CHB Group Research Articles

Morphological characteristics of CT blend sign predict hematoma expansion and outcomes in intracerebral hemorrhage in elderly patients.

The underlying basis of the blend sign on brain computed tomography (CT) in patients with intracerebral hemorrhage (ICH) is unclear. Few studies have examined the morphological alterations in the CT blend sign in ICH. Therefore, we assessed changes in the CT blend sign and their association with hematoma expansion (HE) and adverse outcomes in ICH patients. We recorded the clinical and radiographic parameters of patients with ICH and blend sign on brain CT. The patients were categorized into two groups, with changes in the relatively hypoattenuating region of the blend sign (CHB group) and with no changes in the relatively hypoattenuating region of the blend sign (NHB groups). We performed univariate and multivariate logistic regression analyses to examine the correlations between CHB and HE and poor outcomes. Furthermore, receiver operating characteristic curve analysis was used to confirm the predictive power of CHB. In total, 183 patients were included in the study, of whom 74 (40.4%) demonstrated changes in the hypoattenuating region of the blend sign, whereas 109 (59.6%) did not. Compared with the NHB group, patients in the CHB group exhibited significantly higher levels of HE and adverse outcomes. After adjustment for confounding factors, CHB was independently associated with HE (odds ratio, 19.401 [95% CI, 7.217-52.163]; p < 0.001) and poor 3-month outcomes (odds ratio, 2.638 [95% CI, 1.391-5.003]; p = 0.003) in the multivariate analysis. The sensitivity, specificity, positive predictive value, and negative predictive value of CHB for predicting HE were 0.877, 0.768, 0.791, and 0.862, respectively, whereas these values for predicting poor outcomes were 0.789, 0.641, 0.688, and 0.752, respectively. Changes of a hypoattenuating region within the blend sign have good predictive accuracy for HE and short-term adverse outcomes in elderly patients with ICH. ClinicalTrials.gov, NCT05548530.

AI Digital Pathology Using qFibrosis Shows Heterogeneity of Fibrosis Regression in Patients with Chronic Hepatitis B and C with Viral Response.

This study aimed to understand the dynamic changes in fibrosis and its relationship with the evaluation of post-treatment viral hepatitis using qFibrosis. A total of 158 paired pre- and post-treatment liver samples from patients with chronic hepatitis B (CHB; n = 100) and C (CHC; n = 58) were examined. qFibrosis was employed with artificial intelligence (AI) to analyze the fibrosis dynamics in the portal tract (PT), periportal (PP), midzonal, pericentral, and central vein (CV) regions. All patients with CHB achieved a virological response after 78 weeks of treatment, whereas patients with CHC achieved a sustained viral response after 24 weeks. For patients initially staged as F5/6 (Ishak system) at baseline, the post-treatment cases exhibited a significant reduction in the collagen proportionate area (CPA) (25-69%) and number of collagen strings (#string) (9-72%) across all regions. In contrast, those initially staged as F3/4 at baseline showed a similar CPA and #string trend at 24 weeks. For regression patients, 27 parameters (25 in the CV region) in patients staged as F3/4 and 15 parameters (three in the PT and 12 in the PP regions) in those staged as F5/6 showed significant differences between the CHB and CHC groups at baseline. Following successful antiviral treatment, the pre- and post-treatment liver samples provided quantitative evidence of the heterogeneity of fibrotic features. qFibrosis has the potential to provide new insights into the characteristics of fibrosis regression in both patients with CHB and CHC as early as 24 weeks after antiviral therapy.

Liver Fatty Acid-binding Protein Is a More Reliable Biomarker for Liver Injury in Nonalcoholic Steatohepatitis than Other Etiologies of Hepatitis.

Liver fatty acid-binding protein (LFABP) controls hepatocyte lipid metabolism and can be a biomarker in liver diseases. We compared the correlation of LFABP levels with liver histology in viral hepatitis and nonalcoholic fatty liver disease (NAFLD) and investigated the utility of serum LFABP as a biomarker for liver damage. We included 142 patients (60 chronic viral hepatitis B [CHB], 35 chronic viral hepatitis C [CHC], 47 NAFLD) and 40 healthy controls. LFABP levels were determined in all participants, and a liver biopsy was performed on patients. The nonalcoholic steatohepatitis (NASH) activity score (NAS), hepatosteatosis, liver inflammation, and fibrosis were evaluated for NAFLD patients. Ishak's histological scores were used for viral hepatitis. The correlation between LFABP levels and histologic scores was assessed in each group. Serum LFABP levels in CHB, CHC, NAFLD, and control groups were 2.2, 3.5, 7.6, and 2.1 ng/mL, respectively. LFABP levels were significantly higher in the NAFLD group compared to the control, CHC, and CHB groups. LFABP was significantly higher in the NASH group than in nonalcoholic steatohepatitis, 8 ng/mL and 5.4 ng/mL, respectively (P = .001). In the NAFLD group, LFABP levels showed a moderate positive correlation with NAS score (r = 0.58, P <.001), ballooning degeneration (r = 0.67, P <.001), and lobular inflammation (r = 0.62, P <.001). A logistic regression study showed that the level of LFABP was predictive of NASH independent of age, gender, homeostasis model of IR, body mass index, aspartate aminotransferase, and alanine aminotransferase (OR = 1.869, P = .01). LFABP specifically correlates with liver histology in NAFLD compared to viral hepatitis. Additionally, it can distinguish NASH from simple steatosis. LFABP may be a valuable biomarker for hepatocyte injury in NASH.

