108 Military Central Hospital

Thành Phố Nam Định, Vietnam

108 Military Central Hospital

Thành Phố Nam Định, Vietnam
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Hoan N.X.,University of Tübingen | Hoan N.X.,108 Military Central Hospital | Van Tong H.,University of Tübingen | Van Tong H.,Hanoi Medical University | And 11 more authors.
Oncotarget | Year: 2017

The clinical manifestations of hepatitis B viral infection (HBV) include chronic hepatitis B (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). The contribution of negative regulator suppressor of cytokine signaling-3 (SOCS3) promoter variants in HBV disease and SOCS3 hypermethylation in tumor tissues were investigated. The SOCS3 promoter region was screened for polymorphisms in 878 HBV patients and in 272 healthy individuals. SOCS3 promoter methylation was examined by bisulfite sequencing. SOCS3 mRNA expression was quantified in 37 tumor and adjacent non-tumor liver tissue specimens. The minor allele rs12953258A was associated with increased susceptibility to HBV infection (OR=1.3, 95%CI=1.1-1.6, adjusted P=0.03). The minor allele rs111033850C and rs12953258A were observed in increased frequencies in HCC and LC patients compared to CHB patients (HCC: OR=1.7, 95%CI=1.1-2.9, adjusted P=0.046; LC: OR=1.4, 95%CI=1.1-1.9, adjusted P=0.017, respectively). HBV patients with rs111033850CC major genotype had decreased viral load (P=0.034), whereas the rs12953258AA major genotype contributed towards increased viral load (P=0.029). Tumor tissues revealed increased hypermethylation compared to adjacent non-tumor tissues (OR=5.4; 95%CI= 1.9-17.1; P=0.001). Increased SOCS3 expression was observed in HBV infested tumor tissues than non- HBV related tumor tissues (P=0.0048). SOCS3 promoter hypermethylation was associated with relatively low mRNA expression in tumor tissues (P=0.0023). In conclusion, SOCS3 promoter variants are associated with HBV susceptibility and SOCS3 hypermethylation stimulates HCC development.


Nguyen H.M.,Duy Tan University | Sy B.T.,108 Military Central Hospital | Trung N.T.,Duy Tan University | Hoan N.X.,University of Tübingen | And 4 more authors.
PLoS ONE | Year: 2017

Hepatitis D virus (HDV) infection plays an important role in liver diseases. However, the molecular epidemiology and impact of HDV infection in chronic hepatitis B (CHB) remain uncertain in Vietnam. This cross-sectional study aimed to investigate the prevalence and genotype distribution of HDV among HBsAg-positive patients in Central Vietnam. 250 CHB patients were tested for HDV using newly established HDV-specific RT-PCR techniques. HDV genotypes were determined by direct sequencing. Of the 250 patients 25 (10%) had detectable copies of HDV viral RNA. HDV-2 was predominant (20/25; 80%) followed by HDV-1 (5/25; 20%). Proven HDV genotypes share the Asian nomenclature. Chronic hepatitis B patients with concomitant HDV-1 showed higher HBV loads as compared to HDV-2 infected patients [median log10 (HBV-DNA copies/ml): 8.5 vs. 4.4, P = 0.036]. Our findings indicate that HDV infection is highly prevalent and HDV-2 is predominant in Central Vietnam. The data will add new information to the management of HBsAg-positive patients in a highly HBV endemic region to in- or exclude HDV infection in terms of diagnostic and treatment options. © 2017 Nguyen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Cartwright S.P.,Aston University | Bill R.M.,Aston University | Sy B.T.,Vietnam National University, Ho Chi Minh City | Tran-Van H.,108 Military Central Hospital | Nguyen H.M.,Duy Tan University
BMC Research Notes | Year: 2017

Objective: Patients with dual hepatitis B (HBV) and hepatitis D (HDV) virus infection are at an increased risk of progression to liver cirrhosis and hepatocellular carcinoma than patients with a single viral infection. Treatment of viral hepatitis due to dual HBV/HDV infection represents a challenge. Currently there is no vaccine against HDV. Recombinant production of HDV antigen (HDAg) is the first step towards a potential vaccine candidate and the development of assays for HDV detection. Results: This study demonstrates the expression of one HDAg isoform, S-HDAg, in Pichia pastoris. A recombinant vector carrying a tagged gene encoding S-HDAg under the control of the methanol-inducible promoter AOX1 was designed and integrated into P. pastoris X33. The protein, which was purified using a Ni2+ affinity column and eluted at 100-150 mM imidazole, has potential as a recombinant antigen for further study. © 2017 The Author(s).


