RESUMO
Chronic hepatitis B, a major cause of liver disease and cancer, affects >250 million people worldwide. Currently there is no cure, only suppressive therapies. Efforts to develop finite curative hepatitis B virus (HBV) therapies are underway, consisting of combinations of multiple novel agents with or without nucleos(t)ide reverse-transcriptase inhibitors. The HBV Forum convened a webinar in July 2021, along with subsequent working group discussions to address how and when to stop finite therapy for demonstration of sustained off-treatment efficacy and safety responses. Participants included leading experts in academia, clinical practice, pharmaceutical companies, patient representatives, and regulatory agencies. This Viewpoints article outlines areas of consensus within our multistakeholder group for stopping finite therapies in chronic hepatitis B investigational studies, including trial design, patient selection, outcomes, biomarkers, predefined stopping criteria, predefined retreatment criteria, duration of investigational therapies, and follow-up after stopping therapy. Future research of unmet needs are discussed.
Assuntos
Hepatite B Crônica , Hepatite B , Humanos , Hepatite B Crônica/tratamento farmacológico , Antivirais/uso terapêutico , Vírus da Hepatite B/genética , Resultado do Tratamento , Biomarcadores , Antígenos de Superfície da Hepatite B , DNA Viral , Hepatite B/tratamento farmacológicoRESUMO
OBJECTIVE: To describe the anti-hepatitis B virus (HBV) efficacy, HBeAg serologic changes, HBV perinatal transmission, and safety in pregnant women who are living with human immunodeficiency virus (HIV) and HBV co-infection who were randomized to various antiretroviral therapy (ART) regimens. METHODS: The PROMISE (Promoting Maternal and Infant Survival Everywhere) trial was a multicenter randomized trial for ART-naive pregnant women with HIV infection. Women with HIV and HBV co-infection at 14 or more weeks of gestation were randomized to one of three ART arms: one without HBV treatment (group 1) and two HBV treatment arms with single (group 2) or dual anti-HBV activity (group 3). The primary HBV outcome was HBV viral load antepartum change from baseline (enrollment) to 8 weeks; safety assessments included alanine aminotransferase (ALT) level, aspartate aminotransferase (AST) level, and anemia (hemoglobin less than 10 g/dL). Primary comparison was for the HBV-active treatment arms. Pairwise comparisons applied t test and the Fisher exact tests. RESULTS: Of 3,543 women, 3.9% were HBsAg-positive; 42 were randomized to group 1, 48 to group 2, and 48 to group 3. Median gestational age at enrollment was 27 weeks. Among HBV-viremic women, mean antepartum HBV viral load change at week 8 was -0.26 log 10 international units/mL in group 1, -1.86 in group 2, and -1.89 in group 3. In those who were HBeAg-positive, HBeAg loss occurred in 44.4% at delivery. Two perinatal HBV transmissions occurred in group 2. During the antepartum period, one woman (2.4%) in group 1 had grade 3 or 4 ALT or AST elevations, two women (4.2%) in group 2, and three women (6.3%) in group 3. CONCLUSION: Over a short period of time, HBV DNA suppression was not different with one or two HBV-active agents. HbeAg loss occurred in a substantial proportion of participants. Perinatal transmission of HBV infection was low. Hepatitis B virus-active ART was well-tolerated in pregnancy, with few grade 3 or 4 ALT or AST elevations. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT01061151.
