RESUMEN

BACKGROUND: Although nucleos(t)ide analogues (NAs) are thought to reduce the risk of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), the effect of NA discontinuation on the prognosis of HBV-related HCC after hepatectomy is rarely reported. We aimed to investigate the potential for hepatitis B virus e antigen (HBeAg)-negative HBV-related HCC patients to discontinue NAs based on preoperative hepatitis B virus surface antigen (HBsAg) status. METHODS: This historical cohort study involved 1232 NA-treated HBeAg-negative patients who underwent curative hepatectomy for HBV-related HCC from 2014 to 2019. The recurrence-free survival (RFS) and overall survival (OS) of patients discontinuing NAs before surgery were compared with those continuing NAs. Propensity score matching (PSM) was used to balance baseline characteristics. RESULTS: Of all enrolled patients, 839 (68.1%) patients continued NAs, and 393 (31.9%) patients discontinued NAs. Continuation of NAs was identified as an independent risk factor for RFS (HR 2.047, 95% CI 1.348-3.109, p < 0.001 before PSM and HR 2.756, 95% CI 1.537-4.942, p < 0.001 after PSM) in HBsAg-negative patients. Similarly, subgroup survival analyses showed that NA discontinuation was associated with better RFS (p = 0.029 before PSM and p < 0.001 after PSM) and comparable OS (p = 0.935 before PSM and p = 0.115 after PSM) than NA continuation in HBsAg-negative patients. The interaction between HBsAg status and continuation or discontinuation of NAs was significant (p for interaction <0.001). CONCLUSIONS: These findings demonstrate the potential for HBeAg-negative HBV-related HCC patients who have achieved HBsAg seroclearance to discontinue NAs under strict monitoring.

Asunto(s)

Carcinoma Hepatocelular , Hepatectomía , Antígenos e de la Hepatitis B , Virus de la Hepatitis B , Neoplasias Hepáticas , Puntaje de Propensión , Humanos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/virología , Masculino , Femenino , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/virología , Neoplasias Hepáticas/etiología , Persona de Mediana Edad , Antígenos e de la Hepatitis B/sangre , Pronóstico , Antivirales/uso terapéutico , Antígenos de Superficie de la Hepatitis B/sangre , Nucleósidos/uso terapéutico , Estudios Retrospectivos , Adulto , Anciano , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/virología

RESUMEN

OBJECTIVE: 28-55% of chronic hepatitis B (CHB) patients belong to the grey zone (GZ). By analyzing the pathological characteristics of the liver of patients in the GZ, this study clarified whether the patients in the GZ need anti-hepatitis B virus treatment. METHOD: We reviewed 324 cases of liver pathology that underwent liver biopsy between 2011 and 2022. According to the total score of inflammation G, 0-6 points are classified as mild, 7-12 points are classified as moderate, and 13-18 points are classified as severe. According to the total score of fibrosis F, 0-2 is mild, 3-4 is moderate, and 5-6 is severe. Significant histological diseases (SHD) are defined as the presence of inflammation G ≥ 6 and/or fibrosis F ≥ 2 in liver biopsy specimens. RESULT: 324 GZ patients were scored using the Ishak method, with G7-18 accounting for 9%, F3-6 accounting for 19.2%, and SHD accounting for 37%. The inflammation, fibrosis, and SHD in the HBeAg (+) group were more pronounced than those in the HBeAg (-) group. Among the GZ-A ∼ GZ-D subgroups, the highest proportion of SHD in the GZ-B group was 58.35%. CONCLUSION: More than 1/3 of the patients in GZ need anti-hepatitis B virus treatment. More than half of GZ-B patients need anti-hepatitis B virus treatment. It is very necessary to carry out rescue anti-hepatitis B virus treatment for patients in GZ as soon as possible.

Asunto(s)

Antivirales , Antígenos e de la Hepatitis B , Hepatitis B Crónica , Cirrosis Hepática , Hígado , Humanos , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/patología , Hepatitis B Crónica/virología , Antivirales/uso terapéutico , Masculino , Femenino , Adulto , Hígado/patología , Persona de Mediana Edad , Cirrosis Hepática/virología , Cirrosis Hepática/patología , Cirrosis Hepática/tratamiento farmacológico , Antígenos e de la Hepatitis B/sangre , Biopsia , Virus de la Hepatitis B/efectos de los fármacos , Estudios Retrospectivos , Índice de Severidad de la Enfermedad

RESUMEN

PURPOSE: This study aims to analyze whether undergoing amniocentesis during pregnancy in women diagnosed with hepatitis B virus (HBV) infection leads to HBV transmission to newborns. METHODS: Retrospective data collection was conducted from June 2019 to November 2022 on expectant mothers positive for hepatitis B surface antigen (HBsAg) who underwent amniocentesis at The Third Affiliated Hospital of Sun Yat-sen University, along with data on their newborns. The study summarized the HBV infection status of newborns born to mothers with different expressions of hepatitis B e antigen (HBeAg), antiviral treatment versus no treatment, and different HBV DNA viral loads before delivery. RESULTS: In this study, 346 expectant mothers tested positive for HBsAg, along with 351 newborns (including 5 sets of twins, with 8 infants (2.28%) testing HBsAg-positive at birth. All newborns received dual immunotherapy and were followed up. At 7-12 months, retesting for HBsAg positivity and HBV DNA positivity among infants revealed that out of the infants born with HBsAg positivity, 7 cases had seroconverted to negative, while the remaining infant, who was positive for both HBsAg and HBeAg at birth, tested positive for both HBsAg and HBV DNA at 7-12 months. Thus, one case of vertical transmission of hepatitis B from mother to child occurred in this study. The proportion of infants born with HBsAg + among newborns born to HBeAg-positive mothers (4 cases, 6.06%) was significantly higher than that among newborns born to HBeAg-negative mothers (4 cases, 1.41%) (P < 0.05). The proportion of infants born with HBsAg + showed no significant difference between newborns born to mothers receiving antiviral therapy (2 cases, 2.90%) and those born to mothers not receiving antiviral therapy (6 cases, 2.13%) (P > 0.05). Among expectant mothers with viral load ≥ 6 log 10 IU/mL before delivery, 3 newborns (30.00%) were manifesting HBsAg positivity at birth, significantly higher than the group with viral load < 6 log 10 IU/mL before delivery (5 cases, 1.47%) (P < 0.05). CONCLUSION: Among HBsAg-positive expectant mothers, only a small number of infants are infected with the hepatitis B virus at birth, the proportion of which is relatively low. Infants born to mothers who are HBeAg-positive or have a viral load ≥ 6 log10 IU/mL have a higher risk of being born positive.