Frequency of HBsAg variants in occult hepatitis B virus infected patients and detection by ARCHITECT HBsAg quantitative.

To analyze the amino acid substitution caused by mutations in the major hydrophilic region (MHR) of the S-region genes in the serum samples of occult hepatitis B virus infection (OBI), and to explore the reasons for the missed detection of HBsAg. The full-length gene of the S-region in hepatitis B virus(HBV) in the chronic hepatitis B virus(CHB)(10 samples) and OBI groups(42 samples) was amplified using a lab-developed, two-round PCR amplification technology. The PCR amplification products were sequenced/clone sequenced, and the nucleotide sequences of the S-region gene in HBV were compared to the respective genotype consensus sequence. Only 20 of the 42 samples in the OBI group had the S-region genes successfully amplified, with the lowest HBV DNA load of 20.1IU/ml. As S-region genes in HBV, 68 cloned strains were sequenced. In the OBI and CHB groups MHR region, with a mutation rate of 3.21% (155/4828) and 0.70% (5/710). The genetic mutation rate was significantly higher in the OBI group than in the CHB group (P<0.05). The common mutation types in the MHR region were: I126T, L162R, K122E, C124R, and C147Y.Mutations at s122, s126, and s162 were associated with subgenotypes, most of which being C genotypes. The high-frequency mutation sites L162R and K122E found in this study have not been reported in previous literature. The results of this study confirmed that MHR mutations can cause the missed detection of HBsAg, giving rise to OBI.

Prognostic value of genome-wide methylation in acute-on-chronic hepatitis B liver failure

AimMethylation status of genome varies between pre-acute-on-chronic hepatitis B liver failure (pre-ACHBLF), acute-on-chronic hepatitis B liver failure (ACHBLF), and chronic hepatitis B patients. This study aimed to find better prognostic indicators for acute-on-chronic liver failure. MethodsThe level of global genome methylation in peripheral blood mononuclear cells (PBMCs) was detected. The overall genome methylation rate was determined using MethylFlash™ Methylated DNA Quantification Kit(Colorimetric). DNMT activity were measured using DNA Methyltransferase Activity/Inhibition Assay Kit. Gene expression of DNA methyltransferases (DNMT)，methyl-CpG-binding domain (MBD) were detected by qRT-PCR. ResultsThe global genome methylation level in ACHBLF group was significantly higher than that in chronic hepatitis B group (P<0.001). There was also obvious difference of the global genome methylation level between pre-ACHBLF group and CHB group (P<0.001). Meanwhile, the activity of DNMT in ACHBLF group was significantly higher than that in chronic hepatitis B group (P<0.001). The mRNA expression level of DNMT1 was higher than that in pre-ACHBLF group (P<0.01) and CHB group (PP<0.001). The mRNA expression level of MBD1 in ACHBLF group was also higher than that in CHB group (P<0.001) and healthy controls (HCs) (P<0.01). And the mRNA expression level of MBD3 and MBD4 in ACHBLF, pre-ACHBLF and CHB group were lower than that in HCs (P<0.001). Meanwhile we observed an opposite change in the mRNA expression level of MECP2. The ROC curve suggested that global genome methylation level was a better prognostic predictor than MELD score in ACHBLF (AUC 0.950, SE 0.0237, 95%CI 0.874–0.986 VS AUC 0.863, SE 0.0439, 95%CI 0.765–0.931, P=0.0429). ConclusionsGenome methylation level can be a good biomarker in predicting the severity and prognosis of ACHBLF.

Altered mitochondrial mass and low mitochondrial membrane potential of immune cells in patients with HBV infection and correlation with liver inflammation.

