Alterations of the Gut Microbiome in Chronic Hepatitis B Virus Infection Associated with Alanine Aminotransferase Level.
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ABSTRACT:
SUBMITTER: Yun Y
PROVIDER: S-EPMC6407135 | biostudies-literature | 2019 Feb
REPOSITORIES: biostudies-literature
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Project description:Chronic hepatitis B virus (HBV) infection follows a dynamic and variable course. At different stages in the disease, hepatitis flares might occur, which can be challenging to predict and manage. Flares are believed to be primarily immune-mediated and might mark transitions to inactive disease or clearance of infection, but in certain scenarios they might also lead to hepatic decompensation or death. As such, understanding of the clinical significance of flares in different patient populations and different scenarios is important for optimal management. In this Review, we summarise what is known about flares in different stages of chronic HBV infection; describe flares in the context of the natural history of chronic infection; summarise the immunological mechanisms underlying flares, and describe flares in different clinical scenarios. Each section reviews existing knowledge and highlights key unanswered questions that need to be addressed to improve the understanding of flares, hopefully providing insights into their pathogenesis that can be used to improve current clinical management and ideally to further develop new curative therapeutic approaches for HBV infection. We also propose a working definition of an ALT flare to facilitate future research.
| S-EPMC7158588 | biostudies-literature
Project description:Background & aimsHepatic elastography (HE) is a noninvasive technique that measures liver stiffness and is used to diagnose hepatic fibrosis. It can help patients who are thought to have early-stage disease avoid a staging liver biopsy, but only when confounding variables that increase liver stiffness are excluded. Chronic inflammation from hepatitis C virus (HCV) infection is not considered to be one of these variables.MethodsWe identified 684 patients with HCV and METAVIR fibrosis scores of 0-2 from a prospective, multi-institutional study of liver stiffness in 2880 patients with chronic liver disease. Patients were 49.6 ± 9.0 years old, 64.3% were male, and they had an average body mass index of 26.7 ± 4.1 kg/m(2).ResultsIn a multivariate analysis, inflammation (based on histologic analysis) and level of alanine aminotransferase (ALT) were associated with liver stiffness. The chances of a patient having a level of stiffness that indicates cirrhosis increased with grade of inflammation and level of ALT. By using a conservative 14.5-kPa cutoff for the diagnosis of cirrhosis, grade 3 inflammation had an odds ratio of 9.10 (95% confidence interval, 2.49-33.4). Likewise, levels of ALT greater than 80 and 120 IU/L had odds ratios of 3.84 (95% confidence interval, 2.10-7.00) and 4.10 (95% confidence interval, 2.18-7.69), respectively. The effect of the level of ALT persisted when analysis was restricted to patients with fibrosis scores of F0 to F1.ConclusionsIn patients with HCV infection and early-stage fibrosis, increased levels of ALT correlate with liver stiffness among patients in the lowest strata of fibrosis (METAVIR scores 0-2). Patients without fibrosis but high levels of ALT could have liver stiffness within the range for cirrhosis. Inflammation should be considered a confounding variable in analysis of liver stiffness.
| S-EPMC3402604 | biostudies-literature
Project description:BackgroundNormal serum alanine aminotransferase (ALT) levels differ with age, gender, and body mass index. Adjusting the upper limits of normal (ULN) for ALT needs further research in different populations. Aim of this work was to monitor the effect of successful chronic hepatitis C (CHC) treatment on the ALT levels in patients with normal pretreatment ALT.MethodsData of 1160 CHC patients with persistent pretreatment normal liver enzymes were retrospectively analyzed. Treatment response to direct acting antiviral agents (DAAs) therapy was recorded. Changes in ALT levels before and after treatment were analyzed by patients' demographic, laboratory, and radiologic characteristics. Areas under the receiver operating characteristic curve (AUROC) of ALT after treatment were used to generate a new ALT ULN.ResultsMales were 568 (49%) and females 592 (51%) with a mean age of 50.7 years. After treatment, mean (±SD) of ALT levels significantly decreased from (26.3±7.8) to (19.1±10.9). This reduction was more significant in interferon-free than interferon-based regimens. ROC curve analyses suggested a new ALT ULN cut off (26.4 IU/L) in the treated patients (sensitivity=78.6%, specificity=83.8%, AUROC=0.89. This cutoff dropped to 14.7 IU/L in cirrhotic patients (sensitivity=77.4%, specificity=44.7%, AUROC=0.612). The identified cutoffs were 16.3 IU/L (sensitivity=66.7%, specificity=47.5%, AUROC=0.499) and 15.5 IU/L (sensitivity=76.5%, specificity=51.3%, AUROC=0.576) in males and females, respectively.ConclusionThe current ALT ULN needs readjustment to identify new normal cutoffs in CHC patients. Posttreatment cutoffs differ according to gender, pretreatment liver affection, and treatment regimen.
