ABSTRACT
Objective: This study aimed to explore the potential causal relationship between the gut microbiota and/or its metabolites and the progression of chronic hepatitis B (CHB). Method: The gut microbiota was used as the exposure factor. The training set exposure data were obtained from the China Nucleotide Sequence Archive (CNSA). Genome-wide association study (GWAS) data from Asia were used as the outcome variables. Outcome data for both the training and validation sets were sourced from the GWAS Catalog database. A dual-sample Mendelian randomization approach was used to analyze the causal relationships, with the inverse variance-weighted method serving as the main analytical strategy. Sensitivity analysis was conducted to assess the robustness of Mendelian randomization analysis results. Result: In the training set database, analysis using the inverse variance-weighted method revealed a positive correlation between Fusobacterium varium and chronic hepatitis B [OR = 1.122, 95% CI (1.016, 1.240), p = 0.022]. Conversely, Veillonella parvula exhibited a negative correlation with chronic hepatitis B [OR = 0.917, 95% CI (0.852, 0.987), p = 0.021]. Sensitivity analysis revealed no evidence of pleiotropy and heterogeneity. No gut microbiota metabolites with a causal effect on chronic hepatitis B were identified. Additionally, no associations between the gut microbiota and the progression of chronic hepatitis B were found in the validation data from the European cohort. Conclusion: This study suggests that F. varium may facilitate the progression of chronic hepatitis B, whereas V. parvula may impede it. No causal relationships between gut microbiota metabolites and chronic hepatitis B were established.
Subject(s)
Gastrointestinal Microbiome , Genome-Wide Association Study , Hepatitis B, Chronic , Mendelian Randomization Analysis , Humans , Gastrointestinal Microbiome/genetics , Hepatitis B, Chronic/microbiology , China , MaleABSTRACT
BACKGROUND: Gut dysbiosis is present in chronic hepatitis B virus (HBV) infection. In this study, we integrated microbiome and metabolome analysis to investigate the role of gut microbiome in virological response to nucleos(t)ide analogues (NAs) treatment. METHODS: Chronic HBV patients were prospectively recruited for steatosis and fibrosis assessments via liver elastography, with full-length 16S sequencing performed to identify the compositional gut microbiota differences. Fasting plasma bile acids were quantified by liquid chromatography-tandem mass spectrometry. FINDINGS: All patients (n = 110) were characterized into three distinct microbial clusters by their dominant genus: c-Bacteroides, c-Blautia, and c-Prevotella. Patients with c-Bacteroides had a higher plasma ursodeoxycholic acids (UDCA) level and an increase in 7-alpha-hydroxysteroid dehydrogenase (secondary bile acid biotransformation) than other clusters. In NAs-treated patients (n = 84), c-Bacteroides was associated with higher odds of plasma HBV-DNA undetectability when compared with non-c-Bacteroides clusters (OR 3.49, 95% CI 1.43-8.96, p = 0.01). c-Blautia was positively associated with advanced fibrosis (OR 2.74, 95% CI 1.09-7.31, p = 0.04). No such associations were found in treatment-naïve patients. Increased Escherichia coli relative abundance (0.21% vs. 0.03%, p = 0.035) was found in on-treatment patients (median treatment duration 98.1 months) with advanced fibrosis despite HBV DNA undetectability. An enrichment in l-tryptophan biosynthesis was observed in patients with advanced fibrosis, which exhibited a positive correlation with Escherichia coli. INTERPRETATION: Collectively, unique bacterial signatures, including c-Bacteroides and c-Blautia, were associated with virological undetectability and fibrosis evolution during NAs therapy in chronic HBV, setting up intriguing possibilities in optimizing HBV treatment. FUNDING: This study was supported by the Guangdong Natural Science Fund (2019A1515012003).