Assuntos
Coinfecção , Infecções por HIV , Hepatite B Crônica , Hepatite B , Herpesvirus Cercopitecino 1 , Complicações Infecciosas na Gravidez , Lactente , Gravidez , Feminino , Humanos , Vírus da Hepatite B/genética , Infecções por HIV/tratamento farmacológico , Herpesvirus Cercopitecino 1/genética , Gestantes , Antígenos E da Hepatite B/uso terapêutico , Complicações Infecciosas na Gravidez/tratamento farmacológico , HIV/genética , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Hepatite B/tratamento farmacológico , Parto , DNA Viral , Hepatite B Crônica/tratamento farmacológicoRESUMO
INTRODUCTION: Hepatocellular carcinoma (HCC) is an increasing cause of mortality in Nigeria among persons with HIV (PLH), as access to antiretroviral therapy (ART) improves. In this study we describe clinical, radiological, and laboratory characteristics in Nigerian adults with HCC, with and without HIV, and examine how HIV impacts survival. METHODS: This prospective observational study was conducted between August 2018 and November 2021 at two Nigerian hospitals [Jos University Teaching Hospital (JUTH) and Lagos University Teaching Hospital (LUTH)]. Subjects ≥18 years with HCC diagnosed according to American Association for the Study of Liver Diseases (AASLD) criteria were included. Baseline characteristics were compared, and Kaplan-Meier curves were generated to estimate survival. RESULTS: 213 subjects [177 (83%) without HIV and 36 (17%) with HIV (PLH)] were enrolled. Median age was 52 years (IQR 42,60) and most subjects were male (71%). 83% PLH were on antiretroviral therapy (ART). Hepatitis B surface antigen (HBsAg) positivity was similar between the two groups [91/177 (51%) without HIV vs. 18/36 (50%) with HIV; p = 0.86]. 46/213 (22%) subjects had active hepatitis C (anti-HCV+/HCV RNA>10 IU/mL). Cirrhosis was more common in PLH but there were no other significant differences in clinical and tumor characteristics between the groups. Overall, 99% subjects were symptomatic and 78% in late-stage HCC. Median overall survival was significantly shorter in PLH vs. without HIV (0.98 months vs 3.02 months, HR = 1.55, 95%CI 1.02, 2.37, p = 0.04). This association was not significant after adjusting for known risk factors including gender, current alcohol use, alpha-fetoprotein (AFP), albumin, and total bilirubin (HR = 1.38, 95%CI 0.84, 2.29, p = 0.21). CONCLUSION: HCC presented late with an extremely poor overall prognosis, highlighting the urgent need for more intensive surveillance in Nigeria to diagnose HCC at earlier stages. Early diagnosis and management of viral hepatitis, and access to HCC therapies, could prevent early mortality among persons with HCC, especially among PLH.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Adulto , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Nigéria/epidemiologia , Prognóstico , Hospitais de Ensino , AntirretroviraisRESUMO
BACKGROUND & AIMS: Chronic hepatitis B (CHB) infection remains the most frequent etiology of hepatocellular carcinoma globally as well as a major cause of cirrhosis. Despite vaccination, substantial numbers of persons have already been infected with hepatitis B virus and remain at risk of progressive liver disease. METHODS: In 2004, a CHB management algorithm was developed by a panel of North American hepatologists, which was subsequently updated in 2006, 2008, and 2015. Since the most recent version, several developments have altered the management of CHB. Tenofovir alafenamide, with a more favorable safety profile than tenofovir disoproxil fumarate, has been introduced as an initial antiviral choice as well as an alternative for long-term therapy. Quantitation of hepatitis B surface antigen is becoming more widely available in clinical practice, with implications for monitoring response to treatment. Additionally, there has been a shift in how the natural history of CHB is perceived, as newer evidence has challenged the concept that during the immunotolerant phase of infection disease progression is not a concern. Finally, recent analyses indicate that in the United States, the average age of patients with CHB has increased, implying that the presence of comorbidities, including metabolic liver disease, increasing use of biologics associated with aging will increasingly affect disease management. RESULTS: This updated algorithm is intended to serve as a guide to manage CHB while new antiviral strategies are developed. CONCLUSIONS: Recommendations have been based on evidence from the scientific literature, when possible, as well as clinical experience and consensus expert opinion. Points of continued debate and areas of research need are also described.
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Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Algoritmos , Antivirais/uso terapêutico , Carcinoma Hepatocelular/etiologia , Vírus da Hepatite B , Hepatite B Crônica/complicações , Humanos , Neoplasias Hepáticas/etiologia , Estados UnidosRESUMO
BACKGROUND AND AIMS: Chronic HBV is the predominant cause of HCC worldwide. Although HBV coinfection is common in HIV, the determinants of HCC in HIV/HBV coinfection are poorly characterized. We examined the predictors of HCC in a multicohort study of individuals coinfected with HIV/HBV. APPROACH AND RESULTS: We included persons coinfected with HIV/HBV within 22 cohorts of the North American AIDS Cohort Collaboration on Research and Design (1995-2016). First occurrence of HCC was verified by medical record review and/or cancer registry. We used multivariable Cox regression to determine adjusted HRs (aHRs [95% CIs]) of factors assessed at cohort entry (age, sex, race, body mass index), ever during observation (heavy alcohol use, HCV), or time-updated (HIV RNA, CD4+ percentage, diabetes mellitus, HBV DNA). Among 8,354 individuals coinfected with HIV/HBV (median age, 43 years; 93% male; 52.4% non-White), 115 HCC cases were diagnosed over 65,392 person-years (incidence rate, 1.8 [95% CI, 1.5-2.1] events/1,000 person-years). Risk factors for HCC included age 40-49 years (aHR, 1.97 [1.22-3.17]), age ≥50 years (aHR, 2.55 [1.49-4.35]), HCV coinfection (aHR, 1.61 [1.07-2.40]), and heavy alcohol use (aHR, 1.52 [1.04-2.23]), while time-updated HIV RNA >500 copies/mL (aHR, 0.90 [0.56-1.43]) and time-updated CD4+ percentage <14% (aHR, 1.03 [0.56-1.90]) were not. The risk of HCC was increased with time-updated HBV DNA >200 IU/mL (aHR, 2.22 [1.42-3.47]) and was higher with each 1.0 log10 IU/mL increase in time-updated HBV DNA (aHR, 1.18 [1.05-1.34]). HBV suppression with HBV-active antiretroviral therapy (ART) for ≥1 year significantly reduced HCC risk (aHR, 0.42 [0.24-0.73]). CONCLUSION: Individuals coinfected with HIV/HBV on ART with detectable HBV viremia remain at risk for HCC. To gain maximal benefit from ART for HCC prevention, sustained HBV suppression is necessary.
