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1.
J Viral Hepat ; 31(6): 324-341, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38619214

RESUMO

Foreign-born (FB) persons represent a large proportion of adults with chronic hepatitis B (CHB) in Canada due to higher prevalence rates in countries of birth for FB persons. Suboptimal awareness and low rates of hepatitis delta virus (HDV) testing contribute to underdiagnosis and gaps in accurate estimates of Canada HDV prevalence. We aim to provide an assessment of CHB and HDV prevalence in Canada using a comprehensive literature review and meta-analysis. A comprehensive literature review of articles reporting HBsAg seroprevalence and anti-HDV prevalence was conducted to calculate country-specific rates and pooled prevalence of CHB and HDV using meta-analyses. Country-specific CHB and HDV rate estimates were combined with number of FB persons in Canada in 2021 from Statistics Canada to estimate total numbers of FB with CHB and HDV, respectively. These estimates were combined with estimates of Canada-born persons with CHB and HDV to yield the total number of persons with CHB and HDV. In 2021, we estimated 0.550 million (M) (95% CI 0.488-0.615) persons with CHB; 0.344 M (95% CI 0.288-0.401) were FB and 0.206 M (95% CI: 0.200-0.214) were Canada-born. The weighted average HDV prevalence among FB persons in Canada was 5.19% (17,848 [95% CI 9611-26,052] persons), among whom 50% emigrated from Asia and 31% from Africa. When combined with estimates of Canada-born persons with HDV, we estimate 35,059 (95% CI: 18,744-52,083) persons with HDV in Canada. In conclusion, we estimate 0.550 M and 35,059 persons living with CHB and HDV, respectively, in Canada in 2021.


Assuntos
Hepatite D , Vírus Delta da Hepatite , Humanos , Canadá/epidemiologia , Prevalência , Hepatite D/epidemiologia , Vírus Delta da Hepatite/imunologia , Adulto , Estudos Soroepidemiológicos , Emigrantes e Imigrantes/estatística & dados numéricos , Hepatite B Crônica/epidemiologia , Antígenos de Superfície da Hepatite B/sangue , Anticorpos Anti-Hepatite/sangue , Masculino
2.
Liver Int ; 44(7): 1715-1734, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38563728

RESUMO

BACKGROUND AND AIMS: Suboptimal awareness and low rates of hepatitis delta virus (HDV) testing contribute to underdiagnosis and gaps in accurate estimates of U.S. HDV prevalence. We aim to provide an updated assessment of HDV prevalence in the U.S. using a comprehensive literature review and meta-analysis approach. METHODS: A comprehensive literature review of articles reporting HBsAg seroprevalence and anti-HDV prevalence was conducted to calculate country-specific rates and pooled prevalence of CHB and HDV using meta-analyses. Country-specific CHB and HDV rate estimates were combined with number of foreign-born (FB) persons in the U.S. in 2022 from U.S. Census Bureau to estimate total numbers of FB with CHB and HDV, respectively. These estimates were further combined with updated estimates of U.S.-born persons with CHB and HDV to yield the total number of persons with CHB and HDV. RESULTS: In 2022, we estimated 1.971 million (M) (95% CI 1.547-2.508) persons with CHB; 1.547 M (95% CI 1.264-1.831) were FB and 0.424 M (95% CI: 0.282-0.678) were U.S.-born. The weighted average HDV prevalence among FB persons in the U.S. was 4.20% (64 938 [95% CI 33055-97 392] persons), among whom 45% emigrated from Asia, 25% from Africa, and 14% from Europe. When combined with updated estimates of U.S.-born persons with HDV, we estimate 75 005 (95% CI: 42187-108 393) persons with HDV in the U.S. CONCLUSIONS: Including both FB and U.S.-born persons, we estimated that 1.971 M and 75 005 persons were living with CHB and HDV, respectively, in the U.S. in 2022.