Subject(s)
Gastrointestinal Microbiome , Hepatitis B virus , Hepatitis B, Chronic , Humans , Gastrointestinal Microbiome/drug effects , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/virology , Hepatitis B, Chronic/microbiology , Male , Female , Middle Aged , Adult , Hepatitis B virus/genetics , Bacteroides , Antiviral Agents/therapeutic use , Metabolome , Treatment Outcome , Liver Cirrhosis/drug therapy , Liver Cirrhosis/etiology , Liver Cirrhosis/microbiology , Liver Cirrhosis/virology , Viral Load , Bile Acids and Salts/metabolism , Bile Acids and Salts/blood , Metagenomics/methods , Nucleosides/therapeutic use , Nucleosides/analogs & derivativesABSTRACT
The gut microbiota in the hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) is poorly defined. We aim to uncover the characteristics of the gut microbiota in HBV-ACLF and in other HBV associated pathologies. We analyzed the gut microbiome in patients with HBV-ACLF or other HBV associated pathologies and healthy individuals by 16S rRNA sequencing and metagenomic sequencing of fecal samples. 212 patients with HBV-ACLF, 252 with chronic hepatitis B (CHB), 162 with HBV-associated cirrhosis (HBV-LC) and 877 healthy individuals were recruited for the study. CHB and HBV-LC patients are grouped as HBV-Other. We discovered striking differences in the microbiome diversity between the HBV-ACLF, HBV-Other and healthy groups using 16S rRNA sequencing. The ratio of cocci to bacilli was significantly elevated in the HBV-ACLF group compared with healthy group. Further analysis within the HBV-ACLF group identified 52 genera showing distinct richness within the group where Enterococcus was enriched in the progression group whilst Faecalibacterium was enriched in the regression group. Metagenomic sequencing validated these findings and further uncovered an enrichment of Lactobacillus casei paracasei in progression group, while Alistipes senegalensis, Faecalibacterium prausnitzii and Parabacteroides merdae dominated the regression group. Importantly, our analysis revealed that there was a rapid increase of Enterococcus faecium during the progression of HBV-ACLF. The gut microbiota displayed distinct composition at different phases of HBV-ACLF. High abundance of Enterococcus is associated with progression while that of Faecalibacterium is associated with regression of HBV-ACLF. Therefore, the microbiota features hold promising potential as prognostic markers for HBV-ACLF.
Subject(s)
Acute-On-Chronic Liver Failure/microbiology , Bacteria/isolation & purification , Gastrointestinal Microbiome , Hepatitis B, Chronic/microbiology , Acute-On-Chronic Liver Failure/virology , Adult , Bacteria/classification , Bacteria/genetics , Disease Progression , Feces/microbiology , Female , Hepatitis B virus/physiology , Hepatitis B, Chronic/virology , Humans , Male , Metagenomics , Middle AgedABSTRACT
BACKGROUND: Reports on bacterial infection (BI) in decompensated cirrhosis (DC) is mainly from alcoholic cirrhosis. The role of BI as a trigger or complication of acute-on-chronic liver failure (ACLF) in patients with hepatitis B virus decompensated cirrhosis (HBV-DC) remains to be investigated. AIM: To investigate the impact of BI on the outcomes of the patients with HBV-DC admitted into the hospital with or without ACLF. METHODS: This retrospective study included patients with HBV-DC admitted to two tertiary centers in China. In-hospital overall survival, 90-d transplant-free survival, 5-year post-discharge survival, and cumulative incidence of ACLF were evaluated. Risk factors for death were analyzed considering liver transplantation as a competing event. RESULTS: A total of 1281 hospitalized HBV-DC patients were included; 284 had ACLF at admission. The overall prevalence of BI was 28.1%. The patients with BI had a significantly lower in-hospital survival and transplant-free 90-d survival than those without, in both the patients admitted with and without ACLF. The presence of BI significantly increased the risk of developing ACLF [sub-distribution hazard ratio (sHR) = 2.52, 95%CI: 1.75-3.61, P < 0.001] in the patients without ACLF. In the patients discharged alive, those who had an episode of BI had a significantly lower 5-year transplant-free survival. BI was an independent risk factor for death in the patients admitted without ACLF (sHR = 3.28, 95%CI: 1.93-5.57), while in ACLF admissions, the presence of pneumonia, but not other type of BI, independently increased the risk of death (sHR = 1.87, 95%CI: 1.24-2.82). CONCLUSION: BI triggers ACLF in patients with HBV-DC and significantly impairs short-term survival. HBV-DC patients should be monitored carefully for the development of BI, especially pneumonia, to avoid an adverse outcome.
Subject(s)
Acute-On-Chronic Liver Failure/mortality , Bacterial Infections/mortality , Hepatitis B virus , Hepatitis B, Chronic/mortality , Liver Cirrhosis/mortality , Acute-On-Chronic Liver Failure/microbiology , Adult , Bacterial Infections/complications , China , Female , Hepatitis B, Chronic/microbiology , Humans , Liver Cirrhosis/microbiology , Liver Transplantation , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Risk FactorsABSTRACT
Chronic hepatitis B (CHB) is a global epidemic disease that may progress to fibrosis, cirrhosis and hepatocellular carcinoma. The role of the liver-bile acid-microbiota axis in CHB remains unclear. The aims of this study are to elucidate the alteration of the gut microbiota and its functions in bile acid homeostasis in CHB patients with different degrees of fibrosis. In the present study, we evaluated serum and faecal bile acid profiles in healthy controls and CHB patients with biopsy-proven diagnosis: patients had stage 0-1 fibrosis were classified as mild CHB and patients had stage 2-4 fibrosis were classified as moderate/advanced CHB. The levels of serum total bile acids (BAs) and primary BAs were increased in CHB patients with moderate/advanced fibrosis, whereas faecal total and secondary BAs levels were significantly lower. Analyses of gut microbiota exhibited a trend of decreased abundance in bacteria genera responsible for BA metabolism in CHB patients with moderate/advanced fibrosis. CHB is associated with altered bile acid pool which is linked with the dysregulated gut microbiota. The higher level of FGF-19 may act in a negative feedback loop for maintaining the bile acid homeostasis.
