Intrahepatic distribution of hepatitis B virus antigens in patients with and without hepatocellular carcinoma

Safaie, Parham; Poongkunran, Mugilan; Kuang, Ping-Ping; Javaid, Asad; Jacobs, Carl; Pohlmann, Rebecca A.; Nasser, Imad; Lau, Daryl

doi:10.3748/wjg.v22.i12.3404

Cited by 10 publications

(14 citation statements)

References 49 publications

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“…As regards intrahepatic HBcAg immunostaining, our series showed exclusively localization within hepatocyte nuclei which contrasted with previous reports where it had been observed both in nuclear and cytoplasmic locations . In spite of this intracellular distribution disagreement, the previously reported association between higher HAI severity and HBcAg expression was also noticed.…”

Section: Discussioncontrasting

confidence: 99%

“…In the present study, two different patterns of intracellular HBsAg expression have been observed: presence of HBsAg in clusters of hepatocytes or as single cells, each of these with a distinctive intracytoplasmic antigen distribution. This result is in line with previous reports, however, contrary to what has been suggested in other studies, where a membranous pattern of staining turned out to be associated with active viral replication and disease activity, in our cohort, the HBsAg pattern expression was not associated with any of the clinical, virological or histological features analysed.…”

Section: Discussionsupporting

confidence: 89%

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Chronic hepatitis B: The interplay between intrahepatic lymphocyte population and viral antigens in relation to liver damage

Giadans

Rios

Ameigeiras

et al. 2019

Journal of Viral Hepatitis

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In Chronic hepatitis B (CHB) infection, virus and immune response interplay is thoughtto be responsible for pathogenesis. Yet, the impact of each immune cell population and viral protein expression in liver damage is still unknown. Our aim was to study the interplay between intrahepatic immune response and viral activity in relation to CHB liver damage. Immunostaining was performed in 29 liver biopsies from untreated CHB patients to characterize liver infiltrate [Th (CD4+), CTL (CD8+), Treg (FoxP3+), Th17 (IL-17A+) and Th1 (T-bet+)] and viral antigen expression (HBsAg and HBcAg).Inflammatory activity and fibrosis were assessed using the HAI and METAVIR scoring system. All studied populations were identified in the portal-periportal (P-P) areas with a CD4+ lymphocyte predominance, while only CD8+ and FoxP3+ cells were observed in the intralobular area. Both P-P CD4+ and intralobular CD8+ cell frequencies were increased among severe hepatitis cases. Concerning HBsAg and HBcAg expression, a mutually exclusive pattern was observed. HBcAg was mainly detected among HBeAg-positive patients and was associated with hepatitis severity and higher frequency of P-P FoxP3+, intralobular CD8+ and FoxP3+ cells. HBsAg was identified among HBeAg-negative cases with less severe hepatitis grade and lower frequency of P-P CD4+ and intralobular FoxP3+ lymphocytes. In conclusion, the HBV antigen profile expression seen during CHB infection may be reflecting different stages of viral replication which impacts the host immune response and liver damage process. While HBcAg might be an inducer of a regulatory microenvironment, the intralobular CTL population seemed to have a key role in hepatitis severity. K E Y W O R D Schronic hepatitis B, inflammatory infiltrate, liver damage, viral antigen

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 89%

Chronic hepatitis B: The interplay between intrahepatic lymphocyte population and viral antigens in relation to liver damage

Giadans

Rios

Ameigeiras

et al. 2019

Journal of Viral Hepatitis

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“…The HBV-infected liver contains a mosaic of hepatocytes expressing HBV antigens in different quantities and localizations (23–25) and from different sources (cccDNA or HBV DNA integration) (26). Here, we analyzed, to our knowledge for the first time, not the distribution of HBV proteins but that of HLA class I/HBV peptide complexes within the hepatic parenchyma.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, although HLA class I/HBV peptide complexes can be directly visualized on liver biopsy specimens of chronically infected patients (17, 18), knowledge related to the efficiency and kinetics of the generation of HLA class I/HBV peptide complexes in chronic HBV (CHB)-infected livers is limited (19, 20). Studies investigating the localization of HBV-infected hepatocytes in the liver of patients with chronic hepatitis B showed a complex mosaic of cells expressing HBV antigens at different levels and localizations (21, 22) and with broad differences in the ratio between HBV surface antigen (HBsAg) and covalently closed circular DNA (cccDNA) levels (23–25). This differential antigenic expression is likely caused by the concomitant presence of hepatocytes infected with HBV for different durations and/or the production of HBV antigens from either integrated HBV DNA or cccDNA (25, 26).…”