Assuntos
Hepatite D , Vírus Delta da Hepatite , Humanos , Estados Unidos/epidemiologia , Vírus Delta da Hepatite/imunologia , Hepatite D/epidemiologia , Hepatite D/diagnóstico , Prevalência , Estudos Soroepidemiológicos , Adulto , Emigrantes e Imigrantes/estatística & dados numéricos , Antígenos de Superfície da Hepatite B/sangue
3.
Hepatology ; 74(2): 607-626, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33655536

RESUMO

BACKGROUND AND AIMS: Although prevalence of chronic hepatitis B (CHB) in the USA includes 0.42 million (range, 0.28-0.67) U.S.-born persons, foreign-born (FB) persons contribute a substantially larger number to the burden of CHB in the USA. Over the past decade, patterns of U.S. immigration have changed and many countries have implemented HBV prevention programs. This study aims to estimate the number of FB persons with CHB in the USA by country of origin, updating our 2011 study. APPROACH AND RESULTS: We performed systematic searches for articles published in 2009-2019 reporting HBsAg seroprevalence in emigrants and in-country populations of 117 countries. Data meeting inclusion criteria were combined with data from our 2011 study to calculate pooled prevalence estimates for 99 countries using meta-analyses (total 2,800 surveys involving 112 million subjects). Combining country-specific CHB rate estimates with the number of FB in the USA in 2018, by country of origin from the U.S. Census Bureau, we estimate that the number of FB with CHB in the USA in 2018 was 1.47 million (95% CI, 1.21-1.73), substantially higher than previously reported. The weighted average CHB prevalence for all FB in the USA in 2018 was 3.07%. Approximately 59% of FB with CHB in the USA in 2018 emigrated from Asia, 19% from the Americas, and 15% from Africa. Subgroup analyses found that for many countries, CHB rates are higher in males than females and have declined over the past three decades, but no consistent pattern is observed between emigrant and in-country rates. CONCLUSIONS: Including FB and U.S.-born persons, the total prevalence of CHB in the USA may be as high as 2.4 million.


Assuntos
Emigrantes e Imigrantes/estatística & dados numéricos , Hepatite B Crônica/epidemiologia , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/sangue , Humanos , Prevalência , Estudos Soroepidemiológicos
4.
Hepatology ; 65(3): 804-812, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28012259

RESUMO

Direct-acting antiviral (DAA) therapy, recently approved for patients with decompensated cirrhosis (DC) secondary to hepatitis C virus (HCV), is associated with improved hepatic function. We analyzed trends in liver transplant (LT) wait-listing (WL) to explore potential impact of effective medical therapy on WL registration. This is a cohort study using the Scientific Registry of Transplant Recipients database from 2003 to 2015. A total of 47,591 adults wait-listed for LT from HCV, hepatitis B virus (HBV), and nonalcoholic steatohepatitis (NASH) were identified. LT indication was defined as DC if the Model for End-Stage Liver Disease (MELD) at WL was ≥15 or hepatocellular carcinoma (HCC). Era of listing was divided into interferon (IFN; 2003-2010), protease inhibitor (PI; 2011-2013), and direct-acting antiviral (DAA; 2014-2015). Annual standardized incidence rates of WL were analyzed using Poisson regression. Adjusted incidences of LT WL for DC in HCV patients decreased by 5% in the PI era (P = 0.004) and 32% in the DAA era (P < 0.001) compared to the IFN era. Listing for DC in HBV also decreased in the PI (-17%; P = 0.002) and DAA eras (-24%; P < 0.001). Conversely, WL for DC in NASH increased by 41% in the PI era (P < 0.001) and 81% in the DAA era (P < 0.001). WL for HCC in both the HCV and NASH populations increased in both the PI and DAA eras (P < 0.001 for all) whereas HCC WL in HBV remained stable (P > 0.05 for all). CONCLUSION: The rate of LT WL for HCV complicated by DC has decreased by over 30% in the era of DAA therapy. Further reductions in WL are anticipated with increased testing, linkage to care, and access to DAA therapy. (Hepatology 2017;65:804-812).