Binh T.T.,Oita University | Binh T.T.,Cho Ray Hospital | Tuan V.P.,Oita University | Tuan V.P.,Cho Ray Hospital | And 12 more authors.
Gut Pathogens | Year: 2017

Background: The incidence of gastric cancer in the Northern city, Hanoi is higher than in the Southern city, Ho Chi Minh, Vietnam. We previously reported that Helicobacter pylori vacA m1 genotype might be responsible for the difference between the two cities, however, the study only included non-cancer patients. The aim of this study is to investigate the non-cardia gastric cancer characteristics and the role of H. pylori virulence on different non-cardia gastric cancer incidence between two cities in Vietnam. Methods and Results: We recruited 282 non-cardia gastric cancer patients that had undergone gastroscopy in two cities, Ho Chi Minh and Hanoi, Vietnam. Characteristics of non-cardia gastric cancer were late age of onset (mean age, 62.5 years), predominance in males (ratio of males/females; 3.9:1), diffuse type (55.3%), and high prevalence of H. pylori infection (79.4%). H. pylori infection and the vacA m1 genotype conferred an increased risk for GC (OR, 2.02; 95% CI 1.4-3.0; P = 0.0003 and OR, 2.7; 95% CI 1.5-4.7; P = 0.001, respectively). Interestingly, the presence of vacA m1 genotype in the gastric cancer group was significantly higher than that in the non-cancer group (68.8% vs 44.9%, P = 0.001) and the significant tendency still observed in Ho Chi Minh (67.6% vs 31.9%, P < 0.0001). Conclusion: We first describe the characteristics of non-cardia gastric cancer in Vietnam. Helicobacter pylori infection was associated with the development of non-cardia GC. vacA m1 genotype might contribute to incidence differences between the two cities. © 2017 The Author(s).


PubMed | University of Tübingen, 108 Military Hospital and 108 Military Central Hospital
Type: Journal Article | Journal: Journal of medical case reports | Year: 2016

Neurosurgery may pose the risk of patients developing nosocomial meningitis caused by infection with hospital pathogens. Rapid detection of the causative pathogens is essential for selecting the appropriate antibiotic treatment. However, the classical culture-based detection of bacterial infection is time-consuming and often fails to establish the correct diagnosis. Molecular techniques offer improved diagnostic means to guide the proper antibiotic therapy.A 32-year-old Vietnamese man underwent neurosurgery and subsequently developed meningitis. The classical bacterial culture method failed to detect any infectious agents, whereas polymerase chain reaction-based assays identified Acinetobacter baumannii as the causative pathogen. In addition, detection of the acquired extended-spectrum beta-lactamase gene VEB and carbapenem resistance genes NDM-1 and IMP suggested that the isolated A. baumannii strain was multidrug resistant. Upon the establishment of the correct diagnosis, an adequate treatment regimen was chosen and he recovered completely.This case report demonstrates the usefulness of the molecular approach as an important addendum and alternative to culture-based diagnosis in order to detect the pathogen causative for meningitis, including the indicators for resistance.


Hong Bang M.H.,108 Military Central Hospital | Van Riep T.,108 Military Central Hospital | Thinh N.T.,108 Military Central Hospital | Huu Song L.E.,108 Military Central Hospital | And 7 more authors.
Anticancer Research | Year: 2010