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Carcinoma Hepatocelular/epidemiologia , Infecções por HIV/epidemiologia , Hepatite B Crônica/epidemiologia , Neoplasias Hepáticas/epidemiologia , Viremia/epidemiologia , Adulto , Fatores Etários , Alcoolismo/epidemiologia , Coinfecção , Feminino , Hepatite C Crônica/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , América do Norte , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de RiscoRESUMO
Importance: People with HIV (PWH) are often coinfected with hepatitis B virus (HBV) and/or hepatitis C virus (HCV), leading to increased risk of developing hepatocellular carcinoma (HCC), but few cohort studies have had sufficient power to describe the trends of HCC incidence and risk among PWH in the combination antiretroviral therapy (cART) era. Objective: To determine the temporal trends of HCC incidence rates (IRs) and to compare rates by risk factors among PWH in the cART era. Design, Setting, and Participants: This cohort study used data from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) study, which was conducted between 1996 and 2015. NA-ACCORD pooled individual-level data from 22 HIV clinical and interval cohorts of PWH in the US and Canada. PWH aged 18 years or older with available CD4 cell counts and HIV RNA data were enrolled. Data analyses were completed in March 2020. Exposures: HBV infection was defined as detection of either HBV surface antigen, HBV e antigen, or HBV DNA in serum or plasma any time during observation. HCV infection was defined by detection of anti-HCV seropositivity, HCV RNA, or detectable genotype in serum or plasma at any time under observation. Main Outcomes and Measures: HCC diagnoses were identified on the basis of review of medical records or cancer registry linkage. Results: Of 109â¯283 PWH with 723â¯441 person-years of follow-up, the median (interquartile range) age at baseline was 43 (36-51) years, 93â¯017 (85.1%) were male, 44â¯752 (40.9%) were White, 44â¯322 (40.6%) were Black, 21â¯343 (19.5%) had HCV coinfection, 6348 (5.8%) had HBV coinfection, and 2082 (1.9%) had triple infection; 451 individuals received a diagnosis of HCC by 2015. Between the early (1996-2000) and modern (2006-2015) cART eras, the crude HCC IR increased from 0.28 to 0.75 case per 1000 person-years. HCC IRs remained constant among HIV-monoinfected persons or those coinfected with HBV, but from 1996 to 2015, IRs increased among PWH coinfected with HCV (from 0.34 cases/1000 person-years in 1996 to 2.39 cases/1000 person-years in 2015) or those with triple infection (from 0.65 cases/1000 person-years in 1996 to 4.49 cases/1000 person-years in 2015). Recent HIV RNA levels greater than or equal to 500 copies/mL (IR ratio, 1.8; 95% CI, 1.4-2.4) and CD4 cell counts less than or equal to 500 cells/µL (IR ratio, 1.3; 95% CI, 1.0-1.6) were associated with higher HCC risk in the modern cART era. People who injected drugs had higher HCC risk compared with men who had sex with men (IR ratio, 2.0; 95% CI, 1.3-2.9), adjusted for HBV-HCV coinfection. Conclusions and Relevance: HCC rates among PWH increased significantly over time from 1996 to 2015. PWH coinfected with viral hepatitis, those with higher HIV RNA levels or lower CD4 cell counts, and those who inject drugs had higher HCC risk.