Mitochondrial membrane potential (MMP) and mitochondrial mass (MM) affect mitochondrial function and lymphocyte activation, but few studies on HBV infection exist. This study aimed to investigate the regulatory mechanism of mitochondrial dysfunction during HBV infection and its clinical significance by analyzing the alterations of MM and MMPlow in peripheral blood immune cells. The study enrolled 90 participants, including healthy volunteers(HC) and patients with HBV infection, HBV patients were divided into chronic hepatitis B patients (CHB) and liver cirrhosis (LC) according to the study, and CHB was also divided into an inflammation group and a non-inflammation group. Flow cytometry was used to analyze the changes of MM and MMPlow in peripheral blood immune cells. These analyses were correlated with the presence of CHB and LC and indexes related to liver inflammation. The study revealed significant variations in the percentage of MMPlow and MM of CD8+T cells associated with the progression of the disease. The MMPlow percentage of CD8+T cells in the LC group exhibited a notable decrease compared to the HC group and CHB groups. Moreover, MMPlow of CD8+T cells demonstrated potential in distinguishing CHB and LC (AUC=0.7341, P=0.0032). Furthermore, in exploring the link between mitochondrial function of immune cells and liver inflammation, the study found a negative correlation between the MMPlow ratio of CD4+T and CD8+T cells and AST (p=0.0039 and P=0.0070, r=-0.4405 and r=-0.4146), while the MM of CD8+T cells displayed a positive correlation with AST (p=0.0013, r=0.4865). In CHB patients with normal ALT but liver inflammation detected on B-scan ultrasonography, a significant decrease was observed in the MMPlow percentage of CD8+T (66.13 ± 14.27), CD56+NK(57.77 ± 17.40) and CD4-CD8-T (61.98 ± 15.98) cells. Furthermore, it was also found that the percentage of MMPlow in CD4-CD8-T cells could serve as an indicator for early liver inflammation and injury (AUC=0.8408, P=0.0052). In this study, we conducted a systematic analysis of the percentage of lymphocyte MMPlow and MM in various stages of HBV infection. Our findings revealed a correlation between MMPlow and MM and early liver inflammation, as well as the progression of the infection. This study marked the first demonstration of the clinical diagnostic value of MMPlow and MM in HBV infection. Furthermore, this was the first study to discuss the mitochondria of lymphocytes and liver inflammation in HBV infection. It enhanced the understanding of the role of T cells in liver inflammation, and elucidated potential markers for the early detection of liver injury and clinical cirrhosis.

Selenium Donor Inhibited Hepatitis B Virus Associated Hepatotoxicity via the Apoptosis and Ferroptosis Pathways.

The serum selenium level was determined in 45 patients with HBV-positive HCC (HBV+-HCC group), 45 patients with chronic hepatitis B virus infection (CHB group), and 45 healthy cases (HC group). The sodium selenite (Na2SeO3)-treated HepG2.2.15 cells were used to observe the regulatory role of selenium on HBV replication. D-GalN/erastin-added HL7702 was used to determine the regulatory roles of Na2SeO3 on hepatotoxicity or hepatocyte ferroptosis. The wild-type (WT) C57BL/6 mice and HBx-Tg mice were received lipopolysaccharide (LPS)/D-GalN, together with or without Na2SeO3 administration for indicated period. Following euthanasia, the blood and liver tissue samples were collected, and specific markers were evaluated subsequently. The serum selenium level was downregulated in patients with HBV-positive HCC (HBV+-HCC group) (57.2 ± 22.5 μg/L vs. 91.8 ± 43.9 μg/L, P < 0.001), and its higher level could provide a better prognosis in these patients. The treatment using Na2SeO3, a selenium donor, at high concentration (5 μM), suppressed the HBV replication by about 50% in HepG2.2.15 cells (P < 0.001), through promoting apoptotic cell death and inhibiting cellular inhibitor of apoptosis proteins (cIAPs). In addition, low-dose (500 nM) Na2SeO3 could almost totally reversed the hepatotoxicity induced by hepatitis B virus X protein (HBx) (P < 0.001), which were the main causes of HCC in patients. Studies at the cellular levels showed that low-dose Na2SeO3 inhibited the HBx-related hepatotoxicity by blocking ferroptosis, and glutathione peroxidase 4 (GPX4) mediated this regulatory role. Mice model results confirmed that the treatment with Na2SeO3 could mitigated LPS/D-GalN-induced hepatic injury through ferroptosis pathways. Selenium regulated the dual cell death in different HCC stages via different signaling pathways, which could partly explain the anti-HBV and anti-HCC properties of selenium.

Serum Expression Level of MicroRNA-122 and its Significance in different Stages of Hepatitis B Virus Infection.

