High-Throughput Analysis of the T Cell Receptor Beta Chain Repertoire in PBMCs from Chronic Hepatitis B Patients with HBeAg Seroconversion.

T lymphocytes are the most important immune cells that affect both the development and treatment of hepatitis B. We used high-throughput sequencing to determine the diversity in the V and J regions of the TCRß chain in 4 chronic hepatitis B patients before and after HBeAg seroconversion. Here, we demonstrate that the 4 patients expressed Vß12-4 at the highest frequencies of 10.6%, 9.2%, 17.5%, and 7.5%, and Vß28 was the second most common, with frequencies of 7.8%, 6.7%, 5.3%, and 10.9%, respectively. No significant changes were observed following seroconversion. With regard to the Jß gene, Jß2-1 was the most commonly expressed in the 4 patients at frequencies of 5.8%, 6.5%, 11.3%, and 7.3%, respectively. Analysis of the V-J region genes revealed several differences, including significant increases in the expression levels of V7-2-01-J2-1, V12-4-J1-1, and V28-1-J1-5 and a decrease in that of V19-01-J2-3. These results illustrate the presence of biased TCRVß and Jß gene expression in the chronic hepatitis B patients. TRBVß12-4, Vß28, Jß2-1, V7-2-01-J2-1, V12-4-J1-1, and V28-1-J1-5 may be associated with the development and treatment of CHB.

Clinical characteristics of chronic hepatitis B cured by peginterferon in combination with nucleotide analogs.

OBJECTIVES: The purpose of this study was to analyze the clinical characteristics of chronic hepatitis B (CHB) cured by antiviral therapy. METHODS: Forty-two patients with CHB were enrolled. All patients had been treated with peginterferon (Peg-IFN) in combination with nucleoside analogue (NA) therapy for variable amounts of time, and all had been successfully cured of the disease. RESULTS: The combined treatment time for all participants was 124.7 ± 58.8 weeks, and the average Peg-IFN treatment time was 102.6 ± 56.1 weeks. At 24 weeks, Hepatitis B surface antigen (HBsAg) and Hepatitis B e antigen (HBeAg) had decreased more than 50% from baseline. Multivariate logistic regression analysis of the week 96 HBsAg-clearing group and the non-HBsAg-clearing group showed a statistically significant difference in baseline HBV DNA levels and week 48 HBsAg levels. Those which baseline HBV DNA was < 2.75 log10 IU/mL, and week 48 HBsAg levels were < 0.88 log10 IU/mL were more likely to achieve rapid HBsAg clearance at 96 weeks. This suggests that low levels of baseline HBV DNA and week 48 HBsAg are a predictor of rapid HBsAg clearance at 96 weeks. CONCLUSIONS: Individualized extension of combination therapy to more than 96 weeks depending on the patient's response and adverse reaction conditions can help achieve a clinical cure. Patients with low baseline HBV DNA and low HBsAg levels at 48 weeks achieve HBsAg clearance more quickly than other populations.

High mobility group box 1 release from cholangiocytes in patients with acute-on-chronic liver failure.

High mobility group box chromosomal protein 1 (HMGB1) is an important proinflammatory molecule in a number of inflammatory disorders, but little is known about its role in acute-on-chronic liver failure (ACLF). To elucidate the role of HMGB1 in ACLF, the expression of HMGB1 in liver specimens from patients with ACLF was investigated. Immunohistochemical staining was performed to confirm the expression and subcellular localization of HMGB1 in liver specimens obtained from 13 patients with ACLF caused by hepatitis B virus (HBV) infection, 20 patients with chronic viral hepatitis B and 20 healthy controls. In addition, TFK-1 cells (human cholangiocarcinoma cell line) were stimulated with lipopolysaccharide (LPS) or tumor necrosis factor (TNF)-α. The extracellular level of HMGB1 in the culture medium was then determined by ELISA, and cell viability was also examined. In patients with ACLF caused by HBV infection, HMGB1 was found mainly in the cholangiocytes, and cytoplasmic translocation was observed in the cholangiocytes in the liver specimens. In the TFK-1 cell cultures, HMGB1 levels gradually increased from as early as 4 h after stimulation with LPS or TNF-α until the end of the stimulation. LPS and TNF-α actively induced the cytoplasmic translocation of the HMGB1 protein in TFK-1 cells. These data suggest that HMGB1 plays a critical role in the systemic inflammation associated with ACLF.