Subject(s)
Bile Acids and Salts/blood , Bile Acids and Salts/metabolism , Gastrointestinal Microbiome/physiology , Hepatitis B, Chronic/blood , Hepatitis B, Chronic/microbiology , Liver/metabolism , Adult , Bacteria , Case-Control Studies , Feces , Female , Fibroblast Growth Factors/blood , Hepatitis B, Chronic/metabolism , Homeostasis/physiology , Humans , Liver Cirrhosis/blood , Liver Cirrhosis/metabolism , Liver Cirrhosis/microbiology , MaleABSTRACT
The information regarding the effect of hepatitis B virus (HBV) infection on gut microbiota and the relationship between gut microbiota dysbiosis and hepatitis B virus-induced chronic liver disease (HBVCLD) is limited. In this study, we aimed at characterizing the gut microbiota composition in the three different stages of hepatitis B virus-induced chronic liver disease patients and healthy individuals. Faecal samples and clinical data were collected from HBVCLD patients and healthy individuals. The 16S rDNA gene amplification products were sequenced. Bioinformatic analysis including alpha diversity and PICRUSt was performed. A total of 19 phyla, 43 classes, 72 orders, 126 families and 225 genera were detected. The beta-diversity showed a separate clustering of healthy controls and HBVCLD patients covering chronic hepatitis (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC); and gut microbiota of healthy controls was more consistent, whereas those of CHB, LC and HCC varied substantially. The abundance of Firmicutes was lower, and Bacteroidetes was higher in patients with CHB, LC and HCC than in healthy controls. Predicted metagenomics of microbial communities showed an increase in glycan biosynthesis and metabolism-related genes and lipid metabolism-related genes in HBVCLD than in healthy individuals. Our study suggested that HBVCLD is associated with gut dysbiosis, with characteristics including, a gain in potential bacteria and a loss in potential beneficial bacteria or genes. Further study of CHB, LC and HCC based on microbiota may provide a novel insight into the pathogenesis of HBVCLD as well as a novel treatment strategy.
Subject(s)
Carcinoma, Hepatocellular/virology , Dysbiosis/genetics , Gastrointestinal Microbiome , Hepatitis B, Chronic/microbiology , Liver Cirrhosis/virology , Liver Neoplasms/virology , Adult , Bacteria/classification , Case-Control Studies , Dysbiosis/etiology , Feces/microbiology , Female , Hepatitis B virus/pathogenicity , Humans , Male , Metagenomics , Middle Aged , RNA, Ribosomal, 16S/geneticsABSTRACT
Microbial electrochemical technology is emerging as an alternative way of treating waste and converting this directly to electricity. Intensive research on these systems is ongoing but it currently lacks the evaluation of possible environmental transmission of enteric viruses originating from the waste stream. In this study, for the first time we investigated this aspect by assessing the removal efficiency of hepatitis B core and surface antigens in cascades of continuous flow microbial fuel cells. The log-reduction (LR) of surface antigen (HBsAg) reached a maximum value of 1.86 ± 0.20 (98.6% reduction), which was similar to the open circuit control and degraded regardless of the recorded current. Core antigen (HBcAg) was much more resistant to treatment and the maximal LR was equal to 0.229 ± 0.028 (41.0% reduction). The highest LR rate observed for HBsAg was 4.66 ± 0.19 h-1 and for HBcAg 0.10 ± 0.01 h-1. Regression analysis revealed correlation between hydraulic retention time, power and redox potential on inactivation efficiency, also indicating electroactive behaviour of biofilm in open circuit control through the snorkel-effect. The results indicate that microbial electrochemical technologies may be successfully applied to reduce the risk of environmental transmission of hepatitis B virus but also open up the possibility of testing other viruses for wider implementation.
Subject(s)
Bioelectric Energy Sources , Electricity , Hepatitis B virus/immunology , Hepatitis B, Chronic/therapy , Hepatitis B Core Antigens/immunology , Hepatitis B Surface Antigens/immunology , Hepatitis B virus/pathogenicity , Hepatitis B, Chronic/immunology , Hepatitis B, Chronic/microbiology , Humans , Immunologic Factors , Liver/immunology , Liver/pathology , Liver/virology , Urine/microbiologyABSTRACT
BACKGROUND: Patients with hepatitis B-related acute-on-chronic liver failure (HB-ACLF) may have an increased circulating microbial burden. This study aimed to assess circulating microbial load and composition and to explore the association between the circulating microbiome and both systemic inflammation (SI) and clinical outcome in HB-ACLF. METHODS: Plasma from 50 HB-ACLF patients, 23 healthy controls and 25 patients with compensated liver cirrhosis (C-LC) was analysed for chemokines/cytokines and bacterial DNA and further analysed by 16S rDNApyrosequencing. Linear discriminant analysis effect size (LEfSe) and inferred metagenomics analyses were performed. RESULTS: The circulating bacterial DNA was significantly increased in HB-ACLF patients compared to that in the control groups. The overall microbial diversity was significantly decreased in HB-ACLF patients. HB-ACLF patients were enriched with Moraxellaceae, Sulfurovum, Comamonas and Burkholderiaceae but were depleted in Actinobacteria, Deinococcus-Thermus, Alphaproteobacteria, Xanthomonadaceae and Enterobacteriaceae compared to controls. Network analysis revealed a direct positive correlation between Burkholderiaceae and chemokine IP-10 in HB-ACLF patients. The relative abundance of Prevotellaceae independently predicted 28-day mortality. Inferred functional metagenomics predicted an enrichment of bacteria with genes related to methane, alanine, aspartate, glutamate, pyrimidine, purine and energy metabolism. CONCLUSIONS: HB-ACLF patients display increased circulating microbial burden, altered microbiome composition and a shift in microbiome functionality. The alteration in circulating microbiota is associated with SI and clinical outcome in HB-ACLF.