Asunto(s)

Amniocentesis , ADN Viral , Antígenos de Superficie de la Hepatitis B , Antígenos e de la Hepatitis B , Virus de la Hepatitis B , Hepatitis B , Transmisión Vertical de Enfermedad Infecciosa , Complicaciones Infecciosas del Embarazo , Carga Viral , Humanos , Femenino , Embarazo , Estudios Retrospectivos , Recién Nacido , Hepatitis B/transmisión , Adulto , Antígenos de Superficie de la Hepatitis B/sangre , Complicaciones Infecciosas del Embarazo/virología , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/aislamiento & purificación , ADN Viral/sangre , Antígenos e de la Hepatitis B/sangre , Antivirales/uso terapéutico , Masculino , Madres , Adulto Joven

RESUMEN

OBJECTIVE: To determine the histopathological findings in patients with HBeAg-positive chronic HBV infection (immunotolerant phase in old terminology) and HBeAg-negative chronic HBV infection (inactive carrier phase in old terminology). STUDY DESIGN: Observational study. Place and Duration of the Study: Department of Gastroenterology, University of Health Sciences, Diyarbakir Gazi Yasargil Education and Research Hospital, Diyarbakir, Turkiye and Diyarbakir and Mersin University School of Medicine, Diyarbakir, Turkiye, from May 2014 to August 2022. METHODOLOGY: The difference between fibrosis and histological activity indices of 289 patients in the immunotolerant and inactive carrier phase who had liver biopsy was examined statistically. Additionally, the relationship of these data with age and gender was investigated. RESULTS: While 236 (81.7%) of the patients were in the inactive carrier phase, 53 (18.3%) patients were in the immunotolerant phase. The mean fibrosis score of patients in the immunotolerant stage was 2.0 ± 1.2, while it was 2.0 ± 1.0 in inactive carriers (p = 0.753). The number of patients with a fibrosis score of two and above was 21 (39.6%) in immunotolerant patients and 52 (22.0%) in inactive carrier patients (p = 0.004). In patients under 30 years of age, the mean fibrosis score was 1.7 ± 1.0. It was 2.0 ± 1.1 in those over 30 years of age (p = 0.016). CONCLUSION: Biochemical parameters or viral load cannot clearly reflect cellular damage in the liver. In the future, HBV DNA positivity alone may be the only criterion for the treatment. KEY WORDS: Chronic viral hepatitis B, Fibrosis, Immune tolerance phase, Inactive carrier phase.

Asunto(s)

Antígenos e de la Hepatitis B , Hepatitis B Crónica , Cirrosis Hepática , Humanos , Masculino , Hepatitis B Crónica/patología , Hepatitis B Crónica/inmunología , Femenino , Adulto , Antígenos e de la Hepatitis B/sangre , Persona de Mediana Edad , Cirrosis Hepática/patología , Cirrosis Hepática/inmunología , Virus de la Hepatitis B/inmunología , Biopsia , Hígado/patología , Portador Sano , Adulto Joven

RESUMEN

BACKGROUND: Most people diagnosed with chronic hepatitis B (CHB) need treatment to help reduce the risk of liver disease and limit disease transmission. Therapeutic vaccine (TV) candidates have been under study for their clinical effects on inducing HBV-specific host immune responses. This review aimed to systematically synthesize updated evidence on the efficacy and safety of TVs in patients with CHB. METHODS: This systematic review was performed by searching different databases from January to February 2021. Completed randomized controlled trials that reported TVs' efficacy and/or safety for treating CHB compared with the standard of care (SOC) or placebo were included. Efficacy and safety estimates were reported as the logarithm of the odds ratio and risk differences, respectively. I2 > 50% was considered significant heterogeneity. Significant publication bias was considered when Egger's test P value < .10. The risk of bias was assessed using the Cochrane Risk of Bias tool. The GRADE methodology was used to assess the certainty of the evidence for each outcome. RESULTS: Twenty-four articles with 2889 pooled samples were included. TVs made a significant difference in hepatitis B envelope antigen (HBeAg) SC (log OR = 0.76, P = .01) and (log OR = 0.40, P = .03) compared to placebo and combination therapy, respectively. HBeAg SC was significantly affected by TVs at the end of follow up (log OR = 0.49, P = .01), with significant HBsAg mean difference (MD = -0.62, P = .00). At the end of treatment, the TVs had no significant effect on HBV DNA negativity over the SOC (log OR = 0.62, P = .09) or placebo (log OR = -0.07, P = .91). TVs do not significantly affect the risk of serious adverse events (RD 0.02, 95% CI 0.00-0.04). CONCLUSION: In patients with CHB, TVs had significant effects on HBeAg SC compared to the SOC or placebo. There was no significant difference between serious adverse events. TVs are promising treatment strategy to overcome CHB.