This study aims to determine the serum expression level of miRNA-122 and its significance in the different stages of Hepatitis B virus infection. The study subjects were recruited and grouped for Hepatitis B associated with Chronic Hepatitis B infection, hepatic sclerosis, hepatocellular carcinoma, and healthy controls were also considered. Venous blood was collected from the participants including the controls and routine blood tests and quantification of miRNA-122 were done and analyzed in each case of hepatitis B infection and compared with that of healthy controls. The miRNA-122 was determined, which came to be highest in patients with Chronic Hepatitis B while patients with hepatic sclerosis and patients with hepatocellular carcinoma showed a subsequent number of copies. The number of copies of miRNA-122 in the CHB, hepatic sclerosis, and HCC group was significantly higher than in the healthy control. The quantification of miRNA-122 and subsequently plotting the ROC curve has shown that miRNA-122 can be considered as a biomarker of hepatitis B for screening and diagnosis purposes.

Effect of substituting hydroponic barley forage with or without enzymes on performance of growing rabbits

This study aims to evaluate the effect of hydroponic barley (HB) by substituting control diet with 25% HB with or without enzymes on rabbit performance, nutrient digestibility, and economic efficiency. A total number of 60 growing male HyPlus rabbits (average body weight 669 ± 12 g, 30 days of age) were utilized in the present study. The rabbits were randomly assigned to three groups (n = 20 rabbits per group). The first group served as a control (C). The other two groups were fed the control diet substituted with 25% hydroponic barley HB (group CHB), and the control diet substituted with 25% HB added with 0.5 g/kg enzymes (CHBE). The experiment lasted for 56 days. The results revealed that daily body weight gain improved (P < 0.05) by 18.64% and 23.94%, and feed conversion ratio improved by 3.74% and 17.91% than control, respectively, during 30–86 days of age in CHB and CHBE groups. The economic efficiency was improved (P < 0.05) by 32.17% and 39.60% in CHB and CHBE diets, respectively, compared to control; and nutrient digestibility, and mineral retention of growing rabbits were also improved (P < 0.05) by substituting HB with or without enzymes compared to control diet. Overall, the best rabbit performances were observed in both CHB and CHBE groups. In conclusion, these results suggest that substituting 25% of concentrated control diet by hydroponic barley with or without enzymes have positive effects in a sustainable way on growth performance, nutrient digestibility, and economic efficiency of growing rabbits.

Evulation of prolidase enzyme, and galectin levels as a marker for fibrosis in patients with chronic hepatitis B.

The fibrosis can be detected using non-invasive methods including prolidase activity, proline levels and galectin-3 (GAL-3) detection in the serum. The aim of this study was to investigate the liver fibrosis through non-invasive methods in chronic hepatitis B patients. This prospective case control study includes 56 patients with Chronic Active Hepatitis B (CAHB), 57 patients with Inactive Hepatitis B (IHB), and 60 healthy matched control subjects. The first group included the CAHB [hepatitis B surface antigen (HBsAg): positive; HBV DNA >2,000 IU/mL; normal or high alanine aminotransferase (ALT) value] undergo a liver biopsy, while the second group included the IHB (HBsAg: positive; HBV DNA: negative; normal ALT value). The third group comprised the healthy controls. Serum prolidase enzyme activities (SPEA), proline and galectin-3 levels were measured for each group. Patients with CAHB had significantly higher SPEA levels (1,004.3±186.8 IU/L) than did the controls (196.5±306 IU/L) (p<0.001). Significantly higher serum GAL-3 levels were found in the CHB group compared with HBV carrier and the control groups (27.4±32.2 ng/mL, 6.5±13.4 ng/mL, 3.1±5.7 ng/mL, respectively, p<0.001). The relationship between serum prolidase activity, hidroxiprolyne and fibrosis (p<0.05). There were no significant differences in ALT levels between inactive HBV carriers and the control groups (p>0.05). We suppose that hidroxiprolyne levels and prolidase enzyme activity might be an indicator as a marker for fibrosis in CAHB and the evaluation of response to treatment.

Correlation of Serum M-CSF, CER, and TIMP-1 Levels with Liver Fibrosis in Viral Hepatitis.