Assuntos
Didesoxiadenosina/uso terapêutico , Doença Hepática Terminal/etiologia , Doença Hepática Terminal/cirurgia , Transplante de Fígado/métodos , Sistema de Registros , Listas de Espera , Adulto , Antivirais/uso terapêutico , Estudos de Coortes , Doença Hepática Terminal/patologia , Doença Hepática Terminal/virologia , Feminino , Hepatite B/complicações , Hepatite B/diagnóstico , Hepatite B/tratamento farmacológico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/patologia , Cuidados Pré-Operatórios/métodos , Melhoria de Qualidade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Estados Unidos
7.
Hepatology ; 56(2): 422-33, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22105832

RESUMO

Estimates of the prevalence of chronic hepatitis B (CHB) in the United States differ significantly, and the contribution of foreign-born (FB) persons has not been adequately described. The aim of this study was to estimate the number of FB persons in the United States living with CHB by their country of origin. We performed a systematic review for reports of HBsAg seroprevalence rates in 102 countries (covering PubMed from 1980 to July 2010). Data from 1,373 articles meeting inclusion criteria were extracted into country-specific databases. We identified 256 seroprevalence surveys in emigrants from 52 countries (including 689,078 persons) and 1,797 surveys in the general populations of 98 countries (including 17,861,035 persons). Surveys including individuals with lower or higher risk of CHB than the general population were excluded. Data were combined using meta-analytic methods to determine country-specific pooled CHB prevalence rates. Rates were multiplied by the number of FB living in the United States in 2009 by country of birth from the U.S. Census Bureau to yield the number of FB with CHB from each country. We estimate a total of 1.32 million (95% confidence interval: 1.04-1.61) FB in the United States living with CHB in 2009; 58% migrated from Asia and 11% migrated from Africa, where hepatitis B is highly endemic. Approximately 7% migrated from Central America, a region with lower CHB rates, but many more emigrants to the United States. This analysis suggests that the number of FB persons living with CHB in the United States may be significantly greater than previously reported. Assuming 300,000-600,000 U.S.-born persons with CHB, the total prevalence of CHB in the United States may be as high as 2.2 million.


Assuntos
Emigrantes e Imigrantes/estatística & dados numéricos , Saúde Global/estatística & dados numéricos , Hepatite B Crônica/etnologia , África/etnologia , Ásia/etnologia , América Central/etnologia , Europa (Continente)/etnologia , Feminino , Humanos , Masculino , América do Norte/etnologia , Oceania/etnologia , Gravidez , Prevalência , América do Sul/etnologia , Estados Unidos/epidemiologia
8.
Clin Liver Dis ; 27(4): 997-1022, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37778782

RESUMO

Hepatitis B infection affects approximately 262 million people worldwide and is responsible for 900,000 deaths annually. This article reviews the major factors limiting HBV elimination, which includes limited linkage to care and complicated HBV testing and treatment guidelines. The article then provides solutions to these pressing issues.


Assuntos
Hepatite B Crônica , Hepatite B , Humanos , Vírus da Hepatite B/genética , Hepatite B/diagnóstico , Hepatite B/prevenção & controle , DNA , Vacinação , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/prevenção & controle
10.
Gastroenterology ; 137(5): 1680-6, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19632234