Assuntos
Carcinoma Hepatocelular/epidemiologia , Infecções por HIV/epidemiologia , Hepatite B Crônica/epidemiologia , Hepatite C Crônica/epidemiologia , Neoplasias Hepáticas/epidemiologia , Adulto , Idoso , Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , Canadá/epidemiologia , Quimioterapia Combinada , Feminino , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Risco , Abuso de Substâncias por Via Intravenosa/epidemiologia , Estados Unidos/epidemiologia , Carga ViralRESUMO
BACKGROUND & AIMS: Seroclearance of hepatitis B surface antigen (HBsAg) is the desired end point of treatment for chronic hepatitis B virus (HBV) infection, according to guidelines. We performed a systematic review and meta-analysis to evaluate the strength of the association between HBsAg seroclearance and long-term clinical outcomes. METHODS: We performed a systematic review of the PubMed, EMBASE, and Cochrane Library databases for articles that assessed HBsAg status and reported the incidence of hepatocellular carcinoma (HCC), liver decompensation, liver transplantation, and/or all-cause mortality during follow-up evaluation. We performed a meta-analysis of rate ratios (RR) using a random-effects model independently for each end point and for a composite end point. RESULTS: We analyzed data from 28 studies, comprising a total of 188,316 patients with chronic HBV infection (treated and untreated), and 1,486,081 person-years (PY) of follow-up evaluation; 26 reported data on HCC, 7 on liver decompensation, and 13 on liver transplantation and/or death. The composite event rates were 0.19/1000 PY for the HBsAg seroclearance group and 2.45/1000 PY for the HBsAg-persistent group. Pooled RRs for the HBsAg seroclearance group were 0.28 for liver decompensation (95% CI, 0.13-0.59; P = .001), 0.30 for HCC (95% CI, 0.20-0.44; P < .001), 0.22 for liver transplantation and/or death (95% CI, 0.13-0.39; P < .001), and 0.31 for the composite end point (95% CI, 0.23-0.43; P < .001). No differences in RR estimates were observed among subgroups of different study or patient characteristics. CONCLUSIONS: In a systematic review and meta-analysis, we found seroclearance of HBsAg to be associated significantly with improved patient outcomes. The results are consistent among different types of studies, in all patient subpopulations examined, and support the use of HBsAg seroclearance as a primary end point of trials of patients with chronic HBV infection.
Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Hepatite B , Neoplasias Hepáticas , Carcinoma Hepatocelular/epidemiologia , DNA Viral , Antígenos de Superfície da Hepatite B , Antígenos E da Hepatite B , Vírus da Hepatite B/genética , Hepatite B Crônica/epidemiologia , HumanosRESUMO
BACKGROUND: Severe hepatotoxicity in people with human immunodeficiency virus (HIV) receiving efavirenz (EFV) has been reported. We assessed the incidence and risk factors of hepatotoxicity in women of childbearing age initiating EFV-containing regimens. METHODS: In the Promoting Maternal and Infant Survival Everywhere (PROMISE) trial, ART-naive pregnant women with HIV and CD4 count ≥ 350 cells/µL and alanine aminotransferase ≤ 2.5 the upper limit of normal were randomized during the antepartum and postpartum periods to antiretroviral therapy (ART) strategies to assess HIV vertical transmission, safety, and maternal disease progression. Hepatotoxicity was defined per the Division of AIDS Toxicity Tables. Cox proportional hazards models were constructed with covariates including participant characteristics, ART regimens, and timing of EFV initiation. RESULTS: Among 3576 women, 2435 (68%) initiated EFV at a median 121.1 weeks post delivery. After EFV initiation, 2.5% (61/2435) hadâ severe (grade 3 or higher) hepatotoxicity with an incidence of 2.3 (95% confidence interval [CI], 2.0-2.6) per 100 person-years. Events occurred between 1 and 132 weeks postpartum. Of those with severe hepatotoxicity, 8.2% (5/61) were symptomatic, and 3.3% (2/61) of those with severe hepatotoxicity died from EFV-related hepatotoxicity, 1 of whom was symptomatic. The incidence of liver-related mortality was 0.07 (95% CI, .06-.08) per 100 person-years. In multivariable analysis, older age was associated with severe hepatotoxicity (adjusted hazard ratio per 5 years, 1.35 [95% CI, 1.06-1.70]). CONCLUSIONS: Severe hepatotoxicity after EFV initiation occurred in 2.5% of women and liver-related mortality occurred in 3% of those with severe hepatotoxicity. The occurrence of fatal events underscores the need for safer treatments for women of childbearing age.