Objective This research is aimed at investigating the relationship between liver fibrosis in viral hepatitis and macrophage colony-stimulating factor (M-CSF), tissue inhibitor of matrix metalloproteinase (TIMP-1), and ceruloplasmin (CER) in serum level. Methods Patients were randomly selected among those admitted to our hospital, and 60 healthy volunteers were chosen to serve as control participants. The levels of serum M-CSF, CER, and TIMP-1 were compared. According to the severity of their liver fibrosis, patients with CHB were separated into four groups: S1, S2, S3, and S4. Serum levels of M-CSF, CER, and TIMP-1 were correlated with liver fibrosis and hepatitis markers, and the diagnostic usefulness of the three indices was assessed with liver cirrhosis patients. Results Increases in M-CSF and TIMP-1 in the CHB group but decreases in CER were statistically significant (P < 0.05). Serum levels of M-CSF, CER, TIMP-1, HA, PC-III, C-IV, and LN differed significantly across the four study groups (P < 0.05). Over time, as liver fibrosis worsened, we observed a progressive uptick in M-CSF, TIMP-1, LN, HA, C-IV, and PC-III levels and a progressive downtick in CER levels, with significant (P < 0.05) differences between the groups. There was a significant positive correlation between liver fibrosis and serum M-CSF, PC-III, TIMP-1, HA, LN, and C-IV levels in the CHB group (P < 0.05) and a significant negative correlation between serum CER and these same factors (P < 0.05). The AUC of 0.956 for diagnosing the S4 stage was greater than that of 0.857, 0.851, and 0.817 for M-CSF, CER, and TIMP-1, respectively. Conclusions In CHB patients, the liver fibrosis degree is associated with the M-CSF, CER, and TIMP-1 levels, and the combined clinical detection of these three markers has better diagnostic significance.

Impact of in vitro fertilization-embryo transfer on mother-to-infant transmission in women with chronic HBV infection.

In vitro fertilization-embryo transfer (IVF-ET) may increase the risk of mother-to-child transmission (MTCT) of hepatitis B virus (HBV). The purpose of this study was to investigate the impact and safety of IVF-ET on MTCT in women with chronic HBV infection (CHB). The data of 298 women who got pregnant by IVF-ET and their 375 children were collected retrospectively. Mothers were divided into the CHB group (n=224) and the control group (HBsAg negative, n=74). After birth, newborns were routinely vaccinated with the hepatitis B vaccine, and infants in the CHB group were injected with hepatitis B immunoglobulin within 2h after birth. Demographic information, clinical data and laboratory test results were collected. The primary outcome measures were the MTCT rate of HBV, and the secondary outcome measures were the safety of the mother and infant. There was no case of HBV MTCT in all 282 newborns born in the CHB group and 93 neonates born in the control group. Of the two groups, the birth weight (3056.74 ± 601.65 vs. 2926.24 ± 704.86, P=.083), length (49.22 ± 1.97 vs. 48.74 ± 3.09, P=.167), 5-min Apgar score (9.97 ± 0.21 vs. 9.90 ± 0.51, P=.212), days of pregnancy (265.70 ± 12.73 vs. 262.02 ± 17.50, P=.064) and neonatal malformation rate (0.71% vs. 0, P=1.000) were similar. Two cases of neonatal malformation occurred in the CHB group. The incidences of pregnancy and childbirth complications were similar between the two groups. IVF-ET does not increase the risk of MTCT in women with chronic HBV infection, and it is safe for mothers and infants.

The Correlation of Mean Platelet Volume and Neutrophil-lymphocyte Ratio Measurements, and the Ishak Fibrosis Score in Our Patients with Chronic Hepatitis B

Background:The ishak score determined by liver biopsy is the most reliable indicator of fibrosis, but biopsy is an invasive procedure. Numerous noninvasive tests have been investigated to determine the hepatic fibrosis score. We aimed to investigate the relationship between the mean platelet volume(MPV) and neutrophillymphocyte ratio (NLR) measurements in patients with chronic hepatitis B virus (CHB) infection, and liver fibrosis stage, which was determined by biopsy and ishak score. Material and Method:CHB patients followed between 2016 and 2020 in our gastroenterology outpatient clinic were included in our study. CHB patients; They were divided into two groups as non-cirrhotic group (ishak fibrosis score in biopsy; F0-F4) and cirrhotic group (F5-F6). Then, 30 healthy control (HC) groups consisting of health personnel who had routine health screenings and blood tests in the same period were formed. MPV, NLR measurements of these two main groups and CHB subgroups and liver biopsy results of CHB patients were evaluated retrospectively, and possible relationships between the groups were investigated. Results:There was no statistically significant difference between the mean age and gender of the cases in the CHB and HC groups. A total of 54 patients with CHB were identified, of which 13 patients were cirrhotic and 41 patients were non-cirrhotic. MPV measurements were found to be significantly higher in the CHB group than in the SC group (11.15±1.77; 10.02±0.92; p=0.002). While there was no significant difference between NLR measurements, it was found to be higher in the CHB group (1.98±0.81; 1.81±0.69). While there was no significant difference between the cirrhotic and non-cirrhotic subgroups of the CHB group in terms of NLR (1.86±0.68; 2.36±1.04) and MPV (11.09±1.89; 11.35±1.36) measurements, NLR and MPV measurements were higher in the cirrhotic group. Conclusion:In our study, MPV values were found to be significantly increased in patients in the CHB group compared to the HC group. In addition, although not statistically significant, NLR and MPV measurements were found to be higher in the cirrhotic group than in the non-cirrhotic group. According to our study, it can be thought that with increasing MPV and NLR measurements in HBV patients, there may be an increase in chronicity and fibrosis scores without an invasive procedure such as biopsy.

