Transforming growth factor ß as a possible independent factor in chronic hepatitis B.

To investigate the association between immune-cell-related cytokines and the development of chronic hepatitis B (CHB), patients with chronic hepatitis B virus (HBV) infection in the immunotolerant (IT) phase (n = 30) or hepatitis B envelope antigen (HBeAg)-positive CHB (n = 250) were enrolled in this study. Serological indicators and plasma cytokine levels were measured at the time of enrollment. The results showed that there were significant differences in the median age of the patients (27 vs. 31 years), alanine aminotransferase levels (ALT, 29.85 vs. 234.70 U/L), alanine aminotransferase levels (AST, 23.40 vs. 114.90 U/L), HBsAg levels (4.79 vs. 3.88 log10 IU/ml), HBeAg levels (1606.36 vs. 862.47 S/CO), and the HBV DNA load (8.17 vs. 6.71 log10 IU/ml) between the IT and CHB groups (all P < 0.01). The median values of Fms-like tyrosine kinase 3 ligand (FLT3-L), interferon-gamma (IFN-γ), interleukin- 17A (IL-17A), and transforming growth factor beta (TGF-ß1) were significantly higher in the IT group than in the CHB group (FLT3-L, 41.62 vs. 27.47 pg/ml; IFN-γ, 42.48 vs. 33.18 pg/ml; IL-17A, 15.66 vs. 8.90 pg/ml; TGF-ß1, 4921.50 vs. 2234 pg/ml; all P < 0.01). The median IFN-α2, TGF-ß3 and IL-10 levels in the IT group were significantly lower than those in the CHB group (IFN-α2, 15.24 vs. 35.78 pg/ml, P = 0.000; TGF-ß3, 131.69 vs. 162.61 pg/ml, P = 0.025; IL-10, 5.02 vs. 7.9 pg/ml, P = 0.012). Multivariate logistic regression analysis indicated that TGF-ß 1 (OR = 0.999, 95% CI 0.999-1.000, P < 0.001) and TGF-ß2 levels (OR = 1.008, 95%CI 1.004-1.012, P < 0.001) were modestly but significantly associated with the incidence of CHB. The results suggest that TGF-ß level might be an independent factor related to the occurrence of CHB.

Association of cytokines with hepatitis B virus and its antigen.

To investigate the characteristics of cytokines in patients with different HBV infection status and their correlation with HBV DNA, HBsAg, and HBeAg levels. Peripheral blood samples were collected from patients with chronic HBV infection in immune tolerance phase (IT), HBeAg-positive chronic hepatitis B (CHB), and acute hepatitis B (AHB) groups, and levels of cytokines were detected by Luminex technique, and analyzed by FLEXMAP 3D analyzer. The correlation between cytokines and HBV DNA load, HBsAg, HBeAg, and alanine aminotransferase (ALT) level in patients with chronic HBV infection was analyzed. In total 312 subjects (184 males and 128 females) were enrolled in the study. There were significant differences among IT, CHB, and AHB groups in Flt-3L value (P = .003; H = 12.312), IFN-γ (P = .001; H = 11.723), IL-10 (P = .001; H = 18.736), IL-17A ((P = .001; H = 12.735), and TGF-ß1 (P = .001; Z = 48.571). IFN-α2 levels in CHB group were significantly higher than those in IT and AHB groups (15.24 vs 35.78 pg/mL, P = .000; Z = 3.727; 13.88 vs 35.78 pg/mL, P = .024; Z = -2.258. In CHB group, the levels of HBsAg and ALT were positively correlated with the levels of IL-10 (r = .173; P = .006; r = 0.176; P = .006, respectively), while HBeAg level was positively correlated with the IFN-α2 level (r = .153; P = .016). In AHB group, the HBsAg level was positively correlated with Flt-3L, IFN-α2, IL-10, and IL-6 (r = .402; P = .023; r = .436; P = .016; r = .524, P = .002; r = .405; P = .022, respectively). HBeAg level was positively correlated with IFN-γ and IL-17A levels (r = .400; P = .023; r = .373; P = .036, respectively), and ALT level was positively correlated with IL-6 levels (r = .367; P = .039). In either AHB or CHB group, HBV DNA load was only related to TGF-ß level (r = .493; P = .004; r = -.218, P = 0.009 respectively). The correlation between Flt-3L and HBsAg (F = 7.422; P = .007); IL-17, IL-6, and HBeAg (F = 5.757; P = .017; F = 6.156; P = .014) were statistically significant. There was significant correlation between TGF-ß2 and HBV DNA (F = 11.795; P = .001), and between ALT and HBsAg, HBV DNA (F = 26.089; P = .000; F = 4.724; P = .031). HBsAg, HBeAg, and HBV DNA were correlated with cytokines and ALT in patients with HBV infection. The level of IFN-α2 was significantly higher in patients with CHB. HBV DNA load was only correlated with the level of TGF-ß in acute or CHB.