Asunto(s)

Vacunas contra Hepatitis B , Hepatitis B Crónica , Humanos , Antígenos e de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/inmunología , Vacunas contra Hepatitis B/uso terapéutico , Vacunas contra Hepatitis B/administración & dosificación , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/inmunología , Ensayos Clínicos Controlados Aleatorios como Asunto

RESUMEN

BACKGROUND/AIMS:  Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and the third leading cause of cancer-related mortality. Extensive literature suggests that long noncoding RNAs play a role in the progression of HCC and hold potential as diagnostic biomarkers for this disease. MATERIALS AND METHODS:  We examined the serum levels of HOX antisense intergenic RNA (HOTAIR) in 49 hepatitis patients, 31 liver cirrhosis (LC), and 37 HCC patients using quantitative real-time polymerase chain reaction. Correlations between serum HOTAIR levels and clinical data were evaluated in HCC patients. The receiver operating characteristic curve was utilized to analyze the diagnostic potency of HOTAIR. RESULTS:  The HOTAIR levels in serum were significantly higher in HCC patients compared to those with hepatitis (P = .003) and LC patients (P = .048). There was a significant association between the serum levels of HOTAIR and positivity of hepatitis B e antigen (HBeAg) (P = .039) as well as portal vein tumor thrombus (P = .040) in HCC patients. The area under the curve (AUC) for HOTAIR for distinguishing HCC from hepatitis and LC was 0.697. The combined AUC for HOTAIR, HBeAg, and alpha-fetoprotein (AFP) was 0.777. CONCLUSION:  Serum HOTAIR functions as a potential diagnostic marker for hepatitis B virus-related HCC. Combining HOTAIR with clinical data and AFP can reinforce the diagnostic precision on HCC.

Asunto(s)

Biomarcadores de Tumor , Carcinoma Hepatocelular , Neoplasias Hepáticas , ARN Largo no Codificante , Humanos , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/virología , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/virología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/diagnóstico , ARN Largo no Codificante/sangre , Masculino , Femenino , Persona de Mediana Edad , Biomarcadores de Tumor/sangre , Adulto , Cirrosis Hepática/sangre , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/virología , Cirrosis Hepática/genética , Curva ROC , Anciano , Virus de la Hepatitis B/genética , Hepatitis B Crónica/sangre , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/diagnóstico , Antígenos e de la Hepatitis B/sangre , Hepatitis B/complicaciones , Hepatitis B/sangre , Hepatitis B/diagnóstico

RESUMEN

BACKGROUND AND AIMS: Data on the safety and effectiveness of tenofovir alafenamide (TAF) plus peginterferon-alpha (Peg-IFN-α) in children with chronic hepatitis B (CHB) are lacking. The current study aimed to present the characteristics of four pediatric CHB patients who obtained a functional cure by using TAF and Peg-IFN-α. METHODS: In this case series study initiated in May 2019, ten children who had no clinical symptoms or signs received response-guided (HBV DNA undetectable, hepatitis B e antigen [HBeAg] loss or seroconversion, and hepatitis B surface antigen [HBsAg] loss or seroconversion) and functional cure-targeted (HBsAg loss or seroconversion) TAF (25 mg/d, orally) plus Peg-IFN-α-2b (180 µg/1.73m2, subcutaneously, once weekly) in combination (9/10) or sequential (1/10) therapy. The safety and effectiveness of these treatments were monitored. RESULTS: As of April 2024, four out of ten children obtained a functional cure after a mean of 31.5 months of treatment, and the other six children are still undergoing treatment. These four cured children, aged 2, 4, 8, and 6 years, were all HBeAg-positive and had alanine aminotransferase levels of 80, 47, 114, and 40 U/L; HBV DNA levels of 71200000, 93000000, 8220, and 96700000 IU/mL; and HBsAg levels of 39442.8, 15431.2, 22, and 33013.1 IU/mL, respectively. During treatment, all the children (10/10) experienced mild or moderate adverse events, including flu-like symptoms, anorexia, fatigue, and cytopenia. Notably, growth retardation (8/10) was the most significant adverse event; and it occurred in three cured children (3/4) treated with combination therapy and was present to a low degree in the other cured child (1/4) treated with sequential therapy. Fortunately, all three cured children recovered to or exceeded the normal growth levels at 9 months posttreatment. CONCLUSIONS: TAF plus Peg-IFN-α-2b therapy is potentially safe and effective for pediatric CHB patients, which may provide important insights for future clinical practice and study designs targeting functional cures for children with CHB.

Asunto(s)

Antivirales , Quimioterapia Combinada , Hepatitis B Crónica , Interferón-alfa , Polietilenglicoles , Proteínas Recombinantes , Tenofovir , Humanos , Tenofovir/uso terapéutico , Tenofovir/administración & dosificación , Tenofovir/análogos & derivados , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/virología , Masculino , Femenino , Antivirales/uso terapéutico , Antivirales/efectos adversos , Antivirales/administración & dosificación , Niño , Proteínas Recombinantes/uso terapéutico , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Polietilenglicoles/uso terapéutico , Polietilenglicoles/efectos adversos , Polietilenglicoles/administración & dosificación , Interferón-alfa/uso terapéutico , Interferón-alfa/administración & dosificación , Interferón-alfa/efectos adversos , Preescolar , Resultado del Tratamiento , Interferón alfa-2/uso terapéutico , Interferón alfa-2/administración & dosificación , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/efectos de los fármacos , ADN Viral/sangre , Alanina/uso terapéutico , Alanina/análogos & derivados

