Drug-induced hepatotoxicity and association with slow acetylation variants NAT2*5 and NAT2*6 in Cameroonian patients with tuberculosis and HIV co-infection.

BACKGROUND: Human immunodeficiency virus (HIV) and tuberculosis (TB) are major contributors to morbidity and mortality in sub-Saharan Africa including Cameroon. Pharmacogenetic variants could serve as predictors of drug-induced hepatotoxicity (DIH), in patients with TB co-infected with HIV. We evaluated the occurrence of DIH and pharmacogenetic variants in Cameroonian patients. METHODS: Treatment-naïve patients with HIV, TB or TB/HIV co-infection were recruited at three hospitals in Cameroon, between September 2018 and November 2019. Appropriate treatment was initiated, and patients followed up for 12 weeks to assess DIH. Pharmacogenetic variants were assessed by allele discrimination TaqMan SNP assays. RESULTS: Of the 141 treatment naïve patients, the overall incidence of DIH was 38% (53/141). The highest incidence of DIH, 52% (32/61), was observed among HIV patients. Of 32 pharmacogenetic variants, the slow acetylation variants NAT2*5 was associated with a decreased risk of DIH (OR: 0.4; 95%CI: 0.17-0.96; p = 0.038), while NAT2*6 was found to be associated with an increased risk of DIH (OR: 4.2; 95%CI: 1.1-15.2; p = 0.017) among patients treated for TB. Up to 15 SNPs differed in ≥ 5% of allele frequencies among African populations, while 25 SNPs differed in ≥ 5% of the allele frequencies among non-African populations, respectively. CONCLUSIONS: DIH is an important clinical problem in African patients with TB and HIV. The NAT2*5 and NAT2*6 variants were found to be associated with DIH in the Cameroonian population. Prior screening for the slow acetylation variants NAT2*5 and NAT2*6 may prevent DIH in TB and HIV-coinfected patients.

Expression of SUMO and NF-κB genes in hepatitis B virus-associated hepatocellular carcinoma patients: An observational study.

Alterations in signaling pathways and modulation of cell metabolism are associated with the pathogenesis of cancers, including hepatocellular carcinoma (HCC). Small ubiquitin-like modifier (SUMO) proteins and NF-κB family play major roles in various cellular processes. The current study aims to determine the expression profile of SUMO and NF-κB genes in HCC tumors and investigate their association with the clinical outcome of HCC. The expression of 5 genes - SUMO1, SUMO2, SUMO3, NF-κB p65, and NF-κB p50 - was quantified in tumor and adjacent non-tumor tissues of 58 HBV-related HCC patients by real-time quantitative PCR and was analyzed for the possible association with clinical parameters of HCC. The expression of SUMO2 was significantly higher in HCC tumor tissues compared to the adjacent non-tumor tissues (P = .01), while no significant difference in SUMO1, SUMO3, NF-κB p65, and NF-κB p50 expression was observed between HCC tumor and non-tumor tissues (P > .05). In HCC tissues, a strong correlation was observed between the expression of SUMO2 and NF-κB p50, between SUMO3 and NF-κB p50, between SUMO3 and NF-κB p65 (Spearman rho = 0.83; 0.82; 0.772 respectively; P < .001). The expression of SUMO1, SUMO2, SUMO3, NF-κB p65, and NF-κB p50 was decreased in grade 3 compared to grades 1 and 2 in HCC tumors according to the World Health Organization grades system. Our results highlighted that the SUMO2 gene is upregulated in tumor tissues of patients with HCC, and is related to the development of HCC, thus it may be associated with the pathogenesis of HCC.

Complement receptor type 1 and 2 (CR1 and CR2) gene polymorphisms and plasma protein levels are associated with the Dengue disease severity.

