T he clinical course and long-term outcome of hepatitis B virus (HBV) infection is affected by several factors including viral genotype. For instance, it has been reported that the HBV genotype C induces more severe liver disease than HBV genotype B in Asia, 1,2 whereas HBV genotype A has been more frequently associated with the development of chronic infection than HBV genotype D in Europe. 3 Eight genotypes (A to H) of HBV have been identified based on divergence over the entire genomic sequence of more than 8%. 4-7 HBV genotypes have specific geographic distributions, 8,9

Recently, three distinct genotypes (1, 2 and 3) of human parvovirus B19 (B19) have been identified. However, the characteristics and distribution of B19 genotypes in Vietnam have not been investigated. Phylogenetic analysis using 49 subgenomic NS1/VP1u regions and two coding NS1-VP1/VP2 regions has been applied to investigate the prevalence of B19 genotypes in Vietnamese patients co-infected with Hepatitis B virus. Genetic analysis of the subgenomic NS1/ VP1u region of B19 revealed that two genotypes of B19 were identified in these populations, with predominance of genotype 1 (47/49, 96 %) followed by genotype 2 (2/49, 4 %), but not genotype 3. Further, phylogenetic analysis of subgenomic B19 genomes revealed two major subgroups within genotype 1 (B19-1A and B19-1B) with an estimated nucleotide difference of >5 % between each subgroup, forming different branches. The mean percentage of amino acid variation between subgroup B19-1A and B19-1B was >2 % of the NS1, VP1 and VP2 proteins. Our results indicated that two of the three known genotypes of B19 were present in Vietnamese patients, with genotype 1 predominating, and that this genotype can be classified into at least two subgroups, B19-1A and B19-1B. INTRODUCTIONHuman parvovirus B19 (B19) is a member of the genus Erythrovirus within the family Parvoviridae . Parvoviruses are non-enveloped and are amongst the smallest DNA-containing viruses that are capable of infecting mammalian cells . B19 has a diverse spectrum of clinical manifestations, including erythema infectiosum, hydrops fetalis, aplastic anaemia (Anderson et al., 1983;Young & Brown, 2004), arthritis (Takahashi et al., 1998;Moore, 2000), myocarditis (Bültmann et al., 2003;Bock et al., 2005; Tschöpe et al., 2005;Bock, 2006), vasculitic syndromes (Finkel et al., 1994;Dingli et al., 2000), neurological disorders (Barah et al., 2001) and hepatic inflammation (Naides et al., 1996;Yoto et al., 1996;Hillingsø et al., 1998;Karetnyi et al., 1999; He et al., 2003).The genome of B19 consists of a linear, single-stranded DNA molecule of about 5600 nt (Morinet, 1992;Zhi et al., 2004), which contains three open reading frames encoding the non-structural protein NS1 (77 kDa) and the two structural proteins VP1 (84 kDa) and VP2 (58 kDa) (Cotmore et al., 1986). Genetic diversity among B19 strains has been shown to be very low, with <1-2 % nucleotide divergence of the full-length sequences. Partial sequence data from different coding regions of the viral genome have confirmed a slightly higher degree of variability with a larger number of strains from distinct epidemiological settings and geographical areas (Erdman et al., 1996). However, some B19 strainsThe GenBank/EMBL/DDBJ accession numbers for the nucleotide sequences of B19 samples determined in this study are DQ357064 (V147) and DQ357065 (V115). obtained from patients with persistent infection show a higher degree of variability, particularly in the VP1-unique (VP1u) region, demonstrating 4 and 8 % divergence at the DNA and protein levels, respectively (Hemaue...

Hepatitis B virus infection is a high-risk factor for hepatocellular carcinoma. The human major histocompatibility complex class I chain-related gene A (MICA) is a ligand of the NKG2D receptor that modulates the NK and T-cell-mediated immune responses and is associated with several diseases. This study determined the effects of MICA polymorphisms during HBV infection and HBV-induced HCC. We conducted a case-controlled study in a Vietnamese cohort and genotyped ten functional MICA polymorphisms including the microsatellite motif in 552 clinically classified hepatitis B virus patients and 418 healthy controls. The serum soluble MICA levels (sMICA) were correlated with MICA variants and liver enzyme levels. We demonstrated a significant contribution of MICA rs2596542G/A promoter variant and nonsynonymous substitutions MICA-129Met/Val, MICA-251Gln/Arg, MICA-175Gly/Ser, triplet repeat polymorphism and respective haplotypes with HBV-induced HCC and HBV persistence. The circulating sMICA levels in HBV patient groups were elevated significantly compared with healthy controls. A significant contribution of studied MICA variants to sMICA levels was also observed. The liver enzymes alanine amino transferase (ALT), aspartate transaminase (AST), total bilirubin and direct bilirubin were positively correlated with sMICA levels suggesting sMICA as a biomarker for liver injury. We conclude that MICA polymorphisms play a crucial role in modulating innate immune responses, tumour surveillance and regulate disease susceptibility during HBV infection.

