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1.
J. Health Biol. Sci. (Online) ; 10(1): 1-5, 01/jan./2022. ilus, tab
Article in Portuguese | LILACS | ID: biblio-1411581

ABSTRACT

Objetivo: o presente estudo tem por objetivo realizar uma análise do perfil espaço-temporal da hepatite B no estado do Pará, entre os anos de 2006 e 2018. Métodos: trata-se de um trabalho epidemiológico, ecológico e descritivo, realizado no estado do Pará por meio de seus municípios e regiões de saúde. A base de dados foi levantada perante consulta ao Departamento de Informática do SUS (DATASUS). Foram calculadas as variações percentuais anuais (APC) nas taxas de incidência de hepatite B, mediante a modelagem pelo método Jointpoint, usando o ano calendário como variável de regressão. Resultados: no estado do Pará, foram notificados, no período do estudo, 3,228 casos, sendo, 48,3% em homens e 51,7% em mulheres, com média de 248,3 casos por ano (61,8 de desvio padrão). A taxa de incidência média entre os anos de 2006 a 2018, nos 144 municípios no estado do Pará, obteve uma grande variação de 0 a 21,54 casos por 100.000 mil habitantes. Conclusão: apesar da dispersão nas taxas de incidência, obteve-se uma tendência crescente da ocorrência de casos de hepatite B no período estudado, sugerindo a necessidade de medidas de saúde pública mais eficazes no combate ao HBV.


Objective: this study aims to analyze the spatiotemporal profile of hepatitis B in the State of Pará from 2006 to 2018. Methods: this is an ecological and descriptive epidemiological study carried out in the State of Pará through its municipalities and health regions. The database was collected from the consultation with the SUS Computer Department (DATASUS). The annual percentage changes (APC) in the hepatitis B incidence rates were calculated through modeling by the Jointpoint method, using the calendar year as a regressive variable. Results: in the state of Pará, 3,228 cases were reported, of which 48.3% were men and 51.7% were women, with an average of 248.3 cases per year (61.8 standard deviations). The average incidence rate between the years 2006 to 2018 in the 144 municipalities in the state of Pará obtained a wide variation from 0 to 21.54 cases per 100,000 inhabitants. Conclusions: despite the dispersion in incidence rates, there was an incre


Subject(s)
Hepatitis B , Unified Health System , Epidemiologic Studies , Hepatitis B virus , Time Series Studies , Public Health , Epidemiology , Incidence
2.
Rev. colomb. gastroenterol ; 37(2): 163-172, Jan.-June 2022. tab, graf
Article in English, Spanish | LILACS | ID: biblio-1394945

ABSTRACT

Abstract Introduction: Hepatocellular carcinoma (HCC) is the most frequent malignant primary liver tumor globally. In 2018, it ranked sixth and represented the fourth cause of death from cancer; the five-year overall survival is 18 %. Most cases of HCC develop in patients with cirrhosis of any etiology, especially because of hepatitis B and C viruses, alcohol, and recently nonalcoholic steatohepatitis (NASH). Aim: To analyze the clinical characteristics, diagnostic methods, treatments, prognostic variables, and survival. Materials and methods: This retrospective descriptive study was conducted on a cohort of patients diagnosed with cirrhosis and treated between January 2011 and December 2020 at a health care center in Bogotá. The diagnosis of HCC was confirmed radiologically or by biopsy. We analyzed the information descriptively with absolute frequency measures in the case of categorical variables. For continuous variables, the information was summarized with measures of central tendency (mean or median) and their relevant measures of dispersion. Results: We included 152 patients diagnosed with HCC, with a mean age of 69.4 years; 51.3 % were men. The leading cause of HCC was nonalcoholic fatty liver disease (NAFLD), which accounted for almost a third of cases (32 %); other causes were alcohol (15 %) and hepatitis C virus (14 %). The median manifestation of the tumor was two nodules with a size close to 4 cm. Besides, 35 % of patients had a BCLC (Barcelona Clinic Liver Cancer) stage with curative options, and 25 % received curative treatment options. The first-line systemic therapy used in this cohort was sorafenib®, used in 35 patients (33.7 %). Survival curves showed that women, Child-Pugh class A, and BCLC stage 0 had higher median survival. Multivariate analysis showed a higher risk of death for males (hazard ratio [HR]: 2.16; confidence interval [CI]: 1.24-3.76), Child-Pugh class B (HR: 2.14; CI 1.16-3.95), and Child-Pugh class C (HR: 7.52; CI 2.88-19.57). Conclusions: NAFLD is the leading cause of HCC in this cohort. A third of patients are diagnosed in early BCLC stages with a curative treatment option, and 25 % are treated with curative therapies. Sorafenib was the first-line therapy in advanced HCC. Overall survival after diagnosis of HCC remains low, being necessary to join forces in the follow-up of patients with cirrhosis to improve these outcomes.