Subject(s)
Acute-On-Chronic Liver Failure/blood , Hepatitis B, Chronic/blood , Liver Cirrhosis/blood , Microbiota , Acute-On-Chronic Liver Failure/microbiology , Acute-On-Chronic Liver Failure/mortality , Adult , Biomarkers/blood , Case-Control Studies , Cytokines/blood , DNA, Bacterial/blood , Female , Hepatitis B, Chronic/microbiology , Humans , Inflammation Mediators/blood , Liver Cirrhosis/microbiology , Male , Middle Aged , Predictive Value of TestsABSTRACT
Mutations occurring in viral polymerase gene of hepatitis B virus (HBV) due to the use of nucleos(t)id analogs reduce the activity of the drugs by causing antiviral resistance. In this study, it was aimed to evaluate mutations responsible for drug resistance and drug resistance mutation rates in patients followed up by the diagnosis of chronic hepatitis B (CHB). A total of 318 CHB patients were included in the study. HBV mutations were detected using the INNO-LiPA commercial kit based on the reverse hybridization principle. Drug resistance mutation was detected in 46.86% (149/318) of the patients. The rates of drug resistance were found 36.79% (117/318) for lamivudine resistance, 12.58% (40/318) for entecavir (ETV), and 7.86% (25/318) for adefovir. In 10 patients, the possible tenofovir (TDF) resistance (3.14%) was found. Single-drug and double-drug resistances were detected in 34.59% and in 11.01% of the patients, respectively. Triple drug resistance was detected in only 1.26% of the patients. Unlike various studies in Turkey and in other countries, remarkable resistance to ETV and TDF were found in this study. The high rate of the probable TDF resistance was striking, with 3.14%.
Subject(s)
Drug Resistance, Viral/genetics , Hepatitis B virus/genetics , Hepatitis B, Chronic/microbiology , Adolescent , Adult , Aged , Aged, 80 and over , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Child , Child, Preschool , DNA, Viral/genetics , Drug Resistance, Multiple, Viral/genetics , Female , Hepatitis B virus/drug effects , Hepatitis B, Chronic/drug therapy , Humans , Male , Middle Aged , Mutation , RNA-Directed DNA Polymerase/genetics , Retrospective Studies , Turkey , Young AdultABSTRACT
Hepatitis B can cause acute or chronic liver damage due to hepatitis B virus (HBV) infection. Cirrhosis or hepatocellular carcinoma (HCC) caused by chronic HBV infection often leads to increased mortality. However, the gut and liver have the same embryonic origin; therefore, a close relationship must exist in terms of anatomy and function, and the gut microbiota plays an important role in host metabolic and immune modulation. It is believed that structural changes in the gut microbiota, bacterial translocation, and the resulting immune injury may affect the occurrence and development of liver inflammation caused by chronic HBV infection based on the in-depth cognition of the concept of the "gut-liver axis" and the progress in intestinal microecology. This review aims to summarize and discuss the immunologic role of the gut microbiota in chronic HBV infection.
