Published online Jan 27, 2022. doi: 10.4254/wjh.v14.i1.260
Peer-review started: May 15, 2021
First decision: July 8, 2021
Revised: July 10, 2021
Accepted: December 31, 2022
Article in press: December 31, 2021
Published online: January 27, 2022
The combination of various laboratory methods with histopathological findings is not always adequate to predict the progression and treatment response in patients with chronic viral B hepatitis (CHB). Therefore, efforts are being made to determine new parameters that may be useful in the follow-up of the disease.
It has been reported that differences in intracytoplasmic hepatitis B surface antigen (HBsAg) staining patterns are associated with viremia and active inflammation in CHB. However, HBsAg expression was evaluated semiquantitatively in these studies, and different classifications were used for the HBsAg staining pattern.
To investigate the relationship between image analysis-based quantitation of HBsAg expression and staining patterns with clinicopathological factors and treatment.
The study group consisted of 140 patients who were followed up and treated after the diagnosis of CHB. All cases were treated with entecavir. The evaluation of immunohistochemical HBsAg staining was performed in whole tissue sections by image analysis and expressed as a percentage of HBsAg staining (p-HBsAg). The staining pattern was also evaluated separately according to 3 different previously defined classifications. The correlations among immunohistochemical and clinicopathological findings were analyzed by χ2 and t-tests. The log-rank test was employed for comparisons of response rates. A Cox proportional hazards regression model was applied for multivariate analysis. Spearman’s correlation test was used to determine relationships between p-HBsAg and the other continuous variables.
There was a positive correlation between p-HBsAg and the serum levels of hepatitis B virus (HBV) DNA and HBsAg. The p-HBsAg was significantly higher in younger patients than in older patients, and the mean p-HBsAg level was significantly higher in the HBeAg-negative group than in the HBeAg-positive group. In the HBeAg-positive group, the average p-HBsAg level was significantly higher in patients with higher HBV DNA values than in those with low HBV DNA levels. Furthermore, an inverse relationship was noted between p-HBsAg and either hepatitis activity index (HAI) or the fibrosis score. Regarding staining pattern, diffuse cytoplasmic staining in many discrete hepatocytes was higher among cases with higher HBV DNA levels, and their number decreased among patients with HAI ≥ 9. However, submembranous staining was more frequent in subjects with higher HAI and fibrosis scores. In the same group, the p-HBsAg and HBsAg expression patterns were correlated with the viral response (VR) and serological response (SR). Multivariate analysis revealed that p-HBsAg was an independent factor associated with VR and SR. In the HBeAg-negative group, no correlation was observed between either the p-HbsAg or the membranous staining pattern and HBV DNA, HAI, or fibrosis. Diffuse staining was more frequent in cases with a higher level of HBV DNA. On the other hand, globular staining was rarely observed in these cases. In this group, the most valuable determinant of VR was the HAI score.
We have demonstrated that the expression pattern of HBsAg shows lower clinical significance in predicting the response to therapy than the percentage of HBsAg expression. Therefore, the quantitative evaluation of HBsAg expression in pretreatment-naïve liver biopsies of patients with CHB may predict the response to antiviral therapy, especially in cases with HBeAg positivity.
The evaluation of HBsAg expression by image analysis in pretreatment-naïve liver biopsies may be a valuable tool to predict the response to antiviral therapy. However, our findings should be supported by additional large-scaled studies.