| S-EPMC6817060 | biostudies-literature
Project description:Accurate estimation of hepatic necroinflammation caused by chronic hepatitis C (CHC) is crucial for prediction of prognosis and design of therapeutic strategy, which is particularly true for CHC patients with normal alanine aminotransferase (ALT) level. Recent studies have shown that sphingolipids have a close relationship with hepatitis C virus infection. The present study aimed to identify plasma sphingolipids related to hepatic necroinflammation. We included 120 treatment-naïve CHC patients and 64/120 had normal ALT levels (<40 U/L). CHC patients who underwent liver biopsies were subjected to Scheuer scoring analysis for scope of hepatic inflammation. Plasma sphingolipids were detected by high-performance liquid chromatography tandem mass spectrometry. Our results showed 44 plasma sphingolipids were detected altogether. Of all detected sphingolipids, hexosylceramide (HexCer) (d18∶1/22∶0) and HexCer (d18∶1/24∶0) showed a significant difference among G0/G1, G2, and G3/G4 (P<0.05). For identifying hepatic necroinflammation (G≥2), after adjusting other factors, the odds ratio (OR) of HexCer (d18∶1/22∶0) reached 1.01 (95% confidence interval [CI]: 1.00-1.02). Furthermore, the area under the curve (AUC) of HexCer (d18∶1/22∶0) was 0.7 (P = 0.01) and approached that of ALT (AUC = 0.78). However, in CHC patients with normal ALT, HexCer (d18∶1/22∶0) was an independent factor (OR: 1.02, 95% CI: 1.01-1.03) to identify the hepatic necroinflammation (G≥2). HexCer (d18∶1/22∶0) not only showed the largest AUC (0.78, P = 0.001), but also exhibited the highest specificity of all indicators. These results indicate that plasma HexCer (d18∶1/22∶0) is a potential indicator to distinguish hepatic necroinflammation in CHC patients. For CHC with normal ALT, the ability of HexCer (d18∶1/22∶0) to distinguish hepatic necroinflammation might be superior to conventional serum indicators.
| S-EPMC3988168 | biostudies-literature
Project description:This study assessed the association of alanine-aminotransferase (ALT) and hepatitis C virus (HCV) RNA levels with pro-inflammatory and pro-fibrogenic cytokines and chemokines during acute HCV infection to provide further insight into the potential HCV immunopathogenesis.Participants in the ATAHC study, a prospective study of recent HCV infection, with detectable HCV RNA at the time of HCV detection were included. Plasma levels of 27 cytokines and chemokines were measured and their correlation with ALT and HCV RNA levels were assessed. Log10 transformed cytokines and ALT values were used in the analysis.Among 117 individuals, the plasma levels of interferon-gamma inducible protein-10 (IP-10) and macrophage inflammatory protein-1beta (MIP-1?) were positively correlated with ALT levels (IP-10: r = 0.42, P < 0.001; MIP-1?: r = 0.29, P = 0.001) and HCV RNA levels (IP-10: rs = 0.44, P < 0.001; MIP-1?: rs = 0.43, P < 0.001). Using linear regression, after adjusting for sex, age, infection duration, symptomatic infection, HIV co-infection, interferon-lambda rs12979860 genotype, HCV genotype, and assay run, higher ALT levels (? = 0.20; 95 % CI: 0.07, 0.32; P = 0.002) and HCV RNA levels >400,000 IU/mL (vs. <8,500 IU/mL; ? = 0.16; 95 % CI: 0.03, 0.28; P = 0.014) were independently associated with higher IP-10 levels. HCV RNA levels >400,000 IU/mL (vs. <8,500 IU/mL; ? = 0.16; 95 % CI: 0.01, 0.31; P = 0.036) were associated with higher MIP-1? levels.During acute HCV infection, high ALT and HCV RNA levels were associated with increased IP-10 levels, while high HCV RNA levels were also associated with increased MIP-1? levels. These data suggest that IP-10 and MIP-1? may have a role in HCV immuno-pathogenesis starting early in acute HCV infection.