RESUMEN

Background: About 20% of on-treatment patients with chronic hepatitis B (CHB) experienced low-level viraemia (LLV), which is associated with persistent low-grade inflammation, fibrosis progression, and increased risk of hepatocellular carcinoma. We aimed to investigate the high-risk factors related to LLV. Methods: In this retrospective study, patients receiving entecavir (ETV) treatment from January 2018 to January 2023 were enrolled, and were divided into a LLV (HBV DNA 20-2000 IU/mL) cohort and a complete virological response (CVR) (HBV DNA < 20 IU/mL) cohort according to the virological response at week 48 posttreatment. Treatment baseline characteristics were retrieved from electronic medical records. Multivariate logistic regression was performed. Results: Totally, 1653 patients were enrolled, male patients accounted for 73.0%; the median age was 44 years; the mean HBV DNA level was 5.9 Log10 IU/ml. Among them, 472 (28.6%) experienced LLV. Multivariate analysis showed that HBeAg positivity (OR = 2.650, 95% CI: 2.000-3.511, p < 0.001), HBV DNA ≥ 6.0 Log10 IU/mL (OR = 1.370, 95% CI: 1.054-1.780, p = 0.019), qHBsAg ≥ 9000 IU/mL (OR = 4.472, 95% CI: 3.410-5.866, p < 0.001), cirrhosis (OR = 1.650, 95% CI: 1.234-2.207, P = 0.001), LSM ≥ 13.0 kPa (OR = 1.644, 95% CI: 1.203-2.246, p = 0.002), and PLT < 100×109/L (OR = 1.450, 95% CI: 1.094-1.922, p = 0.010) at baseline were related to the development of LLV. Conclusions: High HBV DNA/HBsAg quantification/LSM, low PLT, HBeAg positivity, and liver cirrhosis were high-risk factors associated with LLV in patients receiving entecavir treatment.

Asunto(s)

Antivirales , ADN Viral , Guanina , Virus de la Hepatitis B , Hepatitis B Crónica , Viremia , Humanos , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/complicaciones , Masculino , Guanina/análogos & derivados , Guanina/uso terapéutico , Femenino , Adulto , Factores de Riesgo , Antivirales/uso terapéutico , Estudios Retrospectivos , Persona de Mediana Edad , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/efectos de los fármacos , ADN Viral/sangre , Antígenos e de la Hepatitis B/sangre , Cirrosis Hepática/virología , Carga Viral/efectos de los fármacos

RESUMEN

Abstract: This study determined the hepatitis B e antigen (HBeAg) status of people living with chronic hepatitis B (CHB) in Far North Queensland (FNQ), Australia and their age of HBeAg loss. It was hoped that this would provide data to explain the stark difference in the incidence of hepatocellular carcinoma (HCC) between Aboriginal and Torres Strait Islander individuals living with CHB in FNQ, a finding that has been hypothesised to relate to differences in hepatitis B virus genotype. We identified every FNQ resident with CHB, determined their country of birth, their HBeAg status, the age they lost HBeAg and whether they identified as an Aboriginal, a Torres Strait Islander or a non-Indigenous individual. We then ascertained whether these demographic and virological variables were correlated. Of 1,474 individuals living with CHB in FNQ, 278 (19%) were Aboriginal, 507 (34%) were Torres Strait Islanders and 689 (47%) were non-Indigenous. Aboriginal individuals were less likely to be HBeAg positive (26/278, 9%) than Torres Strait Islander (91/507, 18%) and non-Indigenous (126/689, 18%) individuals, p < 0.0001. Aboriginal individuals lost HBeAg at an earlier age (median (interquartile range): 30 (23-39) years) than Torres Strait Islander (38 (29-49) years) and non-Indigenous (36 (29-47) years) individuals, p < 0.0001. Aboriginal individuals with CHB in FNQ are more likely to be HBeAg negative than Torres Strait Islander and non-Indigenous individuals and lose HBeAg at a younger age. This provides a biological basis for local clinicians' observation that Aboriginal individuals with CHB in FNQ are at a lower risk of HCC and data to support the principle of genotype-based care in the region.

Asunto(s)

Antígenos e de la Hepatitis B , Virus de la Hepatitis B , Hepatitis B Crónica , Nativos de Hawái y Otras Islas del Pacífico , Humanos , Antígenos e de la Hepatitis B/sangre , Femenino , Hepatitis B Crónica/epidemiología , Masculino , Adulto , Persona de Mediana Edad , Queensland/epidemiología , Virus de la Hepatitis B/genética , Carcinoma Hepatocelular/epidemiología , Australia/epidemiología , Adulto Joven , Genotipo , Neoplasias Hepáticas/epidemiología , Anciano , Aborigenas Australianos e Isleños del Estrecho de Torres

RESUMEN

Background and aims: Limited data have been reported on achieving functional cure using pegylated interferon (Peg-IFN) alpha-2b treatment for postpartum hepatitis B e antigen (HBeAg)-negative women with chronic hepatitis B virus (HBV) infection. This study was to assess the effectiveness and safety of Peg-IFN alpha-2b in HBV postpartum women without HBeAg and identify factors linked to the functional cure. Methods: A total of 150 HBeAg-negative postpartum women were retrospectively recruited.47 patients received Peg-IFN alpha-2b [Peg-IFN(+) group] and 103 patients did not [Peg-IFN(-) group]. Propensity score matching (PSM) was used to adjust the baseline imbalance between the two groups. The patients were followed for at least 48 weeks. The primary endpoints were hepatitis B surface antigen(HBsAg) loss and HBsAg seroconversion at 48 weeks. Logistic regression analysis was used to assess factors associated with HBsAg loss at 48 weeks. Results: At week 48,the HBsAg loss and seroconversion rate in Peg-IFN(+) group were 51.06%(24/47) and 40.43%(19/47), respectively. Even after PSM, Peg-IFN(+) group still showed higher HBsAg loss rate (50.00% vs 7.14%,p<0.001) and higher HBsAg seroconversion rate (38.10% vs 2.38%,p<0.001). Baseline HBsAg levels (Odds Ratio [OR]: 0.051, 95% Confidence Interval [CI]: 0.003-0.273, P=0.010), HBsAg at week 24 (OR:0.214, 95%CI:0.033-0.616, P=0.022), HBsAg decline at week 24 (OR:4.682, 95%CI: 1.624-30.198, P=0.022) and postpartum flare (OR:21.181, 95%CI:1.872-633.801, P=0.030) were significantly associated with HBsAg loss at week 48 after Peg-IFN alpha-2b therapy. Furthermore, the receiver operating characteristic curve (ROC) showed that the use of baseline HBsAg<182 IU/mL, HBsAg at week24 < 4 IU/mL and HBsAg decline at week24>12IU/mL were good predictors of HBsAg loss. No serious adverse events were reported. Conclusion: Peg-IFN alpha-2b treatment could achieve a high rate of HBsAg loss and seroconversion in HBeAg-negative postpartum women with reliable safety, particularly for patients experience postpartum flare and have low baseline HBsAg levels.