Resumen Introducción: el hepatocarcinoma (HCC) es el tumor hepático primario maligno más frecuente en el mundo: en 2018 ocupó la sexta posición y representó la cuarta causa de muerte por cáncer; la supervivencia global a 5 años es del 18 %. La mayoría de los casos de HCC se desarrolla en pacientes con cirrosis de cualquier etiología, especialmente por virus de la hepatitis B y C, alcohol y, recientemente, por la esteatohepatitis no alcohólica (NASH). Objetivo: analizar las características clínicas, métodos de diagnóstico, tratamientos, variables pronósticas y supervivencia. Metodología: estudio descriptivo retrospectivo de una cohorte de pacientes con diagnóstico de cirrosis atendidos entre enero de 2011 y diciembre de 2020 en un centro de atención médica de Bogotá, con diagnóstico de HCC confirmado radiológicamente o por biopsia. La información se analizó de forma descriptiva con medidas de frecuencia absoluta en el caso de las variables categóricas; para las variables continuas se resumió la información con medidas de tendencia central (media o medianas) y su respectiva medida de dispersión. Resultados: se incluyeron 152 pacientes diagnosticados con HCC, con edad promedio de 69,4 años, 51,3 % eran hombres. La principal causa de HCC fue el hígado graso no alcohólico (NAFLD), que representó casi una tercera parte de los casos (32 %); otras causas fueron el alcohol (15 %) y el virus de la hepatitis C (14 %). La mediana de presentación del tumor fue de 2 nódulos con un tamaño cercano a 4 cm. El 35 % de los pacientes tenía un estadio BCLC (Barcelona Clinic Liver Cancer) con opciones curativas y el 25 % de los pacientes recibió opciones curativas de tratamiento. La terapia sistémica de primera línea utilizada en esta cohorte fue el sorafenib®, que se utilizó en 35 pacientes (33,7 %). Las curvas de supervivencia mostraron que las mujeres, el estadio Child-Pugh A y el estadio BCLC 0 presentaron mayores medianas de supervivencia. El análisis multivariado evidenció un mayor riesgo de muerte al ser hombre (Hazard ratio [HR]: 2,16; intervalo de confianza [IC]: 1,24 a 3,76), estar en los estadios Child-Pugh B (HR: 2,14; IC: 1,16 a 3,95) y Child-Pugh C (HR: 7,52; IC: 2,88 a 19,57). Conclusiones: el NAFLD es la principal causa de HCC en la presente cohorte, una tercera parte de los pacientes se diagnostica en estadios BCLC tempranos con opción curativa de tratamiento, y un 25 % se trata con terapias curativas. El sorafenib fue la terapia de primera línea en HCC avanzado. La supervivencia global luego del diagnóstico de HCC sigue siendo baja, y es necesario aunar esfuerzos en el seguimiento de los pacientes con cirrosis para mejorar estos resultados.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Therapeutics , Hepatitis B virus , Carcinoma, Hepatocellular , Diagnosis , Non-alcoholic Fatty Liver Disease , Sorafenib , Hepatitis B , Liver Neoplasms , Patients , Survival , Confidence Intervals , Causality , Multivariate Analysis , Central Trend Measures , Neoplasms
3.
Acta sci., Health sci ; 44: e56401, Jan. 14, 2022.
Article in English | LILACS | ID: biblio-1367453

ABSTRACT

Blood-borne viruses, includingthe human immunodeficiency virus and hepatitis B virus, have certain common epidemiological characteristics and these viruses infect millions of people worldwide. This study aimed to determine the job satisfaction and the level of knowledge and practices regarding infectious diseases of employees working as hairdressers and barbers.This descriptive and cross-sectional study comprised 1200 hairdressers and barbers. The study sample comprised 628 people who consented to participate in the study. The mean age of the participants who participated in the study was 28, 13 ± 6. 9 years. The mean job satisfaction score of the participants was 3.85 ± 0.58. The job satisfaction score was found to be higher among those with sufficient knowledge of hepatitis B (p < 0.005). Employees should be provided performance trainings to achieve job satisfaction. It is recommended that employees be encouraged to wear gloves and gowns to protect their health and prevent contamination.


Subject(s)
Humans , Male , Female , Adult , Barbering/instrumentation , HIV , Knowledge , Beauty and Aesthetics Centers , Hepatitis B/epidemiology , Hepatitis B/virology , Hepatitis B virus , Communicable Diseases/transmission , Communicable Diseases/epidemiology , Occupational Health/ethnology , Acquired Immunodeficiency Syndrome/epidemiology , Acquired Immunodeficiency Syndrome/virology , Personal Protective Equipment/supply & distribution , Personal Protective Equipment/virology , Job Satisfaction , Occupational Groups
4.
Rev. saúde pública (Online) ; 56: 1-8, 2022. tab, graf
Article in English | LILACS, BBO | ID: biblio-1377236

ABSTRACT

ABSTRACT OBJECTIVE To determine the seroprevalence of hepatitis B and C among immigrants residing refugee camps in Muzaffarabad, Azad Kashmir, Pakistan, and to identify possible risk factors for hepatitis B virus (HBV) and hepatitis C virus (HCV) transmission. METHODS Around 1,225 individuals inhabiting Muzaffarabad refugee camps, participated in the study. A qualitative Immuno-Chromatographic Technique was used for initial screening and PCR test was used for detection of HBV and HCV in participants. The major risk factors for HBV and HCV transmission were assessed using a questionnaire approach. RESULTS Around 86 (7.0%) individuals were observed for hepatitis B surface antigen (HBsAg) presence, and 215 (17.5%) individuals were found positive for Anti-HCV. Only 32 (2.6%) individuals were confirmed for HBV DNA and 126 (10.3%) individuals were positive for HCV RNA after PCR. Demographically, both HBsAg and Anti-HCV were found more prevalent in female (4.4% HBsAg and 10.8% Anti-HCV) population as compared to male (2.6% HBsAg and 6.7% Anti-HCV) population. Surprisingly, the HBsAg (23.5%) and Anti-HCV (41.1%) appeared to be more frequent in the age group 62-75 years. Previous history of hepatitis in the family (p < 0.0001), blood transfusion (p = 0.0197) dental treatment (p < 0.0001) and tattooing or piercing on any part of the body (p = 0.0028) were assessed as significant risk factors in HBV and HCV transmission. CONCLUSIONS Presence of 7.0% HBsAg and 17.5% Anti-HCV in a small fragment of the migrant population cannot be overlooked. Lack of awareness among people and negligence of health department could escalate the situation.


Subject(s)
Humans , Male , Female , Middle Aged , Aged , Refugees , Hepatitis C/diagnosis , Hepatitis C/epidemiology , Hepatitis B/epidemiology , Pakistan/epidemiology , Brazil , Seroepidemiologic Studies , Hepatitis B virus/genetics , Hepacivirus/genetics , Hepatitis C Antibodies , Hepatitis B Surface Antigens
5.
Frontiers of Medicine ; (4): 216-226, 2022.
Article in English | WPRIM | ID: wpr-929209

ABSTRACT

Hepatocellular carcinoma (HCC), which makes up the majority of liver cancer, is induced by the infection of hepatitis B/C virus. Biomarkers are needed to facilitate the early detection of HCC, which is often diagnosed too late for effective therapy. The tRNA-derived small RNAs (tsRNAs) play vital roles in tumorigenesis and are stable in circulation. However, the diagnostic values and biological functions of circulating tsRNAs, especially for HCC, are still unknown. In this study, we first utilized RNA sequencing followed by quantitative reverse-transcription PCR to analyze tsRNA signatures in HCC serum. We identified tRF-Gln-TTG-006, which was remarkably upregulated in HCC serum (training cohort: 24 HCC patients vs. 24 healthy controls). In the validation stage, we found that tRF-Gln-TTG-006 signature could distinguish HCC cases from healthy subjects with high sensitivity (80.4%) and specificity (79.4%) even in the early stage (Stage I: sensitivity, 79.0%; specificity, 74.8%; 155 healthy controls vs. 153 HCC patients from two cohorts). Moreover, in vitro studies indicated that circulating tRF-Gln-TTG-006 was released from tumor cells, and its biological function was predicted by bioinformatics assay and validated by colony formation and apoptosis assays. In summary, our study demonstrated that serum tsRNA signature may serve as a novel biomarker of HCC.