Background and Aims: This study examined the efficacy of arabinoxylan rice bran (MGN-3) in conjunction with an interventional therapy (IT) for the treatment of hepatocellular carcinoma patients. Patients and Methods: A total of sixty-eight patients with hepatocellular carcinoma (stages I and II) participated in the study. Patients were randomized to receive IT (30 patients, control group) or IT+MGN-3 (38 patients), and randomly divided into two groups using a computer-generated randomization list. Patients and investigators were blinded. IT included transarterial oily chemoembolization (TOCE) or a combination of TOCE and percutaneous ethanol injection treatment (PEIT). Results: Patients in the IT+MGN-3 group showed: (i) lower recurrence of the disease, 31.6% (12/38), as compared to 46.7% (14/30) for the control; (ii) higher survival after the second year, 35%, as compared to 6.7% for the control; (iii) significantly lower alpha-fetoprotein level, a 38% decrease (p=0.0001), as compared to baseline value, while the control showed no significant change; and (iv) a significant decrease in tumor volume, in contrast to the control, which showed no significant change. When the results were analyzed according to each IT modality, MGN-3+IT sub-groups displayed a greater response to treatment, in every aspect examined, than the IT sub-groups alone. However, the patients in the MGN-3+TOCE+PEIT sub-group demonstrated greater reduction in AFP levels and longer survival time than the MGN-3+TOCE sub-group. Conclusion: MGN-3 in conjunction with IT may be useful for the treatment of hepatocellular carcinoma and warrants further investigation in multiple clinical trials.


Nguyen H.K.L.,National Institute of Hygiene and Epidemiology | Nguyen P.T.K.,108 Military Central Hospital | Nguyen T.C.,National Institute of Hygiene and Epidemiology | Hoang P.V.M.,National Institute of Hygiene and Epidemiology | And 6 more authors.
Influenza and other Respiratory Viruses | Year: 2015

Objectives: Influenza A/H1N1pdm09 virus was first detected in Vietnam on May 31, 2009, and continues to circulate in Vietnam as a seasonal influenza virus. This study has monitored genotypic and phenotypic changes in this group of viruses during 2010-2013 period. Design and setting: We sequenced hemagglutinin (HA) and neuraminidase (NA) genes from representative influenza A/H1N1pdm09 and compared with vaccine strain A/California/07/09 and other contemporary isolates from neighboring countries. Hemagglutination inhibition (HI) and neuraminidase inhibition (NAI) assays also were performed on these isolates. Sample: Representative influenza A/H1N1pdm09 isolates (n = 61) from ILI and SARI surveillances in northern Vietnam between 2010 and 2013. Main outcome measures and results: The HA and NA phylogenies revealed six and seven groups, respectively. Five isolates (8·2%) had substitutions G155E and N156K in the HA, which were associated with reduced HI titers by antiserum raised against the vaccine virus A/California/07/2009. One isolate from 2011 and one isolate from 2013 had a predicted H275Y substitution in the neuraminidase molecule, which was associated with reduced susceptibility to oseltamivir in a NAI assay. We also identified a D222N change in the HA of a virus isolated from a fatal case in 2013. Conclusions: Significant genotypic and phenotypic changes in A/ H1N1pdm09 influenza viruses were detected by the National Influenza Surveillance System (NISS) in Vietnam between 2010 and 2013 highlighting the value of this system to Vietnam and to the region. Sustained NISS and continued virological monitoring of seasonal influenza viruses are required for vaccine policy development in Vietnam. 3. © 2015 The Authors.


PubMed | University of Tübingen, 108 Military Central Hospital, Vietnamese German Center for Medical Research and Robert Koch Institute
Type: | Journal: Oncotarget | Year: 2016

This study investigates the association of Interferon-stimulated gene 15 (ISG15) polymorphisms, ISG15 serum levels and expression with HBV-related liver diseases. The ISG15 promoter and the two exons of the gene were screened for polymorphisms in 766 HBV-infected patients and in 223 controls. Soluble ISG15 levels were measured by ELISA. ISG15 mRNA expression was quantified by qRT-PCR in 36 tumor and adjacent non-tumor tissues. The exon 2 allele rs1921A was found associated with decreased progression of HBV-related liver diseases (LC vs. CHB: OR = 0.6, 95%CI = 0.4-0.8, adjusted P = 0.003; HCC vs. CHB: OR = 0.6, 95%CI = 0.4-0.9, adjusted P = 0.005). The rs1921AA genotype was associated with low levels of AST, ALT and total bilirubin, but with high prothrombin levels (P < 0.05). ISG15 serum levels were higher among HBV patients compared to controls (P < 0.0001) and positively associated with HBV-related liver diseases, with highest levels among LC patients. ISG15 levels were correlated with HBV-DNA loads (P = 0.001). In non-tumor tissues from HCC patients, ISG15 mRNA expression was increased in HBV compared to non-HBV infection (P = 0.016). The ISG15 rs1921 variant and ISG15 expression are associated with HBV-related liver diseases. Taken together, ISG15 appears to be a proviral factor involved in HBV replication and triggering progression of HBV-related liver diseases.


