Ming-Wei Lai1,2,3, Chao-Wei Hsu2,3, Chih-Lang Lin2,4, Rong-Nan Chien2,4, Wey-Ran Lin2,3, Chi-Sheng Chang2, Kung-Hao Liang2,5, Chau-Ting Yeh6,7. 1. Division of Pediatric Gastroenterology, Department of Pediatrics, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan City, Taiwan. 2. Liver Research Center, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan City, Taiwan. 3. Molecular Medicine Research Center, College of Medicine, Chang Gung University, Taoyuan City, Taiwan. 4. Liver Research Unit, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan. 5. Medical Research Department, Taipei Veterans General Hospital, Taipei, Taiwan. 6. Liver Research Center, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan City, Taiwan. chautingy@gmail.com. 7. Molecular Medicine Research Center, College of Medicine, Chang Gung University, Taoyuan City, Taiwan. chautingy@gmail.com.
Abstract
BACKGROUND: Seroclearance of hepatitis B surface antigen (HBsAg) has been rarely achieved in the treatment of chronic hepatitis B (CHB) patients. We administered HBsAg-based recombinant vaccine in patients with low HBsAg concentrations. METHODS: Twenty hepatitis B e antigen-negative patients, with HBsAg < 1000 IU/ml, were enrolled. Vaccines were administered every 8 weeks for 48 weeks (seven doses). HBsAg levels and anti-HBs were assayed longitudinally until 48 weeks post-vaccination. HLA genotyping and cDNA microarray were performed to search for response predictors. RESULTS: Nineteen patients completed the study. At the end of vaccination, HBsAg declined significantly (Δ = - 0.27 ± 0.49 log IU/ml, p = 0.0005). The annual decline rate was significantly greater than that of an age-, gender-, and baseline HBsAg-matched control group (Δ = - 0.18 ± 0.46 versus + 0.11 ± 0.42 log IU/ml/year; p = 0.0229). Two patients achieved HBsAg seroclearance. Fourteen had significant HBsAg decline (Δ = - 0.64 ± 0.88 log IU/ml). No significant adverse events occurred during the trial. cDNA microarray identified the top up- and down-regulated genes in responders as HLA-DQ and HLA-DMB, respectively. HLA genotyping identified HLA-DQB1*04, HLA-DRB1*04, and HLA-B*40 as predictors for non-response (p = 0.0499, 0.0152, and 0.0314, respectively). CONCLUSIONS: In low-level HBsAg CHB patients, serial HBsAg-based vaccinations were safe, resulting in significant HBsAg decline. HLA gene expression and genotypes played a role in vaccine responsiveness (ClinicalTrials.gov Identifier: NCT01817725).
BACKGROUND: Seroclearance of hepatitis B surface antigen (HBsAg) has been rarely achieved in the treatment of chronic hepatitis B (CHB) patients. We administered HBsAg-based recombinant vaccine in patients with low HBsAg concentrations. METHODS: Twenty hepatitis B e antigen-negative patients, with HBsAg < 1000 IU/ml, were enrolled. Vaccines were administered every 8 weeks for 48 weeks (seven doses). HBsAg levels and anti-HBs were assayed longitudinally until 48 weeks post-vaccination. HLA genotyping and cDNA microarray were performed to search for response predictors. RESULTS: Nineteen patients completed the study. At the end of vaccination, HBsAg declined significantly (Δ = - 0.27 ± 0.49 log IU/ml, p = 0.0005). The annual decline rate was significantly greater than that of an age-, gender-, and baseline HBsAg-matched control group (Δ = - 0.18 ± 0.46 versus + 0.11 ± 0.42 log IU/ml/year; p = 0.0229). Two patients achieved HBsAg seroclearance. Fourteen had significant HBsAg decline (Δ = - 0.64 ± 0.88 log IU/ml). No significant adverse events occurred during the trial. cDNA microarray identified the top up- and down-regulated genes in responders as HLA-DQ and HLA-DMB, respectively. HLA genotyping identified HLA-DQB1*04, HLA-DRB1*04, and HLA-B*40 as predictors for non-response (p = 0.0499, 0.0152, and 0.0314, respectively). CONCLUSIONS: In low-level HBsAg CHB patients, serial HBsAg-based vaccinations were safe, resulting in significant HBsAg decline. HLA gene expression and genotypes played a role in vaccine responsiveness (ClinicalTrials.gov Identifier: NCT01817725).
Entities:
Keywords:
Hepatitis B virus; Human leukocyte antigen; Surface antigen clearance; Therapeutic vaccine; Vaccine
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