Asunto(s)

Antivirales , Antígenos de Superficie de la Hepatitis B , Antígenos e de la Hepatitis B , Hepatitis B Crónica , Interferón alfa-2 , Interferón-alfa , Polietilenglicoles , Periodo Posparto , Proteínas Recombinantes , Humanos , Femenino , Hepatitis B Crónica/tratamiento farmacológico , Polietilenglicoles/uso terapéutico , Proteínas Recombinantes/uso terapéutico , Adulto , Antígenos e de la Hepatitis B/sangre , Antivirales/uso terapéutico , Interferón-alfa/uso terapéutico , Estudios Retrospectivos , Interferón alfa-2/uso terapéutico , Antígenos de Superficie de la Hepatitis B/sangre , Resultado del Tratamiento , Virus de la Hepatitis B/inmunología , Virus de la Hepatitis B/efectos de los fármacos , Adulto Joven , Seroconversión

RESUMEN

Antigen presentation by HLA class II molecules to CD4+ T cells is an essential step for generating antibodies to hepatitis B antigens. In this study, we investigated the association between the HLA-DRB1 gene and the status of antibodies to hepatitis B surface and e antigens. Our results revealed a significant association between the status of anti-HBsAg and HLA-DRB1*04:03 (OR = 4.11, 95% CI = 1.50-10.84, p = 0.005, Padj. = 0.05) as well as HLA-DRB1*15:01 (OR = 1.74, 95% CI = 1.20-2.50, p = 0.002, Padj. = 0.045). MHC II binding predictions and in silico docking demonstrated strong binding affinity of HBsAg peptides to these two HLA-DRB1 molecules. Conversely, the status of anti-HBeAg was inversely associated with HLA-DRB1*14:54 (OR = 0.34, 95% CI = 0.18-0.64, p = 0.001, Padj. = 0.011), and in silico analysis revealed weak binding affinity of HBeAg peptides to HLA-DRB1*14:54. In conclusion, these findings support the involvement of HLA-DRB1 in humoral immunity against HBV infection.

Asunto(s)

Alelos , Cadenas HLA-DRB1 , Anticuerpos contra la Hepatitis B , Antígenos de Superficie de la Hepatitis B , Antígenos e de la Hepatitis B , Humanos , Cadenas HLA-DRB1/genética , Cadenas HLA-DRB1/inmunología , Antígenos de Superficie de la Hepatitis B/inmunología , Antígenos de Superficie de la Hepatitis B/genética , Masculino , Femenino , Adulto , Anticuerpos contra la Hepatitis B/inmunología , Anticuerpos contra la Hepatitis B/sangre , Antígenos e de la Hepatitis B/inmunología , Antígenos e de la Hepatitis B/genética , Persona de Mediana Edad , Hepatitis B/inmunología , Hepatitis B/virología , Adulto Joven , Unión Proteica , Virus de la Hepatitis B/inmunología , Virus de la Hepatitis B/genética , Simulación del Acoplamiento Molecular

RESUMEN

BACKGROUND: Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) co-infection are significant public health issues, despite the availability of an effective HBV vaccine for nearly three decades and the great progress that has been made in preventing and treating HIV. HBV and HIV both modulate micro-ribonucleic acids (microRNA) expression to support viral replication. The aim of this study was to describe the pattern of microRNA expression in patients coinfected with chronic HBV and HIV with varying disease severity, as indicated by Hepatitis B e antigen (HBeAg) status, HBV viral load, alanine transaminase (ALT) levels, and HIV viral load. METHODS: Plasma microRNAs, specific to HBV, were measured by quantitative real-time polymerase chain reaction (qRT-PCR) in HBV and HIV-negative healthy controls (n = 23) and patients coinfected with chronic HBV-HIV (n = 50). MicroRNA expression levels were compared between patients with high vs low HBV viral load, HBeAg positive vs HBeAg negative, high vs low ALT levels, and high vs low HIV viral load. Additionally, HBV viral load, ALT levels, and HIV viral load were correlated with microRNA expression levels. RESULTS: Significantly higher expression levels of selected microRNAs were observed in chronic HBV-HIV coinfected patients compared to healthy controls. Significantly higher expression levels of hsa-miR-122-5p, hsa-miR-192-5p, and hsa-miR-193b-3p were observed in patients with high HBV viral load compared with low HBV viral load patients, and the levels of these microRNAs were correlated with HBV viral load levels. Significantly higher levels of hsa-miR-15b-5p and hsa-miR-181b-5p were observed in HBeAg-negative patients. CONCLUSION: This study demonstrates the potential use of hsa-miR-15b-5p, hsa-miR-122-5p, hsa-miR-181b-5p, hsa-miR-192-5p and hsa-miR-193b-3p as additional diagnostic biomarkers in chronic HBV disease progression.

Asunto(s)

Coinfección , Infecciones por VIH , Virus de la Hepatitis B , Hepatitis B Crónica , MicroARNs , Carga Viral , Humanos , Hepatitis B Crónica/virología , Hepatitis B Crónica/sangre , Hepatitis B Crónica/complicaciones , MicroARNs/sangre , MicroARNs/genética , Infecciones por VIH/complicaciones , Infecciones por VIH/virología , Infecciones por VIH/sangre , Infecciones por VIH/epidemiología , Masculino , Coinfección/virología , Coinfección/epidemiología , Coinfección/sangre , Femenino , Adulto , Sudáfrica/epidemiología , Virus de la Hepatitis B/genética , Persona de Mediana Edad , Antígenos e de la Hepatitis B/sangre , Prevalencia , Adulto Joven , Alanina Transaminasa/sangre

