Changes of cytokine levels and T cell surface molecules in patients with chronic hepatitis B and the association with functional cure.

This study aimed to examine changes in levels of cytokine and T cell surface molecules in chronic hepatitis B (CHB) patients receiving sequential interferon therapy following 1-year nucleos(t)ide analogs (NAs) treatment. Cytokine levels were measured in 30 patients, and T cell surface molecule expression was measured in 48 patients receiving sequential interferon therapy and 24 patients only receiving NA mono-therapy. An HBsAg titer of <0.05 IU/ml was defined as a "functional cure." In the cured group (HBsAg < 0.05 IU/ml), a decreasing probability was observed in IFN-γ (after Week 0), and IL-22 and IP-10 (after Week 12). In the non-cured group (HBsAg ≥ 0.05 IU/ml), a probability of slightly decreasing was observed for IFN-γ (after Week 12), and a probability of increasing IP-10 concentration (after Week 0) was observed. Generalized estimating equation (GEE) analyses showed significant differences in the levels of IL-10, IL-23, CCL-3, IL-1ß, IL-2, and IL-12P70 between the two groups. In GEE analysis, there were significant differences in expressions of CD45RO+ between the cured group and the non-cured group. The frequencies of T cells expressing Tim-3, CD62L, and CD152 were significantly lower in the sequential interferon therapy group than in the NA mono-therapy group. Changes in cytokine levels (IFN-γ, IP-10, IL-10, IL-23, CCL-3, IL-1ß, IL-2, and IL-12P70) and T cell surface molecules (CD45RO+ ) may predict HBsAg seroconversion in CHB patients receiving sequential interferon therapy. The period from Weeks 12 to 24 during sequential interferon therapy may be a critical time of immune status change.

Soluble ST2 plasma concentrations predict mortality in HBV-related acute-on-chronic liver failure.

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a rapidly progressing and frequently fatal condition. The aim of this study was to determine whether interleukin- (IL-) 33 and soluble ST2 (sST2) were associated with disease severity and mortality in HBV-ACLF. We found that plasma levels of sST2 but not IL-33 were higher in HBV-ACLF patients compared with chronic hepatitis B (CHB) patients and healthy controls. However, plasma levels of IL-33, TNF-α, IFN-γ, and IL-10 did not correlate with sST2 levels. Similarly, immunohistochemistry revealed low IL-33 expression and high ST2 expression in liver sections of patients with HBV-ACLF. Evaluation of dynamic changes of sST2 in HBV-ACLF showed that plasma sST2 levels increased over time in patients who died during the 180-day follow-up but decreased in those who survived. In addition, plasma sST2 level after week 1 correlated with disease severity, as assessed by total bilirubin, prothrombin time, and model for end-stage liver disease score. Results of Kaplan-Meier survival analysis showed that higher sST2 concentration (≥87 ng/mL) at week 3 was associated with poor survival. These findings indicate the potential usefulness of sST2 as a predictor of disease severity and in making treatment decisions for patients with HBV-ACLF.

[Dynamic expression profile of HBsAg according to hepatic parenchyma cells' volume at different liver fibrosis stages in the immune clearance phase].

The aim of this study was to determine the dynamic expression profile of hepatitis B surface antigen (HBsAg) according to hepatic parenchyma cells' volume at different stages of liver fibrosis during the immune clearance phase. Eighty-nine patients with HBeAg-positive chronic hepatitis B (CHB) in the immune clearance stage were recruited for study. Each patient's serum HBsAg levels were detected by electrochemiluminescence. The serum HBsAg levels were apportioned according to hepatic parenchyma cells' volume at liver fibrosis stages 1, 2, 3, and 4 and compared by ANOVA. The unapportioned serum HBsAg levels (IU/mL) at liver fibrosis stages 1 (227.2+/-237.7), 2 (211.0+/-131.4), 3(300.1+/-144.6), and 4 (278.7+/-148.8) were not significantly different (all comparisons, P range: 0.061 to 0.759). However, when the serum HBsAg levels were apportioned by the same hepatic parenchyma cells' volume at liver fibrosis stages 1 (343.9+/-359.8), 2 (336.4+/-209.5), 3 (508.7+/-245.1), and 4 (525.2+/-274.8), the levels were significantly different (all comparisons, F = 3.045 and P = 0.033; stage 1 vs. 3, P = 0.041; stage 1 vs. 4, P = 0.046; stage 2 vs. 3, P = 0.028; stage 2 vs. 4, P = 0.034). During the immune clearance phase of chronic hepatitis B, increased HBsAg expression is associated with increased hepatic parenchyma cells' volume and progressive liver fibrosis stage.

