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HBsAg as an important predictor of HBeAg seroconversion following antiviral treatment for HBeAg-positive chronic hepatitis B patients.

ABSTRACT: BACKGROUND: Serum quantitative hepatitis B surface antigen (HBsAg) levels may be an important predictor of hepatitis B e antigen (HBeAg) seroconversion (SC) in HBeAg-positive chronic hepatitis B (CHB) patients during antiviral treatment. The pattern of HBsAg variation in CHB patients either with or without SC following tenofovir disoproxil fumarate (TDF) treatment is not clearly understood. METHODS: Twenty patients with full experimental data were enrolled, and liver biochemistry, serum HBV DNA, and circulating CD4+CD25+ regulatory T cell (Treg) levels were determined at baseline and every 12 weeks after the initiation of TDF treatment (for a total of 96 weeks). In addition, the relationship between HBsAg or HBeAg and alanine aminotransferase (ALT), HBV DNA and Treg levels in SC and non-SC patients was analyzed. RESULTS: In all, 9 patients had undergone HBeAg seroconversion by week 72 of TDF treatment, and biochemical and virological indexes and Treg percentages declined to normal levels. Furthermore, the positive correlation between HBsAg and ALT, HBV DNA and Treg levels was significant for SC patients, but not for non-SC patients. However, for HBeAg, significant positive correlations were or not observed for both SC and non-SC patients. CONCLUSIONS: The quantitation of HBsAg is a more useful indicator than HBeAg for distinguishing SC and non-SC patients during TDF treatment. Moreover, HBsAg may be related to immune regulatory property of CHB patients during antiviral treatment.

SUBMITTER: Yang J

PROVIDER: S-EPMC4230803 | biostudies-other | 2014

REPOSITORIES: biostudies-other

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HBsAg as an important predictor of HBeAg seroconversion following antiviral treatment for HBeAg-positive chronic hepatitis B patients.

Yang Jiezuan J Chen Jiajia J Ye Ping P Jin Linfeng L Wu Wei W Sheng Guoping G Li Lan-Juan LJ

Journal of translational medicine 20140625

<h4>Background</h4>Serum quantitative hepatitis B surface antigen (HBsAg) levels may be an important predictor of hepatitis B e antigen (HBeAg) seroconversion (SC) in HBeAg-positive chronic hepatitis B (CHB) patients during antiviral treatment. The pattern of HBsAg variation in CHB patients either with or without SC following tenofovir disoproxil fumarate (TDF) treatment is not clearly understood.<h4>Methods</h4>Twenty patients with full experimental data were enrolled, and liver biochemistry, s ...[more]

PMID: 24962263

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Project description:As alternative indexes of hepatitis B virus (HBV), covalently closed circular DNA (cccDNA) transcriptional activity, hepatitis B surface antigen (HBsAg), hepatitis B core-related antigen (HBcrAg), and peripheral blood RNA known as pgRNA, have been advocated as novel serum markers for prediction of prognosis and treatment response in chronic hepatitis B (CHB). Since the availability of commercial quantitative assays of HBsAg in 2011, HBsAg has been widely used for predicting treatment response of patients with CHB. Patients who received interferon therapy have shown a sharper reduction of HBsAg level than those who received nucleoside drug (NAs) therapy. Upon peginterferon treatment, sustained responders have presented a larger reduction of HBsAg level than the non-responders. An absence of HBsAg decline, together with < 2log reduction in HBV DNA at week 12, can serve as a stopping rule in HBsAg-negative patients infected with genotype D HBV. A sharp reduction of HBsAg titer in the NAs therapy is a predictor of HBsAg clearance in long-term treatment. HBcrAg, which consists of three species of related proteins sharing an identical 149 amino acid sequence, including HbcAg, hepatitis B e antigen (HBeAg), and a truncated 22-kDa precore protein, is still detectable in situations where serum HBV DNA levels become undetectable or HBsAg loss is achieved. Therefore, HBcrAg remains a measurable serum marker to correlate with cccDNA in this situation. The decline in HBcrAg has been observed with NAs therapy and the pattern of decline might provide prognostic information on the risk of HBV post-treatment reactivation. Peripheral blood RNA, which is known as pgRNA, directly derives from cccDNA and reflects intrahepatic cccDNA level. Quantitative pgRNA has been suggested to be helpful in CHB management. However, commercial quantitative assays are lacking. Additionally, the use of simultaneous and continuous clearance of HBV RNA and HBV DNA in serum has been suggested to be a safe stopping rule of NAs therapy for patients with CHB. However, clinical studies of large sample sizes are needed to prove the feasibility and significance of using serum HBV RNA as the assessment standard of antiviral therapy in CHB and the safety of the stopping rule in clinics.