Subject(s)
Biomarkers , Biomarkers, Tumor/genetics , Carcinoma, Hepatocellular/diagnosis , Hepatitis B virus , Humans , Liver Neoplasms/diagnosis , RNA, Transfer/genetics
6.
Article in English | WPRIM | ID: wpr-929022

ABSTRACT

OBJECTIVES@#Hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) is the most common type of liver failure in China, with a high mortality. Early rapid reduction of HBV-DNA load can improve the survival rate of HBV-ACLF patients. At present, the commonly used drugs are nucleoside (acid) analogues, such as entecavir (ETV), tenofovir, and so on. The newly listed tenofovir alafenamide fumarate (TAF) has attracted great attention of clinicians because of its stronger antiviral effect, higher transaminase normalization rate, better bone and kidney safety, and zero drug resistance. However, there are few clinical research data on the efficacy and safety of TAF in the treatment of Chinese HBV-ACLF patients, and there is a lack of pharmacoeconomic evaluation. This study aims to compare the efficacy, safety, and cost-effectiveness between TAF and ETV in patients with HBV-ACLF.@*METHODS@#The data were collected from 196 HBV-ACLF patients (80 patients in the TAF group and 116 patients in the ETV group) who were hospitalized in Xiangya Hospital, Central South University from May 2020 to March 2021. Biochemistry and virology were detected before and after treatment (at baseline, Week 2, 4, and 12). Clinical features, disease prognosis, and cost-effectiveness were compared between the 2 groups. According to the baseline, HBV-ACLF patients were divided into 4 stages including pre-liver failure stage, early stage, medium stage, and end stage. And the liver transplantation rate and mortality was also compared. Pharmacoeconomic evaluation was taken using cost-effectiveness analysis and cost minimization analysis..@*RESULTS@#After 4 weeks of treatment, there were no significant differences in the efficacy (liver function, viral load) between the 2 groups (all P>0.05). The TAF group showed lower creatinine [(80.35±18.77) μmol/L vs (105.59±82.32) μmol/L, P<0.05] and higher estimated glomerular filtration rate (eGFR) levels [(95.65±23.21) mL/(min·1.73 m2) vs (82.68±26.32) mL/(min·1.73 m2), P<0.05] than the ETV group. After 12 weeks of treatment, the analysis of overall the liver transplantation rate and mortality between the 2 groups showed similar conclusion. However, the TAF group had a lower the liver transplantation rate and mortality than the ETV group in patients with pre-liver failure (0vs13.89%, P<0.05). No evident distinction was found in the liver transplantation rate and mortality during the early, medium, or end stages of liver failure (13.04% vs 17.65%, 37.50% vs 37.04%, and 54.55% vs 68.42%, respectively). Ratio of cost to effectiveness in the ETV group was higher than that in the TAF group.@*CONCLUSIONS@#TAF is not more efficient than ETV group in improving liver function and reducing viral load for HBV-ACLF patients and they also show similar safety. However, TAF has a greater advantage over ETV not only in preserving renal function, but also in reducing the liver transplantation rate and mortality in patients with pre-liver failure. TAF can provide economic benefit to patients with HBV-ACLF.


Subject(s)
Acute-On-Chronic Liver Failure/drug therapy , Alanine/therapeutic use , Antiviral Agents/therapeutic use , Guanine/analogs & derivatives , Hepatitis B virus/genetics , Hepatitis B, Chronic/drug therapy , Humans , Tenofovir/analogs & derivatives , Treatment Outcome
7.
Article in Chinese | WPRIM | ID: wpr-939631

ABSTRACT

Drugs may induce hepatitis B virus (HBV) reactivation (HBV-R). Here we have reviewed the definition and harm of HBV-R, the risk drugs and their underlying mechanism, the influence factors, as well as the early intervention measures. It is shown that multiple drugs, including chemotherapy drugs, immunotherapy drugs, directly acting antivirals, cell therapy, etc., can induce HBV-R by affecting host immunity or directly activating HBV transcription factors. HBV-R could cause severe liver damage, even interruption of treatment of original diseases, affecting the prognosis of patients. Through precisely identifying risk drugs, monitoring the influence factors, and prescribing preventive anti-HBV regimen if necessary, the incidence of HBV-R can be significantly reduced. It is also suggested that clinical physicians should not only pay attention to the early identification and intervention of HBV-R, but also further study the mechanism of HBV-R in depth, especially the underlying mechanism between host, HBV and risk factors. This will help to promote the discovery of more valuable markers for risk prediction and targets for early intervention, and to further reduce the risk of HBV-R and improve the prognosis of patients.


Subject(s)
Hepatitis B virus , Humans , Immunotherapy , Risk Factors
8.
Article in Chinese | WPRIM | ID: wpr-936146

