Clinical significance and evolution of hepatic HBsAg expression in HBeAg-positive patients receiving interferon therapy
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Serum hepatitis B surface antigen (HBsAg) level is important in the management of chronic hepatitis B (CHB). However, it is unclear whether serum HBsAg reflects its expression in liver and the hepatic HBsAg evolution following interferon therapy.
Forty-five HBeAg-positive CHB patients receiving interferon-based therapy within a randomized, controlled, multicenter study during 1998–1999 were included. The hepatic HBsAg expressions were categorized into cytoplasmic, inclusion, marginal and negative patterns by immunohistochemical staining. The HBsAg-positive hepatocytes were quantified by image-based cytometry and correlated to HBV serological and virological profiles for clinical implications. The evolution of hepatic HBsAg levels was analyzed among 22 patients with paired liver biopsies before and after interferon therapy, sequentially.
There was a positive correlation between pretreatment serum HBsAg and hepatic HBsAg levels (r = 0.67, P < 0.0001). The hepatic HBsAg expression pattern significantly evolved from cytoplasmic/inclusion pattern to marginal/negative pattern after interferon treatment. The serum HBV-DNA, HBsAg and hepatic HBsAg levels all decreased significantly after interferon therapy. Among 36 % patients with HBeAg loss after therapy, pretreatment hepatic HBsAg levels were significantly lower compared with those without HBeAg loss. After multivariate analysis, low pretreatment hepatic HBsAg levels rather than serum HBsAg titers were associated with a higher rate of HBeAg loss (OR: 4.97, 95 % CI: 1.12–22.00, P = 0.035).
The serum HBsAg level positively reflects the HBsAg level in liver which evolves significantly after interferon therapy. A lower hepatic HBsAg level is associated with HBeAg loss after interferon treatment. Hepatic HBsAg may have clinical significance in CHB patients receiving interferon treatment.
KeywordsCytometry Hepatitis B Hepatitis B surface antigen Histology Immunohistochemical staining
Hepatitis B surface antigen
Chronic hepatitis B
Histology activity index
We thank Mr. Ju-Yi Tsai from, Cell-Bio Biotechnology Company, Taiwan for his technical support on TissueFAX Plus cytometry. We also thank the fourth Core Laboratory of the Department of Medical Research, National Taiwan University Hospital for technical assistance. This work was supported by grants from the National Taiwan University Hospital (NTUH 100-S1914), the Department of Health, and the National Science Council, Executive Yuan, Taiwan.
Conflict of interest
Jia-Horng Kao: Consultant for Abbott, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, Omrix, Roche; on speaker’s bureau for Abbott, Roche, Bayer, Bristol-Myers Squibb, GlaxoSmithKline, Novartis; Ding-Shinn Chen: Consultant for Novartis and GlaxoSmithKline; Pei-Jer Chen: Consultant for Gilead Sciences, Novartis and Roche; All other authors declare no competing interests.
- 3.Tseng TC, Liu CJ, Su TH, Wang CC, Chen CL, Chen PJ, et al. Serum hepatitis B surface antigen levels predict surface antigen loss in hepatitis B e antigen seroconverters. Gastroenterology. 2011;141:517–25, 525.e1-2.Google Scholar
- 4.Tseng TC, Liu CJ, Yang HC, Su TH, Wang CC, Chen CL, et al. High levels of hepatitis B surface antigen increase risk of hepatocellular carcinoma in patients with low HBV load. Gastroenterology. 2012;142:1140–1149.e3; quiz e13-4.Google Scholar
- 6.Su TH, Liu CJ, Tseng TC, Liu CH, Yang HC, Chen CL, et al. Longitudinal Change of HBsAg in HBeAg-negative Patients with Genotype B or C Infection. PLoS One. 2013;8:e55916.Google Scholar