Hepatitis B virus infection in clustering of infection in families with unfavorable prognoses in northwest China.

Hepatitis B virus (HBV) infection and its associated liver diseases have characteristics of familial clustering in China. However, the reasons for this are not understood fully. To address this issue, the prevalence HBV infection and the characteristics of unfavorable prognoses in clustering of infection in families in northwest China were investigated. Families with clustering of infection and unfavorable prognoses were enrolled, and general information and serum samples were collected. The clinical features and sequelae of HBV infection were compared among the blood relatives (including the first-, second-, and third-degree blood relatives) and spouses using the chi-square test or Fisher's exact test. A total of 102 clusterings of infection families with unfavorable prognoses were interviewed. In the first-, second-, and third-degree blood relatives and spouses, the prevalences of cirrhosis of the liver were 29.2%, 11.9%, and 8.7%, respectively, while those of hepatocellular carcinoma (HCC) were 21.8%, 1.4%, and 4.3%, respectively (P<0.05). The mean ages of the onset of cirrhosis of the liver in the first-, second-, and third-degree blood relatives and spouses were 57 ± 9.91, 47 ± 9.96, 38 ± 10.35, and 57 ± 8.49 years, respectively, while the mean ages of the onset of HCC were 60 ± 7.92, 49 ± 8.57, 41 ± 3.54, and 50 ± 0 years, respectively, (P<0.05). The first-, second-, and third-degree blood relatives from clustering of infection in families with unfavorable prognoses had prevalences of cirrhosis or HCC in descending order of relationship. The findings suggest that genetic factors may be associated with a familial tendency for cirrhosis of the liver and HCC.

[Combined immunoprophylaxis induces changes in anti-hepatitis B surface protein titer in infants born to mothers with positivity for hepatitis B surface antigen].

OBJECTIVE: To conduct a prospective randomized controlled trial of infants born to hepatitis B virus (HBV) surface antigen (HBsAg)-positive mothers in order to investigate the dynamic changes in the titer of anti-HBV surface protein (HBS) induced by treatment with combined immunoprophylaxis (200 IU hepatitis B immunoglobulin (HBIG) and 5 or 10 mug yeast recombinant hepatitis B vaccine), to compare the protective effect of 5 and 10 mug hepatitis B vaccine, and to provide an immunization strategy, monitoring mode and booster immunization schedule for the high-risk group. METHODS: Two-hundred-and-sixty-nine infants born to HBsAg positive mothers were given combined immunoprophylaxis at birth, and the venous blood samples (at birth, and 1, 7 and 12 months) were tested for HBV DNA load, and HBsAg and anti-HBS titers. RESULTS: The overall 1-year protective rate of combined immunoprophylaxis was 95.9%. There was no significant difference between the infectious rates of infants given the 5 mug or the 10 mug hepatitis B vaccine (x2 = 0.876, P = 0.377). The geometric mean titers (GMTs) of anti-HBS were 144.1 mIU/ml at 1-month old and 564.9 mIU/ml at the age of 7 months old (the highest point), but declined to 397.6 mIU/ml at the age of 12 months old. The rate of infants with anti-HBS titer less than 100 mIU/ml was 20.9%, and that of less than 10 mIU/ml was 7.4% at 7-month-old; the rate of infants with anti-HBS titer less than 100 mIU/ml increased to 30.2% and that of less than 10 mIU/ml increased to 15.9% at 12-month-old. At 7-month-old, the GMT of the 10 mug vaccine group was higher than that of the 5 mug vaccine group (675.3 mIU/ml vs. 25.0 mIU/ml, P = 0.001) and the rate of infants with anti-HBS titer less than 10 mIU/ml was significantly lower in the 10 mug vaccine group (2.3% vs. 12.6%, P = 0.002); at 12-month-old, the rate of infants with anti-HBS titer less than 100 mIU/ml was also significantly lower in the 10 mug group (20.6% vs. 40.2%, P = 0.001). CONCLUSION: Combined immunoprophylaxis is therapeutically efficacious for treating infants born to HBsAg positive mothers. Monitoring these infants' anti-HBs titer will help to identify non- or low-responders in a timely manner. The high-dose hepatitis B vaccine is preferable to the low-dose, and should be considered for use in immunization strategies for these infants.

Safety and efficacy comparison of polyethylene glycol, hemp seed oil, and 5% sugar brine for bowel preparation in older patients: study protocol for a randomized controlled trial.

