[Study of the correlation between elevated level of T-bet expression and liver damage in peripheral plasma cells of patients with autoimmune hepatitis].

Objective: To study the correlation between the level of T-bet expression and liver damage in peripheral plasma cells of patients with autoimmune hepatitis (AIH) in order to provide reference for the study of pathogenesis and development of diseases. Methods: The peripheral venous blood and clinical examination data of 29 cases with AIH and 6 healthy volunteers were collected. The percentage of subpopulations of peripheral blood B cells and the proportion of T-bet(+) cells in each subgroup were detected by flow cytometry. Plasma cells (CD19(+)CD10(-)CD27(hi)CD38(hi)), primary B cells (CD19(+)CD10(-)CD27(-)IgD(+)), transitional B cells (CD19(+)CD10(+)), and memory B cells (CD19(+)CD10(-)CD27(+)IgD(-)) were the included subsets of B cells. Serum immunoglobulin G (IgG) and alanine aminotransferase (ALT) levels, the proportion of B cells in peripheral blood subsets and IgG level, the proportion of T-bet(+) cells in each subset and the proportion of T-bet(+) plasma cells in each subset in B cells, the proportion of T-bet(+) plasma cells and the level of serum ALT were analyzed for correlation analysis. Statistical analysis was performed using two independent sample t-tests and linear regression. Results: The serum IgG level of AIH patients with abnormal ALT (19.47 ± 1.039)g/L was significantly higher than that of normal ALT patients (15.5 ± 1.069)g/L, and the difference was statistically significant (t = 2.65, P < 0.05). The percentage of peripheral plasma cells in B cells of AIH patients (2.80 ± 0.14) % was higher than that of healthy volunteers (0.73 ± 0.09) %, and the difference was statistically significant (P < 0.01). The percentage of T-bet(+) cells in peripheral plasma cells of AIH patients (23.54 ± 1.61) % was higher than that of healthy volunteers (6.59±0.59) % , and the difference was statistically significant (P < 0.01). The correlation analysis showed that the proportion of T-bet(+) cells in peripheral plasma cells of AIH patients was positively correlated with the proportion of plasma cells to B cells (r = 0.224 7, P < 0.01), and the percentage of peripheral plasma cells to B cells was positively correlated with the level of serum IgG (r = 0.299 1, P < 0.01). Serum IgG level was correlated with the level of ALT, reflecting an indicator of liver damage (t = 2.65, P < 0.05). Conclusion: The increase of T-bet expression in the peripheral plasma cells of AIH patients is associated with liver damage, which is a new mechanism of AIH pathogenesis and disease progression.

[Clinical effect and safety of pegylated interferon-α-2b injection (Y shape, 40 kD) in treatment of HBeAg-positive chronic hepatitis B patients].

Objective: To investigate the clinical effect and safety of long-acting pegylated interferon-α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 µg/week) in the treatment of HBeAg-positive chronic hepatitis B (CHB) patients, with standard-dose Peg-IFN-α-2a as positive control. Methods: This study was a multicenter, randomized, open-label, and positive-controlled phase III clinical trial. Eligible HBeAg-positive CHB patients were screened out and randomized to Peg-IFN-α-2b (Y shape, 40 kD) trial group and Peg-IFN-α-2a control group at a ratio of 2:1. The course of treatment was 48 weeks and the patients were followed up for 24 weeks after drug withdrawal. Plasma samples were collected at screening, baseline, and 12, 24, 36, 48, 60, and 72 weeks for centralized detection. COBAS® Ampliprep/COBAS® TaqMan® HBV Test was used to measure HBV DNA level by quantitative real-time PCR. Electrochemiluminescence immunoassay with Elecsys kit was used to measure HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe). Adverse events were recorded in detail. The primary outcome measure was HBeAg seroconversion rate after the 24-week follow-up, and non-inferiority was also tested. The difference in HBeAg seroconversion rate after treatment between the trial group and the control group and two-sided confidence interval (CI) were calculated, and non-inferiority was demonstrated if the lower limit of 95% CI was > -10%. The t-test, chi-square test, or rank sum test was used according to the types and features of data. Results: A total of 855 HBeAg-positive CHB patients were enrolled and 820 of them received treatment (538 in the trial group and 282 in the control group). The data of the full analysis set showed that HBeAg seroconversion rate at week 72 was 27.32% in the trial group and 22.70% in the control group with a rate difference of 4.63% (95% CI -1.54% to 10.80%, P = 0.1493). The data of the per-protocol set showed that HBeAg seroconversion rate at week 72 was 30.75% in the trial group and 27.14% in the control group with a rate difference of 3.61% (95% CI -3.87% to 11.09%, P = 0.3436). 95% CI met the non-inferiority criteria, and the trial group was non-inferior to the control group. The two groups had similar incidence rates of adverse events, serious adverse events, and common adverse events. Conclusion: In Peg-IFN-α regimen for HBeAg-positive CHB patients, the new drug Peg-IFN-α-2b (Y shape, 40 kD) has comparable effect and safety to the control drug Peg-IFN-α-2a.