The pathological outcome of dengue disease results from complex interactions between dengue virus (DENV) and host genetics and immune response. Complement receptor types 1 and 2 (CR1 and CR2) mediate complement activation through the alternative pathway. This study investigated the possible association of genetic polymorphisms and plasma levels of CR1 and CR2 with dengue disease. A total of 267 dengue patients and 133 healthy controls were recruited for this study. CR1 and CR2 gene polymorphisms were analyzed by Sanger sequencing, while plasma CR1 and CR2 levels were measured by ELISA. The frequency of the CR1 minor allele rs6691117G was lower in dengue patients and those with severe dengue compared to healthy controls. Plasma CR1 and CR2 levels were decreased in dengue patients compared to healthy controls (P < 0.0001) and were associated with platelet counts. CR1 levels were lower in dengue patients with warning signs (DWS) compared to those without DWS, while CR2 levels were decreased according to the severity of the disease and after 5 days (T1) and 8 days (T2) of follow-up. CR2 levels were decreased in dengue patients positive for anti-DENV IgG and IgM and patients with bleeding and could discriminate DWS and SD from dengue fever patients (AUC = 0.66). In conclusion, this study revealed a reduction in CR2 levels in dengue patients and that the CR1 SNP rs6691117A/G is associated with the dengue severity. The correlation of CR2 levels with platelet counts suggests that CR2 could be an additional biomarker for the prognosis of severe dengue disease.

Establishment of cancer cell line originating from a patient with high-grade serous ovarian carcinoma.

Aim: Ovarian cancer is a serious malignancy with high prevalence and mortality. Methods: We isolated and characterized an ovarian high-grade serous cancer cell line (M4) from a tumor of a Vietnamese patient with ovarian carcinoma. Results: The M4 cancer cell line showed good proliferation and stability in culture. Morphologically, the M4 cells showed similar characteristics to tumor cells such as a polyhedral shape, large irregular nuclei, high nuclear/cytoplasmic ratio, high nuclear density and expressing cancer markers like CA125, p53 and Ki67 markers. Conclusion: We have successfully isolated and characterized the M4 cell line from a Vietnamese patient with ovarian carcinoma.

Outcome prediction model and prognostic biomarkers for COVID-19 patients in Vietnam.

Background: Accurate prognosis is important either after acute infection or during long-term follow-up of patients infected by severe acute respiratory syndrome coronavirus 2. This study aims to predict coronavirus disease 2019 (COVID-19) severity based on clinical and biological indicators, and to identify biomarkers for prognostic assessment. Methods: We included 261 Vietnamese COVID-19 patients, who were classified into moderate and severe groups. Disease severity prediction based on biomarkers and clinical parameters was performed by applying machine learning and statistical methods using the combination of clinical and biological data. Results: The random forest model could predict with 97% accuracy the likelihood of COVID-19 patients who subsequently worsened to the severe condition. The most important indicators were interleukin (IL)-6, ferritin and D-dimer. The model could still predict with 92% accuracy after removing IL-6 from the analysis to generalise the applicability of the model to hospitals with limited capacity for IL-6 testing. The five most effective indicators were C-reactive protein (CRP), D-dimer, IL-6, ferritin and dyspnoea. Two different sets of biomarkers (D-dimer, IL-6 and ferritin, and CRP, D-dimer and IL-6) are applicable for the assessment of disease severity and prognosis. The two biomarker sets were further tested through machine learning algorithms and relatively validated on two Danish COVID-19 patient groups (n=32 and n=100). The results indicated that various biomarker sets combined with clinical data can be used for detection of the potential to develop the severe condition. Conclusion: This study provided a simple and reliable model using two different sets of biomarkers to assess disease severity and predict clinical outcomes in COVID-19 patients in Vietnam.

Association of PKLR gene copy number, expression levels and enzyme activity with 2,3,7,8-TCDD exposure in individuals exposed to Agent Orange/Dioxin in Vietnam.