BackgroundHepatitis D virus (HDV) infection is considered to cause more severe hepatitis than hepatitis B virus (HBV) monoinfection. With more than 9.5 million HBV-infected people, Vietnam will face an enormous health burden. The prevalence of HDV in Vietnamese HBsAg-positive patients is speculative. Therefore, we assessed the prevalence of HDV in Vietnamese patients, determined the HDV-genotype distribution and compared the findings with the clinical outcome.Methods266 sera of well-characterized HBsAg-positive patients in Northern Vietnam were analysed for the presence of HDV using newly developed HDV-specific RT-PCRs. Sequencing and phylogenetic analysis were performed for HDV-genotyping.ResultsThe HDV-genome prevalence observed in the Vietnamese HBsAg-positive patients was high with 15.4% while patients with acute hepatitis showed 43.3%. Phylogenetic analysis demonstrated a predominance of HDV-genotype 1 clustering in an Asian clade while HDV-genotype 2 could be also detected. The serum aminotransferase levels (AST, ALT) as well as total and direct bilirubin were significantly elevated in HDV-positive individuals (p<0.05). HDV loads were mainly low (<300 to 4.108 HDV-copies/ml). Of note, higher HDV loads were mainly found in HBV-genotype mix samples in contrast to single HBV-infections. In HBV/HDV-coinfections, HBV loads were significantly higher in HBV-genotype C in comparison to HBV-genotype A samples (p<0.05).ConclusionHDV prevalence is high in Vietnamese individuals, especially in patients with acute hepatitis B. HDV replication activity showed a HBV-genotype dependency and could be associated with elevated liver parameters. Besides serological assays molecular tests are recommended for diagnosis of HDV. Finally, the high prevalence of HBV and HDV prompts the urgent need for HBV-vaccination coverage.

Hepatitis E virus (HEV) infection may cause acute hepatitis and lead to hepatic failure in developing and developed countries. We studied HEV seroprevalences in patients with hepatitis B virus (HBV) infection to understand the consequences of HEV superinfection in a Vietnamese population. This cross-sectional study was conducted from 2012 to 2013 and included 1318 Vietnamese patients with HBV-related liver diseases and 340 healthy controls. The case group included patients with acute (n = 26) and chronic hepatitis B (n = 744), liver cirrhosis (n = 160), hepatocellular carcinoma (n = 166) and patients with both liver cirrhosis and hepatocellular carcinoma (n = 222). Anti-HEV IgG and IgM antibodies were assessed in patients and controls by ELISA. HEV-RNA was identified by PCR assays and sequencing. Seroprevalences of anti-HEV IgG among hepatitis B patients and controls were 45% and 31%, respectively (adjusted P = 0.034). Anti-HEV IgM seroprevalences were 11.6% and 4.7% in patients and controls, respectively (adjusted P = 0.005). Seroprevalences were higher among the elder individuals. When stratifying for patient groups, those with liver cirrhosis had the highest anti-HEV IgG (52%) and anti-HEV IgM (19%) seroprevalences. Hepatitis B patients with current HEV infection had abnormal liver function tests compared to patients with past or without HEV infection. One HEV isolate was retrieved from a patient with both liver cirrhosis and hepatocellular carcinoma and identified as HEV genotype 3. This study indicates high prevalences of HEV infection in Vietnamese HBV patients and among healthy individuals and shows that HEV superinfection may influence the outcome and progression of HBV-related liver disease.

BackgroundAs 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.MethodsWe 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.ResultsThe prevalence of vitamin D inadequacy (<30 ng/mL) was high among healthy individuals (81.7 %) as well as in HBV patients (84.3 %). Vitamin D deficiency (<20 ng/ml) or severe deficiency (<10 ng/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).ConclusionsVitamin 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.

Aims/IntroductionAdipose tissue‐derived hormones are associated with metabolic disorders including type 2 diabetes mellitus. The present study investigated the levels of adiponectin and pro‐inflammatory cytokines including tumor necrosis factor‐α (TNF‐α), interleukin‐1 beta (IL‐1β) and IL‐10 in Vietnamese patients with type 2 diabetes mellitus, and their correlations with clinical parameters of overweight and type 2 diabetes mellitus.Materials and MethodsBased on body mass index, 73 patients with type 2 diabetes mellitus were categorized either as overweight or non‐overweight. As healthy controls, 57 overweight and non‐overweight individuals without type 2 diabetes mellitus were included. The adiponectin, TNF‐α, IL‐1β and IL‐10 levels were measured in the sera samples in all study participants by enzyme‐linked immunosorbent assay and were correlated with clinical parameters.ResultsThe adiponectin levels were lower in patients with type 2 diabetes mellitus (2.5 ± 1.5 μg/mL) compared with controls (16 ± 18.6 μg/mL; P < 0.0001), and were decreased in overweight individuals compared with those who were not overweight. The TNF‐α and IL‐1β levels were increased, whereas the IL‐10 levels were decreased in patients with type 2 diabetes mellitus and in overweight controls compared with non‐overweight controls (P < 0.0001). The adiponectin levels were correlated with the TNF‐α, IL‐1β, IL‐10 levels, and the clinical parameters of overweight and type 2 diabetes mellitus. The quantitative insulin sensitivity check index and homeostasis model assessment insulin resistance indexes were correlated with the relative ratios of adiponectin/TNF‐α, adiponectin/IL‐1β, adiponectin/IL‐10, TNF‐α/IL‐10 and IL‐1β/IL‐10.ConclusionsAdiponectin and pro‐inflammatory cytokines are associated with type 2 diabetes mellitus, and might serve as a prognostic marker and a therapeutic intervention for overweight‐related type 2 diabetes mellitus.

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