RESUMO

BACKGROUND & AIMS: In the last decade, significant progress has been made in the treatment of liver disease associated with chronic hepatitis, especially in patients infected with the hepatitis B virus (HBV). To investigate whether the population-wide application of antiviral therapies has impacted liver transplant waiting list registration, we analyzed longitudinal trends in waiting list registration for patients with hepatitis B and C and those with nonviral liver disease. METHODS: This study represented a retrospective analysis of registry data containing all US liver transplant centers. All adult, primary liver transplantation candidates registered to the Organ Procurement and Transplantation Network between 1985 and 2006 were included in the analysis. Standardized incidence rates were calculated for waiting list registration for liver transplantation by underlying disease (HBV and HCV infection and other) and by indication for transplantation (fulminant liver disease, hepatocellular carcinoma [HCC], and end-stage liver disease [ESLD]). RESULTS: Of 113,927 unique waiting list registrants, 4793 (4.2%) had HBV, and 40,923 (35.9%) had HCV infections; the remaining 68,211 (59.9%) had neither. The incidence of waiting list registration for ESLD and fulminant liver disease decreased, whereas that for HCC increased. The decrease in ESLD registration was most pronounced, and the increase in HCC was least dramatic among registrants with hepatitis B. The decrease in registration for ESLD secondary to HCV infection was also significantly larger than that for ESLD patients with nonviral etiologies. CONCLUSIONS: The pattern of liver transplantation waiting list registration among patients with hepatitis B suggests that the widespread application of oral antiviral therapy for HBV contributed to the decreased incidence of decompensated liver disease.


Assuntos
Hepatite B Crônica/cirurgia , Hepatite C Crônica/cirurgia , Falência Hepática/cirurgia , Transplante de Fígado/estatística & dados numéricos , Sistema de Registros , Listas de Espera , Adulto , Feminino , Hepatite B Crônica/complicações , Hepatite B Crônica/epidemiologia , Hepatite C Crônica/complicações , Hepatite C Crônica/epidemiologia , Humanos , Incidência , Falência Hepática/epidemiologia , Falência Hepática/virologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Obtenção de Tecidos e Órgãos/organização & administração , Estados Unidos/epidemiologia
11.
N Engl J Med ; 352(26): 2673-81, 2005 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-15987916

RESUMO

BACKGROUND: Treatment with adefovir dipivoxil for 48 weeks resulted in histologic, virologic, and biochemical improvement in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. We evaluated the effect of continued therapy as compared with cessation of therapy. METHODS: One hundred eighty-five HBeAg-negative patients with chronic hepatitis B were assigned to receive 10 mg of adefovir dipivoxil or placebo once daily for 48 weeks (ratio, 2:1). After week 48, patients receiving adefovir dipivoxil were again randomly assigned either to receive an additional 48 weeks of the drug or to switch to placebo. Patients originally assigned to placebo were switched to adefovir dipivoxil. Patients treated with adefovir dipivoxil during weeks 49 through 96 were subsequently offered continued therapy. The primary end points were changes in hepatitis B virus (HBV) DNA and alanine aminotransferase levels. RESULTS: Treatment with adefovir dipivoxil resulted in a median decrease in serum HBV DNA of 3.47 log copies per milliliter (on a base-10 scale) at 96 weeks and 3.63 log copies per milliliter at 144 weeks. HBV DNA levels were less than 1000 copies per milliliter in 71 percent of patients at week 96 and 79 percent at week 144. In the majority of patients who were switched from adefovir dipivoxil to placebo, the benefit of treatment was lost (median change in HBV DNA levels from baseline, -1.09 log copies per milliliter; only 8 percent of patients had levels below 1000 copies per milliliter at week 96). Side effects during weeks 49 through 144 were similar to those during the initial 48 weeks. Resistance mutations rtN236T and rtA181V were identified in 5.9 percent of patients after 144 weeks. CONCLUSIONS: In patients with HBeAg-negative chronic hepatitis B, the benefits achieved from 48 weeks of adefovir dipivoxil were lost when treatment was discontinued. In patients treated for 144 weeks, benefits were maintained, with infrequent emergence of viral resistance.