BACKGROUND: The incidence of colorectal cancer among the middle-aged and elderly is gradually increasing in China. Colonoscopy is an effective method for the early diagnosis of colorectal cancer, and bowel preparation is one of many important factors affecting colonoscopy. Although there are many studies on intestinal cleansers, the results are not ideal. There is evidence that hemp seed oil has certain potential effects in intestinal cleansing, but prospective studies on this topic are still lacking. METHODS: This is a randomized, double-blind, single-center clinical study. We randomly assigned 690 participants to groups each administered 3 L of polyethylene glycol (PEG), 30 mL of hemp seed oil and 2 L of PEG, or 30 mL of hempseed oil, 2 L of PEG, and 1000 mL of 5% sugar brine. The Boston Bowel Preparation Scale was considered the primary outcome measure. We evaluated the interval between consumption of bowel preparation and first bowel movement. Secondary indicators included the time of cecal intubation, detection rate of polyps and adenomas, willingness to repeat the same bowel preparation, whether the protocol was tolerated, and whether there were adverse reactions during bowel preparation and were evaluated after counting the total number of bowel movements. DISCUSSION: This study aimed to test the hypothesis that hemp seed oil (30 mL) increases the quality of bowel preparation and reduces the amount of PEG. Previously, we found that its combination with 5% sugar brine can reduce the occurrence of adverse reactions. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200057626. Prospectively registered on March 15, 2022.

Asialoglycoprotein receptor interacts with the preS1 domain of hepatitis B virus in vivo and in vitro.

BACKGROUND: The preS1 domain of the large envelope protein has been identified as an essential viral structure involved in hepatitis B virus (HBV) attachment. However, the cellular receptor(s) for HBV has not yet been identified. AIMS: To identify a cell-surface receptor for HBV, which could elucidate the molecular mechanism of HBV infection. METHODS: A novel yeast two-hybrid system was used to screen proteins interacting with the preS1 region of HBV. Their interaction was verified by yeast cotransformation, coimmunoprecipitation and mammalian two-hybrid assay, while their intracellular and tissue localization was analyzed by confocal microscopy and immunohistochemistry, respectively. RESULTS: Asialoglycoprotein receptor (ASGPR) interacted specifically and directly with the preS1 domain of HBV in vivo and in vitro. The levels of expression of preS1 and ASGPR in the liver were similar and correlated with each other. CONCLUSIONS: ASGPR is a candidate receptor for HBV that mediates further steps of HBV entry.

Characteristics of Peripheral Lymphocyte Subsets in Patients With Acute-On-Chronic Liver Failure Associated With Hepatitis B.

Background and Aims: Acute-on-chronic liver failure (ACLF) is a rare, but dramatic clinical syndrome. There is substantial evidence suggesting that immunity-mediated inflammation plays an important role in HBV-ACLF. Our aim was to characterize the proportion and cell counts of peripheral blood lymphocyte subsets in acute-on-chronic liver failure patients caused by HBV infection. Methods: One hundred and seventeen patients were enrolled in this study, including those with HBV-related ACLF (HBV-ACLF; n = 70), and HBV related non-ACLF patients (HBV non-ACLF; n = 47). Demographics, clinical and laboratory data at hospital admission were retrospectively analyzed. The percentage and cell count of peripheral lymphocyte subsets were evaluated by flow cytometry. Comparison analysis was performed by t-test or non-parametric Mann-Whitney U-test. Actuarial probabilities of death were calculated by the Kaplan-Meier method. Results: Both circulating lymphocyte count and lymphocyte percentage were significantly reduced in patients with HBV-ACLF (P < 0.001). The CD8+ T cell, CD4+ T cell, and CD16+CD56+ NK cell counts were significantly decreased in HBV-ACLF. Consistently, flow cytometric analysis showed that CD8+ T cell counts were significantly decreased in non-survivors, while no significant differences were found in CD4+ T cell, CD19+ B cell, or CD56+CD16+ NK cell counts. Furthermore, the group with the lower CD8+ T cell count displayed a significantly higher mortality rate compared with the group with the higher CD8+ T cell count. Conclusions: The abnormal prevalence of lymphocyte subsets may be important in the pathogenesis of HBV-ACLF. The decrease in CD8+ T cell counts may be related to poor survival in HBV-ACLF patients.

Overview of bile acid signaling in the cardiovascular system.