Predictors of sustained functional cure in hepatitis B envelope antigen-negative patients achieving hepatitis B surface antigen seroclearance with interferon-alpha-based therapy.

Hepatitis B surface antigen (HBsAg) loss is considered a functional cure in chronic hepatitis B (CHB). However, the durability of HBsAg loss after stopping treatment remains unknown. This study aimed to assess the sustained functional cure achieved by interferon therapy in hepatitis B envelope antigen (HBeAg)-negative CHB patients. In this prospective study, 176 HBeAg-negative CHB patients with functional cure were enrolled for 12 weeks of cessation treatment, and treatment information and baseline data were collected. Hepatitis B virus (HBV) biomarkers and clinical biochemical indicators were evaluated every 3 months; liver imaging examinations were performed every 3-6 months during the 48-week follow-up. The sustained functional cure was evaluated. After the 48-week follow-up, the sustained functional cure rate was 86.63%. The cumulative rates of HBsAg reversion and HBV DNA reversion were 12.79% and 2.33%, respectively. Consolidation treatment ≥ 12 weeks after HBsAg loss achieved a significantly higher rate of sustained functional cure and significantly lower rate of HBsAg reversion than consolidation treatment < 12 weeks (76.19% vs 90.00%, P = 0.022 and 23.81% vs 9.23%, P = 0.014, respectively). Patients with hepatitis B surface antibody (HBsAb) had higher rate of sustained functional cure than patients achieving HBsAg loss but without HBsAb (89.86% vs 73.53%, P = 0.012). Consolidation treatment ≥ 12 weeks (odds ratio [OR] 16.478; 95% confidence interval [CI], 2.135-127.151; P = 0.007) and high HBsAb levels (OR 8.312; 95% CI, 1.824-37.881; P = 0.006) were independent predictors of sustained functional cure. Results suggested that 12 weeks of consolidation therapy after HBsAg clearance and elevated HBsAb levels help to improve functional cure.

Evaluation of a logistic regression model for predicting liver necroinflammation in hepatitis B e antigen-negative chronic hepatitis B patients with normal and minimally increased alanine aminotransferase levels.

Liver necroinflammation is the indicator for treating patients with chronic hepatitis B (CHB) infection. However, there is no suitable non-invasive index for diagnosing liver necroinflammation. This study aimed to create a non-invasive index to predict liver necroinflammation in patients who lack clear-cut clinical inflammation parameters. Patients who were hepatitis B e antigen (HBeAg)-negative and underwent liver histological diagnosis, had a normal or minimally increased alanine aminotransferase (ALT) level were enrolled. Liver necroinflammation was defined as histological active index ≥4. A logistic regression model (LRM) was established based on the parameters independently associated with liver necroinflammation. Of all 550 patients, 36.73% had necroinflammation. In patients with an abnormal ALT level, the rate of necroinflammation was 52.49%. The area under the curve (AUC) of the ALT level for predicting necroinflammation was 0.655 (95% confidence interval [CI], 0.609-0.702), and that of the HBV DNA level ≥2000 IU/mL combined with an abnormal ALT level was 0.618. By using the LRM, the AUC improved to 0.769 (95% CI, 0.723-0.815) with a Youden index of 0.519 and diagnostic accuracy of 75.3%. The cutoff value ≥0.7 in the LRM had a specificity of 97.4% and positive predictive value of 85.0% for predicting necroinflammation. By using the cutoff value <0.15 in the LRM, the presence of necroinflammation could be excluded with a negative predictive value of 90.8%. This study indicated that the LRM can be used to effectively diagnose liver necroinflammation in HBeAg-negative patients with CHB who have normal or minimally elevated ALT levels.

[Design and Optimization of Surface Plasmon Resonance Sensor Based on Side Polished Single-Mode Fiber].

Fiber-coupling surface Plasmon resonance sensor has attractive advantages of information transmission such as small volume, anti-electric magnetic field interference, and online real-time remote detection. In order to improve the performance of the sensor, the effect of the residual fiber thickness and the silver film thickness to the sensitivity of the sensor and the depth of the resonance peaks and full width ar half maximum (FWHM) are analyzed respectively. The results show that the increasing fiber residual thickness weakens the SPR phenomenon, and that the increasing silver film thickness widens the resonance peak, while the sensitivity of the sensor does not change monotonously. Through the integration of refractive index sensing sensitivity and full width at half maximum, figure of merit is presented and regarded as the optimized objective. The optimal design is achieved in the case of the fiber residual thickness for 66. 5 µm, and the silver film thickness for 50 nm. The optimized design with the figure of merit of 98. 67 is expected to be applied in the bio-chemical sensing and analysis.