Subject(s)
Carcinoma, Hepatocellular/virology , Gastrointestinal Microbiome/immunology , Hepatitis B virus/physiology , Hepatitis B, Chronic/virology , Intestines/microbiology , Liver Cirrhosis/virology , Liver Neoplasms/immunology , Liver/pathology , Animals , Bacterial Translocation , Carcinoma, Hepatocellular/immunology , Carcinoma, Hepatocellular/microbiology , Hepatitis B, Chronic/immunology , Hepatitis B, Chronic/microbiology , Humans , Immunomodulation , Liver Cirrhosis/immunology , Liver Cirrhosis/microbiology , Liver Neoplasms/microbiology , Liver Neoplasms/virologyABSTRACT
AIM: To elucidate tongue coating microbiota and metabolic differences in chronic hepatitis B (CHB) patients with yellow or white tongue coatings. METHODS: Tongue coating samples were collected from 53 CHB patients (28 CHB yellow tongue coating patients and 25 CHB white tongue coating patients) and 22 healthy controls. Microbial DNA was extracted from the tongue samples, and the bacterial 16S ribosomal RNA gene V3 region was amplified from all samples and sequenced with the Ion Torrent PGM™ sequencing platform according to the standard protocols. The metabolites in the tongue coatings were evaluated using a liquid chromatography-mass spectrometry (LC-MS) platform. Statistical analyses were then performed. RESULTS: The relative compositions of the tongue coating microbiotas and metabolites in the CHB patients were significantly different from those of the healthy controls, but the tongue coating microbiota abundances and diversity levels were not significantly different. Compared with the CHB white tongue coating patients, the CHB yellow tongue coating patients had higher hepatitis B viral DNA (HBV-DNA) titers (median 21210 vs 500, respectively, P = 0.03) and a significantly lower level of Bacteroidetes (20.14% vs 27.93%, respectively, P = 0.013) and higher level of Proteobacteria (25.99% vs 18.17%, respectively, P = 0.045) in the microbial compositions at the phylum level. The inferred metagenomic pathways enriched in the CHB yellow tongue coating patients were mainly those involved in amino acid metabolism, which was consistent with the metabolic disorder. The abundances of bacteria from Bacteroidales at the order level were higher in the CHB white tongue coating patients (19.2% vs 27.22%, respectively, P = 0.011), whereas Neisseriales were enriched in the yellow tongue coating patients (21.85% vs 13.83%, respectively, P = 0.029). At the family level, the abundance of Neisseriaceae in the yellow tongue patients was positively correlated with the HBV-DNA level but negatively correlated with the S-adenosyl-L-methionine level. CONCLUSION: This research illustrates specific clinical features and bacterial structures in CHB patients with different tongue coatings, which facilitates understanding of the traditional tongue diagnosis.
Subject(s)
Bacteria/isolation & purification , Gastrointestinal Microbiome/physiology , Hepatitis B virus/isolation & purification , Hepatitis B, Chronic/microbiology , Tongue/microbiology , Adult , Bacteria/genetics , Bacteria/metabolism , Case-Control Studies , DNA, Viral/isolation & purification , Female , Healthy Volunteers , Hepatitis B virus/genetics , Hepatitis B, Chronic/diagnosis , Hepatitis B, Chronic/metabolism , Humans , Male , Medicine, Chinese Traditional/methods , Metagenomics , Middle Aged , RNA, Ribosomal, 16S/geneticsABSTRACT
BACKGROUND AND STUDY AIMS: Occult hepatitis B infection (OBI) is known to be mostly prevalent in chronic hepatitis C (CHC) patients and OBI reactivation might be life-threatening in patients undergoing interferon (IFN)-free direct acting antiviral (DAA) therapy. As previous studies have revealed a relationship between OBI and non-response to IFN-based antiviral therapy, the aim of the current study was to determine if there was a higher prevalence of OBI in IFN non-responders than responders. PATIENTS AND METHODS: This retrospective cross-sectional study was conducted in CHC patients who had previously received IFN-based antiviral therapy. Serum samples of 100 HBsAg negative CHC patients were tested for HBV DNA, anti-HBc IgG, anti-HBs, ALT and AST. The presence of OBI was compared between 50 IFN responders and 50 IFN non-responders. Patients with a history of previous HBV infection, patients with evidence of cirrhosis and patients who had received IFN therapy within the last one year were excluded from the study. RESULTS: Anti-HBc IgG positivity was determined in 53% of the patients. HBV DNA positivity, indicating OBI was determined in 1 (1%) patient. This patient was anti-HBc IgG positive, anti-HBs negative, ALT and AST levels were normal. The HBV DNA and anti-HBc IgG positivity rates were higher in the non-responder group than in the responder group, but the difference was not statistically significant (pâ¯=â¯0.31 and pâ¯=â¯0.07 respectively). CONCLUSION: According to the results of this study, the prevalence of OBI is lower than expected amongst CHC patients in Turkey and it may not be necessary to apply routine screening to IFN non-responders for OBI infection before DAA therapy. However, there is a need for multicentre studies with larger patient series.
Subject(s)
Antiviral Agents , Hepatitis B virus , Hepatitis B, Chronic , Hepatitis C, Chronic , Interferons , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , Coinfection , DNA, Viral/isolation & purification , Female , Hepatitis B Antibodies/isolation & purification , Hepatitis B Surface Antigens/blood , Hepatitis B virus/drug effects , Hepatitis B virus/isolation & purification , Hepatitis B virus/physiology , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/epidemiology , Hepatitis B, Chronic/immunology , Hepatitis B, Chronic/microbiology , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/epidemiology , Hepatitis C, Chronic/immunology , Hepatitis C, Chronic/microbiology , Humans , Interferons/administration & dosage , Interferons/adverse effects , Male , Middle Aged , Prevalence , Statistics as Topic , Turkey/epidemiology , Virus Activation/immunologyABSTRACT
A 55-year-old man with history of chronic hepatitis B cirrhosis presented to an emergency department in California with abdominal pain, constipation, and jaundice. The patient developed methicillin-susceptible S. aureus bacteremia with a concurrent transient E. coli. This organism carried mcr-1 in a plasmid similar to other mcr-1-carrying plasmids from the USA. The spread of mcr-1 into carbapenem-resistant isolates is of great concern and monitoring of this resistance mechanism is important.