ABSTRACT

OBJECTIVE@#To evaluate the effects of hepatitis B virus (HBV) on helper T lymphocytes 17 (Th17), regulatory T lymphocyte (Treg) and Th17/Treg ratio in chronic hepatitis B patients in different alanine aminetransferase (ALT) stages.@*METHODS@#In the study, 336 chronic hepatitis B patients in the first hospital of Lanzhou University were analyzed. The hepatitis B antigen antibody parameters were measured by chemiluminescence immunoassay analyzer, the liver function parameters were measured by automatic biochemical analyzer, the HBV loads were measured by quantitative PCR, Th17, Treg and Th17/Treg ratios were detected by flow cytometry. Among them, 111 cases (ALT < 40 U/L) of ALT were normal hepatitis B, 108 cases of chronic hepatitis B with ALT above normal upper limit and < 2 times higher (40 U/L≤ALT < 80 U/L), and 117 cases of chronic hepatitis B with ALT above 2 times normal upper limit (80 U/L≤ALT). According to the viral load, they were divided into low replication group with HBV DNA < 4.0 lg copies/mL, medium replication group with 4.0 lg copies/mL≤HBV DNA < 6.0 lg copies/mL and high replication group with HBV DNA ≥ 6.0 lg copies / mL. Dunnett T3 variance analysis were used to analyze the effects of HBV on Th17, Treg and Th17/Treg ratio in the chronic hepatitis B patients in different ALT stages. The changes of virological and immunological indexes before and after treatment were observed for 24 weeks of antiviral therapy in the hepatitis B patients with ALT≥double upper limit of normal group.@*RESULTS@#In the ALT normal group, different virus load HBV had minor effects on Th17, Treg and Th17/Treg ratio. In the ALT≥2 times upper limit of normal group, with the virus load increased, Th17 (3.18%±0.79% in low replication group, 3.78%±0.92% in medium replication group and 4.57%±1.15% in high replication group), Treg cells (5.52%±1.58% in low replication group, 5.89%±1.84% in medium replication group and 6.37%±2.35% in high replication group) and their ratio Th17/Treg (0.57±0.25 in low replication group, 0.65±0.29 in medium replication group and 0.73±0.36 in high replication group) were significantly increased (P < 0.05). After entecavir treatment 24 weeks, the patient' s HBV-DNA decreased significantly, Th17 (3.89%±1.02% vs. 2.06%±0.46%), Treg (6.02%±2.03% vs. 5.06%±1.25%), Th17/Treg ratio (0.65±0.28 vs. 0.41±0.14) decreased significantly (P < 0.05).@*CONCLUSION@#Investigation on the effects of HBV on Th17 and Treg cells and their ratios in different ALT states can clarify the effects of HBV on the body from the immunological perspective and can further understand the ALT grouping for antiviral treatment theoretical significance, which is helpful for clinical treatment.


Subject(s)
Alanine/therapeutic use , Alanine Transaminase/therapeutic use , Antiviral Agents/therapeutic use , DNA, Viral/therapeutic use , Hepatitis B/drug therapy , Hepatitis B virus/genetics , Hepatitis B, Chronic/drug therapy , Humans , T-Lymphocytes, Regulatory
9.
Chinese Journal of Hepatology ; (12): 389-394, 2022.
Article in Chinese | WPRIM | ID: wpr-935956

ABSTRACT

Objective: To investigate the effectiveness of nucleos(t)ide analogues in the treatment of HBeAg-positive chronic hepatitis B with normal alanine aminotransferase and high level of HBV DNA. Methods: Treatment-naïve chronic hepatitis B patients who were followed up at the Center of Infectious Diseases, West China Hospital of Sichuan University from January 2019 to January 2020 were selected as subjects. Demographic characteristics, the results of laboratory examination before treatment and one year after treatment were retrospectively collected. Patients were divided into tenofovir dipivoxil (TDF) and propofol fumurate tenofovir (TAF) treatment group according to different types of medication. The changes of serum HBV DNA level, HBeAg serological conversion and HBsAg quantitative level were analyzed and compared between the two groups. Results: A total of 38 cases were enrolled. Among them, there were 16 and 22 cases in the TDF and TAF group, respectively. There was no statistically significant difference in demographic characteristics, baseline HBV DNA levels and HBsAg quantitative levels between the two groups. Virological response was achieved in 60.5% (23/38) of patients after one year of antiviral therapy. Serum HBV DNA levels below the lower limit of detection [68.2% (15/22) vs. 50.0% (8/16), P=0.258] and higher HBeAg seroconversion rate [18.2%] (4/22) vs. 6.3% (1/16), P=0.374] was obtained in TAF than TDF group; however, there was no statistically significant differences between the two. Serum HBsAg quantitative level was significantly reduced with TDF and TAF treatment. In addition, alanine aminotransferase elevation was reduced in TAF than TDF treated group. Multivariate logistic regression analysis showed that patient age was an independent predictor of a virological response to antiviral therapy. Conclusion: HBeAg-positive CHB patients with normal alanine aminotransferase, and high HBV DNA level can obtain better curative effect after TDF and TAF treatment.


Subject(s)
Alanine Transaminase , Antiviral Agents/therapeutic use , DNA, Viral , Hepatitis B Surface Antigens , Hepatitis B e Antigens , Hepatitis B virus/genetics , Hepatitis B, Chronic , Humans , Retrospective Studies , Tenofovir/therapeutic use , Treatment Outcome
10.
Chinese Journal of Hepatology ; (12): 316-322, 2022.
Article in Chinese | WPRIM | ID: wpr-935944

ABSTRACT

Objective: To dynamically observe the clinical efficacy of entecavir and the changes of PD-1+CXCR5+CD4+T lymphocytes and sPD-1 levels in peripheral blood of HBeAg-positive chronic hepatitis B virus carriers treated with entecavir, and further explore its clinical significance. Methods: There were 31 cases of chronic hepatitis B virus carriers in the treatment group (A), 32 cases of chronic hepatitis B virus carriers in the treatment group (B), and 15 cases of chronic hepatitis B virus carriers in the non-treatment group (C).Three groups peripheral blood samples and clinical data at 0, 24 and 48 weeks were collected and compared. PD-1+CXCR5+CD4+T lymphocytes were detected by flow cytometry, and the level of sPD-1 was detected by enzyme-linked immunosorbent assay. ANOVA and Spearman correlation analysis were performed on the measurement data among the three groups. Results: At week 0, the serum levels of HBsAg, HBeAg and HBV DNA were significantly higher in groups A and C than group B. PD-1+CXCR5+CD4+T lymphocytes in peripheral blood were significantly higher in group B (4.70%±1.58%) than group A (3.25%±1.01%) and group C (2.77%±0.67%) (F=16.65, P<0.05). There was no significant difference between group A and group C (P>0.05). Peripheral blood sPD-1 in group B [(1 866.62±1 472.70) pg/ml] was significantly higher than group A [(824.86±538.66) pg/ml] and group C [(618.19±602.62) pg/ml] (F=10.95, P<0.05). There was no significant difference between group A and group C (P>0.05). At 48 weeks, the serum HBsAg did not decrease significantly in groups A and C than baseline (P>0.05), but were significantly higher than group B (P<0.05). Serum HBeAg levels were decreased significantly in groups A and B than baseline (P<0.05). <0.05), but group A was significantly higher than group B (P<0.05), and there was no significant difference between group A and group C (P>0.05). Serum HBV DNA level was significantly lower in groups A and B than group C (P<0.05), and there was no significant difference between group A and group B (P>0.05). Peripheral blood PD-1+CXCR5+CD4+T lymphocytes were significantly lower in Group A (1.56%±0.73%) and group B (1.32%±0.43%) than group C (2.64%±0.85%) (P<0.05). Peripheral blood sPD-1 were significantly lower in group A [(289.05±215.86) pg/ml] and group B [(236.01±173.92) pg/ml] than group C [(650.34±598.46) pg/ml] (P<0.05). There was no significant difference between group A and group B. Correlation analysis results: In group A at 48 weeks, the decreased level of PD-1+CXCR5+CD4+T lymphocyte ratio had no correlation with the decreased level of HBsAg and HBV DNA, but was positively correlated with the decreased level of HBeAg (r=0.376, P<0.05). The decreased level of sPD-1 had no correlation with the changes of HBsAg, but was positively correlated with the decreased levels of HBeAg and HBV DNA (r=0.598 and 0.384, P<0.05). In group B at 48 weeks, the decreased levels of PD-1+CXCR5+CD4+T lymphocytes and sPD-1 were positively correlated with the decreased levels of HBsAg, HBeAg, and HBV DNA (P<0.05). Conclusion: Hepatitis B virus replication and expressions in HBeAg-positive chronic hepatitis B virus carriers were significantly inhibited after 48 weeks of antiviral treatment, which is related not only to entecavir treatment, but also to the immunological mechanism involved in sPD-1. Moreover, the inhibition of HBeAg expression is associated with a decrease in the number and/or activity of PD-1+CXCR5+CD4+T lymphocytes.