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Fármacos Anti-HIV , Doença Hepática Induzida por Substâncias e Drogas , Infecções por HIV , Idoso , Alcinos , Fármacos Anti-HIV/efeitos adversos , Benzoxazinas/efeitos adversos , Contagem de Linfócito CD4 , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Ciclopropanos , Feminino , HIV , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Lactente , GravidezRESUMO
Direct-acting antiviral (DAA) therapy has transformed the management of human immunodeficiency virus (HIV) and hepatitis C (HCV) coinfected patients with advanced liver disease. STOP-Coinfection was a multicenter prospective and retrospective, open-label study using sofosbuvir-based DAA therapy to treat HIV/HCV-coinfected participants pre- or post-liver transplant (LT). Sixty-eight participants with end-stage liver disease (Child-Turcotte-Pugh score ≥7 and Model for End-Stage Liver Disease score 6-29) were enrolled, 26 had hepatocellular carcinoma. Forty-two participants were treated pre-LT and 26 post-LT. All participants completed therapy without need for dose reduction or transfusion; eight required two or more courses of therapy. Ninety-three percent achieved a sustained virologic response and DAA therapy was well tolerated. Despite HCV cure, 12 end-stage liver disease participants required subsequent LT, 7 for decompensated liver disease. Thirteen participants died, 10 with decompensated liver disease pre-LT and three post-LT. Overall, transplant free survival was 42.8% at 4 years and post-LT survival was 87.9% at 5 years. We conclude that sofosbuvir-based DAA therapy is safe and highly effective in HCV-HIV patients with decompensated liver disease and post-LT, with post-LT survival rates comparable to other indications. This removes one of the last barriers to liver transplantation in this challenging cohort of recipients.
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Coinfecção , Doença Hepática Terminal , Infecções por HIV , Hepatite C Crônica , Hepatite C , Transplante de Fígado , Antivirais/uso terapêutico , Criança , Coinfecção/tratamento farmacológico , Doença Hepática Terminal/complicações , Doença Hepática Terminal/cirurgia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Hepacivirus , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Índice de Gravidade de Doença , Sofosbuvir/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Spontaneous clearance of acute hepatitis C virus (HCV) infection is more common in women than in men, independent of known risk factors. METHODS: To identify sex-specific genetic loci, we studied 4423 HCV-infected individuals (2903 male, 1520 female) of European, African, and Hispanic ancestry. We performed autosomal, and X chromosome sex-stratified and combined association analyses in each ancestry group. RESULTS: A male-specific region near the adenosine diphosphate-ribosylation factor-like 5B (ARL5B) gene was identified. Individuals with the C allele of rs76398191 were about 30% more likely to have chronic HCV infection than individuals with the T allele (OR, 0.69; P = 1.98â ×â 10-07), and this was not seen in females. The ARL5B gene encodes an interferon-stimulated gene that inhibits immune response to double-stranded RNA viruses. We also identified suggestive associations near septin 6 and ribosomal protein L39 genes on the X chromosome. In box sexes, allele G of rs12852885 was associated with a 40% increase in HCV clearance compared with the A allele (OR,â 1.4; P =â 2.46â ×â 10-06). Septin 6 facilitates HCV replication via interaction with the HCV NS5b protein, and ribosomal protein L39 acts as an HCV core interactor. CONCLUSIONS: These novel gene associations support differential mechanisms of HCV clearance between the sexes and provide biological targets for treatment or vaccine development.
Assuntos
Hepatite C , Fatores Sexuais , Feminino , Estudo de Associação Genômica Ampla , Hepacivirus/genética , Hepatite C/genética , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Proteínas Ribossômicas/genética , Septinas/genética , Carga ViralRESUMO
Among individuals with HIV infection, liver disease remains an important cause of morbidity and mortality, even with the availability of agents that cure hepatitis C infection and suppress hepatitis B replication. The causes of liver disease are multifaceted and continue to evolve as the population ages and new etiologies arise. Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis and hepatitis viruses such as A, D, and E have emerged even as hepatitis C has receded. Newer antiretroviral agents may increase risk of weight gain and subsequent fatty infiltration, and prior use of nucleotide-based therapies may continue to impact liver health. Several barriers including economics, social stigma, and psychiatric disease impact identification of liver disease, as well as management and treatment interventions. Hepatocellular carcinoma is emerging as a more common and late-diagnosed complication in those with HIV infection and liver disease.
