The expression levels of LC3-II and P62 were increased by PA,

The expression levels of LC3-II and P62 were increased by PA,

suggesting that PA inhibits the autophagic process after autophagosome formation. PA also increased the expression level of Rubicon, a negative regulator of autophagosome-lysosome fusion. The inhibition of autophagy by PA was observed earlier (4h) than PA-induced apoptosis (8h). To examine the effect of learn more PA’s autophagy inhibition on apoptosis, HepG2 cells were transfected with siRNA against Atg7 or Rubicon, followed by PA treatment. Autoph-agy inhibition by Atg7 konckdown exacerbated PA-induced apoptosis. Interestingly, Rubicon knockdown clearly abolished PA-induced inhibition of autophagic flux, reduced ER stress and ameliorated PA-induced apoptosis. Consistent with in vitro findings, mice on HFD for 3 months or more showed increased hepatocyte apoptosis compared with mice on control diet, evidenced by increase in serum ALT levels or caspase-activity and TUNEL-positive cells in the liver. Rubicon expression was increased for 1 month or more and increase of LC3-II and P62 were observed in murine livers on HFD for 2 months or more. Injection of PolyI:C into Mx1-Cre Atg7 fl/fl mice which had been given 1 month HFD inhibited liver autophagy and clearly induced live injury as evidenced by increase in serum ALT levels and TUNEL-positive hepatocytes

accompanied by JNK activation. siRNA-mediated in vivo knockdown of Rubicon ameliorated autophagy inhibition in livers of mice on HFD for 4 months. It inhibited ER stress and hepatocyte apoptosis. Conclusion: Increased expression

of Rubicon induced by HFD, as well as PA, suppresses click here autophagic flux and promotes hepatocyte apoptosis by increasing ER stress. Enhancement of autophagy by inhibiting Rubicon 上海皓元医药股份有限公司 may provide new approaches for treatment of NAFLD. Disclosures: Tetsuo Takehara – Grant/Research Support: Chugai Pharmaceutical Co., MSD K.K. The following people have nothing to disclose: Satoshi Tanaka, Hayato Hikita, Yasutoshi Nozaki, Yugo Kai, Tasuku Nakabori, Yoshinobu Saito, Ryotaro Saka-mori, Takuya Miyagi, Naoki Hiramatsu, Tomohide Tatsumi Obesity, insulin resistance, and diabetes have become the leading causes of renal and nonalcoholic fatty liver disease (NAFLD), and nonalcoholic steatohepatitis (NASH). Currently, there is no established therapy of NASH. Lifestyle alterations including diet and exercise often fail to prevent or reverse NASH. The purpose of the present study was to determine if in mice fed a Western (high fat, high sucrose, cholesterol) diet with established obesity, insulin resistance, NAFLD, and NASH, treatment with the dual agonist of the nuclear receptor the farnesoid X receptor (FXR) and the G protein coupled receptor TGR5, 6α-ethyl-3α,7α,23-trihydroxy-24-nor-5β-cholan-23-sulfate sodium salt (INT-767) decreases the progression of liver disease.

All had received continuous lamivudine treatment for 6 months or

All had received continuous lamivudine treatment for 6 months or more. Other inclusion criteria were: HBV DNA levels ≥1 × 106 copies/mL (measured by the COBAS Amplicor HBV Monitor assay; Roche Diagnostics, Branchburg,