Assuntos
Adenina/análogos & derivados , Adenina/uso terapêutico , Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Organofosfonatos/uso terapêutico , Adenina/administração & dosagem , Adenina/efeitos adversos , Adolescente , Adulto , Animais , Antivirais/administração & dosagem , Antivirais/efeitos adversos , DNA Viral/sangue , Método Duplo-Cego , Esquema de Medicação , Farmacorresistência Viral , Feminino , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Humanos , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Organofosfonatos/administração & dosagem , Organofosfonatos/efeitos adversos , Estudos Prospectivos , Fatores de Tempo
12.
Antiviral Res ; 150: 93-100, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29248746

RESUMO

In early 2017, the Hepatitis B Foundation invited 30 experts in the fields of hepatitis B and liver cancer research to identify projects they deemed important to the goal of finding a cure for chronic hepatitis B and D and the diseases with which these viral infections are associated. They were also asked to identify general categories of research and to prioritize sub-project topics within those areas. The experts generally agreed on broadly defined areas of research, but there was usually little difference between the highest and lowest scoring projects; for the most part, all programs described in this document were considered valuable and necessary. An executive summary of this discussion was recently published (Alter et al., Hepatology 2017). The present manuscript reports the areas of research identified by the workshop participants, provides a brief rationale for their selection, and attempts to express differences among the priorities assigned to each area of research, when such distinctions were expressed.


Assuntos
Antivirais/farmacologia , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Pesquisa , Humanos
13.
N Engl J Med ; 348(9): 808-16, 2003 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-12606735

RESUMO

BACKGROUND: In preclinical and phase 2 studies, adefovir dipivoxil demonstrated potent activity against hepatitis B virus (HBV), including lamivudine-resistant strains. METHODS: We randomly assigned 515 patients with chronic hepatitis B who were positive for hepatitis B e antigen (HBeAg) to receive 10 mg of adefovir dipivoxil (172 patients), 30 mg of adefovir dipivoxil (173), or placebo (170) daily for 48 weeks. The primary end point was histologic improvement in the 10-mg group as compared with the placebo group. RESULTS: After 48 weeks of treatment, significantly more patients who received 10 mg or 30 mg of adefovir dipivoxil per day than who received placebo had histologic improvement (53 percent [P<0.001], 59 percent [P<0.001], and 25 percent, respectively), a reduction in serum HBV DNA levels (by a median of 3.52 [P<0.001], 4.76 [P<0.001], and 0.55 log copies per milliliter, respectively), undetectable levels (fewer than 400 copies per milliliter) of serum HBV DNA (21 percent [P<0.001], 39 percent [P<0.001], and 0 percent, respectively), normalization of alanine aminotransferase levels (48 percent [P<0.001], 55 percent [P<0.001], and 16 percent, respectively), and HBeAg seroconversion (12 percent [P=0.049], 14 percent [P=0.01], and 6 percent, respectively). No adefovir-associated resistance mutations were identified in the HBV DNA polymerase gene. The safety profile of the 10-mg dose of adefovir dipivoxil was similar to that of placebo; however, there was a higher frequency of adverse events and renal laboratory abnormalities in the group given 30 mg of adefovir dipivoxil per day. CONCLUSIONS: In patients with HBeAg-positive chronic hepatitis B, 48 weeks of 10 mg or 30 mg of adefovir dipivoxil per day resulted in histologic liver improvement, reduced serum HBV DNA and alanine aminotransferase levels, and increased the rates of HBeAg seroconversion. The 10-mg dose has a favorable risk-benefit profile for long-term treatment. No adefovir-associated resistance mutations were identified in the HBV DNA polymerase gene.


Assuntos
Adenina/análogos & derivados , Adenina/uso terapêutico , Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Organofosfonatos , Adenina/efeitos adversos , Adolescente , Adulto , Idoso , Alanina Transaminase/sangue , Antivirais/efeitos adversos , DNA Viral/sangue , Método Duplo-Cego , Feminino , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/sangue , Hepatite B Crônica/patologia , Hepatite B Crônica/virologia , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade
14.
N Engl J Med ; 348(9): 800-7, 2003 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-12606734