ROCK2 Polymorphism and Expression Contribute to Increased Susceptibility and Poor Prognosis in Hepatocellular Carcinoma.

AimTo analyze the association between ROCK2 gene polymorphism/expression and susceptibility/prognosis of hepatocellular carcinoma (HCC).MethodsPeripheral venous blood from 204 hepatocellular carcinoma patients (HCC group), 242 chronic hepatitis B patients (CHB group), 215 liver cirrhosis patients (LC group) and 201 healthy volunteers (normal group) were collected. ROCK2 gene (including the rs9808232 locus) was amplified by PCR and the products were sequenced. Tumor tissues from patients with HCC and liver tissues from CHB, LC and normal groups were collected, and mRNA and protein expression of ROCK2 gene in liver tissues were tested by RT-qPCR and immunofluorescence, respectively.ResultsCompared with the normal group, the mRNA and protein expression levels of ROCK2 in the HCC group increased significantly (P < 0.05), but there are no obvious increases in the CHB and LC groups (P > 0.05). ROCK2 gene rs9808232 polymorphism was associated with an increased susceptibility of HCC, and genotypes AC and CC may be risk factors for HCC (P < 0.001). There was a significant association between the ROCK2 gene rs9808232 polymorphism and the route of metastasis in HCC patients (P < 0.05). According to the Kaplan–Meier analysis, the overall survival of patients with AC and CC genotypes of ROCK2 rs9808232 was much shorter than that of patients with AA genotype (median overall survival, 25.5 months vs 16.0 months; Log rank P = 0.006). The overall survival time of patients with high ROCK2 expression is much shorter than that of patients with low ROCK2 expression (median overall survival time, 15.0 months vs 20.5 months; Log rank P = 0.008). Compared with genotype AA, the ROCK2 protein levels of genotypes AC and CC were distinctly increased in the HCC group, especially genotype CC (P< 0.05).ConclusionROCK2 gene rs9808232 polymorphism may contribute to its expression in liver tissue, which may increase the susceptibility and poor prognosis of HCC.

Association of PD-L1 gene polymorphisms and circulating sPD-L1 levels with HBV infection susceptibility and related liver disease progression.

Soluble molecules of programmed death ligand 1 (sPD-L1) are known to modulate T-cell depletion, an important mechanism of hepatitis B virus (HBV) persistence and liver disease progression. In addition, PD-L1 polymorphisms in the 3'-UTR can influence PD-L1 expression and have been associated with cancer risk, although not definitively. The purpose of this study was to investigate the association of PD-L1 polymorphisms and circulating levels of sPD-L1 in HBV infection and live disease progression. In this study, five hundred fifty-one HBV infected patients of the three clinically well-defined subgroups chronic hepatitis B (CHB, n=186), liver cirrhosis (LC, n=142) and hepatocellular carcinoma (HCC, n=223) and 240 healthy individuals (HC) were enrolled. PD-L1 polymorphisms (rs2297136 and rs4143815) were genotyped by in-house validated ARMS assays. Logistic regression models were applied in order to determine the association of PD-L1 polymorphisms with HBV infection as well as with progression of related liver diseases. Plasma sPD-L1 levels were quantified by ELISA assays. The PD-L1 rs2297136 AA genotype was associated with HBV infection susceptibility (HBV vs. HC: OR=1.6; 95%CI=1.1-2.3; p=0.0087) and disease progression (LC vs. CHB: OR=1.8; 95%CI=1.1-2.9; p=0.018). Whereas, the rs2297136 GG genotype was a protective factor for HCC development. Plasma sPD-L1 levels were significantly high in HBV patients (p<0.0001) and higher in the LC followed by CHB and HCC groups. High sPD-L1 levels correlated with increased liver enzymes and with advanced liver disease progression (Child-pugh C>B>A, p<0.0001) and BCLC classification (BCLC D>C>B>A, p=0.031). We could, for the first time, conclude that PD-L1 rs2297136 polymorphism and plasma sPD-L1 protein levels associate with HBV infection and HBV-related liver disease progression.