NJ; lower limit of detection 300 copies/mL); ALT value between 1.5 and 10 × ULN; and for women of child-bearing potential, negative serum pregnancy test prior to study entry, and willingness to use at least two contraception methods including a barrier method. Patients with the following criteria were excluded: coinfection with hepatitis C, hepatitis D, and human immunodeficiency virus; pregnancy or breast-feeding; use of known nephrotoxic or hepatotoxic agents; treatment with http://www.selleckchem.com/products/abt-199.html immunomodulatory agents or corticosteroids within 6 months prior to study entry; decompensated liver disease AT9283 with clinical complications of cirrhosis; prothrombin time >3 seconds prolonged relative to the normal control; serum albumin <30 g/L and bilirubin >2.5 × ULN; or other laboratory parameters, including hemoglobin <9.0 g/dL (unless due to

haemoglobinopathy), absolute neutrophil count <1.5 × 109/L, platelet count <100 × 109/L, creatinine >133 μmol/L, serum amylase >1.5 × ULN, lipase >1.5 × ULN, alpha-fetoprotein level >20 ng/mL, and ultrasonography performed prior to baseline with findings indicative of hepatocellular carcinoma. The efficacy variable was serum HBV DNA levels. The primary efficacy endpoint was a reduction in log10 serum HBV DNA level from baseline at week 12. Secondary efficacy endpoints included: reduction in log10 serum HBV DNA level from baseline at week 4; proportion of patients with HBeAg seroconversion at week 12; proportion of patients with HBsAg seroconversion at week 12; and proportion of patients with ALT normalization at week 12. Evaluation of safety of the study drug was based on

adverse event (AE) and serious AE data, DLT data, clinical laboratory reports, physical examinations, and vital signs. The predetermined amount of creatinine increase was set as >125% of the baseline creatinine level, and this was for easy alertness of MCE公司 possible abnormal data to the investigators. HBeAg seroconversion was defined as loss of HBeAg with the development of antibody to HBeAg. Virologic rebound was defined as an increase of HBV DNA level by more than 1 log compared with the nadir in patients who achieved more than 1 log reduction of HBV DNA during the treatment period compared with baseline HBV DNA levels. Surveillance of possible LB80380 and adefovir viral mutations were not conducted because of the limited duration of LB80380 treatment of 12 weeks and adefovir treatment for 24 weeks. Evaluation of patient disposition was based on the enrolled population. The per-protocol (PP) population included all patients who were treated for at least 12 weeks with LB80380 with at least 80% compliance and had no major protocol violations.

All had received continuous lamivudine treatment for 6 months or

All had received continuous lamivudine treatment for 6 months or more. Other inclusion criteria were: HBV DNA levels ≥1 × 106 copies/mL (measured by the COBAS Amplicor HBV Monitor assay; Roche Diagnostics, Branchburg,

NJ; lower limit of detection 300 copies/mL); ALT value between 1.5 and 10 × ULN; and for women of child-bearing potential, negative serum pregnancy test prior to study entry, and willingness to use at least two contraception methods including a barrier method. Patients with the following criteria were excluded: coinfection with hepatitis C, hepatitis D, and human immunodeficiency virus; pregnancy or breast-feeding; use of known nephrotoxic or hepatotoxic agents; treatment with Selleck NVP-AUY922 immunomodulatory agents or corticosteroids within 6 months prior to study entry; decompensated liver disease PD-0332991 cell line with clinical complications of cirrhosis; prothrombin time >3 seconds prolonged relative to the normal control; serum albumin <30 g/L and bilirubin >2.5 × ULN; or other laboratory parameters, including hemoglobin <9.0 g/dL (unless due to

haemoglobinopathy), absolute neutrophil count <1.5 × 109/L, platelet count <100 × 109/L, creatinine >133 μmol/L, serum amylase >1.5 × ULN, lipase >1.5 × ULN, alpha-fetoprotein level >20 ng/mL, and ultrasonography performed prior to baseline with findings indicative of hepatocellular carcinoma. The efficacy variable was serum HBV DNA levels. The primary efficacy endpoint was a reduction in log10 serum HBV DNA level from baseline at week 12. Secondary efficacy endpoints included: reduction in log10 serum HBV DNA level from baseline at week 4; proportion of patients with HBeAg seroconversion at week 12; proportion of patients with HBsAg seroconversion at week 12; and proportion of patients with ALT normalization at week 12. Evaluation of safety of the study drug was based on