Section: Introductionmentioning

confidence: 99%

Spatiotemporal Differences in Presentation of CD8 T Cell Epitopes during Hepatitis B Virus Infection

Khakpoor

Chen

et al. 2019

J Virol

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The inability of patients with chronic HBV infection to clear HBV is associated with defective HBV-specific CD8+ T cells. Hence, the majority of immunotherapy developments focus on HBV-specific T cell function restoration. However, knowledge of whether distinct HBV-specific T cells can equally target all the HBV-infected hepatocytes of a chronically infected liver is lacking. In this work, analysis of CHB patient liver parenchyma and in vitro HBV infection models shows a nonuniform distribution of HBV CD8+ T cell epitopes that is influenced by the presence of IFN-γ and availability of newly translated viral antigens. These results suggest that CD8+ T cells recognizing different HBV epitopes can be necessary for efficient immune therapeutic control of chronic HBV infection.

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“…Las proteínas del VHB incluyen la proteína del core de la nucleocápside (HBcAg), la proteína de envoltura o superficie (HBsAg), y la proteína soluble de la nucleocápside (HBeAg). (1) Diferentes marcadores subrogados que correlacionan con la clínica son usados en la práctica clínica para monitorear y predecir la progresión de la enfermedad. El HBsAg es el principal marcador de infección por VHB, es detectable 1 a 2 semanas después de la exposición y su eliminación del torrente sanguíneo, que ocurre en muy pocos casos, se considera signo de eliminación del virus.…”

Section: Introductionunclassified

Validación de un inmunoensayo tipo ELISA para la cuantificación de los niveles séricos de antígeno de superficie en pacientes con infección crónica por virus de la hepatitis B.

et al. 2017

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Introducción: Durante la etapa aguda de la infección por el virus de la hepatitis B y el período inicial de una infección crónica, el DNA está en forma episomal (libre o extracromosomal) y replica en el hepatocito produciendo entre otros viriones infectivos, DNA polimerasa y antígeno de superficie del virus (HBsAg). Objetivo: Validar un inmunoensayo tipo ELISA para cuantificar los niveles de HBsAg en pacientes con hepatitis B crónica. Método: Se realizó un estudio experimental de desarrollo tecnológico. Se llevó a cabo la normalización y validación de un inmunoensayo enzimático heterogéneo de doble anticuerpo para la cuantificación de HBsAg en sueros humanos. 115 muestras de sueros de pacientes con hepatitis B crónica con resultados de carga viral se correlacionaron con las concentraciones de HBsAg. Resultados y discusión: El método presentó coeficientes de variación intra e interensayo de 9,8 y 13,2% respectivamente. El rango de trabajo se estimó entre 0.15 y 60ng/mL. El porcentaje de recuperación estuvo entre el 90 y 110% y el ajuste lineal de la curva estándar presentó un coeficiente de determinación superior a 0,99. La correlación alcanzada entre los niveles de DNA y la concentración de HBsAg fue de 62.5%. Conclusiones: La evaluación del ELISA para la cuantificación de HBsAg desarrollado en el laboratorio mostró que cumple los parámetros de validación para su uso clínico.

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Intrahepatic distribution of hepatitis B virus antigens in patients with and without hepatocellular carcinoma

Cited by 10 publications

References 49 publications

Chronic hepatitis B: The interplay between intrahepatic lymphocyte population and viral antigens in relation to liver damage

Chronic hepatitis B: The interplay between intrahepatic lymphocyte population and viral antigens in relation to liver damage

Spatiotemporal Differences in Presentation of CD8 T Cell Epitopes during Hepatitis B Virus Infection

Validación de un inmunoensayo tipo ELISA para la cuantificación de los niveles séricos de antígeno de superficie en pacientes con infección crónica por virus de la hepatitis B.

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