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Infecções por HIV/complicações , Hepatite Viral Humana/complicações , Hepatopatias/etiologia , Fígado/virologia , Antirreumáticos/uso terapêutico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Fígado Gorduroso/complicações , Fígado Gorduroso/epidemiologia , Fígado Gorduroso Alcoólico/complicações , Fígado Gorduroso Alcoólico/epidemiologia , Infecções por HIV/epidemiologia , Hepatite A/complicações , Hepatite A/epidemiologia , Hepatite B/complicações , Hepatite B/epidemiologia , Hepatite C/complicações , Hepatite C/epidemiologia , Hepatite D/complicações , Hepatite D/epidemiologia , Hepatite E/complicações , Hepatite E/epidemiologia , Vírus de Hepatite , Hepatite Viral Humana/epidemiologia , Humanos , Fígado/lesões , Hepatopatia Gordurosa não AlcoólicaRESUMO
Current recommendations concerning hepatitis C virus (HBV) reactivation are limited, with nearly all guidelines focused on its occurrence in patients with hematological malignancies or some solid tumors, who are treated with immunosuppressive therapies. Few of the guidelines address reactivation in patients receiving immunosuppression with organ transplants or treatment with any of the many immunosuppressive agents in use today for the treatment of multiple different diseases, or in patients receiving the direct-acting antivirals used in the treatment of hepatitis C virus (HCV). This article covers the immunology of HBV reactivation, mechanisms of viral clearance, and recommendations for screening and prophylaxis.
Assuntos
Imunidade Adaptativa/imunologia , Vírus da Hepatite B/fisiologia , Hepatite B/virologia , Imunidade Inata/imunologia , Imunossupressores/uso terapêutico , Ativação Viral/imunologia , Imunidade Adaptativa/efeitos dos fármacos , Feminino , Hepatite B/fisiopatologia , Humanos , Imunidade Inata/efeitos dos fármacos , Masculino , Programas de Rastreamento/métodos , Prevenção Primária , Prognóstico , Medição de RiscoRESUMO
Organ transplantation is a lifesaving procedure for many patients. To prevent rejection or graft-versus-host disease, recipients require long-term immunosuppression. In patients who have ever been exposed to hepatitis B, it is possible for reactivation to occur; this includes patients who are anti-hepatitis B core antibody-positive only or both anti-hepatitis B core antibody-positive and hepatitis B surface antibody-positive. The susceptibility to this varies with the nature of the transplant. Hepatitis B can be transmitted from donor to recipient. It is important to assess the hepatitis B status and formulate a strategy to prevent transmission and prevent reactivation.
Assuntos
Doença Enxerto-Hospedeiro/imunologia , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B/prevenção & controle , Transplante de Fígado/efeitos adversos , Ativação Viral/imunologia , Antivirais/uso terapêutico , Transmissão de Doença Infecciosa , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/fisiopatologia , Hepatite B/tratamento farmacológico , Vírus da Hepatite B/imunologia , Humanos , Transplante de Fígado/métodos , Masculino , Programas de Rastreamento , Prognóstico , Análise de Sobrevida , Transplantados , Resultado do Tratamento , Ativação Viral/efeitos dos fármacosRESUMO
Patients with malignancies require chemotherapy and other immunosuppressive therapies for treatment. Because of this immunosuppression, in patients who have ever been exposed to hepatitis B it is possible for reactivation to occur. This reactivation can be fatal. Reactivation is particularly likely in patients who receive B cell-active agents such as rituximab. The occurrence of reactivation flares may also delay further chemotherapy, which can negatively affect the outcome of the underlying malignancy. Accordingly, it is important to screen patients for markers of hepatitis B and institute antiviral prophylaxis to prevent reactivation.
Assuntos
Neoplasias Hematológicas/epidemiologia , Vírus da Hepatite B/fisiologia , Hepatite B Crônica/prevenção & controle , Hospedeiro Imunocomprometido , Neoplasias/epidemiologia , Ativação Viral/imunologia , Causas de Morte , Feminino , Neoplasias Hematológicas/imunologia , Anticorpos Anti-Hepatite B/imunologia , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/fisiopatologia , Humanos , Masculino , Programas de Rastreamento , Neoplasias/imunologia , Prevalência , Prevenção Primária/métodos , Prognóstico , Medição de Risco , Análise de Sobrevida , Ativação Viral/efeitos dos fármacosRESUMO
Because of the relatively high prevalence of both hepatitis B infection and various forms of autoimmune inflammatory diseases treated with aggressive immunotherapy, reactivation of hepatitis B occurs in a substantial number of patients. The risk of reactivation depends on the degree and duration of immunosuppression. A large number of drug treatments have resulted in reactivation of hepatitis B virus infection and, based on the mechanisms and extent of immunosuppression, recommendations for some of the newer classes of immunosuppressive drugs are provided.