adverse event (AE) and serious AE data, DLT data, clinical laboratory reports, physical examinations, and vital signs. The predetermined amount of creatinine increase was set as >125% of the baseline creatinine level, and this was for easy alertness of medchemexpress possible abnormal data to the investigators. HBeAg seroconversion was defined as loss of HBeAg with the development of antibody to HBeAg. Virologic rebound was defined as an increase of HBV DNA level by more than 1 log compared with the nadir in patients who achieved more than 1 log reduction of HBV DNA during the treatment period compared with baseline HBV DNA levels. Surveillance of possible LB80380 and adefovir viral mutations were not conducted because of the limited duration of LB80380 treatment of 12 weeks and adefovir treatment for 24 weeks. Evaluation of patient disposition was based on the enrolled population. The per-protocol (PP) population included all patients who were treated for at least 12 weeks with LB80380 with at least 80% compliance and had no major protocol violations.

All had received continuous lamivudine treatment for 6 months or

All had received continuous lamivudine treatment for 6 months or more. Other inclusion criteria were: HBV DNA levels ≥1 × 106 copies/mL (measured by the COBAS Amplicor HBV Monitor assay; Roche Diagnostics, Branchburg,

NJ; lower limit of detection 300 copies/mL); ALT value between 1.5 and 10 × ULN; and for women of child-bearing potential, negative serum pregnancy test prior to study entry, and willingness to use at least two contraception methods including a barrier method. Patients with the following criteria were excluded: coinfection with hepatitis C, hepatitis D, and human immunodeficiency virus; pregnancy or breast-feeding; use of known nephrotoxic or hepatotoxic agents; treatment with Selleckchem INK128 immunomodulatory agents or corticosteroids within 6 months prior to study entry; decompensated liver disease GW-572016 cost with clinical complications of cirrhosis; prothrombin time >3 seconds prolonged relative to the normal control; serum albumin <30 g/L and bilirubin >2.5 × ULN; or other laboratory parameters, including hemoglobin <9.0 g/dL (unless due to

haemoglobinopathy), absolute neutrophil count <1.5 × 109/L, platelet count <100 × 109/L, creatinine >133 μmol/L, serum amylase >1.5 × ULN, lipase >1.5 × ULN, alpha-fetoprotein level >20 ng/mL, and ultrasonography performed prior to baseline with findings indicative of hepatocellular carcinoma. The efficacy variable was serum HBV DNA levels. The primary efficacy endpoint was a reduction in log10 serum HBV DNA level from baseline at week 12. Secondary efficacy endpoints included: reduction in log10 serum HBV DNA level from baseline at week 4; proportion of patients with HBeAg seroconversion at week 12; proportion of patients with HBsAg seroconversion at week 12; and proportion of patients with ALT normalization at week 12. Evaluation of safety of the study drug was based on

adverse event (AE) and serious AE data, DLT data, clinical laboratory reports, physical examinations, and vital signs. The predetermined amount of creatinine increase was set as >125% of the baseline creatinine level, and this was for easy alertness of 上海皓元 possible abnormal data to the investigators. HBeAg seroconversion was defined as loss of HBeAg with the development of antibody to HBeAg. Virologic rebound was defined as an increase of HBV DNA level by more than 1 log compared with the nadir in patients who achieved more than 1 log reduction of HBV DNA during the treatment period compared with baseline HBV DNA levels. Surveillance of possible LB80380 and adefovir viral mutations were not conducted because of the limited duration of LB80380 treatment of 12 weeks and adefovir treatment for 24 weeks. Evaluation of patient disposition was based on the enrolled population. The per-protocol (PP) population included all patients who were treated for at least 12 weeks with LB80380 with at least 80% compliance and had no major protocol violations.