RESUMO

BACKGROUND: Adefovir dipivoxil, a nucleotide analogue, demonstrated clinically significant antiviral activity in patients with chronic hepatitis B in phase 1 and 2 clinical trials. METHODS: We randomly assigned 185 patients with chronic hepatitis B who were negative for hepatitis B e antigen (HBeAg) to receive either 10 mg of adefovir dipivoxil or placebo once daily for 48 weeks in a 2:1 ratio and a double-blind manner. The primary end point was histologic improvement. RESULTS: At week 48, 64 percent of patients who had base-line liver-biopsy specimens available in the adefovir dipivoxil group had improvement in histologic liver abnormalities (77 of 121), as compared with 33 percent of patients in the placebo group (19 of 57, P<0.001). Serum hepatitis B virus (HBV) DNA levels were reduced to fewer than 400 copies per milliliter in 51 percent of patients in the adefovir dipivoxil group (63 of 123) and in 0 percent of those in the placebo group (0 of 61, P<0.001). The median decrease in log-transformed HBV DNA levels was greater with adefovir dipivoxil treatment than with placebo (3.91 vs. 1.35 log copies per milliliter, P<0.001). Alanine aminotransferase levels had normalized at week 48 in 72 percent of patients receiving adefovir dipivoxil (84 of 116), as compared with 29 percent of those receiving placebo (17 of 59, P<0.001). No HBV polymerase mutations associated with resistance to adefovir were identified. The safety profile of adefovir dipivoxil was similar to that of placebo. CONCLUSIONS: In patients with HBeAg-negative chronic hepatitis B, 48 weeks of adefovir dipivoxil treatment resulted in significant histologic, virologic, and biochemical improvement, with an adverse-event profile similar to that of placebo. There was no evidence of the emergence of adefovir-resistant HBV polymerase mutations.


Assuntos
Adenina/análogos & derivados , Adenina/uso terapêutico , Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Organofosfonatos , Adenina/efeitos adversos , Adolescente , Adulto , Idoso , Alanina Transaminase/sangue , Antivirais/efeitos adversos , Biópsia , DNA Viral/sangue , Método Duplo-Cego , Feminino , Antígenos E da Hepatite B , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/patologia , Hepatite B Crônica/virologia , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade
15.
J Virus Erad ; 3(1): 1-6, 2017 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-28275452

RESUMO

Hepatitis B infection remains a significant disease burden around the world, with an estimated two billion individuals infected and 350 million living with chronic hepatitis B. Current antivirals are efficacious, but require lifelong treatment for the majority of infected individuals. The field is galvanised to improve diagnostics and treatment with the goal to develop shorter, finite treatments leading to viral control after treatment discontinuation. Achievement of complete and functional cure is challenged by the complexity of the virus life cycle, the lack of adequate preclinical models, the cccDNA-mediated persistence of HBV in liver cells, the lack of validated biomarkers to predict viral control and cure, and the probable need for combination treatment involving antiviral- and immune-based strategies. Experts from diverse stakeholder groups participating in the HBV Forum (a project of the Forum for Collaborative Research) contributed their expertise and perspective to resolving issues and overcoming barriers in the regulatory path for novel HBV therapeutic strategies; addressing gaps in preclinical models, diagnostics, clinical trial design, biomarkers and endpoints, and public health efforts. Interviewees highlighted the need for open and collaborative ongoing dialogues among stakeholders in a neutral space as a critical process to move the field forwards. The Forum model facilitates dialogue and deliberation of this nature, with dedicated experts from all stakeholder groups participating. The promise of an HBV cure is exciting. Now is the time to work together toward that goal.