Rapid downregulation of programmed death-1 and interferon-γ-inducible protein-10 expression is associated with favourable outcome during antiviral treatment of chronic hepatitis B.

The dynamics of programmed death-1 (PD-1) as well as cytokine/chemokine expression and its correlation with virological response in patients with chronic hepatitis B (CHB) is unclear. This study was conducted in 29 treatment-naïve patients undergoing telbivudine treatment for 52 weeks. The results showed that PD-1 expression on both CD4+ and CD8+ T cells was positively correlated with hepatitis B virus (HBV) DNA levels (r = 0.621, P < 0.0001; r = 0.548, P = 0.002, respectively), and in virological responders, this decrease was directly correlated with a decrease in HBV DNA levels (r = 0.664, P = 0.002; r = 0.572, P = 0.01, respectively). Furthermore, at the end of 52 weeks, in virological responders, the decreased rate in the frequency of PD-1+ CD8+ T cells was significantly higher than in non-virological responders (58.3% vs 25.7%, P = 0.001), and at weeks 24 and 52, in virological responders, PD-1 expression on CD4+ and CD8+ T cells was lower than in non-virological responders (P = 0.01 and P = 0.035; P < 0.0001 and P < 0.0001, respectively). In 34 cytokines/chemokines detected in serum, IP-10 expression was positively correlated with viral load, level of ALT and PD-1 expression on CD8+ and CD4+ T cells at baseline (r = 0.36, P = 0.055, r = 0.635, P < 0.0001, r = 0.414, P = 0.026, and r = 0.402, P = 0.030, respectively). Moreover, the decrease in IP-10 in serum directly correlated with a decrease in ALT levels (r = 0.751, P < 0.0001). At weeks 24 and 25, IP-10 expression was significantly lower than baseline in virological responders (both P = 0.005); however, this was not observed in nonresponders. Based on the above findings, PD-1 and IP-10 may be used as predictors for virological response, and blockade of their pathway may improve the outcome of patients with CHB.

Prognostic value of clinical and immunological markers in acute phase of SFTS virus infection.

SFTS virus (SFTSV) is a novel bunyavirus that causes severe fever with thrombocytopenia syndrome (SFTS), an emerging infectious disease that occurred in China in recent years, with an average case fatality rate of 10-12%. Intervention in the early clinical stage is the most effective measure to reduce the mortality rate of disease. To elucidate the natural course of and immune mechanisms associated with the pathogenesis of SFTSV, 59 laboratory-confirmed SFTS patients in the acute phase, who were hospitalized between October 2010 and September 2011, were enrolled in this study, and the patients sera were dynamically collected and tested for SFTSV viral RNA load, 34 cytokines or chemokines and other related laboratory parameters. All clinical diagnostic factors in the acute phase of SFTS were evaluated and assessed. The study showed that the severity of the disease in 11 (18.6%) patients was associated with abdominal pain (p 0.007; OR = 21.95; 95% CI, 2.32-208.11) and gingival bleeding (p 0.001; OR=122.11; 95% CI, 6.41-2328). The IP-10, TNF-α, IL-6, IL-10, granzyme B and HSP70 levels were higher over the 7-8 days in severe cases, accompanied by altered AST, CK and LDH levels. HSP70 (p 0.012; OR=8.29; 95% CI, 1.58-43.40) was independently correlated with the severity of the early acute phase of SFTSV infection. The severity of SFTS can be predicted based on the presence of symptoms such as abdominal pain and gingival bleeding and on the level of HSP70 in the acute phase of the disease.