2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) is the most toxic congener of dioxin and has serious long-term effects on the environment and human health. Pyruvate Kinase L/R (PKLR) gene expression levels and gene variants are associated with pyruvate kinase enzyme deficiency, which has been identified as the cause of several diseases linked to dioxin exposure. In this study, we estimated PKLR gene copy number and gene expression levels using real-time quantitative PCR (RT-qPCR) assays, genotyped PKLR SNP rs3020781 by Sanger sequencing, and quantified plasma pyruvate kinase enzyme activity in 100 individuals exposed to Agent Orange/Dioxin near Bien Hoa and Da Nang airfields in Vietnam and 100 healthy controls. The means of PKLR copy numbers and PKLR gene expression levels were significantly higher, while pyruvate kinase enzyme activity was significantly decreased in Agent Orange/Dioxin-exposed individuals compared to healthy controls (P < 0.0001). Positive correlations of PKLR gene copy number and gene expression with 2,3,7,8-TCDD concentrations were observed (r = 0.2, P = 0.045 and r = 0.54, P < 0.0001, respectively). In contrast, pyruvate kinase enzyme activity was inversely correlated with 2,3,7,8-TCDD concentrations (r = -0.52, P < 0.0001). PKLR gene copy number and gene expression levels were also inversely correlated with pyruvate kinase enzyme activity. Additionally, PKLR SNP rs3020781 was found to be associated with 2,3,7,8-TCDD concentrations and PKLR gene expression. In conclusion, PKLR copy number, gene expression levels, and pyruvate kinase enzyme activity are associated with 2,3,7,8-TCDD exposure in individuals living in Agent Orange/Dioxin-contaminated areas.

Long-Term Follow-Up Of Anti-Mullerian Hormone Levels After Laparoscopic Endometrioma Cystectomy.

Objective: The study aims to evaluate long-term ovarian reserve change by serum anti-Mullerian hormone (AMH) level and determine the factors that affect the changes after laparoscopic endometrioma cystectomy. Methods: In a prospective longitudinal study, 104 patients with unilateral (n=77) and bilateral (n=27) endometrioma underwent laparoscopic endometrioma cystectomy. AMH levels were measured preoperatively and at 1, 3, 6, and 12 months postoperatively. Multivariate linear regression analysis was performed to determine factors related to AMH level changes. Results: Median preoperative AMH levels significantly declined from 3.77 ng/mL to 1.60 ng/mL (P<0.001), 1.66 ng/mL (P<0.001), 1.67 ng/mL (P<0.001), and 1.72 ng/mL (P<0.001) at 1, 3, 6, and 12 months postoperatively, respectively. The rate of decrease in AMH was unchanged six months after surgery, 52.2%, 53.7%, 54.8% at 1, 3, 6 months, respectively, and declined to 43.2% at 12 months. Although most factors were associated with AMH level changes in monovariant linear regression, multivariant linear regression analysis showed only three factors that reached the statistical significance, including bilateral endometriomas, mean size of the endometrioma, and preoperative AMH levels. Conclusions: Serum AMH levels decline significantly after laparoscopic cystectomy of endometriomas but recovered at 12 months compared with the first 6 months with unilateral endometrioma. Bilateral endometriomas, size of the cyst, and preoperative AMH levels might independently affect AMH levels at 12 months after surgery.

Fetoscopic Laser Ablation for the Selective Fetal Reduction in Twin-Twin Transfusion Syndrome Stage II-IV: The Experience of a New Fetal Medicine Center.

Objective: To evaluate the surgery outcomes of fetoscopic laser ablation (FLA) for selective umbilical cord in treating twin-twin transfusion syndrome (TTTS) with special conditions and neonatal outcomes post-operation. Methods: A prospective study, 21 monochorionic diamniotic (MCDA) twins diagnosed with TTTS stage II-IV according to Quintero classification from 16 to 26 weeks of gestation, among that, 12 cases of TTTS stage II with selective intrauterine growth restriction (sIUGR), 6 cases of TTTS stage II with proximate cord insertions, 3 cases of TTTS stage IV underwent fetoscopic laser ablation for the selective fetal reduction at Hanoi Obstetrics and Gynecology Hospital from September 2019 to July 2021. Complications and surgical outcomes were noted. Prenatal care was carried out every 2 weeks post operation until birth. Newborn neurologic complications were assessed at birth, three months, and six months after birth using Denver II test and magnetic resonance imaging (MRI). Results: The mean gestational age at operation was 20.30 weeks. The average operation duration was 39.52 minutes. No complications of operation, such as bleeding or infection, were recorded. The mean gestational age at birth was 34.70 ± 4.33 weeks, with a mean duration of 12.97 ± 6.87 weeks between intervention and delivery. The survival rate of newborns after the operation was 90.48%. There were two stillbirths (9.52%) within seven days after the operation. No short-term neurological complications have been reported with follow-up of the newborn to 6 months after birth. Conclusion: Our study showed that fetoscopic laser ablation of selected fetal reduction surgery for treatment of special conditions of TTTS had no complications of operation, high neonatal survival result (90.48%), no short-term neurological complications. This should be considered for TTTS in cases of indication.