16.
Transplantation ; 80(8): 1086-92, 2005 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-16278590

RESUMO

BACKGROUND: This study analyzes the biochemical, serological, and virological efficacy and the safety of adefovir dipivoxil in patients with renal disturbances. METHODS: Twelve patients with lamivudine-resistant hepatitis B virus (HBV) chronic infection were treated for a median time of 15 (3-19) months. The daily dosage was 10 mg initially and then adjusted according to renal function. RESULTS: Median (range) ALT values remained stable: 55 (13-117) and 37 (17-266) UI/L. After the 12th month, the median decline in serum HBV DNA was from 8.76 (6.3-9.7) to 2.97 (1.15-5.65) log10 Eq/ml (median decline of -5.5 log10). No virologic breakthrough was observed. One of the six HBeAg-positive patients lost HBe Ag but without HBe seroconversion; none had HBs Ag loss. There were no significant clinical and biochemical adverse effects. In the 11 nonhemodialysed patients, the creatinine clearance significantly improved from 70 (30-100) to 88 (38-125) ml/mn (P=0.01) and the mean serum creatinine levels increased only slightly from 114 (91-839) to 130 (81-561) micromol/ml (NS). Serum phosphorus remained stable. The urinary level of protein decreased from 0.16 (0.08-8.63) to 0.12 (0.01-0.74) g/day (NS). CONCLUSIONS: Adefovir dipivoxil is safe for the treatment of chronic hepatitis B in patients with varying degrees of renal dysfunction and lamivudine-resistant HBV and results in biochemical and virological efficacy similar to that reported in the general population.


Assuntos
Adenina/análogos & derivados , Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Transplante de Rim , Organofosfonatos/uso terapêutico , Diálise Renal , Insuficiência Renal/complicações , Adenina/efeitos adversos , Adenina/farmacocinética , Adenina/uso terapêutico , Adulto , Idoso , Antivirais/efeitos adversos , Antivirais/farmacocinética , Farmacorresistência Viral , Feminino , Vírus da Hepatite B , Hepatite B Crônica/sangue , Hepatite B Crônica/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Organofosfonatos/efeitos adversos , Organofosfonatos/farmacocinética , Viremia/tratamento farmacológico
17.
Antiviral Res ; 121: 69-81, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26112647

RESUMO

This year marks the 50th anniversary of the discovery of the Australia antigen (Blumberg et al., 1965), which in 1967 was identified to be the hepatitis B virus (HBV) surface antigen. Even though several antiviral medications have been in use for the management of chronic HBV infection for more than 20years, sustained clearance of HBsAg, similar to the sustained viral response (SVR) or cure in chronic hepatitis C, occurs in only a minority of treated patients. Moreover, even after 10years of effective suppression of HBV viremia with current therapy, there is only a 40-70% reduction in deaths from liver cancer. Recent success in developing antivirals for hepatitis C that are effective across all genotypes has renewed interest in a similar cure for chronic HBV infection. In this article, we review a wave of newly identified drug targets, investigational compounds and experimental strategies that are now under clinical evaluation or in preclinical development. The paper forms part of a symposium in Antiviral Research on "An unfinished story: From the discovery of the Australia antigen to the development of new curative therapies for hepatitis B."


Assuntos
Antivirais/farmacologia , Antivirais/uso terapêutico , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/imunologia , Hepatite B Crônica/tratamento farmacológico , Animais , Antivirais/isolamento & purificação , Descoberta de Drogas/tendências , Humanos
18.
AIDS ; 16(3): 387-96, 2002 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-11834950

