Chengbo Yu

Bioartificial liver system based on choanoid fluidized bed bioreactor improve the survival time of fulminant hepatic failure pigs

Bioartificial liver (BAL) support system has been proposed as potential treatment method for end‐stage liver diseases. We described an improved BAL system based on a choanoid fluidized bed bioreactor containing alginate–chitosan encapsulated primary porcine hepatocytes. The feasibility, safety, and efficiency of this device were estimated using an allogeneic fulminant hepatic failure (FHF) model. FHF was induced with intravenous administration of D‐galactosamine. Thirty FHF pigs were divided into three groups: (1) an FHF group which was only given intensive care; (2) a sham BAL group which was treated with the BAL system with empty encapsulation, and (3) a BAL group which was treated with the BAL system containing encapsulated freshly isolated primary porcine hepatocytes. The survival times and biochemical parameters of these animals were measured, and properties of the encapsulations and hepatocytes before and after perfusion were also evaluated. Compared to the two control groups, the BAL‐treated group had prolonged the survival time and decreased the blood lactate levels, blood glucose, and amino acids remained stable. No obvious ruptured beads or statistical decline in viability or function of encapsulated hepatocytes were observed. This new fluidized bed BAL system is safe and efficient. It may represent a feasible alternative in the treatment of liver failure. Biotechnol. Bioeng. 2011;108:2229–2236.

Prevalence of Hepatitis B in Insular Regions of Southeast China: A Community-Based Study

Objective Hepatitis B virus (HBV) infection remains a significant public health problem. The purpose of this study was to investigate the seroepidemiology of HBV in people living in the insular regions, and to provide the most recent baseline data for planning and monitoring of health. Methods A cross-sectional, community-based survey was conducted without age restriction, on two isolated islands, Zhoushan and Yuhuan, China. The study sample was selected by random multistage cluster sampling. Serological samples and demographic information were collected from 15878 participants. Results The prevalences of anti-HBV core antibody (anti-HBc), hepatitis B virus surface antigen (HBsAg), and anti-HBV surface antibody (anti-HBs) were 33.1, 10.4, and 56.1%, respectively. We found statistically significant differences of HBV markers in men versus women (P<0.01). The prevalence of HBV infection increased with age. There were significant differences in the rates of HBsAg and anti-HBc positivity between the two islands (P<0.01). Alanine aminotransferase (ALT) levels were elevated (>38 IU/L) in 15.6% and 7.2% of the HBsAg-positive and negative groups, respectively. Elevated ALT levels were significantly higher in males (12.0%) compared with females (5.8%) (P<0.01). The α-fetoprotein (AFP) positivity rate was 0.6% in HBsAg-positive participants over the age of 30. Conclusion Due to the geographic location, we found that the HBV prevalence and potential for the development of hepatocellular carcinoma remained high in insular regions of southeast China, and are far above the national figures. Although a vaccination program has been in effect over the last 20 years, several additional measures should be adopted by the government to limit the spread of hepatitis B. These include the management of high risk persons and the floating population living on the islands, expansion of the immune population, and increased health education for fisherman.

Effectiveness of HBV Vaccination in Infants and Prediction of HBV Prevalence Trend under New Vaccination Plan: Findings of a Large-Scale Investigation

Background Hepatitis B virus (HBV) infection remains a severe public health problem. Investigating its prevalence and trends is essential to prevention. Methods To evaluate the effectiveness of HBV vaccination under the 1992 Intervention Program for infants and predicted HBV prevalence trends under the 2011 Program for all ages. We conducted a community-based investigation of 761,544 residents of 12 counties in Zhejiang Province selected according to their location, population density, and economic development. The HBV prevalence trends were predicted by a time-shifting approach. HBV surface antigen (HBsAg) and alanine amino transferase (ALT) were determined. Results Of the 761,544 persons screened for HBsAg, 54,132 were positive (adjusted carrier rate 6.13%); 9,455 had both elevated ALT and a positive HBsAg test (standardized rate 1.18%). The standardized HBsAg carrier rate for persons aged ≤20 years was 1.51%. Key factors influencing HBV infection were sex, age, family history, drinking, smoking, employment as a migrant worker, and occupation. With the vaccination program implemented in 2011, we predict that by 2020, the HBsAg carrier rate will be 5.27% and that for individuals aged ≤34 years will reach the 2% upper limit of low prevalence according to the WHO criteria, with a standardized rate of 1.86%. Conclusions The national HBV vaccination program for infants implemented in 1992 has greatly reduced the prevalence of HBV infection. The 2011 program is likely to reduce HBV infection in Zhejiang Province to a low moderate prevalence, and perinatal transmission is expected to be controlled by 2020.