Prognostic significance of the angiopoietin-2 for early prediction of septic shock in severe sepsis patients.

Aim: The current study investigated the plasma levels of angiopoietin-1/-2 and their association with clinical outcomes of sepsis. Methods: Angiopoietin-1 and -2 levels were quantified in plasma from 105 patients with severe sepsis by ELISA. Results: Angiopoietin-2 levels elevated according to the severity of sepsis progression. Angiopoietin-2 levels were correlated with mean arterial pressure and platelets counts, total bilirubin, creatinine, procalcitonin, lactate levels and SOFA score. Angiopoietin-2 levels accurately discriminated for sepsis with an AUC = 0.97 and septic shock from severe sepsis patients (AUC = 0.778). Conclusion: Plasma angiopoietin-2 levels may serve as an additional biomarker for severe sepsis and septic shock.

The study investigated the plasma levels of angiopoietin-1/-2 and their association with clinical outcomes of sepsis in plasma from 105 patients with severe sepsis by ELISA. The results showed that angiopoietin-2 levels elevated according to the severity of sepsis progression and were correlated with important clinical parameters such as mean arterial pressure and platelets counts, procalcitonin, lactate levels and SOFA score. Angiopoietin-2 levels accurately discriminated for sepsis and septic shock. Thus, plasma angiopoietin-2 levels may serve as an additional biomarker for severe sepsis and septic shock.

Low Prevalence of HEV Infection and No Associated Risk of HEV Transmission from Mother to Child among Pregnant Women in Vietnam.

Infections with HEV in low- and middle-income countries (LMICs) are associated with increased rates of preterm birth, miscarriage, and stillbirth. The aim of the present study was to investigate HEV infections in pregnant women and the possibility of mother-to-child transmission, and associated outcomes. A total of 183 pregnant women in their third trimester were recruited and followed until delivery. Anti-HEV IgG and IgM were determined via enzyme-linked immunosorbent assay (ELISA), and HEV nucleic acids were detected in stool and cord blood samples. HEV genotypes were identified by Sanger sequencing, and phylogenetic analyses were performed. Mother-to-child transmission and associated adverse outcomes were not observed. Only 2% of patients (n = 4/183) tested positive for anti-HEV IgM, and 8% (n = 14/183) tested positive for anti-HEV IgG antibodies. Cord blood (n = 150) analysis showed that there was no IgM detected, while 4% (n = 6/150) tested positive for anti-HEV IgG, which was consistent with mothers testing positive for anti-HEV IgG. Nucleic acid tests for HEV RNA yielded 2% (n = 4/183) from the serum and stool of pregnant women, and none from cord blood. The HEV isolates belonged to the genotype HEV-3a, with 99% homology with humans and 96% with pigs. No association was found between the risk of HEV infection and pregnancy outcomes or HEV transmission from mother to child. HEV-3 infections of zoonotic origin in pregnancy might have eventually resolved without complications.

Maternal vascular endothelial growth factor receptor and interleukin levels in pregnant women with twin-twin transfusion syndrome.