| S-EPMC4765111 | biostudies-literature
Project description:IntroductionAlterations in the immune system can result in alanine aminotransferase (ALT) flares either during pregnancy or after delivery in women with chronic hepatitis B virus (HBV) infection. The aim of this study was to prospectively assess changes in serum biochemical and virological markers of HBV infection during and after pregnancy in a large North American cohort of pregnant women with chronic HBV.MethodsAdult pregnant women enrolled in the Hepatitis B Research Network between 2011 and 2016 were included. Serum ALT values and HBV DNA viral levels were obtained at <28 weeks and >28 weeks of gestation and <16 weeks, 16-31 weeks, and 32-48 weeks postpartum. Outcomes of ALT flares included severity, duration, and initiation of antiviral therapy.ResultsAmong the 158 pregnant women with chronic HBV, the median age was 33 years, 73% were Asian, and 63% were hepatitis B e antigen (HBeAg) negative. The median HBV DNA level was substantially higher in the HBeAg-positive vs HBeAg-negative women (1.3 × 10 vs 343 IU/mL), but serum ALT levels at their first study visit were similar. Among untreated pregnant women, there was a very mild increase in serum ALT postpartum among both HBeAg-positive and HBeAg-negative women (P < 0.001). Serum ALT flares (range 107-513 U/L) developed in 3.4% (5/149) during pregnancy and in 4.3% (4/92) after delivery. Twenty-two percent were initiated on antiviral therapy. After withdrawal of prophylactic anti-HBV therapy, 17.2% (5/29) developed serum ALT flares (range 107-208 U/L) within 14 weeks of drug discontinuation, and 3 additional women had flares despite continuous anti-HBV therapy during pregnancy or postpartum. Many ALT flares were not associated with significant changes in HBV DNA levels. No flares were severe with elevations of bilirubin or clinical decompensation.DiscussionSpontaneous ALT flares in untreated pregnant women with chronic HBV are infrequent, mild, and self-limited both prepartum and postpartum. Although flares after the withdrawal of antiviral therapy postpartum are more common, they were also mild and self-limited. Further studies of the immunopathogenesis of pregnancy-related flares are needed, as well as effects on long-term outcome of the mother and infant.
| S-EPMC7132838 | biostudies-literature
Project description:Gut dysbiosis has been reported in chronic hepatitis B (CHB) infection, however its role in CHB progression and antiviral treatment remains to be clarified. Herein, the present study aimed to characterize gut microbiota (GM) in patients with chronic hepatitis B virus infection-associated liver diseases (HBV-CLD) by combining microbiome with metabolome analyses and to evaluate their effects on peripheral immunity. Fecal samples from HBV-CLD patients (n = 64) and healthy controls (n = 17) were collected for 16s rRNA sequencing. Fecal metabolomics was measured with untargeted liquid chromatography-mass spectrometry in subgroups of 58 subjects. Lineage changes of peripheral blood mononuclear cells (PBMCs) were determined upon exposure to bacterial extracts (BE) from HBV-CLD patients. Integrated analyses of microbiome with metabolome revealed a remarkable shift of gut microbiota and metabolites in HBV-CLD patients, and disease progression and antiviral treatment were found to be two main contributing factors for the shift. Concordant decreases in Turicibacter with 4-hydroxyretinoic acid were detected to be inversely correlated with serum AST levels through host-microbiota-metabolite interaction analysis in cirrhotic patients. Moreover, depletion of E.hallii group with elevated choline was restored in patients with 5-year antiviral treatment. PBMC exposure to BE from non-cirrhotic patients enhanced expansion of T helper 17 cells; however, BE from cirrhotics attenuated T helper 1 cell count. CHB progression and antiviral treatment are two main factors contributing to the compositional shift in microbiome and metabolome of HBV-CLD patients. Peripheral immunity might be an intermediate link in gut microbe-host interplay underlying CHB pathogenesis.