Cantilevered Versus non-cantilevered resilient bar attachment for 2-implant retained mandibular overdentures. A short term crossover study of chewing efficiency and bite force.

Aim of the study: This study compared chewing efficiency and maximum bite force between cantilevered and non-cantilevered resilient bar attachment used for 2-implant retained mandibular overdentures. Materials and methods: Eight completely edentulous participants (4 men, 4 women) with atrophied mandibular ridges receive 2 implants in the canine region. After 3 months, each patient received Hader bar with 7mm distal cantilevers and mandibular overdenture with 3 clips (CHB group). After another 3 months, distal cantilevers were sectioned and patients received Hader bar without cantilevers and mandibular overdentures with one clip (HB). Chewing efficiency (using unmixed fraction (UF) in a colored gum) and bite force were measured 3 months after using conventional dentures CD, CHB, and HB. Results: The highest unmixed fraction (UF) was noted with 5 cycles and the lowest number was noted with 50 cycles. UF decreased with the increase of number of chewing strokes. For all chewing strokes, the highest the UF was noted with CD, followed by HB, and the lowest UF was noted with CHB. At 30 and 50 strokes, there was a significant difference between each 2 groups, and HB showed significant higher UF than CHB. The highest maximum bite force was noted with CHB, followed by HB, and the lowest was noted with CD. Conclusion: it could be concluded that both cantilevered and non-cantilevered bar attachments for 2 implant overdentures achieved higher chewing efficiency and maximum bite force than conventional dentures in patients with atrophied mandibular ridges.

MIF promoter polymorphism increases peripheral blood expression levels, contributing to increased susceptibility and poor prognosis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. The etiology and pathogenesis of HCC remain unclear. Macrophage migration inhibitory factor (MIF) plays a critical role in the pathogenesis of hepatocellular carcinoma. The association between MIF polymorphisms and its expression level in HCC has rarely been demonstrated. In the present study, the peripheral blood of 202 patients with HCC (HCC group), 242 patients with chronic hepatitis B (CHB group), 215 patients with liver cirrhosis (LC group) and 227 healthy volunteers (normal group) were collected, DNA was extracted and the target fragment of MIF gene was amplified using PCR. The products were then sequenced, and the expression levels of MIF protein were tested using ELISA. The results showed that the MIF rs755622 polymorphism was associated with an increased susceptibility and metastasis of HCC, and that the genotypes GC and CC were associated with poor prognosis of HCC. Compared with the normal, CHB and LC groups, the expression of MIF in the peripheral blood of the HCC group was significantly increased, and the high expression was associated with to poor prognosis. In the HCC group, MIF protein levels for genotypes GC and CC were increased compared with those of genotype GG. The current study indicated that the MIF rs755622 polymorphism is associated with susceptibility and metastasis of HCC, and that the GC and CC genotypes may be indicators of poor prognosis, which may be ascribed to the MIF rs755622 polymorphism leading to elevated MIF protein expression in peripheral blood.

Restricted TcR \u03b2 chain CDR3 clonotype is associated with resolved acute hepatitis B subjects

BackgroundT cells play an important role in the prognosis of hepatitis B virus (HBV) infection, and are involved in the seroconversion of a patient from HBsAb negative to positive. To compare the T-cell receptor β-chain variable region (TcRBV) complementarity-determining region 3 (CDR3) in subjects with or without hepatitis B surface antigen (HBsAg) convert to hepatitis B surface antibody (HBsAb), the TcRBV was determined using high throughput sequencing (HTS).MethodsThe clonotype and diversity of CDR3 in peripheral blood mononuclear cells of subjects with resolved acute hepatitis B (AHB, HBsAb+, HBsAg-) (n = 5), chronic hepatitis B (CHB, HBsAb-, HBsAg+) (n = 5), and healthy controls (HC, HBsAb-, HBsAg-) (n = 3) were determined and analyzed using HTS (MiSeq).ResultsThe overlapping rate of CDR3 clones of any two samples in AHB group was 2.00% (1.74% ~ 2.30%), CHB group was 1.77% (1.43% ~ 2.61%), and HC group was 1.82% (1.62% ~ 2.12%), and there was no significant difference among the three groups by Kruskal-Wallis H test. However, among the top 10 cumulative frequencies of clonotypes, only the frequency of clonotype (TcRBV20–1/BD1/BJ1–2) in AHB group was lower than that of HC group (P < 0.001). Moreover, exclude the 10 top clonotypes, there are 57 markedly different frequency of clones between AHB and CHB groups (18 clones up, 39 clones down), 179 (180–1) different clones between AHB and HC groups, and 134 different clones between CHB and HC groups. With regard to BV and BJ genotypes, there was no significant different frequency among the groups. Furthermore, there was no significant difference in the diversity of TcRBV CDR3 among the three groups (P > 0.05).ConclusionsThus, there are 57 TcRBV clonotypes that may be related to HBsAg seroconversion of AHB subjects, but the diversity of TcRBV CDR3 is not significantly related to the HBsAb positive status.