Subject(s)
Bacteremia/diagnosis , Escherichia coli Proteins/genetics , Escherichia coli/genetics , Staphylococcus aureus/genetics , Bacteremia/drug therapy , California , Carbapenems/therapeutic use , Drug Resistance, Multiple, Bacterial/genetics , Escherichia coli/isolation & purification , Escherichia coli Infections/diagnosis , Escherichia coli Infections/drug therapy , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/microbiology , Humans , Liver Cirrhosis/virology , Male , Middle Aged , Plasmids/genetics , Staphylococcal Infections/diagnosis , Staphylococcal Infections/drug therapy , Staphylococcus aureus/isolation & purificationABSTRACT
Increasing evidence suggests that altered gut microbiota is implicated in the pathogenesis of hepatitis B virus-induced chronic liver disease (HBV-CLD). However, the structure and composition of the oral microbiota of patients with HBV-CLD remains unclear. High-throughput pyrosequencing showed that decreased oral bacterial diversity was found in patients with HBV-CLD. The Firmicutes/Bacteroidetes ratio was increased significantly, which indicated that dysbiosis of the oral microbiota participated in the process of HBV-CLD development. However, the changing patterns of the oral microbiota in patients with HBV-induced liver cirrhosis (LC) were almost similar to patients with chronic hepatitis B (CHB). HBV infection resulted in an increase in potential H2S- and CH3SH-producing phylotypes such as Fusobacterium, Filifactor, Eubacterium, Parvimonas and Treponema, which might contribute to the increased oral malodor. These key oral-derived phylotypes might invade into the gut as opportunistic pathogens and contribute to altering the composition of the gut microbiota. This study provided important clues that dysbiosis of the oral microbiota might be involved in the development of HBV-CLD. Greater understanding of the relationships between the dysbiosis of oral microbiota and the development of HBV-CLD might facilitate the development of non-invasive differential diagnostic procedures and targeted treatments of HBV-CLD patients harbouring specific oral phylotypes.
Subject(s)
Biodiversity , Hepatitis B virus/physiology , Hepatitis B, Chronic/microbiology , Hepatitis B, Chronic/virology , Microbiota , Mouth/microbiology , Case-Control Studies , Female , Humans , Liver Cirrhosis/microbiology , Male , Microbiota/genetics , Middle Aged , Phylogeny , Pilot Projects , RNA, Ribosomal, 16S/geneticsABSTRACT
AIM: : Although numerous animal studies suggest that probiotic therapy has beneficial effects in various liver diseases, the evidence for beneficial effects in human liver disease is controversial. This study was carried out to investigate the efficacy of probiotic therapy in alleviating small intestinal bacterial overgrowth (SIBO) and permeability in chronic liver disease. METHODS: Fifty-three patients with chronic liver disease were randomized to either probiotic therapy or placebo. Six bacterial species were used: Bifidobacterium bifidum, Bifidobacterium lactis, Bifidobacterium longum, Lactobacillus acidophilus, Lactobacillus rhamnosus, and Streptococcus thermophilus. After 4 weeks, changes in the composition of fecal bacteria, SIBO, intestinal permeability, and clinical symptoms were examined. RESULTS: Three of the six probiotic species, B. lactis, L. rhamnosus, and L. acidophilus, increased in the feces of the probiotic therapy group (P<0.001), whereas there was no change in fecal microbiota in the placebo group. SIBO disappeared in many individuals of the probiotic therapy group, but none in the placebo (24 vs. 0%, P<0.05). General gastrointestinal symptoms also improved more in the probiotic group and improvement in intestinal permeability was slightly but not significantly more frequent in the probiotic arm than the placebo arm (50 vs. 31.3%, P=0.248). Numbers of lactobacilli in stool were correlated negatively with intestinal permeability (P for trend<0.05). Liver chemistry did not improve significantly in either group. CONCLUSIONS: We conclude that short-term probiotic administration in chronic liver disease is effective in alleviating SIBO and clinical symptoms, but ineffective in improving intestinal permeability and liver function.