RESUMEN

BACKGROUND: The objective of antiviral therapy for chronic viral hepatitis B infection (CHB) is to achieve a functional cure. An important viral marker in the serum of patients with CHB is the serum hepatitis B core-related antigen (HBcrAg). However, there is limited research on HBcrAg in juvenile patients with CHB. In this study, we aimed to investigate the correlation between serum HBcrAg and other hepatitis B virus (HBV) markers in children with CHB and its predictive significance for prognosis during antiviral therapy. METHODS: A single-center retrospective study was conducted involving 79 children with CHB, aged between 0 and 16 years. All the children were treated with interferon [or combined nucleos(t)ide analogs] for 48 weeks. HBcrAg, hepatitis B surface antigen (HBsAg), and HBV DNA were measured before treatment, and at 12 and 48 weeks after treatment. The enrolled children were classified into the seroclearance group and the nonseroclearance group based on the therapeutic outcome. RESULTS: HBsAg seroclearance was observed in 28 out of 79 patients and hepatitis B e antigen seroconversion without HBsAg seroclearance was observed in 14 out of 79 patients following the conclusion of the treatment, with baseline HBcrAg titer levels showing no statistical significance in both the seroclearance and nonseroclearance groups ( P  = 0.277). HBsAg and HBV DNA were positively correlated with HBcrAg in children with CHB ( R2  = 0.3289, 0.4388). The area under the receiver operating characteristic curve of the decrease in HBcrAg at 12 weeks of treatment as a predictor of seroclearance at 48 weeks of treatment, exhibited a value of 0.77. CONCLUSION: A decrease in serum HBcrAg levels in children with hepatitis B serves as a prognostic indicator.

Asunto(s)

Antivirales , Biomarcadores , ADN Viral , Antígenos del Núcleo de la Hepatitis B , Antígenos de Superficie de la Hepatitis B , Antígenos e de la Hepatitis B , Hepatitis B Crónica , Humanos , Niño , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/sangre , Hepatitis B Crónica/inmunología , Hepatitis B Crónica/virología , Femenino , Masculino , Antivirales/uso terapéutico , Estudios Retrospectivos , Preescolar , Lactante , Adolescente , Antígenos del Núcleo de la Hepatitis B/sangre , Antígenos del Núcleo de la Hepatitis B/inmunología , Biomarcadores/sangre , Antígenos e de la Hepatitis B/sangre , ADN Viral/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/inmunología , Virus de la Hepatitis B/genética , Resultado del Tratamiento , Curva ROC , Valor Predictivo de las Pruebas , Recién Nacido , Seroconversión

RESUMEN

OBJECTIVE: Selected populations of patients with chronic hepatitis B (CHB) may benefit from a combined use of pegylated interferon-alpha (pegIFN-α) and nucleos(t)ides (NUCs). The aim of our study was to assess the immunomodulatory effect of pegIFN-α on T and natural killer (NK) cell responses in NUC-suppressed patients to identify cellular and/or serological parameters to predict better T cell-restoring effect and better control of infection in response to pegIFN-α for a tailored application of IFN-α add-on. DESIGN: 53 HBeAg-negative NUC-treated patients with CHB were randomised at a 1:1 ratio to receive pegIFN-α-2a for 48 weeks, or to continue NUC therapy and then followed up for at least 6 months maintaining NUCs. Serum hepatitis B surface antigen (HBsAg) and hepatitis B core-related antigen (HBcrAg) levels as well as peripheral blood NK cell phenotype and function and HBV-specific T cell responses upon in vitro stimulation with overlapping HBV peptides were measured longitudinally before, during and after pegIFN-α therapy. RESULTS: Two cohorts of pegIFN-α treated patients were identified according to HBsAg decline greater or less than 0.5 log at week 24 post-treatment. PegIFN-α add-on did not significantly improve HBV-specific T cell responses during therapy but elicited a significant multispecific and polyfunctional T cell improvement at week 24 post-pegIFN-α treatment compared with baseline. This improvement was maximal in patients who had a higher drop in serum HBsAg levels and a lower basal HBcrAg values. CONCLUSIONS: PegIFN-α treatment can induce greater functional T cell improvement and HBsAg decline in patients with lower baseline HBcrAg levels. Thus, HBcrAg may represent an easily and reliably applicable parameter to select patients who are more likely to achieve better response to pegIFN-α add-on to virally suppressed patients.

Asunto(s)

Antivirales , Antígenos e de la Hepatitis B , Hepatitis B Crónica , Interferón-alfa , Células Asesinas Naturales , Polietilenglicoles , Proteínas Recombinantes , Humanos , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/inmunología , Hepatitis B Crónica/sangre , Interferón-alfa/uso terapéutico , Antivirales/uso terapéutico , Proteínas Recombinantes/uso terapéutico , Femenino , Adulto , Masculino , Polietilenglicoles/uso terapéutico , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/efectos de los fármacos , Persona de Mediana Edad , Antígenos e de la Hepatitis B/sangre , Antígenos del Núcleo de la Hepatitis B/inmunología , Antígenos del Núcleo de la Hepatitis B/sangre , Quimioterapia Combinada , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/inmunología , Linfocitos T/inmunología , Linfocitos T/efectos de los fármacos , Resultado del Tratamiento , Nucleósidos/uso terapéutico

RESUMEN

BACKGROUND: Interferon-alpha (IFNα) is a common treatment for chronic hepatitis B virus (HBV) infection, but its efficacy varies widely among patients. GTPASE, an interferon-stimulated gene (ISG), has recently been identified as a factor in antiviral immunity, though its role in HBV infection is not fully understood. OBJECTIVE: This study investigates the role of GTPASE in enhancing the antiviral effects of IFNα against HBV and elucidates its mechanism of action. METHODS: We analyzed the impact of GTPASE overexpression and silencing on HBV replication and clearance in HBV-infected cells. Molecular docking studies assessed the interaction between GTPASE and HBV surface antigens (HBs). Clinical samples from HBV patients undergoing Peg-IFNα treatment were also evaluated for GTPASE expression and its correlation with treatment efficacy. RESULTS: Overexpression of GTPASE led to significant inhibition of HBV replication, increased HBeAg seroconversion, and enhanced HBsAg clearance. GTPASE directly bound to HBs proteins, reducing their levels and affecting viral particle formation. Silencing GTPASE reduced these effects, while combined treatment with Peg-IFNα and GTPASE overexpression further improved antiviral outcomes. Mutational analysis revealed that specific sites in GTPASE are crucial for its antiviral activity. CONCLUSIONS: GTPASE acts as a positive regulator in IFNα-induced antiviral immunity against HBV. It enhances the therapeutic efficacy of IFNα by targeting HBs and modulating viral replication. GTPASE levels may serve as a predictive biomarker for response to Peg-IFNα therapy, highlighting its potential for improving individualized treatment strategies for chronic HBV infection.