Project description:AimTo evaluate the effect of single nucleotide polymorphisms of interleukin (IL)-28B, rs12979860 on progression and treatment response in chronic hepatitis C.MethodsPatients (n = 64; 37 men, 27 women; mean age, 44 ± 12 years) with chronic hepatitis C, genotype 1, received treatment with peg-interferon plus ribavirin. Genotyping of rs12979860 was performed on peripheral blood DNA. Histopathological assessment of necroinflammatory grade and fibrosis stage were scored using the METAVIR system on a liver biopsy sample before treatment. Serum viral load, aminotransferase activity, and insulin level were measured. Insulin resistance index, body mass index, waist/hip ratio, percentage of body fat and fibrosis progression rate were calculated. Applied dose of interferon and ribavirin, platelet and neutrophil count and hemoglobin level were measured.ResultsA sustained virological response (SVR) was significantly associated with IL28B polymorphism (CC vs TT allele: odds ratio (OR), 25; CC vs CT allele: OR, 5.4), inflammation activity (G < 1 vs G > 1: OR, 3.9), fibrosis (F < 1 vs F > 1: OR, 5.9), platelet count (> 200 × 10(9)/L vs < 200 × 10(9)/L: OR, 4.7; OR in patients with genotype CT: 12.8), fatty liver (absence vs presence of steatosis: OR, 4.8), insulin resistance index (< 2.5 vs > 2.5: OR, 3.9), and baseline HCV viral load (< 10(6) IU/mL vs > 10(6) IU/mL: OR, 3.0). There was no association with age, sex, aminotransferases activity, body mass index, waist/hip ratio, or percentage body fat. There was borderline significance (P = 0.064) of increased fibrosis in patients with the TT allele, and no differences in the insulin resistance index between groups of patients with CC, CT and TT alleles (P = 0.12). Spearman's rank correlation coefficient between insulin resistance and stage of fibrosis and body mass index was r = 0.618 and r = 0.605, respectively (P < 0.001). Significant differences were found in the insulin resistance index (P = 0.01) between patients with and without steatosis. Patients with the CT allele and absence of a SVR had a higher incidence of requiring threshold dose reduction of interferon (P = 0.07).ConclusionIL28B variation is the strongest host factor not related to insulin resistance that determines outcome of antiviral therapy. Baseline platelet count predicts the outcome of antiviral therapy in CT allele patients.

Project description:PurposeThe purpose of this study was to investigate immunological variations between a group that received the hepatitis B vaccine and a non-vaccine group. We focused on a cohort that achieved HBsAg seroclearance after Peg-IFNα treatment of CHB.MethodsWe enrolled twenty-eight individuals who achieved HBsAg seroclearance after Peg-IFNα treatment. They were divided into two groups: a vaccine group (n = 14) and a non-vaccine group (n = 14). We assessed lymphocyte subpopulations, B cell- and T cell-surface costimulatory/inhibitory factors, cytokines and immunoglobulin levels were detected at different time points to explore immune-function differences between both groups.ResultsThe seroconversion rate in the vaccine group at 24 weeks post-vaccination was 100%, which was significantly higher (p = 0.006) than that of the non-vaccine group (50%). Additionally, more individuals in the vaccine group exhibited anti-HBs levels exceeding 100 IUs/L and 300 IUs/L compared to the non-vaccine group (p < 0.05). The vaccine group demonstrated significantly increase total B cells and class-switched B cells at 24 weeks and plasma cells, CD80+B cells, Tfh cells, and ICOS+Tfh cell at 12 weeks, compared with baseline levels (p < 0.05). Conversely, Bregs (CD24+CD27+ and CD24+CD38high) decreased significantly at 24 weeks (p < 0.05). None of the above changes were statistically significance in the non-vaccine group (p > 0.05). Total IgG increased significantly in the vaccine group, and IL-2, IL-5, and IL-6 concentrations increased significantly at week 24 (p < 0.05). Differences in various types of cytokines and immunoglobulins in the plasma of the non-vaccine group were not significant (p > 0.05). Anti-HBs titers positively correlated with Th1/Th2 cells at 24 weeks (r = 0.448 and 0.458, respectively, p = 0.022 and 0.019, respectively), and negatively with CD24+CD38highBreg cells (r = -0.402, p = 0.042).ConclusionsAfter achieving HBsAg seroclearance through Peg-IFNα treatment for CHB, administering the hepatitis B vaccine significantly increased anti-HBs-seroconversion rates and antibody levels. We also observed significant immunological differences between the vaccine and non-vaccine groups. Specifically, the vaccine group exhibited significant increases in B cells, plasma cells, and Tfh cells, while Breg levels was significantly lower. These immunological changes are likely conducive to the production of anti-HBs antibodies. However, in the non-vaccine group, the observed changes were not significantlly significant.

Dataset Information

HBsAg as an important predictor of HBeAg seroconversion following antiviral treatment for HBeAg-positive chronic hepatitis B patients.

Publications

HBsAg as an important predictor of HBeAg seroconversion following antiviral treatment for HBeAg-positive chronic hepatitis B patients.

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