Baseline lymphocyte and cholinesterase levels may be the predictors of chronic herbal drug-induced liver injury.

Objective: To investigate the factors influencing the chronicity of drug-induced liver injury (DILI) caused by Chinese herbal medicine. Methods: Patients with DILI diagnosed by using the RUCAM score were enrolled retrospectively. The subjects were patients with DILI induced by taking Chinese herbal medicine and were followed up for 48 weeks. These patients were divided into a cure group and a chronic group. The biochemical indicators were monitored at baseline and every 3 months. Logistic regression was used to analyze the risk factors of DILI chronicity. The ROC (receiver operator characteristic) curve was used to analyze the diagnostic efficiency of each factor. Results: A total of 420 patients with DILI were enrolled; 122 of them were caused by Chinese herbal medicine, 70.5% (86/122) of them were female, chronic group 31.2% (39/122), and cure group 68.0% (83/122); cholinesterase (ChE) in the chronic group was lower than that in the cure group (5467.10 ± 2010.40 U/L vs. 6248.52 ± 1901.78 U/L, p = 0.04, t = 2.078). There was no significant difference in the age between cured patients and chronic patients (p = 0.156, Z = -1.417). There was no significant difference between the prognosis of different genders (p = 0.521, Z = -0.639). The logistic regression analysis showed that baseline lymphocyte (OR = 0.429, 95%CI = 0.205-0.898, p = 0.025) and cholinesterase (OR = 0.088, 95%CI = 0.008-0.994, p = 0.049) were independent risk factors of drug-induced chronicity. Conclusion: Baseline lymphocyte and cholinesterase may be the predictive factors for the chronicity of Chinese herbal medicine-induced liver injury.

Changes in the Cytokine Profiles of Patients with Chronic Hepatitis B during Antiviral Therapy.

OBJECTIVE: To investigate the changes in the cytokine profiles of chronic hepatitis B (CHB) patients undergoing antiviral treatment. METHODS: Hepatitis B e antigen (HBeAg)-positive patients were treated with Pegylated interferon (PEG-IFN) and entecavir (ETV). Clinical biochemistry and cytokines were detected at baseline and every 3 months. RESULTS: In all, 200 patients completed 48 weeks of treatment, 100 in the PEG-IFN group and 100 in the ETV group. During 3-6 months of treatment, compared with baseline, the PEG-IFN group showed a significant decrease in interferon-gamma (IFN-γ), interleukin-17A (IL-17A), interleukin-6(IL-6), interleukin-10(IL-10), and transforming growth factor beta (TGF-ß) ( P < 0.001) and a significant increase in interferon-alpha 2(IFN-α2) ( P < 0.001). In the ETV group, IL-10 and TGF-ß1 decreased significantly ( P < 0.001). After 3 months, the levels of IFN-α2, IL-17A, and tumor necrosis factor-alpha(TNF-α) in the PEG-IFN group were significantly higher than those in the ETV group ( P < 0.01). The levels of IL-6 and TGF-ß3 were significantly lower than those in the ETV group ( P < 0.01). After 6 months, the levels of IFN-α2, IFN-γ, and TNF-α in the PEG-IFN group were significantly higher than those in the ETV group ( P < 0.01), while the levels of IL-6 and TGF-ß3 were significantly lower than those in the ETV group ( P < 0.01). Compared with ETV, PEG-IFN had higher HBeAg and HBsAg disappearance rates. CONCLUSION: During antiviral therapy, a change in the cytokine profile occurred; in the aspect of immune control and functional cure, PEG-IFN was significantly better than ETV.

Accumulation of myeloid-derived suppressor cells (MDSCs) induced by low levels of IL-6 correlates with poor prognosis in bladder cancer.

Bladder cancer (BC) is one of the most commonly occurring cancers, with a high recurrence rate and poor outcomes in cases of relapsed metastatic disease. Here, we analyzed the markers and significance of myeloid-derived suppressor cells (MDSCs) for BC development and progression. MDSC markers were examined in peripheral blood from 113 BC patients and 20 healthy volunteers. We identified CD11b+CD33lowHLA-DR- CD3- cells as markers of MDSCs in peripheral blood from BC patients. We also demonstrated that MDSC numbers are higher in BC patients than healthy donors, and that MDSC numbers correlate with the clinical grade, stage, and poor prognosis. In addition, serum IL-6 levels are decreased in BC patients with higher MDSC counts. IL-6 blockade increases induction of MDSCs in vitro. Low IL-6 levels inhibit activation of Stat3, resulting in the increased formation of MDSCs in BC. These results indicate that the MDSCs numbers may serve as a novel prognostic marker in BC patients, and that targeting IL-6 signaling may be a promising strategy for BC treatment.