RESUMO
Patients with chronic liver disease progressed to compensated advanced chronic liver disease (cACLD), the risk of liver-related decompensation increased significantly. This study aimed to develop prediction model based on individual bile acid (BA) profiles to identify cACLD. This study prospectively recruited 159 patients with hepatitis B virus (HBV) infection and 60 healthy volunteers undergoing liver stiffness measurement (LSM). With the value of LSM, patients were categorized as three groups: F1 [LSM ≤ 7.0 kilopascals (kPa)], F2 (7.1 < LSM ≤ 8.0 kPa), and cACLD group (LSM ≥ 8.1 kPa). Random forest (RF) and support vector machine (SVM) were applied to develop two classification models to distinguish patients with different degrees of fibrosis. The content of individual BA in the serum increased significantly with the degree of fibrosis, especially glycine-conjugated BA and taurine-conjugated BA. The Marco-Precise, Marco-Recall, and Marco-F1 score of the optimized RF model were all 0.82. For the optimized SVM model, corresponding score were 0.86, 0.84, and 0.85, respectively. RF and SVM models were applied to identify individual BA features that successfully distinguish patients with cACLD caused by HBV. This study provides a new tool for identifying cACLD that can enable clinicians to better manage patients with chronic liver disease.
Assuntos
Ácidos e Sais Biliares , Hepatite B Crônica , Cirrose Hepática , Fígado , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ácidos e Sais Biliares/sangue , Glicina/metabolismo , Vírus da Hepatite B/metabolismo , Hepatite B Crônica/sangue , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/metabolismo , Hepatite B Crônica/virologia , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Cirrose Hepática/metabolismo , Cirrose Hepática/virologia , Algoritmo Florestas Aleatórias , Máquina de Vetores de Suporte , Taurina/metabolismo , Adolescente , Adulto Jovem , Idoso , Reprodutibilidade dos Testes , Análise de Componente PrincipalRESUMO
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 SoroepidemiológicosRESUMO
BACKGROUND AND AIMS: Access to basic health needs remains a challenge for most of world's population. In this study, we developed a care model for preventive and disease-specific health care for an extremely remote and marginalized population in Arunachal Pradesh, the northeasternmost state of India. APPROACH AND RESULTS: We performed patient screenings, performed interviews, and obtained blood samples in remote villages of Arunachal Pradesh through a tablet-based data collection application, which was later synced to a cloud database for storage. Positive cases of hepatitis B virus (HBV) were confirmed and genotyped in our central laboratory. The blood tests performed included liver function tests, HBV serologies, and HBV genotyping. HBV vaccination was provided as appropriate. A total of 11,818 participants were interviewed, 11,572 samples collected, and 5,176 participants vaccinated from the 5 westernmost districts in Arunachal Pradesh. The overall hepatitis B surface antigen (HBsAg) prevalence was found to be 3.6% (n = 419). In total, 34.6% were hepatitis B e antigen positive (n = 145) and 25.5% had HBV DNA levels greater than 20,000 IU/mL (n = 107). Genotypic analysis showed that many patients were infected with HBV C/D recombinants. Certain tribes showed high seroprevalence, with rates of 9.8% and 6.3% in the Miji and Nishi tribes, respectively. The prevalence of HBsAg in individuals who reported medical injections was 3.5%, lower than the overall prevalence of HBV. CONCLUSIONS: Our unique, simplistic model of care was able to link a highly resource-limited population to screening, preventive vaccination, follow-up therapeutic care, and molecular epidemiology to define the migratory nature of the population and disease using an electronic platform. This model of care can be applied to other similar settings globally.
Assuntos
Atenção à Saúde/estatística & dados numéricos , Hepatite B/epidemiologia , Migração Humana/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Relações Comunidade-Instituição , DNA Viral/sangue , Atenção à Saúde/economia , Doenças Endêmicas/economia , Doenças Endêmicas/prevenção & controle , Doenças Endêmicas/estatística & dados numéricos , Feminino , Genótipo , Hepatite B/sangue , Hepatite B/etiologia , Hepatite B/terapia , Anticorpos Anti-Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Hepatite B Crônica/sangue , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/etiologia , Hepatite B Crônica/terapia , Humanos , Índia/epidemiologia , Lactente , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Modelos Teóricos , Prevalência , População Rural/estatística & dados numéricos , Estudos Soroepidemiológicos , Marginalização Social , Vacinação/economia , Vacinação/estatística & dados numéricos , Carga Viral , Adulto JovemRESUMO
Background: This study compares venepuncture versus point-of-care (POC) HBsAg tests on screening cost and linkage to care in prospective outreach screenings in an Asian population in three major cities in Belgium between 10/2014 and 5/2018. Methods: Two community outreach screening programs were organised between 10/2014 and 5/2018. The first screening program used venepuncture and serologic testing for HBsAg. In the second program, HBsAg was tested in finger stick blood POC tests. Positive results were confirmed during outpatient visits with serologic testing. Linkage to care was defined as having received specialist care follow-up with at least one abdominal ultrasound within three months of screening. Results: For 575 participating individuals, 571 valid results were obtained, 456 with venepuncture, and 115 using POC testing. Overall HBsAg seroprevalence was 6.8%. Linkage to care was higher when using POC testing compared to venepuncture (86% or n = 6/7 versus 34% or n = 11/32; p = 0.020). The POC screening program was economically more attractive with a total cost of 1,461.8 or 12.7 per person screened compared to 24,819 or 54.0 per person screened when using venepuncture testing. Results and an appointment for specialist care follow-up were given onsite with POC testing, while with venepuncture testing; results were sent within 20-45 days. Conclusion: In an Asian migrant population in Belgium with an HBsAg seroprevalence of 6.8%, HBV screening based on POC tests resulted in lower costs per person screened (76.5% lower), and higher linkage to care (2.5 times).