Subject(s)
Hepatitis B, Chronic/therapy , Hepatitis C, Chronic/therapy , Intestine, Small/microbiology , Liver Diseases, Alcoholic/therapy , Probiotics , Feces/microbiology , Female , Hepatitis B, Chronic/diagnosis , Hepatitis B, Chronic/microbiology , Hepatitis C, Chronic/diagnosis , Hepatitis C, Chronic/microbiology , Humans , Intestine, Small/metabolism , Liver Diseases, Alcoholic/diagnosis , Liver Diseases, Alcoholic/microbiology , Male , Middle Aged , Permeability , Republic of Korea , Time Factors , Treatment OutcomeABSTRACT
Las determinaciones de la carga viral de los virus de la inmunodeficiencia humana tipo 1 (VIH-1), de la hepatitis C (VHC) y de la hepatitis B (VHB) son marcadores microbiológicos fundamentales para el seguimiento y control de los pacientes infectados por estos virus. Los laboratorios de microbiología disponen de herramientas que garantizan la fiabilidad de sus resultados; entre ellas se encuentran los programas de intercomparación externos, como el Programa de Control de Calidad de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC). En el presente número se muestra el análisis de resultados del Programa de Control de Calidad SEIMC de carga viral de estos virus, incluyendo el genotipado del VHC, realizado durante el año 2012.En el control de VIH-1 se remitieron 5 estándares, de los que 1 (plasma humano seronegativo) no contenía el virus y los otros 4 consistían en plasma de 3 pacientes virémicos distintos en un intervalo de concentraciones de entre 2-5 log10 copias/ml; 2 de ellos eran idénticos, con el fin de analizar la repetibilidad. Una parte significativa de los laboratorios obtuvo de uno a varios resultados fuera de los límites aceptables (media ± 0,25 log10 copias/ml), dependiendo del estándar y del método empleado, en promedio el 22,3% de los centros. La repetibilidad fue excelente y más del 98,9% de los laboratorios obtuvo resultados aceptables (Δ < 0,5 log10 copias/ml). En los controles de VHC y VHB se remitieron 2 estándares con diferente contenido del virus. La mayor parte de los participantes, alrededor del 84% en el caso del VHC y del 88% en el del VHB, obtuvo ambos resultados dentro de los límites de la media ± 1,96 DE log10 UI/ml. Los resultados obtenidos ponen de manifiesto la utilidad de los controles externos para asegurar la calidad de los resultados analíticos, incluyendo la fase postanalítica. Debido a la variabilidad interlaboratorio es aconsejable utilizar un mismo método y el mismo laboratorio en el seguimiento de los pacientes
Human immunodeficiency virus type 1 (HIV-1) and hepatitis B (HBV) and C virus (HCV) viral load determinations are among the most relevant markers for the follow up of patients infected with these viruses. External quality control tools are crucial to ensure the accuracy of results obtained by microbiology laboratories. This article summarized the results obtained from the 2012 SEIMC External Quality Control Programme for HIV-1, HCV, and HBV viral loads. In the HIV-1 program, a total of five standards were sent. One standard consisted in seronegative human plasma, while the remaining four contained plasma from three different viremic patients, in the range of 2-5 log10 copies/mL; two of these standards were identical aiming to determine repeatability. A significant proportion of the laboratories (22.3% on average) obtained values out of the accepted range (mean±0.25 log10 copies/mL), depending on the standard and on the method used for quantification. Repeatability was excellent, with up to 98.9% of laboratories reporting results within the limits (Δ < 0.5 log10 copias/mL). The HBV and HCV program consisted of two standards with different viral load contents. Most of the participants, 84% in the case of HCV and 88% in the HBV, obtained all the results within the accepted range (mean±1.96 SD log10 UI/mL).Data from this analysis reinforce the utility of proficiency programmes to ensure the quality of the results obtained by a particular laboratory, as well as the importance of the post-analytical phase on the overall quality. Due to the remarkable interlaboratory variability, it is advisable to use the same method and the same laboratory for patient follow up (AU)
Subject(s)
Humans , Viral Load/instrumentation , Virology/standards , HIV Infections/microbiology , Hepatitis B, Chronic/microbiology , Hepatitis C, Chronic/microbiology , Hepatitis B virus/isolation & purification , Hepacivirus/isolation & purification , Quality Control , Laboratory Proficiency TestingABSTRACT
OBJECTIVE: To investigate whether Toll-like receptor (TLR) 7 and TLR9-mediated interferon α (IFN-α) production in plasmacytoid dendritic cells (pDCs) is compromised in patients with chronic hepatitis B virus (HBV) infection. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMCs) were prepared from 32 chronic HBV patients and 13 healthy volunteers, and treated with loxoribine or cytidine phosphate guanosine (CpG) oligodeoxynucleotides (ODN). Interferon α in the supernatant was measured by sandwich ELISA. PDC frequency and the expression levels of TLR7 and TLR9 in pDCs were quantified by flow cytometry. The serum viral load of HBV was quantified using a highly sensitive real-time PCR kit. RESULTS: Compared to cells from healthy control group, PBMCs and pDCs from the HBV group showed significantly decreased production of IFN-α in response to ligand for TLR7 (loxoribine) and TLR9 (CpG ODN, P < 0.05). Mechanistically, the number of pDCs in peripheral blood, and the expression of pDC-associated TLR7 and TLR9 were significantly lower in HBV group than in the healthy control group (P < 0.05). In addition, the number of pDCs and the expression of TLR9 on pDCs were correlated inversely with the serum load of HBV. CONCLUSION: Impaired IFN-α production from pDC may contribute to the immunopathogenesis of chronic HBV infection, which may be the result of a reduced amount of pDCs as well as decreased expression of TLR7 and TLR9 on pDCs.