Subject(s)
Antiviral Agents/therapeutic use , DNA, Viral , Guanine/analogs & derivatives , Hepatitis B Surface Antigens , Hepatitis B e Antigens , Hepatitis B virus/genetics , Hepatitis B, Chronic , Humans , Programmed Cell Death 1 Receptor , Receptors, CXCR5/analysis , T-Lymphocytes
11.
Chinese Journal of Hepatology ; (12): 309-315, 2022.
Article in Chinese | WPRIM | ID: wpr-935943

ABSTRACT

Objective: To explore the clinical value of von Willebrand Factor (vWF) and VITRO score (vWF:Ag/platelet count) in assessing disease progression in patients with HBV infection. Methods: Randomly collect relevant clinical data of 308 patients with HBV infection (including 154 cases of chronic hepatitis B, 66 cases of hepatitis B cirrhosis in compensatory period, 88 cases of hepatitis B cirrhosis in decompensated period) from December 1, 2018 to January 5, 2021 in the Second Affiliated Hospital of Chongqing Medical University. The vWF values are measured by a uniform optical method, and all data are included using a uniform standard. Analyze the difference and significance of plasma vWF level and VITRO score in chronic hepatitis B, hepatitis B cirrhosis in the compensatory phase and decompensated phase. Results: The plasma vWF level and VITRO score of the chronic hepatitis B group were (139.47±76.44) and (0.86±0.8), respectively, and the hepatitis B cirrhosis compensated group was (164.95±67.12 and 1.44±1.14), respectively. Hepatitis cirrhosis decompensated group were (317.48±103.32 and 6.81±4.98), respectively; plasma vWF level and VITRO score increased with the progression of HBV infection, and the difference was statistically significant (F=133.669,P=0.000F=137.598,P=0.000).The plasma vWF level and VITRO score in patients with hepatitis B cirrhosis were (185.65±85.07 and 2.3±2.37) in the Child-Pugh A group, (304.74±105.81 and 6.37±5.19) in the B grade group, and (369.48±73.238.28±5.38) in the C grade group; plasma vWF level and VITRO score in patients with hepatitis B cirrhosis increased with the increase of Child-Pugh grade, and the difference was statistically significant (F=60.236, P=0.000F=32.854, P=0.000). The area under the curve (AUC) of plasma vWF level and VITRO score for diagnosing the decompensated stage of hepatitis B cirrhosis were 0.897 [95% confidence interval (CI): 0.855-0.940, P<0.01], 0.949 [95% CI: 0.916-0.982, P<0.01). When the vWF level and VITRO score were taken as cut-off values of 238.5% and 1.65, respectively, the sensitivity of diagnosing the decompensated stage of hepatitis B cirrhosis was 79.5% and 94.3%, the specificity was 92.3% and 87.7%, and the positive predictive value was 80.5% and 94.3%, the negative predictive value was 91.9% and 97.5%, and the diagnostic accuracy was 88.6% and 89.3%. Among the patients with decompensated hepatitis B cirrhosis, the level of vWF in the group with gastrointestinal bleeding (367.24±68.29)% was significantly higher than that in the group without gastrointestinal bleeding (286.15±109.69)%, and the difference was statistically significant (P<0.001) The VITRO score of the group with gastrointestinal bleeding (9.12±5.4) was significantly higher than that of the group without gastrointestinal bleeding (5.36±4.13), and the difference was statistically significant (P<0.01). The vWF level in the spontaneous peritonitis group was (341.73±87.92)% higher than that in the non-spontaneous peritonitis group (296.32±111.74)%, and the difference was statistically significant (P<0.05). There was no statistical difference in VITRO score between the two groups. significance. Conclusion: Plasma vWF level and VITRO score can evaluate the progression of liver disease and the degree of decompensation of liver cirrhosis in patients with HBV infection, and have a predictive effect on various complications after decompensation of liver cirrhosis, and have certain guiding significance for early intervention measures.


Subject(s)
Disease Progression , Gastrointestinal Hemorrhage/etiology , Hepatitis B/complications , Hepatitis B virus , Hepatitis B, Chronic/diagnosis , Humans , Liver Cirrhosis/virology , Peritonitis/complications , von Willebrand Factor/analysis
12.
Chinese Journal of Hepatology ; (12): 99-102, 2022.
Article in Chinese | WPRIM | ID: wpr-935916

ABSTRACT

Covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) is the template for HBV replication. Currently, there is a lack of therapeutic drugs that directly target cccDNA. Therefore, blocking cccDNA supplements as fast as possible and reducing the existing cccDNA is the key to achieving a complete cure of chronic hepatitis B. Previous studies have suggested that cccDNA had a long half-life, but a recent study showed that it only took a few months to update cycle of cccDNA pool, and its number was much less than previously predicted. In the future, with the advent of new antiviral drugs that can completely inhibit HBV replication, it is expected that the cccDNA pool will be completely cleared due to its supplement complete blockade, so as to achieve virological cure of chronic hepatitis B.