[30] The level of infection was monitored by confocal imaging of

[30] The level of infection was monitored by confocal imaging of liver sections to detect mRFP-positive cells. InsP3-Buffer-NLS was efficiently delivered and expressed in nearly 100% of hepatocyte nuclei (Fig 5A, insert). A comparable ��-catenin signaling efficiency of infection was observed in InsP3-Buffer-NES animals (not shown). BrdU uptake was impaired in animals expressing InsP3-Buffer-NLS, compared to control hepatectomized (PH) animals (Fig. 5B). Of note, expression of InsP3-Buffer-NES did not significantly alter BrdU

uptake, when compared to control PH animals, although this value was significantly higher than in InsP3-Buffer-NLS animals (Fig. 5B). Additionally, liver/body weight ratio after PH was reduced in InsP3-Buffer-NLS animals, when compared to sham or PH animals (Fig. 5C). InsP3-Buffer-NES animals had a smaller liver/body weight ratio, when compared to sham animals, although this value was not significantly different from control PH animals. Indeed, IR levels in the nucleus Rucaparib mouse were increased 24 hours after PH in PH animals, compared to sham animals, as evidenced by IHC (Fig. 5D) and immunoblotting (Supporting Fig.

2). The 24-hour time point was chosen because it is the time at which the rate of DNA synthesis reaches its peak in hepatocytes after PH.[2] Positive proliferating cell nuclear antigen labeling in PH animals confirms medchemexpress that hepatocytes are undergoing cell proliferation under these conditions (Supporting Fig. 2). These results show that liver regeneration after PH depends on nuclear InsP3, and increased nuclear IR may contribute, at least

in part, to this process, in accord with our observations in vitro. To investigate whether either cytosolic or nuclear InsP3 participate in insulin’s metabolic actions, we analyzed blood glucose levels and liver glycogen content under control, nuclear (InsP3-Buffer-NLS), and cytosolic (InsP3-Buffer-NES) InsP3 buffering. Using one-way ANOVA with Bonferroni’s post-tests, cytosolic, but not nuclear InsP3 buffering significantly reduced blood glucose levels (Fig. 5E) and increased liver glycogen content, compared to control animals (Fig. 5F). These results are consistent with the idea that nuclear InsP3 mediates insulin’s effects on liver regeneration, but is unrelated to insulin’s metabolic actions. The effects of Ca2+ on hepatocyte proliferation are closely related to the subcellular compartments where it is released. For instance, buffering mitochondrial Ca2+ inhibits apoptosis and accelerates liver regeneration on that basis.[30] On the other hand, buffering cytosolic Ca2+ retards liver regeneration and progression through the cell cycle after PH,[31] although there are a number of mechanisms by which cytosolic Ca2+ can increase,[10] and different sources of cytosolic Ca2+ may have different effects.

We conducted a systematic review of observational

studies

We conducted a systematic review of observational

studies reporting cardiovascular (CV) outcomes in patients receiving clopidogrel with or without a PPI, focusing on the differences between omeprazole/esomeprazole and other PPIs. Methods: The Embase and Medline literature databases were searched for abstracts and full papers on 9 July 2012. References identified during routine drug safety surveillance by AstraZeneca were also included. Reports on non-observational studies (including clinical trials and clinical pharmacology studies) were excluded. Results: In total, 68 observational studies were included in the review. Overall, in 31 references (45.6%) the authors reported a statistically significant increase in CV event rates in patients receiving clopidogrel with a PPI compared with those receiving clopidogrel without a PPI. The remaining 37 references (54.4%) reported no such increase. INCB024360 purchase Twenty-one references reported the results for different PPIs separately. All of these references that showed a significant association between omeprazole or esomeprazole coprescription with clopidogrel and adverse CV events also showed an association of comparable magnitude (with overlapping 95% confidence intervals)

for clopidogrel coprescription with other PPIs. Conclusion: In the 68 observational studies analysed, there was considerable variability in the reported clinical outcomes associated with coprescription of a PPI with clopidogrel. There was no consistent evidence of higher CV event rates in