Asunto(s)

Antivirales , GTP Fosfohidrolasas , Antígenos de Superficie de la Hepatitis B , Virus de la Hepatitis B , Hepatitis B Crónica , Interferón-alfa , Replicación Viral , Humanos , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/virología , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/genética , Replicación Viral/efectos de los fármacos , Antivirales/farmacología , Antivirales/uso terapéutico , Interferón-alfa/farmacología , Interferón-alfa/uso terapéutico , GTP Fosfohidrolasas/metabolismo , GTP Fosfohidrolasas/genética , Antígenos de Superficie de la Hepatitis B/metabolismo , Simulación del Acoplamiento Molecular , Adulto , Masculino , Antígenos e de la Hepatitis B/metabolismo , Células Hep G2 , Femenino , Resultado del Tratamiento

RESUMEN

BACKGROUND AND AIMS: Numerous HBeAg-positive chronic hepatitis B (CHB) patients with persistently normal ALT have significant liver histopathology. It is imperative to identify true "immune tolerant" patients. We aimed to evaluate the liver histopathology features of HBeAg-positive CHB patients with normal ALT and the incidence of liver cirrhosis and HCC in CHB patients during follow-up. METHODS: 179 HBeAg-positive CHB patients with normal ALT who performed liver biopsy from 2009 to 2018 were retrospectively analyzed. Liver necroinflammation ≥ G2 and/or liver fibrosis ≥ S2 was defined as significant liver histopathological change. RESULTS: 57.5% patients were in the indeterminate phase with significant liver histological changes. The proportion of the patients with evident liver necroinflammation was higher in the high-normal ALT group (21-40U/L) when compared with the low-normal ALT group (≤ 20 U/L) (51.3% vs. 30.0%, p < 0.05), and patients aged ≥ 40 years had a higher proportion of significant fibrosis than those aged < 40 years (64.5% vs. 39.9%, p < 0.05). The percentages of patients with ≥ S2 and ≥ G2/S2 in the HBV DNA < 107 IU/mL group were higher than those in the HBV DNA ≥ 107 IU/mL group (72.7% vs. 40.1%, p < 0.01; 81.8% vs. 54.1%, p < 0.05). During follow-up, two of immune tolerant patients and four of indeterminate patients developed into cirrhosis, and one of immune tolerant patients and one of indeterminate patients developed into HCC, respectively. CONCLUSIONS: HBeAg-positive CHB patients with high-normal ALT or HBV DNA < 107 IU/mL were tend to be indeterminate. Liver biopsy or noninvasive approaches are recommended to evaluate liver histopathology, and antiviral therapy is recommended for patients with significant liver histopathology.

Asunto(s)

Alanina Transaminasa , Antígenos e de la Hepatitis B , Hepatitis B Crónica , Cirrosis Hepática , Hígado , Humanos , Hepatitis B Crónica/patología , Hepatitis B Crónica/sangre , Masculino , Femenino , Adulto , Antígenos e de la Hepatitis B/sangre , Estudios Retrospectivos , Hígado/patología , Alanina Transaminasa/sangre , Persona de Mediana Edad , Cirrosis Hepática/patología , Cirrosis Hepática/virología , Virus de la Hepatitis B , ADN Viral/sangre , Biopsia , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/virología , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/virología

RESUMEN

BACKGROUND: Stopping nucleos(t)ide analogue (NA) therapy in patients with chronic hepatitis B (CHB) may trigger a beneficial immune response leading to HBsAg loss, but clinical trials on re-start strategies are lacking. AIM: To assess whether it is beneficial to undergo a prolonged flare after NA cessation. METHODS: One-hundred-and-twenty-seven patients with HBeAg negative, non-cirrhotic CHB with at least 24 months of viral suppression on NA therapy were included. All study participants stopped antiviral therapy and were randomised to either low-threshold (ALT > 80 U/L and HBV DNA > 2000 IU/mL) or high-threshold (ALT > 100 U/L for >4 months, or ALT > 400 U/L for >2 months) for the re-start of therapy. The primary endpoint was HBsAg loss within 36 months of stopping antiviral treatment. The primary analysis was based on intention-to-treat allocation with last observation carried forward. RESULTS: There was a numerical but not statistically significant difference in HBsAg loss between the low-threshold (3 of 64; 4.7%) and the high-threshold (8 of 63; 12.7%) group (risk difference: 8.0%, 95% CI: -2.3 to 19.6, p = 0.123). None of the patients with end-of-treatment HBsAg > 1000 IU/mL achieved HBsAg loss; among those with end-of-treatment HBsAg < 1000 IU/mL, 8 of 15 (53.3%) achieved HBsAg loss in the high-threshold group compared to 3 of 26 (11.5%) in the low-threshold group. CONCLUSIONS: We could not confirm our hypothesis that a higher threshold for restart of therapy after NA withdrawal improves the likelihood of HBsAg loss within 36 months in patients with HBeAg negative CHB. Further studies including only patients with HBsAg level <1000 IU/mL and/or larger sample size and longer follow-up duration are recommended.