Twin-twin transfusion syndrome (TTTS) is an unusual and serious condition that occurs in twin pregnancies when identical twins share a placenta but develop discordant amniotic fluid volumes. TTTS is associated with an increased risk of fetal death and birth defects if untreated. This study investigated the soluble levels of biomarkers including growth factors and interleukins in pregnant women with and without TTTS during pregnancy. We quantified plasma levels of VEGF-R1, VEGF-R2, IL-1ß, IL-6 and IL-8 in twin pregnant women with (n=53) and without TTTS (n=72) and in women with single pregnancy (n=30) by ELISA and analyzed the association of maternal circulating biomarker levels with TTTS. Our results showed that maternal VEGF-R1 levels were significantly higher in twins compared to single pregnancy (P<0.05) and were decreased in the second trimester compared to the first trimester (P = 0.065, 0.019 and 0.072 for twins with and without TTTS and single pregnancy, respectively). VEGF-R2 levels had a trend to be lower in twins compared to single pregnancy. In addition, soluble VEGF-R1 and VEGF-R2 levels were significantly decreased while IL-6 levels were increased after surgical treatment with laser in twin pregnant women with TTTS (P = 0.016, 0.041 and 0.04, respectively). These results suggest that IL-6, VEGF-R1 and VEGF-R2 are involved in vascular regulation and stabilization in twin pregnancies and may contribute to the pathogenesis of TTTS and thus play a prognostic role in the surgical treatment of TTTS.

Natural killer cell receptor variants and chronic hepatitis B virus infection in the Vietnamese population.

OBJECTIVES: Genes of host immunity play an important role in disease pathogenesis and are determinants of clinical courses of infections, including hepatitis B virus (HBV). Killer-cell immunoglobulin-like receptor (KIR), expressed on the surface of natural killer cells (NK), regulate NK cell cytotoxicity by interacting with human leukocyte antigen (HLA) class I molecules and are candidates for influencing the course of HBV. This study evaluated whether variations in KIR gene content and HLA-C ligands are associated with HBV and with the development of liver cirrhosis and hepatocellular carcinoma. METHODS: A Vietnamese study cohort (HBV n = 511; controls n = 140) was genotyped using multiplex sequence-specific polymerase chain reaction (PCR-SSP) followed by melting curve analysis. RESULTS: The presence of the functional allelic group of KIR2DS4 was associated with an increased risk of chronic HBV (OR = 1.86, pcorr = 0.02), while KIR2DL2+HLA-C1 (OR = 0.62, pcorr = 0.04) and KIR2DL3+HLA-C1 (OR = 0.48, pcorr = 0.04) were associated with a decreased risk. The pair KIR2DL3+HLA-C1 was associated with liver cirrhosis (OR = 0.40, pcorr = 0.01). The presence of five or more activating KIR variants was associated with hepatocellular carcinoma (OR = 0.53, pcorr = 0.04). CONCLUSIONS: KIR gene content variation and combinations KIR-HLA influence the outcome of HBV infection.

Upregulation of Enzymes involved in ISGylation and Ubiquitination in patients with hepatocellular carcinoma.

Background: ISGylation is the conjugation of ISG15 with target proteins. ISGylation occurs through an enzymatic cascade, which is similar to that of ubiquitination. Through ISGylation, ISG15 can bind to proteins involved in cell proliferation and differentiation, thus promoting genesis and progression of malignancies. The present study aims to investigate expression of genes involved in ISGylation and ubiquitination in patients with hepatocellular carcinoma and to correlate gene expression with clinical laboratory parameters of these patients. Methods: mRNA expression of genes encoding enzymes involved in the ISGylation process (EFP, HERC5, UBA1, UBC and USP18) was evaluated by quantitative real-time PCR in 38 pairs of tumour and adjacent non-tumour tissues from patients with hepatocellular carcinoma and correlated with distinct clinical laboratory parameters. Results: Relative mRNA expression of EFP, HERC5, UBA1 and USP18 was significantly higher in tumour tissues compared to adjacent non-tumour tissues (P=0.006; 0.012; 0.02 and 0.039, respectively). The correlation pattern of mRNA expression between genes in the tumours differed from the pattern in adjacent non-tumour tissues. Relative expression of EFP, HERC5 and UBA1 in adjacent non-tumour tissues was positively associated with direct bilirubin levels (Spearman's rho=0.31, 0.33 and 0.45; P=0.06, 0.05 and 0.01, respectively) and relative expression of USP18 in adjacent non-tumour tissues correlated negatively with ALT levels (Spearman's rho= -0.33, P=0.03). Conclusions: EFP, HERC5, UBA1, and USP18 genes are upregulated in tumour tissues of patients with HCC and, thus, may be associated with the pathogenesis of hepatocellular carcinoma.