Assuntos
Continuidade da Assistência ao Paciente/estatística & dados numéricos , Emigrantes e Imigrantes/estatística & dados numéricos , Custos de Cuidados de Saúde , Antígenos de Superfície da Hepatite B/sangue , Hepatite B Crônica/diagnóstico , Testes Imediatos , Bélgica/epidemiologia , China/etnologia , Feminino , Hepatite B Crônica/sangue , Hepatite B Crônica/epidemiologia , Humanos , Masculino , Programas de Rastreamento/economia , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Testes Imediatos/economia , Estudos Soroepidemiológicos , Testes Sorológicos/economia , Testes Sorológicos/métodosRESUMO
BACKGROUND/PURPOSE: Hepatitis B virus (HBV) reactivation may occur in >10% of patients with lymphoma and resolved HBV infection who undergo rituximab-containing chemotherapy. Preventive strategies may have marked impact on resource allocation in HBV endemic areas. This study aims to compare the cost-effectiveness between prophylactic antiviral therapy and HBV DNA monitoring for the prevention of HBV-related complications. METHODS: Data sources are studies of HBV-related events and survival for patients with lymphoma and resolved HBV infection published since 2006. Decision tree analysis was used to compare the incremental cost-effectiveness ratio (ICER) of preventing HBV-related death or liver decompensation for patients who undergo first-line rituximab-containing chemotherapy. Sensitivity analysis was performed to examine the impact of the preventive efficacy, the duration of prophylactic antiviral therapy, and the cost of different interventions. The direct medical cost was derived from the database of the NHI Administration, Taiwan. The time frame of our analysis was set to 3 years after the completion of chemotherapy. RESULTS: The median ICER of prophylactic antiviral therapy, according to current practice guidelines, ranged between USD 150,000 and 250,000 if we apply the guidelines generally. When a long-course (12 months after completion of chemotherapy according to clinical guidelines) prophylactic therapy was assumed, Option A was cheaper and more effective only in the anti-HBs-negative subgroup (median ICER US$149,932 vs. US$161,526, p = 0.013). CONCLUSION: Identification of anti-HBs-negative subgroups is critical to improve the cost-effectiveness of prophylactic antiviral therapy in lymphoma patients with resolved HBV infection.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antivirais/uso terapêutico , Análise Custo-Benefício , Hepatite B Crônica/prevenção & controle , Linfoma não Hodgkin/tratamento farmacológico , Ativação Viral , DNA Viral/sangue , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Hepatite B Crônica/sangue , Hepatite B Crônica/tratamento farmacológico , Humanos , Linfoma não Hodgkin/complicações , Rituximab/uso terapêutico , TaiwanRESUMO
BACKGROUND: Hepatitis B is a major public health problem in China. Accurate liver injury assessment is essential for clinical evidence-based treatment. Liver biopsy is considered the gold standard method to stage liver disease, but it is not widely used in resource-limited settings. Therefore, non-invasive liquid biopsy tests are needed. AIM: To assess liver injury in hepatitis B patients using quantified cell free DNA combined with other serum biomarker as a liquid biopsy-based method. METHODS: A cohort of 663 subjects including 313 hepatitis B patients and 350 healthy controls were enrolled. Ultrasound-guided liver biopsies followed by histopathological assessments were performed for the 263 chronic hepatitis B patients to determine the degree of liver injury. Cell-free DNA was quantified using a novel duplex real-time polymerase chain reaction assay. RESULTS: Compared with healthy controls, patients with hepatitis B virus (HBV) infection had significantly higher plasma DNA, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, and HBV DNA levels (P < 0.01). Serum ALT, AST, bilirubin, and plasma DNA levels of patients with marked-severe inflammation were significantly higher than those with mild-moderate inflammation (P < 0.01). There was a statistically significant correlation between hepatocyte inflammation severity and serum bilirubin (R 2 = 0.673, P < 0.01) or plasma DNA (R 2 = 0.597, P < 0.01) levels. The areas under the curves of serum ALT, bilirubin, plasma DNA, and their combination to distinguish between patients with mild-moderate and marked-severe inflammation were 0.8059, 0.7910, 0.7921, and 0.9564, respectively. CONCLUSION: The combination of plasma DNA, serum ALT, and bilirubin could be a candidate liquid biopsy for non-invasive assessment of liver injury in hepatitis B patients.