Trametinib supplier patients receiving both types of drug. In the references that provided results for individual PPIs, there was no evidence that omeprazole or esomeprazole are more likely than other PPIs to affect clinical outcomes in patients receiving clopidogrel. Key Word(s): 1. Clopidogrel; 2. PPI; 3. Drug interactions; 4. Adverse events; Presenting Author: NAZRI MUSTAFFA Additional Authors: YASMINM YACCOB, YEONG YEH LEE, HARSA AMYLIA MAT SAKIM, ZURIANI SOBRI, NOR AIZAL CHE HAMZAH, NOR ASHIDI MAT ISA Corresponding Author: YEONG YEH LEE Affiliations: Universiti Sains Malaysia Objective: Endoscopically, 上海皓元医药股份有限公司 atrophic gastritis is difficult to determine reliably and requires histological confirmation. Current study examines novel computer-aided approaches towards improving endoscopic identification of atrophic gastritis. Methods: After acquisition, digitized images of endoscopic gastritis underwent firstly, image pre-processing followed by feature extraction. Image pre-processing involved image enhancement of regions of interest (ROI), cropping (100 × 100 pixels) and color conversion. Features were then extracted for textures using Gray Level Co-occurrence Matrix (GLCM) technique and color using color moment approach.

We conducted a systematic review of observational

studies

We conducted a systematic review of observational

studies reporting cardiovascular (CV) outcomes in patients receiving clopidogrel with or without a PPI, focusing on the differences between omeprazole/esomeprazole and other PPIs. Methods: The Embase and Medline literature databases were searched for abstracts and full papers on 9 July 2012. References identified during routine drug safety surveillance by AstraZeneca were also included. Reports on non-observational studies (including clinical trials and clinical pharmacology studies) were excluded. Results: In total, 68 observational studies were included in the review. Overall, in 31 references (45.6%) the authors reported a statistically significant increase in CV event rates in patients receiving clopidogrel with a PPI compared with those receiving clopidogrel without a PPI. The remaining 37 references (54.4%) reported no such increase. selleck Twenty-one references reported the results for different PPIs separately. All of these references that showed a significant association between omeprazole or esomeprazole coprescription with clopidogrel and adverse CV events also showed an association of comparable magnitude (with overlapping 95% confidence intervals)

for clopidogrel coprescription with other PPIs. Conclusion: In the 68 observational studies analysed, there was considerable variability in the reported clinical outcomes associated with coprescription of a PPI with clopidogrel. There was no consistent evidence of higher CV event rates in

find more patients receiving both types of drug. In the references that provided results for individual PPIs, there was no evidence that omeprazole or esomeprazole are more likely than other PPIs to affect clinical outcomes in patients receiving clopidogrel. Key Word(s): 1. Clopidogrel; 2. PPI; 3. Drug interactions; 4. Adverse events; Presenting Author: NAZRI MUSTAFFA Additional Authors: YASMINM YACCOB, YEONG YEH LEE, HARSA AMYLIA MAT SAKIM, ZURIANI SOBRI, NOR AIZAL CHE HAMZAH, NOR ASHIDI MAT ISA Corresponding Author: YEONG YEH LEE Affiliations: Universiti Sains Malaysia Objective: Endoscopically, MCE公司 atrophic gastritis is difficult to determine reliably and requires histological confirmation. Current study examines novel computer-aided approaches towards improving endoscopic identification of atrophic gastritis. Methods: After acquisition, digitized images of endoscopic gastritis underwent firstly, image pre-processing followed by feature extraction. Image pre-processing involved image enhancement of regions of interest (ROI), cropping (100 × 100 pixels) and color conversion. Features were then extracted for textures using Gray Level Co-occurrence Matrix (GLCM) technique and color using color moment approach.