Subject(s)
Antiviral Agents/therapeutic use , DNA, Circular/genetics , DNA, Viral , Half-Life , Hepatitis B/drug therapy , Hepatitis B virus/genetics , Hepatitis B, Chronic/drug therapy , Humans , Virus Replication
13.
Chinese Journal of Hepatology ; (12): 52-56, 2022.
Article in Chinese | WPRIM | ID: wpr-935907

ABSTRACT

Objective: To explore the role of nonalcoholic fatty liver disease (NAFLD) in the development of hepatocellular carcinoma (HCC) in patients with prior hepatitis B virus infection (HBsAg-negative and anti-HBC-positive). Methods: 1605 hospitalized patients who were first diagnosed with HCC at Nanfang Hospital between 2015 to 2017 were retrospectively studied. Patients who developed HCC on the basis of active HBV infection (HBsAg-positive, anti-HBc positive) were used as control. Multivariate logistic regression model was used to analyze the relationship between NAFLD and HCC in patients with prior hepatitis B virus infection. Results: Among HCC patients with both HBsAg and anti-HCV negative, the proportion of prior HBV infection accounted for 86.7%. NAFLD prevalence was higher in patients with HCC based on prior HBV infection than active HBV infection (19.7% vs. 8.5%, P < 0.001). After adjusting for gender, age, hypertension, alanine aminotransferase, and liver cirrhosis, patients with HCC based on prior HBV infection were more likely to develop NAFLD (OR: 2.29, 95% CI: 1.40-3.74), and this phenomenon was observed only in patients with non-cirrhosis (OR: 5.26, 95% CI: 2.53-10.96) and aged≥50 years (OR: 2.36, 95% CI: 1.33-4.20). Conclusion: NAFLD may be a risk factor for HCC in a previously infected patients with HBV, especially in non-cirrhotic and population aged≥50 years.


Subject(s)
Carcinoma, Hepatocellular/epidemiology , Hepatitis B/epidemiology , Hepatitis B Surface Antigens , Hepatitis B virus , Humans , Liver Neoplasms/epidemiology , Middle Aged , Non-alcoholic Fatty Liver Disease/epidemiology , Retrospective Studies , Risk Factors
14.
Chinese Journal of Epidemiology ; (12): 728-733, 2022.
Article in Chinese | WPRIM | ID: wpr-935451

ABSTRACT

Objective: To investigate the type, length, and CG loci of HBV DNA CpG islands in HBsAg positive maternal C genotype and its relationship with intrauterine HBV transmission, so as to provide a new perspective for the study of intrauterine transmission of HBV. Methods: From June 2011 to July 2013, HBsAg-positive mothers and their newborns who delivered in the obstetrics and gynecology department of the Third People's Hospital of Taiyuan were collected. Epidemiological data were collected through face-to-face questionnaires and electronic medical records. Serum HBV markers and serum HBV DNA were detected by electrochemiluminescence and quantitative fluorescence PCR, respectively. Intrauterine transmission of HBV was determined by positive HBsAg and/or HBV DNA in femoral venous blood before injection of HBV vaccine/Hepatitis B immunoglobulin within 24 h of birth. A total of 22 mothers and their newborns with HBV DNA load ≥106 IU/ml in intrauterine transmission were selected as the intrauterine transmission group, and 22 mothers with HBV DNA load ≥106 IU/ml without intrauterine transmission were chosen as the control group by random seed method. The distribution prediction of CpG islands of HBV DNA in 39 mothers with genotype C by HBV DNA sequencing was analyzed. Results: Among 39 mothers with HBV C genotype, 19 were in the intrauterine transmission group, and 20 were in the control group. The HBV DNA of 39 patients with genotype C traditional CpG island Ⅱ and Ⅲ, while the control group had traditional CpG island Ⅰ and novel CpG island Ⅳ and Ⅴ. The length of CpG island Ⅱ and Ⅲ and the number of CG loci of CpG island Ⅱ in the intrauterine transmission group differed from those in the control group (P<0.05). The CpG island Ⅱ length ≥518 bp and the number of CG loci ≥40 in the intrauterine transmission group (11/19) were significantly higher than those in the control group (2/20) (P<0.05). The length of CpG island Ⅱ and the number of CG loci in the X gene promoter region (Xp region) were higher than those in the control group (P<0.05). In the HBV intrauterine transmission group, most of maternal (12/19) HBV DNA CpG island Ⅱ completely covered the Xp region, which was significantly higher than that in the control group (5/20), and the number of HBV DNA Xp region CG loci was higher than that in the control group (P<0.05). Conclusions: The distribution of maternal C genotype HBV DNA CpG islands is related to intrauterine transmission. The length of CpG island Ⅱ and the number of CG sites may increase the risk of intrauterine transmission of HBV.


Subject(s)
Biomarkers , CpG Islands , DNA, Viral/genetics , Female , Hepatitis B , Hepatitis B Surface Antigens , Hepatitis B virus/genetics , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Mothers , Pregnancy , Pregnancy Complications, Infectious
15.
Article in Chinese | WPRIM | ID: wpr-935354