Subject(s)
Dendritic Cells/metabolism , Hepatitis B, Chronic/metabolism , Interferon-alpha/metabolism , Toll-Like Receptor 7/antagonists & inhibitors , Toll-Like Receptor 9/antagonists & inhibitors , Adult , Case-Control Studies , Cells, Cultured , Dendritic Cells/drug effects , Down-Regulation , Female , Guanosine/analogs & derivatives , Guanosine/pharmacology , Hepatitis B, Chronic/microbiology , Humans , Leukocytes, Mononuclear/cytology , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/metabolism , Male , Middle Aged , Oligodeoxyribonucleotides/pharmacology , Toll-Like Receptor 7/metabolism , Toll-Like Receptor 9/metabolism , Viral LoadABSTRACT
Introducción Las variaciones del gen C originan las mutaciones precore y las core, que influyen en la producción de AgHBe. El fallo en los tratamientos antivirales se debe a la presencia de las variaciones en el gen P, que originan las mutaciones de la polimerasa viral. Método Hemos realizado estudio genotípico del VHB mediante secuenciación del gen P, y del gen C en pacientes con hepatitis crónica por virus B durante un periodo de cinco años. Resultados El 75% presentaron alguna mutación en la región precore, core o en ambas. El 37% mostró mutaciones de resistencia al tratamiento antiviral. Los genotipos más frecuentes fueron el A y el D. Conclusiones La presencia de mutaciones core/precore en pacientes con hepatitis crónica hace obligado un control más estrecho de estos enfermos. La detección de resistencias debe hacerse lo más rápido posible antes de que se produzca un aumento de la carga viral (AU)
Background Variations of C gene give rise to precore and basal core mutations, which influence HBeAg expression The antiviral treatment failure is due to the presence of variations in the gene P, which cause mutations in the viral polymerase. Methods We performed genotyping of HBV P gene by sequencing, and gene C in patients with chronic hepatitis B over a period of five years. Results A total of 75% of the patients had some mutation in precore or in basal core promoter regions, and 37% demonstrated resistance mutations to antiviral treatment. The most frequent genotypes were A and D. Conclusions The presence of mutations in core/precore regions in patients with chronic hepatitis has led to tighter control of these patients. Detecting for resistance should be done as quickly as possible before there is an increase in viral load(AU)
Subject(s)
Humans , Hepatitis B, Chronic/microbiology , Hepatitis B virus/genetics , Genotype , Viral Core Proteins/genetics , Mutation/genetics , Prospective Studies , Viral LoadABSTRACT
The beneficial effects of Bifidobacteria on health have been widely accepted. Patients with chronic liver disease have varying degrees of intestinal microflora imbalance with a decrease of total Bifidobacterial counts. Since different properties have been attributed to different Bifidobacterium species and there is no information available for the detailed changes in the genus Bifidobacterium in patients with chronic liver disease heretofore, it is meaningful to investigate the structure of this bacterium at the species level in these patients. The aim of this study was to characterize the composition of intestinal Bifidobacterium in patients with hepatitis B virus-induced chronic liver disease. Nested-PCR-based denaturing gradient gel electrophoresis (PCR-DGGE), clone library, and real-time quantitative PCR were performed on the fecal samples of 16 patients with chronic hepatitis B (CHB patients), 16 patients with hepatitis B virus-related cirrhosis (HBV cirrhotics), and 15 healthy subjects (Controls). Though there was no significant difference in the diversity among the three groups (P = 0.196), Bifidobacterium dentium seems to be specifically enhanced in patients as the PCR-DGGE profiles showed, which was further validated by clone library and real-time quantitative PCR. In contrast to the B. dentium, Bifidobacterium catenulatum/Bifidobacterium pseudocatenulatum were detected less frequently in the predominant profile and by quantitative PCR in HBV cirrhotics than in the controls, and the level of this species was also significantly different between these two groups (P = 0.023). Although having no quantitative difference among the three groups, Bifidobacterium longum was less commonly detected in HBV cirrhotics than in CHB patients and Controls by quantitative PCR (P = 0.011). Thus, the composition of intestinal Bifidobacterium was deeply altered in CHB and HBV cirrhotic patients with a shift from beneficial species to opportunistic pathogens. The results provide further insights into the dysbiosis of the intestinal microbiota in patients with hepatitis B virus-induced chronic liver disease and might potentially serve as guidance for the probiotics interventions of these diseases.