PubMed | University of Tübingen, Hai Phong Medical University and 108 Military Central Hospital
Type: | Journal: BMC infectious diseases | Year: 2016

Blood cultures are commonly employed to identify bacterial pathogens causing sepsis. PCR assays to diagnose septicemia require extraction of bacterial DNA from blood samples and thus, delay the initiation of appropriate antimicrobial treatment. The presence of abundant human DNA may hamper the sensitivity of PCR in the detection of bacteria.We used serial dilutions of E. Coli spiked pseudo-blood-sepsis samples to develop a simple method that combines the use of a polar detergent solvent and adjustment of the basic pH to remove human DNA. A 16S rRNA gene-based screening algorithm was established to differentiate Gram-positive and Gram-negative groups of bacteria and the family of Enterobacteriaceae. A stringent validation with appropriate controls was implemented. The method of human DNA removal was then applied on 194 sepsis blood samples and 44 cerebrospinal fluid (CSF) samples by real-time PCR.This uncomplicated and straightforward approach allows to remove up to 98% of human DNA from peripheral blood of septic patients. The inhibitory effect of human DNA is efficiently prevented and the detection limit of real-time PCR is increased to 10 E. Coli CFUs/ml. This sensitivity is 10 times higher compared to conventional real-time PCR assays. The classical blood culture detected 58/194 (30%) of sepsis and 9/44 (21%) of CSF samples. Out of the 194 blood samples tested, the conventional real-time PCR targeting 13 common sepsis causing pathogens correctly detected the bacterial DNA in 16/194 (8%) only and 14/44 (32%) in cerebrospinal fluid samples. Our newly established approach was able to provide correct diagnoses in 78 (40%) of the 194 blood samples and in 14 (32%) of the CSF samples. The combination of both blood cultures and our technique raised the rate of sepsis diagnoses to 112/194 (58%). Of the total group tested positive, 46 (24%) cases showed overlap with the classical methodology.We report a simple optimized in-house protocol for removal of human DNA from blood sepsis samples as a pre-analytical tool to prepare DNA for subsequent PCR assays. With the detection increase of our in-house DNA removal approach, subsequent PCR assays can reach detection limits of 10 E. coli CFUs/ml and significantly improve the diagnostic rate in blood sepsis cases.


PubMed | University of Tübingen, 108 Military Central Hospital, Hanoi Medical University, Duc Giang Hospital and Vietnamese German Center for Medical Research
Type: Journal Article | Journal: BMC infectious diseases | Year: 2016

As an immune modulator, vitamin D is involved in various pathophysiological mechanisms in a plethora of diseases. This study aims to correlate the vitamin D deficiency status and clinical progression of liver diseases associated with hepatitis B virus (HBV) infection in patients in Vietnam and to compare it to healthy controls.We quantified the levels of total vitamin D [25-(OH) D2 and D3] in serum samples from 400 HBV patients (chronic hepatitis B infection [CHB], n=165; HBV-associated liver cirrhosis [LC], n=127; HBV-associated hepatocellular carcinoma [HCC], n=108) and 122 unrelated healthy controls (HC). Univariate and multivariate analyses were performed in order to determine the association between vitamin D levels and distinct clinical parameters.The prevalence of vitamin D inadequacy (<30ng/mL) was high among healthy individuals (81.7%) as well as in HBV patients (84.3%). Vitamin D deficiency (<20ng/ml) or severe deficiency (<10ng/ml) was observed more frequently among HBV patients (52%) and subgroups (CHB, 47.8%; LC, 54.4%; HCC, 55.3%) compared to the control group (32.5%) (P<0.001). Vitamin D levels and HBV-DNA load were strongly and inversely correlated (rho=-0.57, P<0.0001). Multivariate regression analysis also revealed an independent association of HBV-DNA loads with low vitamin D levels (P=0.0004). In addition, reduced vitamin D levels were associated with significant clinical progression of LC (Child-Pugh C versus Child-Pugh A, P=0.0018; Child-Pugh C versus Child-Pugh B, P=0.016).Vitamin D deficiency was observed in the majority of HBV-infected patients and associated with adverse clinical outcomes. Our findings suggest that substitution of vitamin D may be a supportive option in the treatment of chronic liver diseases, in particular of HBV-associated disorders.

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