Prevalence of Hepatitis B and C in HIV-infected Patients: A meta-analysis

BACKGROUND Hepatitis C virus (HCV), hepatitis B virus (HBV) and human immunodeficiency virus (HIV) share similar routes of transmission by sexual intercourse or drug use by parenteral injection, so coinfection is common. This study aimed to determine the prevalence of coinfection with either HCV or HBV in patients infected with HIV. DATA SOURCES A meta-analysis was performed to quantify HBV coinfection with HCV in HIV patients. Published studies in the English and Chinese language medical literature involving cohorts of HIV patients concomitantly infected with HBV and/or HCV were collected from the PubMed database, ISI Web of Science, the Cochrane library clinical trials registry, CNKI (China National Knowledge Infrastructure) and Google Scholar, for relevant articles before November 2009. The search was conducted with the following key words: hepatitis C, HCV, hepatitis B, HBV, human immunodeficiency virus, HIV, and coinfection. Data were extracted from relevant studies by two investigators. RevMan 5.0 software was used to perform the meta-analysis. RESULTS We identified 22 studies involving 17 664 patients. Substantial differences in the HCV rate compared to the HBV rate in HIV patients were found in the overall analysis [odds ratio (OR)=3.00; 95% confidence interval (CI) 1.90-4.73]. A subgroup analysis showed similar results in a European group, but not in Asian or African groups. However, a meta-analysis between HIV+HBV+HCV+ and HIV+HBV+HCV- patients showed no significant difference (OR=0.91; 95% CI 0.57-1.45). Although subgroup analysis still lacked essential differences, different regions seemed to have different patterns. CONCLUSIONS HCV-HIV coinfection is more frequent than HBV-HIV coinfection overall. However, HCV infection does not affect the prevalence of HBV infection in HIV-positive patients.

Factors influencing immunologic response to hepatitis B vaccine in adults

Hepatitis B was still a worldwide health problem. This study aimed to conducted a systematic review and meta-analysis to assess a more precise estimation of factors that influence the response to hepatitis B vaccine in adults. Our included studies examined seroprotection rates close to the end of vaccination schedules in healthy adult populations. This meta-analysis including 21053 adults in 37 articles showed that a significantly decreased response to hepatitis B vaccine appeared in adults (age ≥ 40) (RR:1.86, 95% CI:1.55–2.23), male adults (RR:1.40, 95% CI:1.22–1.61), BMI ≥ 25 adults (RR:1.56, 95% CI:1.12–2.17), smoker (RR:1.53, 95% CI:1.21–1.93), and adults with concomitant disease (RR:1.39, 95% CI:1.04–1.86). Meanwhile, we further found a decreased response to hepatitis B vaccine appeared in adults (age ≥ 30) (RR:1.77, 95% CI:1.48–2.10), and adults (age ≥ 60) (RR:1.30, 95% CI:1.01–1.68). However, there were no difference in response to hepatitis B vaccine both in alcoholic (RR:0.90, 95% CI:0.64–1.26) and 0-1-12 vs. 0-1-6 vaccination schedule (RR:1.39, 95% CI:0.41–4.67). Pooling of these studies recommended the sooner the better for adult hepatitis B vaccine strategy. More vaccine doses, supplemental/additional strengthening immunity should be emphasized on the susceptible population of increasing aged, male, BMI ≥ 25, smoking and concomitant disease. The conventional 0-1-6 vaccination schedule could be still worth to be recommended.

Establishment and Characterization of Immortalized Porcine Hepatocytes for the Study of Hepatocyte Xenotransplantation

BACKGROUND In light of the critical shortage of donor livers, xenogeneic sources offer the best alternative to human hepatocytes for the treatment of acute liver failure. This study investigated whether a combination of simian virus 40 large T antigen (SV40 LT) and human telomerase catalytic subunit (hTERT) genes could immortalize primary porcine hepatocytes that could reverse acute liver failure (ALF) in rats. METHODS We cotransfected SV40 LT and hTERT genes into primary porcine hepatocytes to examine the features of the transfected cell lines. We characterized the potentially therapeutic effect of immortalized porcine hepatocytes in a rat model of ALF induced by 90% hepatectomy. RESULTS An immortalized porcine hepatocyte cell line, HepLi, was expanded by >250 passages. HepLi cells maintained the defining characteristics of primary porcine hepatocytes, including porcine albumin secretion, urea production, and diazepam metabolism. Intrasplenic transplantation of HepLi cells significantly improved liver function, and significantly prolonging the survival of rats with ALF. CONCLUSIONS Cotransfection of SV40 LT and hTERT immortalized primary porcine hepatocytes without tumorigenicity in vitro. The Immortalized porcine hepatocytes served as a potential cell resource for xenotransplantation.

In vitro large-scale cultivation and evaluation of microencapsulated immortalized human hepatocytes (HepLL) in roller bottles.

