HBsAg expression of liver correlates with histological activities and viral replication in chronic hepatitis B

Cheng, Pin-Nan; Chiu, Yen-Cheng; Tsai, Hung‐Wen; Wang, Ru-Hsueh; Chiu, Hung-Chih; Wu, I‐Chin; Chang, Ting‐Tsung

doi:10.1016/s1665-2681(19)30979-2

Cited by 7 publications

(9 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Almost all the untreated CHB patients harbored HBsAg-negative hepatocytes in their livers, and the distribution of HBsAg-positive cells was scattered or clustered ( Fig. 6A ), which was consistent with previous reports 12 13 14 . The frequency of HBsAg-positive hepatocytes was positively correlated with serum HBV DNA and HBsAg levels in treatment-naïve CHB patients ( Fig.…”

Section: Resultssupporting

confidence: 92%

Sodium taurocholate cotransporting polypeptide inhibition efficiently blocks hepatitis B virus spread in mice with a humanized liver

Nakabori

Murai

Nozaki

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Sodium taurocholate cotransporting polypeptide (NTCP) is a recently discovered hepatitis B virus (HBV) receptor. In the present study, we used TK-NOG mice with a humanized liver to examine the impact of endogenous NTCP expression on HBV infection. Upon inoculation with HBV, these mice exhibited clear viremia in 2 weeks, and serum HBV DNA levels gradually increased. The frequency of HBsAg-positive hepatocytes in the liver was 5.1 ± 0.6% at 2 weeks and increased with increasing HBV DNA levels, reaching 92.9 ± 2.8% at 10 to 12 weeks. In vivo siRNA-mediated NTCP knockdown before and after HBV inoculation significantly suppressed the levels of HBV replication and the frequency of HBsAg-positive hepatocytes at 2 weeks, whereas NTCP knockdown 13 weeks after infection did not affect these parameters. Similar to the humanized mouse livers in the early phase of HBV infection, human liver samples from chronic hepatitis B patients, especially those treated with nucleos(t)ide analogues, contained a considerable number of hepatocytes that were negative for the anti-HBs antibody. In conclusion, NTCP inhibition prevents the spread of HBV-infected hepatocytes in mice with a humanized liver. NTCP-targeted therapy has potential for regulating HBV infection in patients with chronic hepatitis B.

show abstract

Section: Resultssupporting

confidence: 92%

Sodium taurocholate cotransporting polypeptide inhibition efficiently blocks hepatitis B virus spread in mice with a humanized liver

Nakabori

Murai

Nozaki

et al. 2016

Sci Rep

View full text Add to dashboard Cite

show abstract

“…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%

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

View full text Add to dashboard Cite

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

show abstract

“…In some studies, serum HBsAg levels were reported to be higher in HBeAg-positive patients [5,13]. Parallel to this, we also observed that HBeAg-positive patients had a higher mean serum HBsAg level than HBeAg-negative patients, but the difference was NS.…”

Section: Discussionsupporting

confidence: 86%

“…Cheng et al . [13], similarly reported that HBsAg expression was higher in patients with HAI ≥ 5 in their study. In a study conducted in Turkey, Başoda [14] evaluated patients in three HAI groups (0–4, 5–9 and 10–18) and observed no difference between groups in terms of HBsAg level.…”

Section: Discussionmentioning

confidence: 60%

The performance of hepatitis B surface antigen quantification as a noninvasive biomarker predicting liver injury and serum hepatitis B virus DNA level

Abdullayeva,

Çelik,

Kuruüzüm

2023

European Journal of Gastroenterology &Amp; Hepatology

View full text Add to dashboard Cite

Objectives Chronic hepatitis B (CHB) is still a major public health problem worldwide. Recently, evidence indicating that serum hepatitis B surface antigen (HBsAg) quantification can be used for monitorization of hepatitis B virus (HBV) infection has been increased. In this study, we evaluated HBsAg levels during the natural course of CHB and identified correlations between HBsAg, HBV DNA levels and liver histopathology. Methods From 6 August 2016 to 7 June 2017, naive patients, who are ≥18 years old, fulfilled the criteria for the diagnosis of CHB and had a liver biopsy within a year before or after admission, were included. HBsAg levels in serum samples were investigated by electrochemiluminescence immunoassay. Results were correlated with serum HBV DNA levels, histologic activity index (HAI) and fibrosis scores. Results In this study 66 patients were included. There was a moderate and significant correlation between HBsAg levels and fibrosis scores (r = 0.386, P = 0.001), but no correlation with HAI. Serum HBsAg levels showed a positive, strong and significant (r = 0.740, P < 0.001) correlation with HBV DNA levels. In hepatitis B e antigen-negative patients, serum HBsAg levels were perfectly correlated with HBV DNA levels (r = 0.992, P < 0.001) and moderately correlated with fibrosis scores (r = 0.360, P = 0.006). Conclusion We found a positive correlation between serum HBsAg levels and the severity of fibrosis scores and serum HBV DNA levels. These findings suggest that serum HBsAg quantification might be a useful noninvasive diagnostic test for the prediction of fibrosis severity and HBV DNA level.

show abstract

HBsAg expression of liver correlates with histological activities and viral replication in chronic hepatitis B

Cited by 7 publications

References 31 publications

Sodium taurocholate cotransporting polypeptide inhibition efficiently blocks hepatitis B virus spread in mice with a humanized liver

Sodium taurocholate cotransporting polypeptide inhibition efficiently blocks hepatitis B virus spread in mice with a humanized liver

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

The performance of hepatitis B surface antigen quantification as a noninvasive biomarker predicting liver injury and serum hepatitis B virus DNA level

Contact Info

Product

Resources

About