LC/MS-Based Global Metabolomic Identification of Serum Biomarkers Differentiating Hepatocellular Carcinoma from Chronic Hepatitis B and Liver Cirrhosis.

Chronic hepatitis B virus (CHB) infection is one of the primary risk factors associated with the development of hepatocellular carcinoma (HCC). Despite having been extensively studied, diagnosing early-stage HCC remains challenging, and diagnosed patients have a poor (3–5%) survival rate. Identifying new approaches to detect changes in the serum metabolic profiles of patients with CHB and liver cirrhosis (LC) may provide a valuable approach to better detect HCC at an early stage when it is still amenable to treatment, thereby improving patient prognosis and survival. In the present study, we, therefore, employed a liquid chromatography-mass spectrometry (LC-MS)-based approach to evaluate the serum metabolic profiles of 30 CHB patients, 29 LC patients, and 30 HCC patients. We then employed appropriate statistical methods to identify those metabolites that were best able to distinguish HCC cases from LC and CHB controls. A mass-based database was then used to putatively identify these metabolites. We then confirmed the identities of a subset of these metabolites through comparisons with the MS/MS fragmentation patterns and retention times of reference standards. The serum samples were then reanalyzed to quantify the levels of these selected metabolites and of other metabolites that have previously been identified as potential HCC biomarkers. Through this approach, we observed clear differences in the metabolite profiles of the CHB, LC, and HCC patient groups in both positive- and negative-ion modes. We found that the levels of taurodeoxy cholic acid (TCA) and 1,2-diacyl-3-β-d-galactosyl-sn-glycerol rose with the progression from CHB to LC to HCC, whereas levels of 5-hydroxy-6E,8Z,11Z,14Z,17Z-eicosapentaenoic acid, and glycyrrhizic acid were gradually reduced with liver disease progression in these groups. The ROC analysis showed that taurodeoxy cholic acid (TCA), 1,2-diacyl-3-β-d-galactosyl-sn-glycerol, 5-hydroxy-6E,8Z,11Z,14Z,17Z-eicosapentaenoic acid, and glycyrrhizic acid had a diagnosis performance with liver disease progression. These four metabolites have a significant correlation with alpha fetal protein (AFP) level and age. Our results highlight novel metabolic biomarkers that have the potential to be used for differentiating between CHB, LC, and HCC patients, thereby facilitating the identification and treatment of patients with early-stage HCC.

An enhanced level of LAMP-2A participates in CD4+T cell hyperactivity in patients with primary biliary cholangitis.

BackgroundPrimary biliary cholangitis (PBC) is an immune-mediated chronic cholestasis, in which T cell homeostasis plays an important role. Lysosomal-associated membrane protein 2 isoform A (LAMP-2A) has been implicated in the regulation of CD4+T cell responses.MethodsWe comprehensively evaluated the immunobiology of CD4+T cells in patients with PBC (PBC, n=42), chronic hepatitis B (CHB, n=20), and healthy control subjects (HC, n=20) by flow cytometry including activation status and LAMP-2A expression. Additionally, we investigated the activation responses of PBC-naïve CD4+T cells by stimulation in vitro and tested the changes caused by deleting the gene encoding LAMP-2A.ResultsFirstly, we found an increased activation status of circulating CD4+T cells from PBC patients compared to the HC subjects, and PBC-naïve CD4+T cells showed enhanced responses after stimulation in vitro. Secondly, PBC-naïve CD4+T cells expressed a significantly higher level of LAMP-2A compared to the HC and CHB groups [PBC vs. HC, 1,954.74 (1,254.28–3,057.14) vs. 1,542.12 (961.18–2,277.98), P=0.03; vs. CHB, 1,153.59 (726.87–1,275.48), P=0.02], and the overreactions of PBC-naïve CD4+T cells could be reversed by interfering with LAMP-2A expression in vitro. Thirdly, the LAMP-2A expression level of PBC-naïve CD4+T cells was related to disease severity and drug response.ConclusionsAn abnormally increased LAMP-2A expression of PBC-naïve CD4+T cells might be related to excessive activation responses. LAMP-2A could be a novel therapeutic target for the treatment of PBC by reversing excessive responses and consequently reducing biliary injury.