Methods: Nineteen patients with CD were followed up All the pati

Methods: Nineteen patients with CD were followed up. All the patients received 5 mg/kg of IFX infusion thrice at weeks 0, 2, and 6, and followed by maintenance

regimen at every 8 weeks. Plasma samples for the evaluation of baseline-TNF were collected just before the first infusion of IFX. Crohn’s disease activity index (CDAI) was evaluated at week 0, 6, and 54. Remission was defined as CDAI below 150. Results: CDAI of all the 19 patients before IFX infusion was 227 ± 76. At week 6, 14 patients (73.7%) reached remission (remission group) and 5 patients (26.3%) did not reach remission (non-remission group). Although a significant difference was not observed between the two groups, the level of baseline-TNF in non-remission group is higher than remission group. At week 54, 11 (78.6%) of 14 patients were maintaining remission and 3 patients (21.4%) INK128 were not maintaining remission. The level of baseline-TNF was significantly higher in non-remission group than the remission group at week 54. Conclusion: In patients with CD, baseline-TNF

is significantly associated with the clinical response in the period of remission maintenance therapy. Baseline-TNF may be a predicting factor of the second failure and a useful measure for personalising the treatment of CD using IFX. Key Word(s): 1. Crohn’s disease; 2. infliximab; 3. TNFalpha Presenting Author: CHRISTINA TJAN ONG Additional Authors: YUQIN CHER, AJMAL KADER, VEENA LOGARAJAH, KONG BOO PHUA Corresponding Author: CHRISTINA

medchemexpress TJAN ONG Affiliations: Yong Loo Lin Medical School, Kk Hospital, Kk Hospital, Kk Hospital Objective: Prevalence Luminespib of Paediatric Inflammatory Bowel Disease (PIBD) is increasing worldwide although data in Southeast-Asian population remains scarce. This study aims to evaluate the characteristics and trends of IBD in a cohort of Southeast-Asian children Methods: IBD database from a pediatric tertiary hospital in Singapore over 18years (1996–2013) was retrospectively reviewed for clinical, radiological and endoscopy data Results: 123 PIBD patients were identified: Crohn’s disease (CD) n = 82; Ulcerative colitis (UC) n = 28; Indeterminate Colitis(IC) n = 13. Mean age = 10.7 y (range: 1.5–17); 72Males:51Females. Newly diagnosed PIBD cases/year have increased significantly: before 2010(n < 8/year), 2011 (n = 13), 2012 (n = 24), 2013 (n = 37). Ethnicity: Chinese 55/123 (44.7%), Indians 39/123 (31.7%), Malays 19/123 (15.4%), Others 10/123 (8.1%). Common presenting features: CD: abdominal pain 70/82 (85.4%), weight loss 62/82 (75.6%), diarrhea 53/82 (64.6%). UC: bloody stools 25/28 (89.3%), diarrhoea 25/28 (89.3%). Physical examination findings: Most common in CD: mouth ulcers 30/82 (36.6%), perianal fistulas 15/82 (18.3%), skin tags/fissures 28/82 (34.1%). Physical findings were less common in UC patients.

97 The antibody response was found to be dose-dependent97 In a p

97 The antibody response was found to be dose-dependent.97 In a phase II–III efficacy trial, nearly 2000 volunteer Nepalese soldiers who lacked detectable anti-HEV antibodies were randomized to receive either 20 µg of this vaccine or a matched placebo, each given as three doses at 0, 1 and 6 months, and were followed up for a median of 804 days.98 The study subjects were overwhelmingly (>99%) male and mostly young (mean age = 25 years). Clinically overt acute hepatitis E occurred less frequently among vaccine recipients who completed the 3-dose schedule

than among placebo recipients, with a vaccine efficacy rate of 95%. Administration of two doses was associated with a somewhat lower efficacy rate of 86%. Adverse events were similar selleckchem except for more frequent injection-site pain with the vaccine. The second vaccine, named as the HEV 239 vaccine, contains a more truncated