Bile acids (BAs) are classically known to play a vital role in the metabolism of lipids and in absorption. It is now well established that BAs act as signaling molecules, activating different receptors (such as farnesoid X receptor, vitamin D receptor, Takeda G-protein-coupled receptor 5, sphingosine-1-phosphate, muscarinic receptors, and big potassium channels) and participating in the regulation of energy homeostasis and lipid and glucose metabolism. In addition, increased BAs can impair cardiovascular function in liver cirrhosis. Approximately 50% of patients with cirrhosis develop cirrhotic cardiomyopathy. Exposure to high concentrations of hydrophobic BAs has been shown to be related to adverse effects with respect to vascular tension, endothelial function, arrhythmias, coronary atherosclerotic heart disease, and heart failure. The BAs in the serum BA pool have relevant through their hydrophobicity, and the lipophilic BAs are more harmful to the heart. Interestingly, ursodeoxycholic acid is a hydrophilic BA, and it is used as a therapeutic drug to reverse and protect the harmful cardiac effects caused by hydrophobic elevated BAs. In order to elucidate the mechanism of BAs and cardiovascular function, abundant experiments have been conducted in vitro and in vivo. The aim of this review was to explore the mechanism of BAs in the cardiovascular system.

Host susceptibility to persistent hepatitis B virus infection.

Genetic epidemiology researches such as twin studies, family-clustering of hepatitis B virus (HBV) infection studies and ethnic difference studies have provided the evidence that host genetic factors play an important role in determining the outcome of HBV infection. The opening questions include which human genes are important in infection and how to find them. Though a number of studies have sought genetic associations between HBV infection/persistence and gene polymorphisms, the candidate gene-based approach is clearly inadequate to fully explain the genetic basis of the disease. With the advent of new genetic markers and automated genotyping, genetic mapping can be conducted extremely rapid. This approach has been successful in some infectious diseases. Linkage analysis can find host genes susceptible to HBV and is of great clinical importance.

Relationship between polymorphism of class II transactivator gene promoters and chronic hepatitis B.

AIM: To investigate the relationship between the polymorphism of class II transactivator (CIITA) gene promoters and chronic hepatitis B (CHB). METHODS: Genomic DNA was prepared from peripheral blood leukocytes. Promoters I, III and IV of gene were analyzed respectively with polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) in 65 patients with CHB, 26 patients with acute hepatitis B (AHB) and 85 normal controls. RESULTS: No abnormal migration was found in PCR-SSCP analysis of the three promoters in the three groups. Also, no sequential difference was observed at the three promoters among the CHB patients, AHB patients and normal controls. CONCLUSION: No polymorphism in promoters I, III and IV of CIITA gene exists in CHB patients, ABH patients and normal controls, suggesting that the promoter of CIITA gene might be a conserved domain.

[Genomic analysis of a familial clustering of chronic hepatitis B patients].

OBJECTIVE: To investigate the peripheral blood monocyte (PBMC) gene expression profile in a familial clustering of patients with chronic hepatitis B (CHB). METHODS: cRNA prepared from PBMC in a family with 5 CHB patients and 4 normal controls was hybridized to high-density oligouncleotide arrays (HG-U133A 2.0 Human GeneChips, Affymetrix), which interrogate the expression of approximately 22,000 human ESTs. Primary image obtained from scanning was analysed with a DNT software package. Real-time PCR was employed to confirm the gene chip results. RESULTS: 55 genes out of 22,000 ESTs were identified differently. Among the 55 genes 14 showed increased expression and 41 showed decreased expression in the familial clustering CHB patients compared with those in normal controls. Most of the genes (57%) were involved in immunity, inflammation, apoptosis, signaling transduction, and cell cycle. CONCLUSION: These results suggest that the hosts with this broad range of gene expression alterations are susceptible to hepatic B infection.

[Expression map of immune-related genes on PBMCs in familial clustering patients with chronic virus hepatitis B].

AIM: To investigate peripheral blood mononuclear cells (PBMCs) immune-related gene expression profile in patients with chronic virus hepatitis B(CHB) by oligonucleotide gene array technique. METHODS: PBMCs were collected from the members of a family of clustering hepatitis B virus (HBV) infection including 5 CHB patients and 4 healthy spouses and RNA prepared from PBMCs was hybridized to high-density oligonucleotide arrays(HG-U133A 2.0 Human Gene Chips, Affymetrix), covering the expression of 22 000 human ESTs. Primary scanned image was analyzed with DNT software package. RESULTS: Out of the 22 000 ESTs, 24 different immune-related genes were identified. Among the 24 genes, 7 genes showed increased expression and 17 genes showed decreased expression in CHB compared with those in healthy spouses. The up-regulated genes were mainly associated with adaptive immunity, while the down-regulated genes were associated with innate immunity. CONCLUSION: Our findings suggest that HBV infection alters a broad range of immunity genes expression and innate immunity-associated genes are important in the defense against HBV chronic infection.