Association of FCN2 polymorphisms and Ficolin-2 levels with dengue fever in Vietnamese patients.

BACKGROUND AND OBJECTIVE: The human ficolin-2, encoded by FCN2, recognizes pathogen-associated acetylated residues on their cell surfaces and activates the lectin complement cascade. This study aimed to investigate the contribution of human ficolin-2 and the functional FCN2 genetic variants in dengue virus (DENV) infection and in clinical progression. METHODS: FCN2 genetic polymorphisms in the promoter, intron 7 and exon 8 were genotyped in 279 patients with dengue fever and in 200 healthy controls by direct Sanger sequencing. The ficolin-2 levels were measured in serum samples by ELISA and correlated with clinical data. RESULTS: The frequencies of +6031GG, +6220GG and +6424TT genotypes were significantly higher in dengue patients compared to healthy controls indicating an increased risk of dengue fever. The SNPs rs11103563 (+6031A/G), rs7872508 (+6220 T/G), and rs7851696 (+6424G/T) significantly regulated ficolin-2 levels in dengue patients (P < 0.0001). Ficolin-2 levels were increased in patients with dengue and Dengue with Warning Signs (DWS) compared to healthy controls (P < 0.0001 and P = 0.038, respectively). Ficolin-2 levels were significantly increased after 10-14 days of admission in both dengue and DWS patients and then slightly decreased after three weeks of discharge, indicating that ficolin-2 levels were modulated during the progression of dengue fever. In addition, ficolin-2 levels were negatively correlated with AST levels and positively correlated with platelet counts. CONCLUSIONS: FCN2 polymorphisms are associated with dengue fever in the Vietnamese population. Ficolin-2 levels are modulated during the progression of dengue fever and correlated with clinical parameters and thus may play a possible role in the pathogenesis of DENV infection.

Upregulation of SMYD3 and SMYD3 VNTR 3/3 polymorphism increase the risk of hepatocellular carcinoma.

SMYD3 (SET and MYND domain-containing protein 3) is involved in histone modification, which initiates oncogenesis by activating transcription of multiple downstream genes. To investigate associations of variable numbers of tandem repeats (VNTR) variants in the SMYD3 gene promoter, SMYD3 serum levels and SMYD3 mRNA expression in hepatitis B virus (HBV) infection and clinical progression of related liver disease. SMYD3 VNTRs were genotyped in 756 HBV patients and 297 healthy controls. SMYD3 serum levels were measured in 293 patients and SMYD3 mRNA expression was quantified in 48 pairs of hepatocellular tumor and adjacent non-tumor liver tissues. Genotype SYMD3 VNTR 3/3 was more frequent among HCC patients than in controls (Padjusted = 0.037). SMYD3 serum levels increased according to clinical progression of liver diseases (P = 0.01); HCC patients had higher levels than non-HCC patients (P = 0.04). Among patients with SMYD3 VNTR 3/3, HCC patients had higher SMYD3 levels than others (P < 0.05). SMYD3 mRNA expression was up-regulated in HCC tumor tissues compared to other tissues (P = 0.008). In conclusion, upregulation of SMYD3 correlates with the occurrence of HCC and SMYD3 VNTR 3/3 appears to increase the risk of HCC through increasing SMYD3 levels. SMYD3 may be an indicator for HCC development in HBV patients.

High Hepatitis E virus (HEV) Positivity Among Domestic Pigs and Risk of HEV Infection of Individuals Occupationally Exposed to Pigs and Pork Meat in Hanoi, Vietnam.