Robust Corrupted Data Recovery and Clustering via Generalized Transformed Tensor Low-Rank Representation.

Tensor analysis has received widespread attention in high-dimensional data learning. Unfortunately, the tensor data are often accompanied by arbitrary signal corruptions, including missing entries and sparse noise. How to recover the characteristics of the corrupted tensor data and make it compatible with the downstream clustering task remains a challenging problem. In this article, we study a generalized transformed tensor low-rank representation (TTLRR) model for simultaneously recovering and clustering the corrupted tensor data. The core idea is to find the latent low-rank tensor structure from the corrupted measurements using the transformed tensor singular value decomposition (SVD). Theoretically, we prove that TTLRR can recover the clean tensor data with a high probability guarantee under mild conditions. Furthermore, by using the transform adaptively learning from the data itself, the proposed TTLRR model can approximately represent and exploit the intrinsic subspace and seek out the cluster structure of the tensor data precisely. An effective algorithm is designed to solve the proposed model under the alternating direction method of multipliers (ADMMs) algorithm framework. The effectiveness and superiority of the proposed method against the compared methods are showcased over different tasks, including video/face data recovery and face/object/scene data clustering.

Plasma Interleukin-6 Level: A Potential Prognostic Indicator of Emergent HBV-Associated ACLF.

Objective: To identify markers that predict the progression to hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF). Methods: We recruited 125 patients with chronic hepatitis B (CHB) between September 2013 and March 2017. During hospitalization, 25 patients progressed to LF and were classified as the LF group, while the remaining 100 patients were classified as the non-LF (NLF) group. We compared the kinetic changes in clinical and immune indicators including age, total bilirubin level, prothrombin time, model for end-stage liver disease score, interleukin (IL)-6, IL-8, and IL-10 cytokine levels, and number of T helper 17 and regulatory T cells between groups to determine their association with progression to HBV-ACLF. The prognostic value of clinical and immune indicators was determined using the area under the receiver operating characteristic curve (AUC) value. Results: Cox regression analysis suggested that the plasma IL-6 level could predict CHB progression to HBV-ACLF (relative risk = 1.082, 95% confidence interval: 1.006-1.164; P=0.034). The AUC value, sensitivity, and specificity of baseline IL-6 level for predicting HBV-ACLF were 82.63%, 83.3%, and 82.9%, respectively (P=0.001). Conclusion: A high plasma IL-6 level in CHB patients could be an early biomarker for HBV-ACLF.

Hepatotoxicity of iodine-131 ablation for post-surgical differentiated thyroid cancer patients with hepatitis B virus infection.

OBJECTIVE: Radioiodine (Iodine-131, 131I) ablation is a standard treatment for differentiated thyroid cancer (DTC) after thyroidectomy. Hepatotoxicity is a rare side effect of 131I, and little information is available on the hepatotoxicity of 131I ablation for post-surgical DTC patients with hepatitis B virus (HBV) infection. METHODS: We performed a retrospective study of 94 post-surgical DTC patients between November 2012 and August 2015 in our hospital. All the patients had been screened for HBV infection and divided into HBV group and non-HBV group. Clinical data were compared between the two groups. RESULTS: 14 patients with HBV infection and 80 patients without HBV infection were analyzed. The baseline characteristics of the two groups had no statistical differences. Incidence of hepatotoxicity was higher in HBV group than in non-HBV group and HBV infection was confirmed as a risk factor of hepatotoxicity by univariate and multivariate regression analysis. CONCLUSION: Post-surgical DTC patients with HBV infection were prone to hepatotoxicity by 131I ablation treatment. Physicians should pay more attention to the liver function of patients at risk.

Plasma Interleukin-10: A Likely Predictive Marker for Hepatitis B Virus-Related Acute-on-Chronic Liver Failure.