HEV capsid see more protein (corresponding to aminoacids 368–606) expressed in Escherichia coli, which has been purified and adsorbed on aluminum hydroxide suspended in buffered saline.99 In a phase II human trial, all volunteers who lacked anti-HEV antibody showed seroconversion one month after three doses of 20 µg each, administered at 0, 1 and 6 months, respectively.100 A large, community-based, randomized, double-blind, placebo-controlled, phase III trial of this vaccine has recently been completed in China.101 This study enrolled nearly 113 000 participants, aged 16–65 years and of either gender, irrespective of their anti-HEV antibody status. Among the approximately 97 000 participants who received three dose of the vaccine (30 µg each, at 0, 1 and 6 months), the protective efficacy rate was 100% during the next one year. Even after two doses of the vaccine, 100% protection was noted, though these data were more limited. No comparative data on the safety and immunogenicity of the two vaccines are available. Further data are needed on the safety of these vaccines among pregnant women and children, and in special groups such as persons with

chronic liver disease. 上海皓元 Studies with both the vaccines have focused on clinical disease and have not studied the HEV infection rates; it thus remains unclear whether these vaccines can reduce transmission of infection in a community. The duration of protection with both the vaccines also remains unclear. In addition, more data are needed on protective efficacy of these vaccines when these are administered post-exposure. The Chinese vaccine has been shown to provide protection against genotype 4 HEV infections, even though it is based on genotype 1 virus. Whether these vaccines provide protection against genotype 3 virus strains prevalent in developed countries needs further study. The exact role for HEV vaccines currently remains unclear.

97 The antibody response was found to be dose-dependent97 In a p

97 The antibody response was found to be dose-dependent.97 In a phase II–III efficacy trial, nearly 2000 volunteer Nepalese soldiers who lacked detectable anti-HEV antibodies were randomized to receive either 20 µg of this vaccine or a matched placebo, each given as three doses at 0, 1 and 6 months, and were followed up for a median of 804 days.98 The study subjects were overwhelmingly (>99%) male and mostly young (mean age = 25 years). Clinically overt acute hepatitis E occurred less frequently among vaccine recipients who completed the 3-dose schedule

than among placebo recipients, with a vaccine efficacy rate of 95%. Administration of two doses was associated with a somewhat lower efficacy rate of 86%. Adverse events were similar selleck inhibitor except for more frequent injection-site pain with the vaccine. The second vaccine, named as the HEV 239 vaccine, contains a more truncated

HEV capsid http://www.selleckchem.com/products/17-AAG(Geldanamycin).html protein (corresponding to aminoacids 368–606) expressed in Escherichia coli, which has been purified and adsorbed on aluminum hydroxide suspended in buffered saline.99 In a phase II human trial, all volunteers who lacked anti-HEV antibody showed seroconversion one month after three doses of 20 µg each, administered at 0, 1 and 6 months, respectively.100 A large, community-based, randomized, double-blind, placebo-controlled, phase III trial of this vaccine has recently been completed in China.101 This study enrolled nearly 113 000 participants, aged 16–65 years and of either gender, irrespective of their anti-HEV antibody status. Among the approximately 97 000 participants who received three dose of the vaccine (30 µg each, at 0, 1 and 6 months), the protective efficacy rate was 100% during the next one year. Even after two doses of the vaccine, 100% protection was noted, though these data were more limited. No comparative data on the safety and immunogenicity of the two vaccines are available. Further data are needed on the safety of these vaccines among pregnant women and children, and in special groups such as persons with

chronic liver disease. 上海皓元 Studies with both the vaccines have focused on clinical disease and have not studied the HEV infection rates; it thus remains unclear whether these vaccines can reduce transmission of infection in a community. The duration of protection with both the vaccines also remains unclear. In addition, more data are needed on protective efficacy of these vaccines when these are administered post-exposure. The Chinese vaccine has been shown to provide protection against genotype 4 HEV infections, even though it is based on genotype 1 virus. Whether these vaccines provide protection against genotype 3 virus strains prevalent in developed countries needs further study. The exact role for HEV vaccines currently remains unclear.