BACKGROUND: Hepatitis E virus (HEV) infection can occur through consumption of undercooked pork meat or exposure to animal feces. Because there are scarce data only in developing countries, we assessed whether pigs might be a potential source of human HEV infections in Vietnam. In addition, we determined anti-HEV seroprevalences in the general population and in individuals professionally exposed to pigs and pork meat. METHODS: The study took place in Hanoi, Vietnam. Liver tissues from domestic pigs (n = 210) and serum samples obtained from individuals occupationally exposed to pigs and pork meat (n = 283) and from unexposed healthy controls (n = 168) were screened for HEV-ribonucleic acid (RNA) by reverse-transcription polymerase chain reaction. The exposed group was divided into pork meat vendors (n = 81), pig farmers (n = 96), and slaughterers (n = 106). Serum samples were subjected to HEV immunoglobulin (Ig)G and IgM enzyme-linked immunosorbent assays. The HEV genotypes were assessed by direct sequencing, followed by phylogenetic analyses. RESULTS: Hepatitis E virus seroprevalence was higher among persons occupationally exposed to pigs/pork meat compared with unexposed individuals (anti-HEV IgM 11% vs 6%, P = .07; anti-HEV IgG 53% vs 31%, P < .0001). Positivity of anti-HEV IgG among slaughterhouse staff was 66%, followed by 51% in pig-farmers and 38% in pork meat vendors (P = .00073). A similar trend was observed for IgM positivity. Of the pig liver tissues, 26 of 210 (12.4%) were positive for HEV-RNA and assessed to be HEV genotype 3. CONCLUSIONS: Hepatitis E virus circulates in domestic pigs in Hanoi and constitutes a permanent zoonotic disease risk. The high HEV seroprevalence among occupationally exposed individuals indicates an associated risk of HEV infection.

Optimisation of quantitative miRNA panels to consolidate the diagnostic surveillance of HBV-related hepatocellular carcinoma.

BACKGROUND: Circulating microRNAs (miRNA) are biomarkers for several neoplastic diseases, including hepatocellular carcinoma (HCC). We performed a literature search, followed by experimental screening and validation in order to establish a miRNA panel in combination with the assessment of alpha-fetoprotein (AFP) levels and to evaluate its performance in HCC diagnostics. METHODS: Expression of miRNAs was quantified by quantitative PCR (qPCR) in 406 serum samples from 118 Vietnamese patients with hepatitis B (HBV)-related HCC, 69 patients with HBV-related liver cirrhosis (LC), 100 chronic hepatitis B (CHB) patients and 119 healthy controls (HC). RESULTS: Three miRNAs (mir-21, mir-122, mir-192) were expressed differentially among the studied subgroups and positively correlated with AFP levels. The individual miRNAs mir-21, mir-122, mir192 or the triplex miRNA panel showed high diagnostic accuracy for HCC (HCC vs. CHB, AUC = 0.906; HCC vs. CHB+LC, AUC = 0.81; HCC vs. CHB+LC+HC, AUC = 0.854). When AFP levels were ≤20ng/ml, the triplex miRNA panel still was accurate in distinguishing HCC from the other conditions (CHB, AUC = 0.922; CHB+LC, AUC = 0.836; CHB+LC+HC, AUC = 0.862). When AFP levels were used in combination with the triplex miRNA panel, the diagnostic performance was significantly improved in discriminating HCC from the other groups (LC, AUC = 0.887; CHB, AUC = 0.948; CHB+LC, AUC = 0.887). CONCLUSIONS: The three miRNAs mir-21, mir-122, mir-192, together with AFP, are biomarkers that may be applied to improve diagnostics of HCC in HBV patients, especially in HBV-related LC patients with normal AFP levels or HCC patients with small tumor sizes.

Vitamin D deficiency and hepatitis viruses-associated liver diseases: A literature review.

The secosteroid hormone vitamin D has, in addition to its effects in bone metabolism also functions in the modulation of immune responses against infectious agents and in inhibiting tumorigenesis. Thus, deficiency of vitamin D is associated with several malignancies, but also with a plethora of infectious diseases. Among other communicable diseases, vitamin D deficiency is involved in the pathogenesis of chronic liver diseases caused by hepatitis B and C viruses (HBV, HCV) and high prevalence of vitamin D deficiency with serum levels below 20 mg/mL in patients with HBV and HCV infection are found worldwide. Several studies have assessed the effects of vitamin D supplementation on the sustained virological response (SVR) to interferon (IFN) plus ribavirin (RBV) therapy in HBV and HCV infection. In these studies, inconsistent results were reported. This review addresses general aspects of vitamin D deficiency and, in particular, the significance of vitamin D hypovitaminosis in the outcome of HBV- and HCV-related chronic liver diseases. Furthermore, current literature was reviewed in order to understand the effects of vitamin D supplementation in combination with IFN-based therapy on the virological response in HBV and HCV infected patients.

