Dataset Information

Differential gene expression, irrespective of circulating Hepatitis B Surface Antigen levels, between Inactive Carrier and Nucleos(t)ide Analogue-Treated Hepatitis B Virus patients.

ABSTRACT: Long-term viremia control in chronic HBV patients occurs either spontaneously in inactive carrier (IC) patients or therapy-induced by nucleos(t)ide analogues (NUC). To better understand the characteristics of viremia control, we evaluated gene expression in purified leukocyte subsets from IC versus NUC-treated patients, and evaluated the putative modulatory effects of hepatitis B surface antigen (HBsAg). We observed that gene expression in NUC-treated patients differed markedly from IC patients, especially in dendritic cells, monocytes, and CD8+ T cells, while serum HBsAg levels had little effect. Nevertheless, based on our findings it cannot be excluded that HBsAg may act locally in the infected liver or preferentially affects HBV-specific cells.

SUBMITTER: Montanari NR

PROVIDER: S-EPMC9016459 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Differential gene expression, irrespective of circulating Hepatitis B Surface Antigen levels, between Inactive Carrier and Nucleos(t)ide Analogue-Treated Hepatitis B Virus patients.

Montanari Noé R NR Conceição-Neto Nádia N Van Den Wyngaert Ilse I Van Oord Gertine W GW Groothuismink Zwier M A ZMA Van Tilburg Sandra S de Man Robert A RA Aerssens Jeroen J Boonstra André A

The Journal of infectious diseases 20220401 8

Long-term viremia control in chronic HBV patients occurs either spontaneously in inactive carrier (IC) patients or therapy-induced by nucleos(t)ide analogues (NUC). To better understand the characteristics of viremia control, we evaluated gene expression in purified leukocyte subsets from IC versus NUC-treated patients, and evaluated the putative modulatory effects of hepatitis B surface antigen (HBsAg). We observed that gene expression in NUC-treated patients differed markedly from IC patients, ...[more]

PMID: 33009569

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Project description:Background & aimsThe dynamics of HBV viral load (VL) in patients with chronic hepatitis B (CHB) on nucleos(t)ide analogue (NA) treatment and its relationship with liver disease are poorly understood. We aimed to study longitudinal VL patterns and their associations with CHB clinical outcomes.MethodsUtilising large scale, routinely collected electronic health records from six centres in England, collated by the National Institute for Health and Care Research Health Informatics Collaborative (NIHR HIC), we applied latent class mixed models to investigate VL trajectory patterns in adults receiving NA treatment. We assessed associations of VL trajectory with alanine transaminase, and with liver fibrosis/cirrhosis.ResultsWe retrieved data from 1,885 adults on NA treatment (median follow-up 6.2 years, IQR 3.7-9.3 years), with 21,691 VL measurements (median 10 per patient, IQR 5-17). Five VL classes were identified from the derivation cohort (n = 1,367, discrimination: 0.93, entropy: 0.90): class 1 'long term suppression' (n = 827, 60.5%), class 2 'timely virological suppression' (n = 254, 18.6%), class 3 'persistent moderate viraemia' (n = 140, 10.2%), class 4 'persistent high-level viraemia' (n = 44, 3.2%), and class 5 'slow virological suppression' (n = 102, 7.5%). The model demonstrated a discrimination of 0.93 and entropy of 0.88 for the validation cohort (n = 518). Alanine transaminase decreased variably over time in VL-suppressed groups (classes 1, 2, 5; all p <0.001), but did not significantly improve in those with persistent viraemia (classes 3, 4). Patients in class 5 had twofold increased hazards of fibrosis/cirrhosis compared with class 1 (adjusted hazard ratio, 2.00; 95% CI, 1.33-3.02).ConclusionsHeterogeneity exists in virological response to NA therapy in CHB patients, with over 20% showing potentially suboptimal responses. Slow virological suppression is associated with liver disease progression.Impact and implicationsTreatment recommendations for people living with chronic hepatitis B virus (HBV) infection are becoming less stringent, meaning that more of the population will be eligible to receive therapy with nucleos(t)ide analogue agents. We explored outcomes of HBV treatment in a large UK dataset, describing different responses to treatment, and showing that the viral load is not completely suppressed after 1 year in about one in five cases, associated with an increased risk of liver complications. As treatment is rolled out more widely, patients and clinicians need to be aware of the potential for incomplete virologic responses. The findings can support the identification of high-risk individuals, improve early fibrosis and cirrhosis prediction, guide monitoring and preventive interventions, and support public health elimination goals.

Dataset Information

Differential gene expression, irrespective of circulating Hepatitis B Surface Antigen levels, between Inactive Carrier and Nucleos(t)ide Analogue-Treated Hepatitis B Virus patients.

Publications

Differential gene expression, irrespective of circulating Hepatitis B Surface Antigen levels, between Inactive Carrier and Nucleos(t)ide Analogue-Treated Hepatitis B Virus patients.

Similar Datasets

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