Assuntos
Hepatite B Crônica/diagnóstico , Testes de Função Hepática/métodos , Fígado/patologia , Adolescente , Adulto , Idoso , Alanina Transaminase/sangue , Bilirrubina/sangue , Biomarcadores/sangue , Ácidos Nucleicos Livres/sangue , China , Estudos de Coortes , Estudos de Viabilidade , Feminino , Voluntários Saudáveis , Hepatite B Crônica/sangue , Hepatite B Crônica/patologia , Humanos , Biópsia Líquida/métodos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Índice de Gravidade de Doença , Adulto JovemRESUMO
Chronic Hepatitis B (HBV) is the most important cause of liver disease worldwide. There is a need for low-cost tests to aid in diagnosis and management of HBV infection in resource-limited settings. We evaluated the utility of several rapid diagnostic tests (RDT) in three different continents (Europe, South America, Africa). The HBsAg RDT showed optimal sensitivity and specificity. The anti-HBeAb RDT showed acceptable sensitivity and excellent specificity. Our results suggest that these RDTs could be used for screening and management of HBV.
Assuntos
Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/sangue , Hepatite B Crônica/diagnóstico , Adulto , Argentina , Técnicas de Diagnóstico do Sistema Digestório , Etiópia , Feminino , Antígenos de Superfície da Hepatite B/imunologia , Antígenos E da Hepatite B/imunologia , Humanos , Masculino , Países Baixos , Curva ROC , Fatores de TempoRESUMO
BACKGROUND: International sustainable development goals for the elimination of viral hepatitis as a public health problem by 2030 highlight the need to optimize strategies for prevention, diagnosis and treatment of hepatitis B virus (HBV) infection. An important priority for Africa is to have affordable, accessible and sustainable prevention of mother to child transmission (PMTCT) programmes, delivering screening and treatment for antenatal women and implementing timely administration of HBV vaccine for their babies. METHODS: We developed a decision-analytic model simulating 10,000 singleton pregnancies to assess the cost-effectiveness of three possible strategies for deployment of tenofovir in pregnancy, in combination with routine infant vaccination: S1: no screening nor antiviral therapy; S2: screening and antiviral prophylaxis for all women who test HBsAg-positive; S3: screening for HBsAg, followed by HBeAg testing and antiviral prophylaxis for women who are HBsAg-positive and HBeAg-positive. Our outcome was cost per infant HBV infection avoided and the analysis followed a healthcare perspective. RESULTS: Based on 10,000 pregnancies, S1 predicts 45 infants would be HBV-infected at six months of age, compared to 21 and 28 infants in S2 and S3, respectively. Relative to S1, S2 had an incremental cost of $3940 per infection avoided. S3 led to more infections and higher costs. CONCLUSION: Given the long-term health burden for individuals and economic burden for society associated with chronic HBV infection, screening pregnant women and providing tenofovir for all who test HBsAg+ may be a cost-effective strategy for South Africa and other low/middle income settings.
Assuntos
Antivirais/uso terapêutico , Análise Custo-Benefício , Vírus da Hepatite B/imunologia , Hepatite B/tratamento farmacológico , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez/tratamento farmacológico , Tenofovir/uso terapêutico , Adulto , Criança , Países em Desenvolvimento , Feminino , Hepatite B/sangue , Hepatite B/diagnóstico , Hepatite B/virologia , Antígenos de Superfície da Hepatite B/sangue , Vacinas contra Hepatite B/administração & dosagem , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/sangue , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Humanos , Lactente , Programas de Rastreamento , Modelos Biológicos , Gravidez , Complicações Infecciosas na Gravidez/sangue , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/virologia , África do Sul , Tenofovir/economia , Vacinação , Adulto JovemRESUMO
AIM: Even during nucleos(t)ide analogue therapy, development of hepatocellular carcinoma (HCC) has been observed in patients with chronic hepatitis B virus (HBV) infection. We simulated the long-term prognosis of liver disease in patients with chronic HBV who received nucleos(t)ide analogue therapy. PATIENTS AND METHODS: A total of 254 patients with chronic HBV receiving nucleos(t)ide analogue therapy were enrolled. Yearly transition probabilities between liver disease states [chronic hepatitis, cirrhosis, HCC, and hepatitis B surface antigen (HBsAg)-negative status] were calculated using a Markov chain model. RESULTS: In the analysis of 1-year liver disease state transition probabilities, the development of HCC occurred in men with chronic hepatitis in their 50s (1.8%) and at least 70 years (2.8%) and in patients with cirrhosis in all age groups (40-49, 50-59, 60-69, and ≥ 70 years). HBsAg-negative status was present in patients with chronic hepatitis in their 50s (1.8%) and 60s (2.6%), and in patients with cirrhosis in their 60s (0.6%). In female patients, the development of HCC occurred in patients with cirrhosis during their 50s (0.8%), 60s (0.8%), and older (4.5%). HBsAg-negative status was simulated in patients with cirrhosis in their 50s (0.8%) and 60s (0.8%). Assuming a chronic hepatitis state at age 40 as the starting condition for simulation over the next 40 years, the probability of developing HCC increased gradually with age in male patients and in female patients after the age of 70 years. CONCLUSION: There is a risk of development of HCC in middle-aged men with chronic hepatitis or cirrhosis and older women with cirrhosis even while receiving nucleos(t)ide analogue therapy.
Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/etiologia , Hepatite B Crônica/tratamento farmacológico , Cirrose Hepática/etiologia , Neoplasias Hepáticas/etiologia , Adenina/análogos & derivados , Adenina/uso terapêutico , Adulto , Idoso , Carcinoma Hepatocelular/diagnóstico , Feminino , Guanina/análogos & derivados , Guanina/uso terapêutico , Antígenos de Superfície da Hepatite B/sangue , Hepatite B Crônica/sangue , Hepatite B Crônica/complicações , Humanos , Lamivudina/uso terapêutico , Cirrose Hepática/diagnóstico , Neoplasias Hepáticas/diagnóstico , Masculino , Cadeias de Markov , Pessoa de Meia-Idade , Nucleosídeos/análogos & derivados , Organofosfonatos/uso terapêutico , PrognósticoRESUMO
Objectives: Human immunodeficiency virus (HIV) and hepatitis B virus (HBV) are both worldwide health concerns with similar routes of transmission and no curative treatment to date. Coinfection is associated with increased morbidity and mortality. We aim to provide epidemiological data about HIV-HBV coinfected patients and asses if management of patients following European recommendation (EACS) was achieved in a large AIDS Reference Center in Belgium. Methods: Retrospective review of the HIV database of Saint-Pierre University Hospital in Brussels (Belgium) focusing on HIV-HBV coinfected patients in active follow-up. We classified patients in six serological profiles: (A) patients with active chronic HBV infection (HBsAg positive and HBeAg positive), (B) patients with persistent chronic HBV infection (HBsAg positive and HBeAg negative), (C) patients with isolated core antibody (isolated anti-HBc positive), (D) patients with resolved HBV infection (anti-HBc positive and anti-HBs positive), (E) vaccinated patients (anti-HBs positive), and (F) patients with all above markers negative. Chronic HBV infection (cHBV) was defined by two positive hepatitis B surface antigens (AgHBs positive) with at least 6-month intervals and chronic HBeAg positive group by a positive AgHBe (Ag HBe positive). We reviewed individual files of HIV-HBV chronically coinfected patients to assess if European recommendations in terms of HBV coinfection management were adequately followed in our center. Results: Among 2601 HIV-infected patients in active follow-up, 98 (3.8%) were chronically infected with HBV. Median age of chronically coinfected patients was 46 years with male predominance and heterosexual Africans representing the majority. Among the chronically coinfected patients, 33.7% were HBeAg positive carriers. Mean HBV DNA and ALT/AST were significantly higher in the chronic HBeAg positive (cHBeAg positive) patients compared to chronic HBeAg negative patients (cHBeAg negative). Nearly 95% of the cHBV patients were treated with two anti-HBV drugs (99% for the cHBeAg positive group), with 79% having Tenofovir (TDF) in their antiretroviral treatment history. 8% were screened for hepatitis D virus (HDV) antibodies. Liver fibrosis, upper endoscopy and alpha-foetoprotein were assessed at least once in the last 5 years in 32%, 31% and 32% of cHBV patients respectively. cHBeAg positive patients were not significantly monitored closer except for liver fibrosis assessment in 52% (p < 0.0017). Conclusion: The prevalence of cHBV coinfection in the Saint-Pierre HIV cohort is lower than in neighboring European countries. Hepatic monitoring should be reinforced in our cHBV and cHBeAg positive patients because of higher risk of progression to cirrhosis progression and hepatocellular carcinoma.