Asunto(s)

Antivirales , Antígenos de Superficie de la Hepatitis B , Antígenos e de la Hepatitis B , Hepatitis B Crónica , Humanos , Hepatitis B Crónica/tratamiento farmacológico , Masculino , Femenino , Antivirales/uso terapéutico , Antígenos e de la Hepatitis B/sangre , Adulto , Persona de Mediana Edad , Antígenos de Superficie de la Hepatitis B/sangre , ADN Viral/sangre , Resultado del Tratamiento , Privación de Tratamiento , Virus de la Hepatitis B/inmunología , Alanina Transaminasa/sangre

Asunto(s)

ADN Viral , Antígenos e de la Hepatitis B , Virus de la Hepatitis B , Hepatitis B Crónica , Humanos , Antígenos e de la Hepatitis B/sangre , ADN Viral/sangre , Guías de Práctica Clínica como Asunto

RESUMEN

The question of whether patients in the immune-tolerant (IT) phase of chronic hepatitis B virus (HBV) infection should undergo antiviral therapy and determine the optimal regimen remains unclear. A comprehensive search of PubMed, Embase, MEDLINE, Cochrane Library, and Wanfang Data from inception to 5 December 2023, was conducted. Studies reporting on key outcomes such as HBV DNA undetectability, HBeAg loss or seroconversion, HBsAg loss or seroconversion, and hepatocellular carcinoma (HCC) incidence in patients in the IT phase of chronic HBV infection were included. In total, 23 studies were incorporated. Approximately 4% of patients in the IT phase achieved spontaneous HBeAg loss over 48 weeks of follow-up. Antiviral therapy demonstrated a favourable impact on HBV DNA negative conversion (Children: risk ratios [RR] = 6.83, 95% CI: 2.90-16.05; Adults: RR = 25.84, 95% CI: 6.47-103.31) and HBsAg loss rates (Children: RR = 9.49, 95% CI: 1.74-51.76; Adults: RR = 7.35, 95% CI: 1.41-38.27) for patients in the IT phase. Subgroup analysis revealed that in adult patients in the IT phase, interferon plus nucleos(t)ide analogues (NA)-treated patients exhibited a higher pooled rate of HBsAg loss or seroconversion than those treated with NA monotherapy (9% vs. 0%). Additionally, the pooled annual HCC incidence for patients in the IT phase was 3.03 cases per 1000 person-years (95% CI: 0.99-5.88). Adult patients in the IT phase had a significantly lower HCC incidence risk than HBeAg-positive indeterminate phase patients (RR = 0.46, 95% CI: 0.32-0.66), with no significant differences observed between IT and immune-active phases. Presently, there is insufficient evidence solely based on reducing the risk of HCC incidence, to recommend treating patients in the IT phase of chronic HBV infection. However, both adult and paediatric patients in the IT phase responded well to antiviral therapy, showing favourable rates of HBsAg loss or seroconversion.

Asunto(s)

Antivirales , Carcinoma Hepatocelular , Antígenos e de la Hepatitis B , Hepatitis B Crónica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/virología , Carcinoma Hepatocelular/inmunología , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/virología , Hepatitis B Crónica/epidemiología , Hepatitis B Crónica/inmunología , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/virología , Neoplasias Hepáticas/inmunología , Antivirales/uso terapéutico , Antígenos e de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/inmunología , Virus de la Hepatitis B/inmunología , Incidencia , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/inmunología , ADN Viral/sangre , Tolerancia Inmunológica , Resultado del Tratamiento , Seroconversión

RESUMEN

Hepatitis B virus (HBV) belongs to the genus Orthohepadnavirus, of Hepadnaviridae family, smallest human deoxyribonucleic acid (DNA) virus with 3200 bp in a partially double-stranded circular DNA. Globally, about 2 billion people are infected with over 65 million of the chronically infected residing in Africa. Ten HBV genotypes (A-J) have been reported across the globe. Based on the World Health Organization (WHO) African Regions including Kenya have high HBV prevalence rates yet the data on prevalence rates of the various HBV genotypes and their associated biomarkers is very scanty. A cross-sectional descriptive study with purposive sampling was conducted in which a census of patients with chronic Hepatitis B (CHB) with history >6-month were reviewed for eligibility. Demographics data was abstracted from patient files and blood samples drawn for genotyping, viral load using Rotor gene Q Polymerase Chain Reaction (PCR) equipment, Hepatitis B surface Antigen (HBsAg), Hepatitis B envelope antigen (HbeAg) and Hepatitis B core antibody (Anti-HBc) using Cobas e411 machine. Out of a total of 83 patients, 43 (52%) were eligible; males 29 (67.4%), females 14 (32.6%) with mean ages of 35.1±10.8 and 34.3±9.3 respectively. Genotypes A were 34(79.1%), B were 5(11.6%), C-D were 0 while E-J were 9(20.9%). All cases of genotype B were associated with co-infection of genotype A. Majority were HBeAg negative with HBV DNA >10 IU/ml (81.4% and 86.0% respectively) with distribution among all the genotypes. Across genotypes, viral load mean percentage comparisons were: A vs. A/B = 2600 (p = 0.09), A vs. E-J = 5260 (p = 0.09) and A/B vs. E-J = 200 (p = 0.28). The most prevalent genotype was A followed by mixed co-infection of genotype A/B. Genotype A was associated with HBV DNA viral loads > 10IU/ml and high rates of HBeAg negativity. Genotypes E-J were also detected though not characterized.

Asunto(s)

Genotipo , Virus de la Hepatitis B , Hepatitis B Crónica , Humanos , Masculino , Femenino , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/aislamiento & purificación , Adulto , Prevalencia , Kenia/epidemiología , Estudios Transversales , Persona de Mediana Edad , Hepatitis B Crónica/virología , Hepatitis B Crónica/epidemiología , Carga Viral , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/genética , Antígenos e de la Hepatitis B/sangre , Hospitales de Enseñanza , ADN Viral/genética , Derivación y Consulta , Adulto Joven