Drug selection for simultaneous treatment of tuberculosis combined with hepatitis C virus infection / 中华肝脏病杂志

Clinically, patients with tuberculosis (TB) combined with hepatitis C virus (HCV) infection often require simultaneous treatment. Consequently, when anti-HCV and TB drugs are used in combination drug-drug interactions (DDIs), anti-TB drug-induced hepatotoxicity, and liver disease states need to be considered. This paper focuses on discussing the metabolic mechanisms of commonly used anti-TB and HCV drugs and the selection options of combined drugs, so as to provide rational drug use for TB patients combined with HCV infection.

Characteristics of CDR3 of TCR beta on CD8+ T cells in chronic hepatitis B patients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To analyze the characteristics of CDR3 of TCRbeta on CD8+ T cells in chronic hepatitis B patients.</p><p><b>METHODS</b>Eight patients with chronic hepatitis B (ALT more than 2 ULN) were enrolled in this study. CD8+ T cells were isolated from peripheral blood. RT-PCR was proformed to amplify the CDR3 of TCRbeta, and the PCR products were sequenced and analyzed.</p><p><b>RESULTS</b>The chronic hepatitis B patients showed obvious clonal expansion of T cell, and three perturbation patterns of T cell expansion were showed in the CDR3 of TCRbeta, including monoclonicity, oligoclonicity and skewed peak patterns. The number of perturbation families of CD8+ subpopulation was significantly higher than that of CD8- subpopulation (10.6+/-4.7 vs. 4.1+/-3.1, t = 6.619, P less than 0.01). In 3 out of 8 patients, the number of perturbation families of CD8+ subpopulation was also higher than that of PBMCs without depleting CD8+ subpopulation.</p><p><b>CONCLUSIONS</b>The characteristics of CDR3 of TCRbeta may help to understand the inflammatory response in CHB patients.</p>

Characteristics of HBcAg(18-27) CTL epitopes of the main epidemic HBV strains in China / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the characteristics of the virology background of HLA-A2 restricted HBcAg(18-27) epitope mutations in HBV infected patients in China.</p><p><b>METHOD</b>30 HBV sequences with different genotypes from Genbank were analyzed by bioinformatics and the mismatched primers were designed for constructing a PCR-RFLP method to screen HBcAg(18-27)V/I in China. The distributions of HBcAg(18-27)V/I of 160 samples with HBV genotype B/C infection from 8 areas in China were screened and analyzed by PCR-RFLP and sequencing. The affinity of HBcAg(18-27)V/I to HLA-A0201 was analyzed through referencing the bioinformatics websites.</p><p><b>RESULTS</b>We successfully constructed a PCR-RFLP method for screening HBcAg(18-27)V/I from genotype B/C, and only 3 samples with HBcAg(18-27)V sequence were found in the 160 samples (3/160, 1.88%). The affinity of HBcAg(18-27)I to HLA-A 0201 was lower than the one of HBcAg(18-27)V through bioinformatic analysis (HLA ligand score was 123 vs 156, and the SYFPEITHI score was 22 vs 24).</p><p><b>CONCLUSION</b>The last amino acid of most HBcAg(18-27) sequences of epidemic HBV strains in China is isoleucine, and not valine. Therefore HBcAg(18-27) sequence background in different HBV genotypes should be thoroughly considered when using it as a reference or control in immunological research about HBV.</p>

Kinetics of HBV mutants conferring adefovir resistance (rtn236t) and a method to detect them rapidly / 中华肝脏病杂志

<p><b>OBJECTIVE</b>The aim was to build a PCR-RFLP method for detecting rtN236T mutants and to observe their kinetics in chronic hepatitis B (CHB) patients.</p><p><b>METHODS</b>Seven CHB patients who had suboptimal viral response or viral breakthrough under adefovir mono-therapy were studied. Part of the HBV reverse transcriptional gene from serial sera samples was sequenced with PCR products or cloned HBV DNA; mutations at rt236 were simultaneously analyzed by a PCR-RFLP assay. Genetic diversity of HBV was observed by calculating Hamming distance within domains B, C and D of RT.</p><p><b>RESULTS</b>Three patients had viral breakthrough and one with suboptimal viral response had adefovir-resistance mutants, one had rtA181V mutation and three had rtN236T mutation. A novel PCR-RFLP assay based on restriction enzyme HpaI or DraI for on the detection of rtN236T mutant was established, which detected 10% minor strains with 100% specificity. Mutants (rtA181V or rtN236T) appeared 0-8 months earlier than the viral breakthrough, then afterwards became the dominant ones. In one patient after stopping the adefovir therapy, 3 months later a wild type virus re-took again the mutant one (rtN236T); in one patient who developed a rt236T mutant after 132 weeks of adefovir treatment, a novel mutant (rtN236V) appeared and then became the dominant one while adefovir treatment continued.</p><p><b>CONCLUSIONS</b>A rapid and easy method was established to detect rtN236T mutants. Mutants for adefovir-resistance accumulated rapidly then became dominant, but they could be taken over again by a wild type or novel mutant HBV.</p>