RESUMO

OBJECTIVE: To assess the safety and efficacy of three new drugs in patients with antiretroviral failure and to correlate retrospectively baseline factors with virological response. DESIGN AND SETTING: Open-label, 48-week, single-arm, multi-center phase II trial conducted at nine US university or government clinics and private practices. PATIENTS AND INTERVENTIONS: Patients with HIV-1 RNA > or =500 copies/ml despite > or =20 weeks of treatment with at least one protease inhibitor received abacavir 300 mg twice a day, amprenavir 1200 mg twice a day and efavirenz 600 mg once a day. Other antiretrovirals were prohibited until week 16 except for substitutions for possible abacavir hypersensitivity. MAIN OUTCOME MEASURES: HIV RNA at weeks 16 and 48. RESULTS: A total of 101 highly treatment-experienced patients enrolled; 60 were naive to non-nucleoside analog reverse transcriptase inhibitors (NNRTI). HIV RNA < 400 copies/ml was attained in 25 out of 101 (25%) patients at 16 weeks (35% of NNRTI-naive and 10% of -experienced patients) and 23 (23%) patients at 48 weeks (33% of naive and 7% of experienced patients). CD4 cells increased by a median of 15 x 10(6) and 43 x 10(6) cells/l at weeks 16 and 48, respectively. Drug-related rash occurred in 50 out of 99 (51%) of patients, and 17 out of 99 (17%) permanently discontinued one or more drugs as a result. Lower baseline viral load, fewer NNRTI-related mutations, absence of decreased abacavir (> or =4-fold) and efavirenz (> or =10-fold) susceptibility, and greater number of drugs to which virus was susceptible were associated with virological response at week 16. CONCLUSIONS: Abacavir, amprenavir and efavirenz durably reduced HIV RNA and increased CD4 cell counts in a subset of treatment-experienced adults. Baseline viral load and some genotypic and phenotypic markers of resistance correlated with HIV RNA response.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Didesoxinucleosídeos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/genética , Oxazinas/uso terapêutico , Sulfonamidas/uso terapêutico , Adulto , Alcinos , Benzoxazinas , Contagem de Linfócito CD4 , Carbamatos , Ciclopropanos , Feminino , Furanos , Genótipo , Infecções por HIV/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , RNA Viral/sangue , Estudos Retrospectivos , Segurança , Falha de Tratamento
19.
Hepatol Int ; 5(2): 654-63, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21484148

RESUMO

PURPOSE: We and others have reported that adding adefovir dipivoxil (adefovir) to lamivudine results in virological and biochemical improvement in cases of lamivudine resistance. The current study assessed the efficacy and safety of combined therapy after 104 weeks of combined treatment and analyzed the frequency of persistent lamivudine resistant HBV. METHODS: A total of 78 patients with compensated CHB (Group A) were maintained on either adefovir 10 mg daily (n = 38) or placebo (n = 40) while continuing lamivudine. An additional 38 patients with decompensated cirrhosis or post liver transplantation (Group B) received lamivudine plus adefovir. The primary endpoint was HBV DNA response at year 2. RESULTS: At week 104 of therapy, a significantly greater proportion of patients in Group A on combination therapy (76%) had a decline in serum HBV DNA to ≤10(5) copies or >2 log(10) reduction from baseline compared to those receiving lamivudine alone (13%; p < 0.001). Fifty-two percent of Group A patients on combination treatment continued to have the M204V/I HBV mutation compared to 92% receiving lamivudine alone (p = 0.0013). Virologic response occurred less frequently in patients expressing persistent lamivudine resistant HBV. In Group B, 87% of patients had HBV DNA response at week 104 (median change from baseline of -5.84 log(10) copies/mL). CONCLUSIONS: The combination of lamivudine and adefovir for 2 years generally proved effective in lamivudine-resistant cases, but there was a persistently high rate of detection of lamivudine resistant mutants and impaired virologic response in compensated patients.

20.
Acad Emerg Med ; 16(2): 168-77, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19076107

RESUMO

Early diagnosis of persons infected with human immunodeficiency virus (HIV) through diagnostic testing and screening is a critical priority for individual and public health. Emergency departments (EDs) have an important role in this effort. As EDs gain experience in HIV testing, it is increasingly apparent that implementing testing is conceptually and operationally complex. A wide variety of HIV testing practice and research models have emerged, each reflecting adaptations to site-specific factors and the needs of local populations. The diversity and complexity inherent in nascent ED HIV testing practice and research are associated with the risk that findings will not be described according to a common lexicon. This article presents a comprehensive set of terms and definitions that can be used to describe ED-based HIV testing programs, developed by consensus opinion from the inaugural meeting of the National ED HIV Testing Consortium. These definitions are designed to facilitate discussion, increase comparability of future reports, and potentially accelerate wider implementation of ED HIV testing.


Assuntos
Infecções por HIV/diagnóstico , Terminologia como Assunto , Comunicação , Serviço Hospitalar de Emergência/economia , Serviço Hospitalar de Emergência/organização & administração , Guias como Assunto , Infecções por HIV/economia , Humanos , Notificação de Abuso
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