology ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/blood ; Hepatitis B, Chronic/drug therapy ; Hepatitis B, Chronic/immunology ; Humans ; Interferons/therapeutic use ; Male ; Nucleic Acids/therapeutic use ; Polymers/therapeutic use ; RNA, Viral/blood ; RNA, Viral/drug effects ; RNA, Viral/immunology ; Seroconversion/drug effects ; Tenofovir/therapeutic use ; Treatment Outcome ; Virus Inactivation/drug effects
Chemical Substances	Antiviral Agents ; DNA, Circular ; Hepatitis B Core Antigens ; Hepatitis B Surface Antigens ; Nucleic Acids ; Polymers ; RNA, Viral ; Interferons (9008-11-1) ; Tenofovir (99YXE507IL) ; Alanine Transaminase (EC 2.6.1.2)
Language	English
Publishing date	2021-07-10
Publishing country	United States
Document type	Clinical Trial, Phase II ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ISSN	2471-254X
ISSN (online)	2471-254X
DOI	10.1002/hep4.1767
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