ABSTRACT

Objective: To investigate the influencing factors of HBV intrauterine transmission and their interaction effects by integrating logistic regression model and Chi-squared automatic interaction detector (CHAID) decision tree model. Methods: A total of 689 pairs of HBsAg-positive mothers and their neonates in the obstetrics department of the Third People's Hospital of Taiyuan from 2007 to 2013 were enrolled, and the basic information of mothers and their neonates were obtained by questionnaire survey and medical record review, such as the general demographic characteristics, gestational week and delivery mode. HBV DNA and HBV serological markers of the mothers and newborns were detected by fluorescence quantitative PCR and electrochemiluminescence immunoassay respectively. The CHAID decision tree model and unconditional logistic regression analysis were used to explore the factors influencing HBV intrauterine transmission in neonates of HBsAg-positive mothers. Results: Among the 689 neonates, the incidence of HBV intrauterine transmission was 11.47% (79/689). After adjusted for confounding factors, the first and second logistic multivariate analysis showed that cesarean delivery was a protective factor for HBV intrauterine transmission (OR=0.25, 95%CI: 0.14-0.43; OR=0.27, 95%CI: 0.15-0.46); both models indicated that maternal HBeAg positivity and HBV DNA load ≥2×105 IU/ml before delivery were risk factors of HBV intrauterine transmission (OR=3.89, 95%CI: 2.32-6.51; OR=3.48, 95%CI: 2.12-5.71), respectively. The CHAID decision tree model screened three significant factors influencing HBV intrauterine transmission, the most significant one was maternal HBeAg status, followed by delivery mode and maternal HBV DNA load. There were interactions between maternal HBeAg status and delivery modes, as well as delivery mode and maternal HBV DNA load before delivery. The rate of HBV intrauterine transmission in newborns of HBeAg-positive mothers by vaginal delivery increased from 19.08% to 29.37%; among HBeAg-positive mothers with HBV DNA ≥2×105 IU/ml, the rate of HBV intrauterine transmission increased to 33.33% in the newborns by vaginal delivery. Conclusions: Maternal HBeAg positivity,maternal HBV DNA ≥2×105 IU/ml and vaginal delivery could be risk factors for HBV intrauterine transmission in newborns. Interaction effects were found between maternal HBeAg positivity and vaginal delivery, as well as vaginal delivery and high maternal HBV DNA load. Logistic regression model and the CHAID decision tree model can be used in conjunction to identify the high-risk populations and develop preventive strategies accurately.


Subject(s)
DNA, Viral/genetics , Decision Trees , Female , Hepatitis B Surface Antigens , Hepatitis B e Antigens , Hepatitis B virus/genetics , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Logistic Models , Mothers , Pregnancy , Pregnancy Complications, Infectious/epidemiology
16.
Article in Chinese | WPRIM | ID: wpr-935268

ABSTRACT

To investigate the associations between gene polymorphisms of signal transducer and activator of transcription 3 (STAT3) and liver cirrhosis (LC) after hepatitis B virus (HBV) infection. A case-control study was conducted in 243 patients with hepatitis B cirrhosis (HBV-LC, case group) and 486 HBV-infected subjects without LC (non-LC, control group) collected from January 2018 to September 2020 at the Changsha Central Hospital Affiliated to Nanhua University. Three single nucleotide polymorphisms (SNPs) of STAT3 gene, including rs4796793C>G, rs2293152C>G, and rs1053004T>C were selected through literature and biological information database, and the genotypes were detected by real-time fluorescent quantitative PCR (RFQ-PCR). The distribution differences of STAT3 SNPs genotypes between the two groups were compared using Chi-square test and haplotype analysis was conducted by Shesis online. The proportion of HBV C genotype in HBV-LC patients was significantly higher than that in the control group (80.91% vs. 70.79%, χ2=7.109, P=0.008), while the logarithm of ALT was significantly lower than that of the control group (1.78±0.43 vs. 1.95±0.54, t=3.801, P=0.000). The genotypes distributions of rs4796793, rs2293152, and rs1053004 were not significantly different between HBV-LC and non-LC in overall analysis and stratified analysis by gender (χ²=2.610, 1.505, 0.586, 2.653, 2.685, 1.583, 0.351, 5.388, 0.339, respectively, P>0.05 for each). Among the subjects infected with HBV genotype C, rs1053004 CC (vs. TT) significantly increased the risk of HBV-LC [odds ratio (OR) = 1.40, 95% confidence interval (CI): 1.03-1.91]. Among the HBV-infected subjects with HBeAg negative, rs4796793 GG genotype (vs. CC) and G allele (vs. C) significantly increased the risks of HBV-LC (OR = 2.17, 95%CI: 1.11-4.23; OR = 1.45, 95%CI: 1.06-1.97, respectively). Haplotypes analysis showed that the frequency of haplotype C-G-T composed of rs4796793, rs2293152, and rs1053004 was significantly lower in HBV-LC than that in the control group (non-LC) (27.3% vs. 35.6%, χ²=9.949, P = 0.001). The correlation between STAT3 and HBV-LC is different in HBV-infected subjects with different infection status. The HBV-infected subjects carrying haplotype rs4796793C-rs2293152G-rs1053004T of STAT3 gene have significantly decreased risk of LC.


Subject(s)
Carcinoma, Hepatocellular/genetics , Case-Control Studies , Genetic Predisposition to Disease , Genotype , Hepatitis B virus/genetics , Hepatitis B, Chronic/genetics , Humans , Liver Cirrhosis/genetics , Liver Neoplasms/genetics , Polymorphism, Single Nucleotide , STAT3 Transcription Factor/genetics
17.
Chinese Journal of Oncology ; (12): 347-353, 2022.
Article in Chinese | WPRIM | ID: wpr-935219

ABSTRACT

Objective: To investigate the influence of HBsAg expression in peritumoral tissue of hepatocellular carcinoma (HCC) patients on their postoperative recurrence. Methods: The HCC patients treated in Shanghai Eastern Hepatobiliary Surgery Hospital from October 2009 to August 2010 were selected. The clinicopathological data and adjacent tissues of 718 patients were collected, and dextran polymer immunohistochemical staining was used to detect the expression of HBsAg in adjacent tissues. According to the expression of HBsAg in adjacent tissues, the tissues were divided into HBsAg positive group and HBsAg negative group. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox regression model was used for multivariate analysis. Results: Among the 718 patients in the whole group, 153 were HBsAg negative and 565 were HBsAg positive. There was a statistically significant difference in serum HBV DNA level between HBsAg-positive and HBsAg-negative patients (P<0.001). The number of patients with serum DNA≥2 000 IU/ml and<2 000 IU/ml in HBsAg negative group were 52 and 93, while the patients in HBsAg positive group were 325 and 205. The cumulative recurrence rates of all patients at 1, 3, and 5 years after surgery were 30.2%, 54.3%, and 62.7%, respectively. The expression of HBsAg was related to the recurrence (P=0.038). Multivariate analysis showed that γ-GT, PT, multiple tumors, tumor length, and portal vein invasion were independent risk factors for recurrence of HCC (P<0.05). In HBeAg-negative patients with low viral load (HBV DNA <2 000 IU/ml) and without cirrhosis, the recurrence rates of HBsAg-positive patients were 14.3% and 31.0% at 3 and 5 years, respectively, compared with HBsAg negative patients (all 0), the difference was statistically significant (P=0.021). Conclusion: The positive expression of HBsAg in peritumoral tissue increases the postoperative recurrence risk of HCC patients.