Assuntos
Assistência ao Convalescente , Terapia Antirretroviral de Alta Atividade , Infecções por HIV , Hepatite B Crônica , Adulto , Assistência ao Convalescente/métodos , Assistência ao Convalescente/organização & administração , Assistência ao Convalescente/estatística & dados numéricos , Terapia Antirretroviral de Alta Atividade/métodos , Terapia Antirretroviral de Alta Atividade/estatística & dados numéricos , Bélgica/epidemiologia , Contagem de Linfócito CD4/métodos , Estudos de Coortes , Coinfecção , Feminino , Infecções por HIV/sangue , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Antígenos de Superfície da Hepatite B/análise , Hepatite B Crônica/sangue , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação das Necessidades , Serviços Preventivos de Saúde/métodos , Serviços Preventivos de Saúde/estatística & dados numéricos , Estudos RetrospectivosRESUMO
Background: Chronic hepatitis B infection affects 240 million people, with the highest prevalence in Africa and Asia, and results in 700 000 deaths annually. Access to diagnostics, particularly for hepatitis B virus viral load quantification (HBV DNA), is a major barrier to treatment. We aimed to test World Health Organization guidelines for hepatitis B management in resource-limited settings. Methods: We compared treatment allocation with and without the use of HBV DNA in a cohort in Uganda. Hepatitis B surface antigen test-positive, human immunodeficiency virus-negative, treatment-naïve adults were recruited prospectively. Following liver ultrasound and routine haematological and biochemical tests, preliminary allocations into treatment and observation groups were made. HBV DNA was performed for each participant and final treatment decisions were made and compared with preliminary allocations. Results: Full assessment was completed for 100 participants; treatment was indicated in 20. Assessment without HBV DNA identified patients for treatment with a positive predictive value of 88.2% and a negative predictive value of 94% compared with assessment using HBV DNA. Conclusions: Where HBV DNA is unavailable, patients with hepatitis B can be assessed by liver ultrasound and routine laboratory tests. These findings will enable physicians in resource-limited settings to initiate treatment more readily and inform policy with regards to viral hepatitis elimination.
Assuntos
DNA Viral , Testes Diagnósticos de Rotina/métodos , Acessibilidade aos Serviços de Saúde , Vírus da Hepatite B , Hepatite B Crônica/diagnóstico , Fígado/patologia , Ultrassonografia , Adolescente , Adulto , Idoso , Análise Química do Sangue , Países em Desenvolvimento , Feminino , Recursos em Saúde , Hematologia , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B/genética , Hepatite B Crônica/sangue , Hepatite B Crônica/diagnóstico por imagem , Hepatite B Crônica/virologia , Humanos , Fígado/diagnóstico por imagem , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Sensibilidade e Especificidade , Testes Sorológicos , Uganda , Carga Viral , Adulto JovemRESUMO
BACKGROUND: The current upper limits of normal (ULN) for serum alanine aminotransferase (ALT) are increasingly challenged. We aimed to re-evaluate the ULN for ALT and assess the potential impact on the classification of natural course of chronic hepatitis B virus (HBV) infection in children. METHODS: Laboratory data obtained from three hospitals in China were retrospectively analysed. In total, 2054 children with chronic HBV infection and 8149 healthy children at age ≤18 years were included in the study. RESULTS: Age-specific and gender-specific ULNs for ALT, at averages of 30 U/L for boys and 24 U/L for girls, were calculated from the data of healthy children. Using the revised ULNs vs. the current ULNs (40-50 U/L), 31-60% vs. 9-17% of the 2054 HBV-infected children had an abnormal result as seen in their ALT baseline analysis, and the highest abnormality rate was seen in the infants. Data of 516 HBV-infected children were applied for the classification of clinical phase, 28.8% vs. 19.8% of the children were classified into the phases of hepatitis B e antigen (HBeAg-)positive/negative hepatitis. During a median follow-up of 62 months, 39 of 153 children underwent HBeAg seroconversion, whereas 3 of them had persistently "normal" ALT, according to the current ULN. CONCLUSIONS: The revision of ULN for ALT in children substantially impacts the classification of the natural course of chronic HBV infection. Mild ALT fluctuation is common during the stage childhood, suggesting a need to rethink the current conceptions of immune tolerance and natural course of chronic HBV infection in the children.
Assuntos
Alanina Transaminase/normas , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/diagnóstico , Adolescente , Fatores Etários , Alanina Transaminase/sangue , Criança , Pré-Escolar , China , Feminino , Antígenos E da Hepatite B/sangue , Antígenos E da Hepatite B/isolamento & purificação , Vírus da Hepatite B/imunologia , Hepatite B Crônica/sangue , Hepatite B Crônica/imunologia , Hepatite B Crônica/virologia , Humanos , Lactente , Testes de Função Hepática/métodos , Testes de Função Hepática/normas , Masculino , Valores de Referência , Estudos Retrospectivos , Fatores SexuaisRESUMO
OBJECTIVES: To evaluate the histopathological changes in the liver after oral antiviral therapy in patients with chronic hepatitis B. METHODS: A total of 79 HBeAg-negative and positive patients who had been on lamivudine, entecavir, or tenofovir disoproxil for at least 3 years prior to inclusion were enrolled between March 2015 and 2016, retrospectively. There were 23 patients on lamivudine, 21 patients on entecavir, and 35 on tenofovir. All patients underwent a follow-up liver biopsy. Biochemical, serological, virological and histopathological data were recorded in all patients and were compared after at least 3 years of treatment with oral antiviral agents. Results: Histological activity index scores were reduced in patients who received lamivudine (p=0.011), entecavir (p=0.002), and tenofovir (p=0.001). Also, in contrast with a significant improvement in fibrosis scores in lamivudine (p=0.033) and tenofovir (p=0.001) groups no improvements were found in patients who received entecavir (p=0.090). Conclusion: Long term treatment with oral antiviral agents was associated with biochemical, virological, serological, and histopathological improvements. Long-term use of anti-viral agents as well as continuous suppression of HBV DNA are prerequisites for histopathological improvement.
Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/patologia , Fígado/patologia , Adulto , Esquema de Medicação , Feminino , Guanina/análogos & derivados , Guanina/uso terapêutico , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/sangue , Hepatite B Crônica/virologia , Humanos , Lamivudina/uso terapêutico , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tenofovir/uso terapêuticoRESUMO
BACKGROUND: The relationship between hepatitis B virus (HBV) infection, leptin and insulin resistance remains unclear. We hypothesised links between serum leptin and insulin resistance in non-diabetic patients with chronic viral hepatitis B infection and their relation to liver fibrosis. METHODS: We recruited 190 untreated patients with chronic HBV infection and 72 healthy controls. Serum leptin, fasting glucose, insulin, liver function tests (LFTs), C-peptide and Homeostasis model assessment-IR (HOMA-IR) were measured/calculated by ELISA and standard techniques. RESULTS: Serum leptin, C-peptide (both P < 0.001), HOMA-IR (P = 0.021) and several LFTs were increased in patients with chronic HBV-infection. In multivariate regression analysis, both HOMA-IR (P = 0.003) and leptin (P = 0.002) were significant independent predictors of HBV infection. There were significant positive correlations (P < 0.01) between leptin and HOMA-IR (r = 0.81), between serum leptin and METAVIR activity (r = 0.95), and between HOMA-IR and BMI (r = 0.75), fasting glucose (r = 0.005), and fasting insulin (r = 0.81). Several LFTs, glucose and insulin correlated modestly (r = 0.61-0.69, P < 0.05) with leptin. CONCLUSION: Serum leptin may be related to the rate of fibrosis progression in nondiabetic patients with chronic HBV infection. Follow-up by serial measurement of serum leptin and HOMA-IR in non diabetic HBV-infected patients may be used as a non-invasive marker of early liver fibrosis.
Assuntos
Biomarcadores/sangue , Hepatite B Crônica/sangue , Leptina/sangue , Cirrose Hepática/sangue , Adulto , Glicemia/genética , Peptídeo C/sangue , Jejum , Feminino , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/genética , Hepatite B Crônica/patologia , Hepatite B Crônica/virologia , Homeostase/genética , Humanos , Insulina/sangue , Resistência à Insulina/genética , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Testes de Função Hepática , Masculino , Pessoa de Meia-IdadeRESUMO
The treatment of chronic hepatitis B (CHB) patients is based on monotherapy with pegylated-interferon (Peg-IFN) or with one of the three most potent nucleot(s)ide analogues (NUCs) with the best resistance profiles, i.e. entecavir (ETV), tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF). Long-term NUCs treatment can achieve virological suppression in almost all patients. However, this requires lifelong therapy, is costly and the rate of hepatitis B surface antigen (HBsAg) seroclearance is low. A one-year course of Peg-IFN has the advantage of providing immune-mediated control of the hepatitis B virus (HBV) infection, the possibility of achieving a sustained off-treatment response in nearly 30% of the patients and ultimately, HBsAg loss in approximately 30%-50% of the latter patients during long-term off treatment follow-up. However, the major limitations to the extensive use of this treatment are the need for parenteral therapy and clinical and laboratory monitoring, the side-effects profile and contraindications in certain patients and the limited effectiveness in a large proportion of patients. Nevertheless, the cost-effectiveness of Peg-IFN can be significantly increased by careful patient selection based upon baseline alanine aminotransferase (ALT), HBV DNA levels, viral genotype, host genetic variants and especially by applying early on-treatment stopping rules based upon HBsAg kinetics. Recently, because of the different mechanisms of action of Peg-IFN and NUCs, the strategy of "adding-on" or "switching to" Peg-IFN in patients being treated with NUCs to accelerate the decline in HBsAg and enhance HBsAg seroclearance rates, has provided interesting results.