Background/Aims Microencapsulated hepatocytes have been proposed as promising bioactive agents for packed-bed or fluidized-bed bioartificial liver assist devices (BLADs) and for hepatocyte transplantation because of the potential advantages they offer of high mass transport rate and an optimal microenvironment for hepatocyte culture. We developed a large-scale and high-production alginate-chitosan (AC) microcapsule roller bottle culture system for the encapsulation of HepLL immortalized human hepatocytes. In this study, the efficacy of upscaling encapsulated HepLL cells production with roller bottle cultivation was evaluated in vitro. Methods Microencapsulated HepLL cells were grown at high yield in large-scale roller bottles, with free cells cultured in roller bottle spinners serving as controls. The mechanical stability and the permeability of the AC microcapsules were investigated, and the growth, metabolism and functions of the encapsulated HepLL cells were evaluated as compared to free cells. Results The microcapsules withstood well the shear stress induced by high agitation rates. The microcapsules were permeable to albumin, but prevented the release of immunoglobulins. Culture in roller bottles of immortalized human hepatocytes immobilized in the AC microcapsules improved cell growth, albumin synthesis, ammonia elimination and lidocaine clearance as compared with free cells cultured in roller bottles. Conclusions Encapsulated HepLL cells may be cultured on a large scale in roller bottles. This makes them possible candidates for use in cell-based liver assist therapies.

Sonographic characteristics of placental site trophoblastic tumor

To investigate clinical features and ultrasound findings in cases of placental site trophoblastic tumor (PSTT).

Construction and cellular immune response induction of HA-based alphavirus replicon vaccines against human-avian influenza (H5N1).

Several approaches are being taken worldwide to develop vaccines against H5N1 viruses; most of them, however, pose both practical and immunological challenges. One potential strategy for improving the immunogenicity of vaccines involves the use of alphavirus replicons and VP22, a herpes simplex type 1 (HSV-1) protein. In this study, we analysed the antigenic peptides and homogeneity of the HA sequences (human isolates of the H5N1 subtype, from 1997 to 2003) and explored a novel alphavirus replicon system of VP22 fused with HA, to assess whether the immunogenicity of an HA-based replicon vaccine could be induced and augmented via fusion with VP22. Further, replicon particles expressing VP22, and enhanced green fluorescent protein (EGFP) were individually used as controls. Cellular immune responses in mice immunised with replicons were evaluated by identifying specific intracellular cytokine production with flow cytometry (FCM). Animal-based experimentation indicated that both the IL-4 expression of CD4(+) T cells and the IFN-gamma expression of CD8(+) T cells were significantly increased in mice immunised with VPR-HA and VPR-VP22/HA. A dose titration effect vis-à-vis both IL-4 expression and IFN-gamma expression were observed in VPR-HA- and VPR-VP22/HA-vaccinated mice. Our results revealed that both VPR-VP22/HA and VPR-HA replicon particles presented a promising approach for developing vaccines against human-avian influenza, and VP22 could enhance the immunogenicity of the HA antigens to which it is fused.

Transmission of Hepatitis B and C Virus Infection Through Body Piercing: A Systematic Review and Meta-Analysis.

AbstractHepatitis B and hepatitis C are 2 types of potentially life-threatening liver diseases with high infection rate. Body piercing represents a progressively popular sociocultural phenomenon which is also a potential exposure approach for hepatitis B virus (HBV) and hepatitis C virus (HCV). Conclusions from those researches with statistically risk assessment of body piercing on HBV and HCV transmission are contradictory.Systematically analyze the association between body piercing and the risk of transmitting hepatitis B virus and hepatitis C virus for general population. Make evidence-based recommendations to the current practice and wake up public awareness of this health-threatening behavior.Comprehensive and high sensitivity search strategies were performed to exhaustively search related studies before 15 January 2015 (MEDLINE, EMBASE, WANFANG, CNKI datasets for published literatures, and Google and Google scholars for related grey articles). Two authors identified relevant studies for the review, abstracted data, and assessed literature quality independently and critically according to the selection criteria and quality assessment standard. Odds ratio (OR) and corresponding 95% confidence interval (CI) were used to estimate risk of HBV and HCV infection in relation to body piercing status. Subgroup analysis and sensitivity analysis were conducted to examine the source of heterogeneity and test the robust of the results.A total of 40 studies were included in this systematic review (10 for Hep-B, 26 for Hep-C, 4 for both Hep-B and Hep-C), the pooled OR (95% CI) for the association between body piercing and transmission of HBV/HCV is 1.80 (1.18, 2.75) and 1.83 (1.27, 2.64), respectively. Subgroup analysis suggested that highest risk of body piercing related to hepatitis C infection was for former soccer and veterans with OR of 4.63 (2.65, 8.10), while strongest association between body piercing and hepatitis B was for samples derived from students/community with OR of 2.40 (1.44, 4.02).The current systematic review and meta-analysis suggests that body piercing is significantly associated with the transmission of HBV as well as HCV, having body piercing probably can increase the risk of getting infected. Evidence from this study strongly recommends that comprehensive and effective programs should be established to provide safer piercing practice.