Assuntos
Artrite Reumatoide/imunologia , Produtos Biológicos/uso terapêutico , Vírus da Hepatite B/fisiologia , Hospedeiro Imunocomprometido , Doenças Inflamatórias Intestinais/imunologia , Ativação Viral/imunologia , Antivirais/uso terapêutico , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/epidemiologia , Feminino , Antígenos de Superfície da Hepatite B/efeitos dos fármacos , Antígenos de Superfície da Hepatite B/imunologia , Humanos , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/epidemiologia , Masculino , Programas de Rastreamento , Prevalência , Prognóstico , Medição de Risco , Análise de Sobrevida , Ativação Viral/efeitos dos fármacosRESUMO
BACKGROUND: Hepatitis B virus (HBV) infection is a leading cause of end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC) in HIV. Factors contributing to the high rates of liver complications among HIV/HBV-coinfected individuals remain unknown. SETTING: North American AIDS Cohort Collaboration on Research and Design. METHODS: We performed a retrospective cohort study among HIV/HBV-coinfected patients in 10 US and Canadian cohorts of the North American AIDS Cohort Collaboration on Research and Design that validated ESLD (ascites, spontaneous bacterial peritonitis, variceal hemorrhage, and/or hepatic encephalopathy) and HCC diagnoses from 1996 to 2010. Multivariable Cox regression was used to examine adjusted hazard ratios [aHRs with 95% confidence interval (CIs)] of liver complications (first occurrence of ESLD or HCC) associated with hypothesized determinants and with increasing durations of HIV suppression (≤500 copies/mL). RESULTS: Among 3573 HIV/HBV patients with 13,790 person-years of follow-up, 111 liver complications occurred (incidence rate = 8.0 [95% CI: 6.6 to 9.7] events/1000 person-years). Rates of liver complication were increased with non-black/non-Hispanic race [aHR = 1.76 (1.13-2.74)], diabetes mellitus [aHR = 2.07 (1.20-3.57)], lower time-updated CD4 cell count [<200 cells/mm: aHR = 2.59 (1.36-4.91); 201-499 cells/mm: aHR = 1.75 (1.01-3.06) versus ≥500 cells/mm], heavy alcohol use [aHR = 1.58 (1.04-2.39)], and higher FIB-4 at start of follow-up [>3.25: aHR = 9.79 (5.73-16.74); 1.45-3.25: aHR = 3.20 (1.87-5.47) versus FIB-4 <1.45]. HIV suppression for ≥6 months was associated with lower liver complication rates compared with those with unsuppressed HIV [aHR = 0.56 (0.35-0.91)]. CONCLUSIONS: Non-black/non-Hispanic race, diabetes, lower CD4 cell count, heavy alcohol use, and advanced liver fibrosis were determinants of liver complications among HIV/HBV patients. Sustained HIV suppression should be a focus for HIV/HBV-coinfected patients to reduce the risks of ESLD/HCC.
Assuntos
Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Hepatite B/complicações , Hepatite B/epidemiologia , Adulto , Contagem de Linfócito CD4 , Canadá , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/epidemiologia , Doença Hepática Terminal/complicações , Varizes Esofágicas e Gástricas , Feminino , Hemorragia Gastrointestinal , Humanos , Fígado , Cirrose Hepática/complicações , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Estados UnidosRESUMO
BACKGROUND: Two million individuals with chronic hepatitis B (CHB) in the United States are at risk for premature death due to liver cancer and cirrhosis. CHB can be prevented by vaccination and controlled with treatment. METHODS: We created a lifetime Markov model to estimate the cost-effectiveness of strategies to prevent or treat CHB in 6 high-risk populations: foreign-born Asian/Pacific Islanders (API), Africa-born blacks (AbB), incarcerated, refugees, persons who inject drugs (PWID), and men who have sex with men (MSM). We studied 3 strategies: (a) screen for HBV infection and treat infected ("treatment only"), (b) screen for HBV susceptibility and vaccinate susceptible ("vaccination only"), and (c) screen for both and follow-up appropriately ("inclusive"). Outcomes were expressed in incremental cost-effectiveness ratios (ICERs), clinical outcomes, and new infections. RESULTS: Vaccination-only and treatment-only strategies had ICERs of $6000-$21 000 per quality-adjusted life-year (QALY) gained, respectively. The inclusive strategy added minimal cost with substantial clinical benefit, with the following costs per QALY gained vs no intervention: incarcerated $3203, PWID $8514, MSM $10 954, AbB $17 089, refugees $17 432, and API $18 009. Clinical complications dropped in the short/intermediate (1%-25%) and long (0.4%-16%) term. Findings were sensitive to age, discount rate, health state utility in immune or susceptible stages, progression rate to cirrhosis or inactive disease, and tenofovir cost. The probability of an inclusive program costing <$50 000 per QALY gained varied between 61% and 97% by population. CONCLUSIONS: An inclusive strategy to screen and treat or vaccinate is cost-effective in reducing the burden of hepatitis B virus among all 6 high-risk, high-prevalence populations.