Assuntos
Antivirais/uso terapêutico , Antígenos de Superfície da Hepatite B/sangue , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Análise Custo-Benefício , Vírus da Hepatite B/genética , Hepatite B Crônica/sangue , Hepatite B Crônica/diagnóstico , Humanos , Interferon-alfa/efeitos adversos , Nucleosídeos/análogos & derivados , Nucleosídeos/uso terapêutico , Polietilenoglicóis , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
AIM: To demonstrate the non-inferiority (15% non-inferiority limit) of monotherapy with tenofovir disoproxil fumarate (TDF) vs the combination of lamivudine (LAM) plus adefovir dipivoxil (ADV) in the maintenance of virologic response in patients with chronic hepatitis B (CHB) and prior failure with LAM. METHODS: This study was a Phase IV prospective, randomized, open, controlled study with 2 parallel groups (TDF and LAM+ADV) of adult patients with hepatitis B e antigen (HBeAg)-negative CHB, prior failure with LAM, on treatment with LAM+ADV for at least 6 mo, without prior resistance to ADV and with an undetectable viral load at the start of the study, in 14 Spanish hospitals. The follow-up time for each patient was 48 wk after randomization, with quarterly visits in which the viral load, biochemical and serological parameters, adverse effects, adherence to treatment and consumption of hospital resources were analysed. RESULTS: Forty-six patients were evaluated [median age: 55.4 years (30.2-75.2); 84.8% male], including 22 patients with TDF and 24 with LAM+ADV. During study development, hepatitis B virus DNA (HBV-DNA) remained undetectable, all patients remained HBeAg negative, and hepatitis B surface antigen (HBsAg) positive. Alanine aminotransferase (ALT) values at the end of the study were similar in the 2 groups (25.1 ± 7.65, TDF vs 24.22 ± 8.38, LAM+ADV, P = 0.646). No significant changes were observed in creatinine or serum phosphorus values in either group. No significant differences between the 2 groups were noted in the identification of adverse effects (AEs) (53.8%, TDF vs 37.5%, LAM+ADV, P = 0.170), and none of the AEs which occurred were serious. Treatment adherence was 95.5% and 83.3% in the TDF and the LAM+ADV groups, respectively (P = 0.488). The costs associated with hospital resource consumption were significantly lower with the TDF treatment than the LAM+ADV treatment (4943 ± 1059 vs 5811 ± 1538, respectively, P < 0.001). CONCLUSION: TDF monotherapy proved to be safe and not inferior to the LAM+ADV combination therapy in maintaining virologic response in patients with CHB and previous LAM failure. In addition, the use of TDF generated a significant savings in hospital costs.
Assuntos
Adenina/análogos & derivados , Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Lamivudina/uso terapêutico , Organofosfonatos/uso terapêutico , Tenofovir/uso terapêutico , Adenina/economia , Adenina/farmacologia , Adenina/uso terapêutico , Adulto , Idoso , Alanina Transaminase/sangue , Antivirais/economia , Antivirais/farmacologia , DNA Viral/isolamento & purificação , Farmacorresistência Viral , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/economia , Quimioterapia Combinada/métodos , Feminino , Antígenos de Superfície da Hepatite B/imunologia , Antígenos E da Hepatite B/imunologia , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/fisiologia , Hepatite B Crônica/sangue , Hepatite B Crônica/imunologia , Custos Hospitalares/estatística & dados numéricos , Humanos , Lamivudina/economia , Lamivudina/farmacologia , Masculino , Pessoa de Meia-Idade , Organofosfonatos/economia , Organofosfonatos/farmacologia , Estudos Prospectivos , Tenofovir/economia , Tenofovir/farmacologia , Falha de Tratamento , Carga Viral/efeitos dos fármacosRESUMO
Transient elastography (TE) is accurate in staging fibrosis noninvasively. However, a reliable serum biomarker with comparable accuracy is also important, especially when TE is unreliable/unavailable. Therefore, we aimed to evaluate the diagnostic performance of serum Golgi protein 73 (GP73) for significant fibrosis in patients with chronic HBV infection. A total of 801 patients with chronic liver disease (CLD; 492 chronic HBV infection and 309 non-HBV liver disease) with liver biopsy performance were enrolled. Healthy controls (n = 180) and hepatocellular carcinoma (HCC) patients (n = 85) were included for comparisons. Liver biopsy was used as the reference method for fibrosis staging. Serum GP73 level was measured in duplicate in double-blind fashion. Serum GP73 was highest in HCC but also significantly higher in chronic hepatitis B than in healthy controls. The elevation of serum GP73 in non-HCC patients was significantly associated with the presence of significant fibrosis independently of ALT level, liver stiffness (LS) value, inflammation grade and other confounding factors. The diagnostic performance of serum GP73 was accurate in antiviral-naïve HBV patients (area under the receiver operating curve [AUROC], 0.76 95% CI: 0.72-0.81) but not in patients with ongoing antiviral treatment (AUROC, 0.60). The utility of serum GP73 was also confirmed in non-HBV CLD (AUROC, 0.80 95% CI: 0.75-0.85). Serum GP73 was comparable to LS (AUROC, 0.78 95% CI: 0.73-0.82) and significantly better than AST to platelet ratio index (APRI) (AUROC, 0.67 95% CI: 0.62-0.72) and FIB-4 (AUROC, 0.68 95% CI: 0.63-0.73). In conclusion, serum GP73 is an accurate serum marker for significant fibrosis in chronic HBV infection, with higher accuracy than APRI and FIB-4. Serum GP73 is potentially a complementary tool for TE when evaluating the necessity of antiviral treatment, particularly in patients without definite antiviral indication.
