CSH guidelines for the diagnosis and treatment of drug-induced liver injury.

Drug-induced liver injury (DILI) is an important clinical problem, which has received more attention in recent decades. It can be induced by small chemical molecules, biological agents, traditional Chinese medicines (TCM), natural medicines (NM), health products (HP), and dietary supplements (DS). Idiosyncratic DILI is far more common than intrinsic DILI clinically and can be classified into hepatocellular injury, cholestatic injury, hepatocellular-cholestatic mixed injury, and vascular injury based on the types of injured target cells.

High serum IL-21 levels after 12 weeks of antiviral therapy predict HBeAg seroconversion in chronic hepatitis B.

Background & Aims: Interleukin-21 (IL-21) stimulates T cell and B cell responses and plays a role in control of chronic viral infections. The role of IL-21 in chronic hepatitis B virus (HBV) infection is not understood.

Methods: Serum IL-21 levels were measured by enzyme immunoassay in 75 HBeAg-positive chronic hepatitis B (CHB) patients undergoing telbivudine treatment.

[C gene-targeting short hairpin RNA suppresses the replication and expression of hepatitis B virus in BHK-21 cells].

Objective: The vaccines currently developed against infectious diseases fail to induce effective antiviral immune responses to control an abrupt outbreak of viral diseases epidemic in a short space of time. Hence there is an urgent need to develop emergency vaccines capable of producing prophylactic effects against infectious diseases. RNA interference (RNAi) is a mechanism that inhibits gene expression by causing the degradation of specific RNA molecules or hindering the transcription of specific genes.

Complementarity-determining region 3 size spectratypes of T cell receptor beta chains in CD8+ T cells following antiviral treatment of chronic hepatitis B.

An increased CD8(+) T cell response to hepatitis B virus (HBV) peptides occurs between 12 and 24 weeks after starting antiviral therapy for chronic hepatitis B. It is not known whether these cells have antiviral function. The aim of this study was to determine whether clonal expansions of CD8(+) T cells at these time points predict the virological response to therapy.

[Characteristics of CDR3 of TCR beta on CD8+ T cells in chronic hepatitis B patients].

Objective: To analyze the characteristics of CDR3 of TCRbeta on CD8+ T cells in chronic hepatitis B patients.

Methods: Eight patients with chronic hepatitis B (ALT more than 2 ULN) were enrolled in this study. CD8+ T cells were isolated from peripheral blood.

[Changes of serum HBsAg in HBeAg positive chronic hepatitis patients with sustained viral response to long-term lamivudine treatment].

Objective: 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.

Methods: 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.

[Characteristics of HBcAg(18-27) CTL epitopes of the main epidemic HBV strains in China].

Objective: To study the characteristics of the virology background of HLA-A2 restricted HBcAg(18-27) epitope mutations in HBV infected patients in China.

Method: 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.

[Kinetics of HBV mutants conferring adefovir resistance (rtn236t) and a method to detect them rapidly].

Objective: The aim was to build a PCR-RFLP method for detecting rtN236T mutants and to observe their kinetics in chronic hepatitis B (CHB) patients.

Methods: 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.

[Distribution of hepatitis B virus genotype B subgenotype in China].

Objective: To investigate the distribution of hepatitis B virus (HBV) genotype B subgenotype in China.

Methods: 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.

Results: For the 511 patients, only subgenotype Ba was identified and subgenotype Bj was not found.

[Affects of HBV genotypes (B/C) on the levels of serum and intrahepatic HBsAg].

Objective: To observe the effects of HBV genotypes on the level of HBsAg in serum and hepatocytes in chronic hepatitis B patients without antiviral therapy.

Methods: Seventy-six chronic hepatitis B inpatients were enrolled into this study, and liver biopsies and histologic diagnosis were performed, and serum samples were collected at the time point of liver biopsy. PCR-RFLP method was adopted to determine the genotype of hepatitis B virus and Abbott Architect HBsAg assay was used to quantify the serum HBsAg.

Analysis of the CDR3 length of TCR alphabeta T cells in the peripheral blood of patients with chronic hepatitis B.

To clarify the characteristics of TCR alphabeta T cells in the peripheral blood of patients with chronic hepatitis B (CHB), we investigated the patterns of Complementarity Determining Region3 (CDR3) length distribution for all 24 TCR BV gene families and 32 TCR AV gene family in the peripheral blood lymphocytes of two patients with CHB and two healthy controls by immunoscope spectratyping technique. We found that the profiles of CDR3 length distribution for all TCR AV and TCR BV family showed Gaussian distribution (the polyclonal TCR alphabeta T cells) in healthy controls, however, the restricted usage of TCR BV and TCR AV family (the oligoclonal TCR alphabeta T cells) has been monitored in two CHB patients, furthermore, the oligoclonal TCR alphabeta T cells showed the different CDR3 sequences and length, it might be correlated to the different epitope of hepatitis B virus (HBV) or the different HLA type of the patients. Detailed analysis of the CDR3 length of TCR alphabeta T cells might be interesting to light on the further study of the individualized immunotherapy of CHB and the further research of the new T lymphocyte epitope vaccine of HBV.

[Analysis of T cell receptor BV dominant usage and CDR3 sequences during acute exacerbation in patients with chronic hepatitis B].

Objectives: 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.

Methods: 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.

[Establishment and application of real-time fluoriescene-based metry polymerase chain reaction for hepatitis B virus genotyping].

Objective: To explore a new method for determining hepatitis B virus (HBV) genotypes B-D with real-time fluorescence-based PCR.

Methods: The PCR primers and probes were designed according to the analysis of 143 complete HBV genomes from GenBank and on the basis of a search for genotype-specific nucleotide sequences which were conserved in the 3 HBV genotypes. Real-time fluorescence-based PCR was performed for HBV genotyping of 128 samples collected from Lanzhou.