BACKGROUND: The pathogenesis of HBV-related acute-on-chronic liver failure (HBV-ACLF) is mainly based on a heightened immune-inflammatory reaction; however, the intimate underlying mechanism remains unclear. OBJECTIVES: The aim of the study was to explore potential key immune molecular targets that could serve as early predictive markers for HBV-ACLF. PATIENTS AND METHODS: Twenty-seven patients with acute exacerbation of chronic hepatitis B (CHB) (defined by: alanine transaminase ≥ 20 ULN, total bilirubin ≥ 5 ULN, 40% < prothrombin time activity ≤ 60%) and without cirrhosis were divided into 18 cases which did not progress to HBV-ACLF (defined by: prothrombin time activity < 40% and development within four weeks of hepatic encephalopathy and/or ascites) and nine cases that developed HBV-ACLF. Nine healthy people defined the normal control group (NC). Interleukin-1ß (IL-1ß), IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, TNF-α and IFN-γ protein levels were assayed by Cytometric Bead Array (CBA) in blood plasma. The ELISA method was applied to confirm IL-10 detection using the CBA method. RESULTS: IL-4, IL-12p70 and IFN-γ were undetectable; IL-1ß, IL-6, IL-8, IL-10 and TNF-α levels were significantly higher than in NC. Moreover, cytokines reached the highest levels in acute exacerbation of CHB, with the exception of IL-2 and IL-8. When comparing the HBV-ACLF patients prior to and at the time of ACLF diagnosis, IL-10 was the only cytokine that exhibited a significant decrease (P = 0.008). IL-10 concentrations were positively correlated to ALT levels (r = 0.711, P < 0.001). CONCLUSIONS: The assessment of plasma IL-10 levels in chronic hepatitis B acute exacerbation may provide an early predictive marker for progression to HBV-ACLF.

Effect of healthcare insurance policy on the quality of life of chronic hepatitis C patients receiving interferon α-2a plus ribavirin therapy.

The aim of this study was to evaluate the effect of pegylated interferon α-2a plus ribavirin therapy on the quality of life (QOL) of chronic hepatitis C patients when this treatment was paid for by healthcare insurance. The QOL questionnaire (GQOLI-74) was used to assess patient QOL. A total of 42 cases received 1-year pegylated interferon α-2a plus ribavirin treatment paid for by Guangzhou Medical Insurance (group A), and 30 cases received treatment self-subsidized by the patients themselves (group B). Another 30 patients did not receive interferon therapy (group C). All groups completed the evaluation twice; prior to interferon treatment (T0) and at the end of treatment (T1). There was no statistically significant difference among the three groups (P>0.05). At T1, patients in group A had higher scores for each questionnaire dimension and a higher total score than those of group C (P<0.05). Patients in group B also had higher scores than those of group C (P<0.05), except for material well-being (P=0.305). Compared with group B, patients in group A had higher scores for mental function, material well-being and a higher total score (P<0.05). Patients in group A had higher scores for each dimension and a higher total score at T1 than at T0 (P=0.05), while patients in group B had higher scores for physical function, social function and a higher total score at T1 than at T0 (P=0.05). Pegylated interferon α-2a plus ribavirin treatment is able to improve the QOL of chronic hepatitis C patients. Patients whose treatment was financed by medical insurance exhibited increased improvement in QOL compared to those who paid for their own treatment.

Effect of GM-CSF in combination with hepatitis B vaccine on revacination of healthy adult non-responders.

OBJECTIVE: To assess the immune effects and safety of using GM-CSF with the yeast-recombinant hepatitis B virus (HBV) vaccine for the re-vaccination of healthy adults who did not respond to a previous vaccination. METHODS: Study participants included 1784 healthy adults and 100 individuals diagnosed as non-responders. These healthy non-responders were randomly assigned to one of the three treatment groups: Group A (34 individuals) was given 150 microg of granulocyte-macrophage colony stimulating factor (GM-CSF) the first day, then 20 microg of the vaccine; Group B (33 individuals) was given 40 microg of the vaccine only; and, group C (33 individuals) was injected with 20 microg of vaccine each time. All participants were injected three times, at time of study enrollment and one and six months later. Anti-HB surface antigen (HBs) antibody titers were tested before treatment and at one (T1), two (T2) and eight (T8) months post-first injection. RESULTS: At T1, the rate of anti-HBs antibody(+) in groups A, B and C was 26.47%, 48.48% and 18.18%, respectively (p = .027). At T8, the seropositive rate of group A (64.71%) and group B (75.76%) was significantly higher than in group C (39.39%) (p = .011); the geometric mean of the antibody titer for groups A and B was higher than for group C (p = .0173). All three treatments were safe and well-tolerated. CONCLUSIONS: Augmentation of the vaccine dose and co-administration of GM-CSF and the standard vaccine dose are effective for HBV vaccine non-responders. In fact, changing the vaccine dose had a better seropositive response than injecting the vaccine in combination with GM-CSF.