Assuntos
Hepatite B Crônica/sangue , Hepatite B Crônica/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Proteínas de Membrana/sangue , Biomarcadores , Biópsia , Estudos Transversais , Técnicas de Imagem por Elasticidade , Feminino , Humanos , Masculino , Prognóstico , Curva ROC , Reprodutibilidade dos TestesRESUMO
INTRODUCTION: Chronic hepatitis B (CHB) is associated with high burden and healthcare costs. Virologic response achieved with antivirals is associated with progression avoidance. This study aimed to estimate the efficiency and clinical impact of antiviral strategies in CHB patients. MATERIAL AND METHODS: A Markov model estimated lifetime complications and direct costs in both, HBeAg-positive and HBeAg-negative cohorts. Strategy 1 (71% of treated population) and strategy 2 (100%), both based on pegylated interferon (peg-IFN) followed by oral tenofovir or entecavir, were compared to no treatment. Progression was based on HBV-DNA levels. Rescue therapy with oral antivirals was applied for peg-IFN failure. Disease costs (C, 2014) and utilities were obtained from literature. RESULTS: Compared to natural history, strategy 1 increased QALY (3.98 in HBeAg-positive, 2.16 in -negative cohort). With strategy 2, survival was up to 5.60 (HBeAg-positive) and 3.05 QALY (in HBeAg-negative). The model predicted avoidance of 128 and 86 carcinomas in HBeAg-positive and -negative patients with strategy 1, and up to 181 and 121 in HBeAg-positive and -negative for strategy 2. Total cost increased up to C102,841 (strategy 1) and C105,408 (strategy 2) in HBeAg-positive, and C85,858 and C93,754 in HBeAg-negative. A C1,581/QALY gained ratio was estimated versus the natural history for both strategies. In conclusion, increasing antiviral coverage would be efficient, reducing complications.
Assuntos
Antivirais/economia , Antivirais/uso terapêutico , Custos de Medicamentos , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/economia , Antivirais/efeitos adversos , Biomarcadores/sangue , Simulação por Computador , Análise Custo-Benefício , DNA Viral/sangue , Progressão da Doença , Farmacorresistência Viral , Substituição de Medicamentos/economia , Quimioterapia Combinada , Guanina/análogos & derivados , Guanina/economia , Guanina/uso terapêutico , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Hepatite B Crônica/sangue , Hepatite B Crônica/virologia , Humanos , Interferon-alfa/economia , Interferon-alfa/uso terapêutico , Cadeias de Markov , Modelos Econômicos , Polietilenoglicóis/economia , Polietilenoglicóis/uso terapêutico , Anos de Vida Ajustados por Qualidade de Vida , Proteínas Recombinantes/economia , Proteínas Recombinantes/uso terapêutico , Tenofovir/economia , Tenofovir/uso terapêutico , Fatores de Tempo , Resultado do Tratamento , Carga ViralRESUMO
BACKGROUND/AIM: The gamma-glutamyl transpeptidase-to-platelet ratio (GPR) is a novel serum model, which was reported more accurate than aspartate transaminase-to-platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4) for diagnosing significant fibrosis and cirrhosis in HBV mono-infection in West Africa. We aimed to evaluate the diagnostic performance of GPR for liver fibrosis in patients with chronic hepatitis B (CHB) and non-alcoholic fatty liver disease (NAFLD). RESULTS: Of 131 patients, 41 (31.3%), 20 (15.3%), and 10 (7.6%) were classified as having significant fibrosis, severe fibrosis and cirrhosis, respectively. To predict significant fibrosis, the AUROC of GPR was higher than that of APRI (0.86 vs 0.75, p = 0.001) and FIB-4 (0.86 vs 0.66, p < 0.001). To predict severe fibrosis, the AUROC of GPR was also higher than that of APRI (0.89 vs 0.77, p = 0.002) and FIB-4 (0.89 vs 0.72, p = 0.001). To predict cirrhosis, no difference was found between the AUROC of GPR and that of APRI (0.92 vs 0.86, p = 0.104). MATERIALS AND METHODS: 131 patients with CHB-NAFLD were included, and the diagnostic performances of GPR, APRI and FIB-4 were compared by receiver operating characteristic (ROC) curves and the area under ROC curves (AUROCs). CONCLUSIONS: The GPR could be used as a non-invasive marker to predict liver fibrosis and cirrhosis in CHB-NAFLD individuals.