RESUMO
Hepatitis B virus (HBV) infection is a lifelong dynamic disease that can be controlled with treatment but cannot yet be cured. Risk of end-stage liver disease and hepatocellular carcinoma (HCC) increases with ongoing inflammation and HBV viremia. Initial treatments consist of tenofovir or entecavir. Patients who require treatment include those with chronic hepatitis, cirrhosis, HCC, or HIV coinfection; patients receiving immunosuppressive treatments; and women in the third trimester of pregnancy who have elevated HBV DNA level. A number of virologic and host immune approaches are being investigated with the aim of achieving HBV eradication. This article summarizes an IAS-USA webinar given by Marion G. Peters, MD, on June 14, 2018.
Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Hepatite B Crônica/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Carcinoma Hepatocelular/complicações , Coinfecção/tratamento farmacológico , Feminino , Hepatite B Crônica/complicações , Humanos , Cirrose Hepática/complicações , Masculino , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Estados UnidosRESUMO
Risk of hepatitis B virus (HBV) reactivation was assessed in B-cell non-Hodgkin lymphoma (NHL) patients with resolved HBV infection (hepatitis B surface antigen negative, hepatitis B core antibody positive) who received obinutuzumab- or rituximab-containing immunochemotherapy in the phase 3 GOYA and GALLIUM studies. HBV DNA monitoring was undertaken monthly to 1 year after the last dose of study drug. In case of HBV reactivation (confirmed, HBV DNA ≥29 IU/mL), immunochemotherapy was withheld and nucleos(t)ide analog treatment (preemptive NAT) started. Immunochemotherapy was restarted if HBV DNA became undetectable or reactivation was not confirmed, and discontinued if HBV DNA exceeded 100 IU/mL on NAT. Prophylactic NAT was allowed by investigator discretion. Among 326 patients with resolved HBV infection, 27 (8.2%) had HBV reactivation, occurring a median of 125 days (interquartile range, 85-331 days) after the first dose. In 232 patients without prophylactic NAT, 25 (10.8%) had HBV reactivation; all received preemptive NAT. Ninety-four patients received prophylactic NAT; 2 (2.1%) had HBV reactivation. No patients developed HBV-related hepatitis. On multivariate Cox analysis, detectable HBV DNA at baseline was strongly associated with an increased risk of reactivation (adjusted hazard ratio [HR], 18.22; 95% confidence interval [CI], 6.04-54.93; P < .0001). Prophylactic NAT was strongly associated with a reduced risk (adjusted HR, 0.09; 95% CI, 0.02-0.41; P = .0018). HBV DNA monitoring-guided preemptive NAT was effective in preventing HBV-related hepatitis during anti-CD20-containing immunochemotherapy in B-cell NHL patients with resolved HBV infection. Antiviral prophylaxis was also effective and may be appropriate for high-risk patients. These trials were registered at www.clinicaltrials.gov as NCT01287741 (GOYA) and NCT01332968 (GALLIUM).
Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B/virologia , Linfoma de Células B/tratamento farmacológico , Rituximab/efeitos adversos , Ativação Viral/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/uso terapêutico , DNA Viral/genética , Feminino , Seguimentos , Hepatite B/induzido quimicamente , Hepatite B/tratamento farmacológico , Vírus da Hepatite B/genética , Humanos , Imunoterapia/efeitos adversos , Linfoma de Células B/imunologia , Linfoma de Células B/virologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos ProspectivosRESUMO
The epidemiology of hepatitis C virus (HCV) has changed significantly over the last decade. Once most prevalent among older adults, the current burden has disproportionately affected young adults including women of childbearing age (WOCA). The Society for Maternal-Fetal Medicine recently issued guidelines that made no change in the recommendation to screen pregnant women based on risk factors. The current burden in young adults including WOCA supports a change in strategy away from risk-based screening to universal HCV screening in pregnancy. Universal screening offers several advantages that position us for a future where HCV treatment in pregnancy can happen and offers us progress toward the elimination of HCV.