Changes of serum HBsAg in HBeAg positive chronic hepatitis patients with sustained viral response to long-term lamivudine treatment / 中华肝脏病杂志

<p><b>OBJECTIVE</b>HBsAg loss is rare in chronic hepatitis B patients, even in the patients with long-term nucleos(t)ide analogue therapy; therefore information about serum HBsAg kinetics will be of value in understanding this unusual occurrence.</p><p><b>METHODS</b>Forty-five consecutive patients were studied, which were all HBeAg positive and never had antiviral therapy prior to lamivudine treatment; they then achieved rapid and good viral responses (defined as undetectable HBV DNA [Roche Lightcycler, less than 1000 copies/ml] at treatment week 24 and they remained so until week 156). Abbott Architect HBsAg assay was used to quantify serum HBsAg and HBV genotypes were determined by direct sequencing.</p><p><b>RESULTS</b>Twenty-six (57.8%) patients had HBeAg loss during the observation and one patient had HBsAg loss following his HBeAg seroconversion. Serum HBsAg levels decreased to 39.5% (median) of their baseline values at week 12, but no further significant reductions of serum HBsAg were found afterwards. Changes of serum HBsAg were comparable between patients with or without HBeAg loss. Serum HBsAg levels at their baselines were higher in HBV genotype B (HBV/B, n = 21) patients than in genotype C (HBV/C, n = 24) patients. HBV/B patients achieved many more HBsAg reductions than HBV/C ones (75.5 vs. 26.0%, median, P less than 0.05) in the first 12 treatment weeks, however HBsAg levels at week 156 were comparable between these two subgroups. HBsAg changes mainly showed two distinct patterns: a biphasic pattern (HBsAg levels were less than 60% of baseline ones at week 12 and 24, n = 25) and a maintaining pattern (HBsAg levels were greater than 80% of the baseline ones at week 12 and 24, n = 14). Logistic regression analysis showed that low serum HBsAg at baseline (odds ratio 0.020, 95% confidence interval 0.002-0.743, P less than 0.05) and HBV/C infection (odds ratio 8.206, 95% confidence interval 1.070-62.948, P less than 0.05) were the determinants of the occurrences of the maintaining pattern.</p><p><b>CONCLUSION</b>In patients we examined, their HBsAg changes were mainly presented as either a biphasic pattern or a maintaining pattern, which were associated with HBV genotypes (B/C) but not with HBeAg loss. This might explain that why HBsAg loss is a rare occurrence even with long-term lamivudine therapy.</p>

Distribution of hepatitis B virus genotype B subgenotype in China / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the distribution of hepatitis B virus (HBV) genotype B subgenotype in China.</p><p><b>METHODS</b>A cohort of 511 patients with chronic HBV genotype B infection, collected from 7 centers across China, were analyzed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or nucleotide sequencing.</p><p><b>RESULTS</b>For the 511 patients, only subgenotype Ba was identified and subgenotype Bj was not found.</p><p><b>CONCLUSION</b>In China, subgenotype Ba was the most prevalent HBV strains, while subgenotype Bj was very rarely found.</p>

Analysis of T cell receptor BV dominant usage and CDR3 sequences during acute exacerbation in patients with chronic hepatitis B / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To understand the role cellular immunology plays in the pathogenesis of chronic hepatitis B (CHB) through analysis of T cell receptor (TCR) beta chain variable region gene (BV) family dominant usage and beta chain complementarity determining region3 (CDR3) sequences of peripheral blood mononuclear cells of the patients.</p><p><b>METHODS</b>TCR BV families were amplified by inverse polymerase chain reaction (RT-PCR), and the dominant usage of BV families and CDR3 repertoire were analyzed by immunoscope technology for 8 CHB patients during their acute exacerbations and for 4 healthy blood donors who served as controls. The clonality of the T cells suspected by immunoscope was further confirmed by CDR3 sequencing.</p><p><b>RESULTS</b>The TCR BV CDR3 repertoire of the 4 healthy blood donors showed a Gaussian distribution. In the 8 CHB patients, however, the clonal expansion of T cells showed different TCR BV families with each patient. The T cells of the clonal expansion shared different CDR3 sequences.</p><p><b>CONCLUSION</b>The peripheral blood T cells of CHB patients during their acute exacerbation showed significantly a clonal expansion and their T cell clonal expansion may be stimulated by several HBV epitopes. These results indicate that cellular immunology is involved in the pathogenesis of the liver inflammation process of CHB.</p>