Subject(s)
Carcinoma, Hepatocellular/pathology , China , DNA, Viral/analysis , Hepatitis B Surface Antigens , Hepatitis B virus/metabolism , Humans , Liver Neoplasms/pathology
18.
Article in English | WPRIM | ID: wpr-928926

ABSTRACT

OBJECTIVE@#To compare the circular pathological changes of chronic hepatitis B (CHB) patients according to the tongue diagnosis.@*METHODS@#Totally 41 CHB patients with typical white tongue coating (WTC) or yellow tongue coating (YTC) were enrolled and 14 healthy volunteers with normal tongue manifestation served as controls. The mRNA expression of peripheral leukocytes was detected by GeneChips, and 9 genes were randomly selected for expression validation. Circular metabolites were detected by gas chromatographymass spectrometry. Biological information was analyzed based on ingenuity pathways analysis or metabolomics database and the integrated networks were constructed by ClueGO.@*RESULTS@#A total of 945 and 716 differentially expressed genes were found in patients with WTC and YTC relative to healthy volunteers respectively. The biological information analysis indicated that CHB patients had obviously increased functions in cell death, apoptosis and necrosis (Z-score ⩾2, P<0.05) and decreased activation in T lymphocytes (Z-score ⩽-2, P<0.05), regardless of the tongue manifestation. Compared to patients with WTC, the YTC patients were predicted to be more active in functions related to virus replication (Z-score ⩾2, P<0.05), and the content of circular fatty acids, such as oleic acid (P=0.098) and lauric acid (P=0.035), and citric acid cycle-related metabolites were higher in the YTC patients (P<0.1). The integrated analysis based on differential genes and metabolites indicated that the most difference in the biological function network between the WTC and YTC patients was tumor necrosis factor receptor associated factor 6 mediated-nuclear factor kappa-B activation process.@*CONCLUSIONS@#CHB patients with YTC had more severe inflammation and fatty acids metabolism aberrant than patients with WTC. The results facilitate the modern pathological annotation of Chinese medicine tongue diagnosis theory and provide a reference for the interpretation of pharmacological mechanisms of Chinese medicine treatment.


Subject(s)
Fatty Acids , Hepatitis B virus/genetics , Hepatitis B, Chronic , Humans , Metabolomics , T-Lymphocytes , Tongue
19.
Article in Chinese | WPRIM | ID: wpr-928704

ABSTRACT

OBJECTIVE@#To evaluate the risk of reentry in HBV reactive blood donors and feasibility of HBV reentry strategy.@*METHODS@#HBsAg+ or HBV DNA+ donors who had been quarantined for more than 6 months in Jiangsu Province could propose for reentry application. Blood samples were routinely screened by dual-ELISA for HBsAg, anti-HCV, HIV Ab/Ag, and anti- Treponema pallidum and those non-reactive ones were tested by minipool nucleic acid testing (NAT) for three times. To identify occult HBV donors, samples of NAT non-reactive were further tested by electrochemiluminescence immunoassay (ECLIA) for HBV seromarkers (including HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb). Donors of only 4 ECLIA patterns were accepted to reentry, including all 5 HBV seromarkers negative, anti-HBs only but having history of hepatitis B vaccine injection, HBcAb only, HBsAb+ / HBcAb+ with HBsAb more than 200 IU/L. Additionally, the detection rate of HBV infection was compared between routine screening mode and ECLIA, as well as the reentry qualified rate of HBsAg+ and HBV DNA+ blood donors.@*RESULTS@#From Oct. 2016 to Aug. 2019, a total of 737 HBV reactive donors had applied for reentry, including 667 HBsAg+ reactive and 70 HBV DNA+ reactive donors. Among 3 screening methods, the highest HBV detection rate (43.15%, 318/737) was observed on ECLIA, while only 4.75% (35/737) on ELISA and 3.12% (23/737) on NAT, respectively. Among 4 qualified patterns of HBV serological markers, the highest proportion was found in the all negative group (22.90%, 155/677), followed by the group with HBsAb+ only and history of hepatitis B vaccine injection (19.35%, 131/677), and the median concentration of HBsAb was 237.7 IU/L. The unqualified rate of HBV DNA+ donors was 82.86%, which was significantly higher than 47.98% of HBsAg+ donors.@*CONCLUSION@#Routine screening tests merely based on ELISA and NAT could miss occult HBV donors and may not be sufficient for blood safety. HBsAb concentration and vaccine injection history should be included in the evaluation of HBV reactive donors who intend to apply for reentry. There is a relatively larger residual risk of occult HBV infection in blood donors quarantined for HBV DNA reactive.


Subject(s)
Blood Donors , DNA, Viral , Hepatitis B , Hepatitis B Surface Antigens , Hepatitis B virus/genetics , Humans
20.
Chinese Journal of Hepatology ; (12): 429-438, 2022.
Article in Chinese | WPRIM | ID: wpr-928467

ABSTRACT

Hepatitis B virus (HBV) infection remains to be the major cause of chronic liver diseases in China. Since the nucleos(t)ide analogues and pegylated interferon-alpha do not directly target the covalently closed circular DNA (cccDNA) in the nuclei of HBV-infected hepatocytes, those standard-of-care medications cannot efficiently cure the infected hepatocytes and rarely achieve the functional cure of chronic hepatitis B (CHB). Therefore, new antiviral drugs targeting distinct steps of HBV replication and immunotherapeutics reinvigorating antiviral immune responses are urgently needed for the functional cure of CHB. Based on the extensive discussion of the biological and clinical significance of new virologic biomarkers and distinct mechanism of drug candidates currently in clinical development, we propose that the selection of virologic and immunological biomarkers for evaluation of therapeutic efficacy as well as setting the therapeutic endpoints in the clinical trials should be based on the mode of action of investigational drugs. In addition, due to the complexity of CHB pathogenesis, selection of specific subpopulation of CHB patients for the clinical trials of drugs with a specific mode of action should also be considered.


Subject(s)
Antiviral Agents/therapeutic use , Biomarkers , DNA, Circular , DNA, Viral , Hepatitis B/drug therapy , Hepatitis B Surface Antigens , Hepatitis B virus/genetics , Hepatitis B, Chronic , Humans , Virus Replication
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