Genetic variants of interferon regulatory factor 5 associated with chronic hepatitis B infection.

AIM: To investigate possible effects of IRF5 polymorphisms in the 3' UTR region of the IFR5 locus on susceptibility to hepatitis B virus (HBV) infection and progression of liver diseases among clinically classified Vietnamese patients. METHODS: Four IFR5 SNPs (rs13242262A/T, rs77416878C/T, rs10488630A/G, and rs2280714T/C) were genotyped in clinically classified HBV patients [chronic hepatitis B (CHB). n = 99; liver cirrhosis (LC), n = 131; hepatocellular carcinoma (HCC), n = 149] and in 242 healthy controls by direct sequencing and TaqMan real-time PCR assays. RESULTS: Comparing patients and controls, no significant association was observed for the four IFR5 variants. However, the alleles rs13242262T and rs10488630G contributed to an increased risk of liver cirrhosis (LC vs CHB: OR = 1.5, 95%CI: 1.1-2.3, adjusted P = 0.04; LC vs CHB: OR = 1.7, 95%CI: 1.1-2.6, adjusted P = 0.019). Haplotype IRF5*TCGT constructed from 4 SNPs was observed frequently in LC compared to CHB patients (OR = 2.1, 95%CI: 1.2-3.3, adjusted P = 0.008). Haplotype IRF5*TCAT occurred rather among CHB patients than in the other HBV patient groups (LC vs CHB: OR = 0.4, 95%CI: 0.2-0.8, adjusted P = 0.03; HCC vs CHB: OR = 0.3, 95%CI: 0.15-0.7, adjusted P = 0.003). The IRF5*TCAT haplotype was also associated with increased levels of ALT, AST and bilirubin. CONCLUSION: Our study shows that IFR5 variants may contribute as a host factor in determining the pathogenesis in chronic HBV infections.

Geographical distribution of complement receptor type 1 variants and their associated disease risk.

BACKGROUND: Pathogens exert selective pressure which may lead to substantial changes in host immune responses. The human complement receptor type 1 (CR1) is an innate immune recognition glycoprotein that regulates the activation of the complement pathway and removes opsonized immune complexes. CR1 genetic variants in exon 29 have been associated with expression levels, C1q or C3b binding and increased susceptibility to several infectious diseases. Five distinct CR1 nucleotide substitutions determine the Knops blood group phenotypes, namely Kna/b, McCa/b, Sl1/Sl2, Sl4/Sl5 and KCAM+/-. METHODS: CR1 variants were genotyped by direct sequencing in a cohort of 441 healthy individuals from Brazil, Vietnam, India, Republic of Congo and Ghana. RESULTS: The distribution of the CR1 alleles, genotypes and haplotypes differed significantly among geographical settings (p≤0.001). CR1 variants rs17047660A/G (McCa/b) and rs17047661A/G (Sl1/Sl2) were exclusively observed to be polymorphic in African populations compared to the groups from Asia and South-America, strongly suggesting that these two SNPs may be subjected to selection. This is further substantiated by a high linkage disequilibrium between the two variants in the Congolese and Ghanaian populations. A total of nine CR1 haplotypes were observed. The CR1*AGAATA haplotype was found more frequently among the Brazilian and Vietnamese study groups; the CR1*AGAATG haplotype was frequent in the Indian and Vietnamese populations, while the CR1*AGAGTG haplotype was frequent among Congolese and Ghanaian individuals. CONCLUSION: The African populations included in this study might have a selective advantage conferred to immune genes involved in pathogen recognition and signaling, possibly contributing to disease susceptibility or resistance.