| S-EPMC9757487 | biostudies-literature
Project description:Background: Circulating miRNAs, a new family of miRNAs presentin plasma and serum, have shown great potential as novel body fluid biomarkers for non-invasive diagnosis and prognosis of several diseases. Methods: In the present study, we employed next-generation sequencing technology to analyze the expression profiles of circulating miRNAs in the serum of chronic hepatitis B (CHB) patients presenting persistently normal alanine aminotransferase with significant histological features (SPNALT),PNALT patients with no significant histological features (NSPNALT),and healthy control patients. Results: MiRNAs were found to be the major constituents of small RNA-annotated reads by comparing the annotate draw sequence reads with miRNA databases and genome and other small RNA libraries. Our results point to a total of 2767 unique reads that can be mapped to human miRNAs or pre-miRNAs in miRbase, and the pre-miRNAs can be further mapped to the human genome. Thirty novel miRNA genes were identified in three groups. The differential expression levels of 143 miRNAs showed significant variation when the SPNALT and control group were compared. Among these, 22 miRNAs were >4-fold up-regulated (P<0.01) in SPNALT group and 4 were >2-fold down-regulated (P<0.01).When the SPNALT and NSPNALT group were compared, the differential expression levels of 84 miRNAs showed significant variation. Among these, 13 miRNAs showed a >4-fold up-regulation (P<0.01) in the SPNALT group and 21 showed a >2-fold down-regulation (P<0.01). Conclusions: Our results show that circulating miRNAs in the serum of SPNALT patients could be more comprehensively detected by the next-generation sequencing technology. Newly identified miRNAs might be used as biomarkers for diagnosis of chronic hepatitis B patients presenting persistently normal alanine aminotransferase with significant histological features.
2016-12-31 | GSE62290 | GEO
Project description:Hepatitis B virus (HBV) can hijack the host bile acids (BAs) metabolic pathway during infection in cell and animal models. Additionally, microbiome was known to play critical role in the enterohepatic cycle of BAs. However, the impact of HBV infection and associated gut microbiota on the BA metabolism in chronic hepatitis B (CHB) patients is unknown. This study aimed to unveil the distinct BA profiles in chronic HBV infection (CHB) patients with no or mild hepatic injury, and to explore the relationship between HBV, microbiome and BA metabolism with clinical implications. Methods: Serum BA profiles were compared between CHB patients with normal ALT (CHB-NALT, n = 92), with abnormal ALT (CHB-AALT, n = 34) and healthy controls (HCs, n = 28) using UPLC-MS measurement. Hepatic gene expression in CHB patients were explored using previously published transcriptomic data. Fecal microbiome was compared between 30 CHB-NALT and 30 HCs using 16S rRNA sequencing, and key microbial function was predicted by PICRUSt analysis. Results: Significant higher percentage of conjugated BAs and primary BAs was found in CHB patients even without apparent liver injury. Combinatory BA features can discriminate CHB patients and HCs with high accuracy (AUC = 0.838). Up-regulation of BA importer Na+ taurocholate co-transporting peptide (NTCP) and down-regulation of bile salt export pump (BSEP) was found in CHB-NALT patients. The microbial diversity and abundance of Lactobacillus, Clostridium, Bifidobacterium were lower in CHB-NALT patients compared to healthy controls. Suppressed microbial bile salt hydrolases (BSH), 7-alpha-hydroxysteroid dehydrogenase (hdhA) and 3-dehydro-bile acid Delta 4, 6-reductase (BaiN) activity were found in CHB-NALT patients. Conclusion: This study provides new insight into the BA metabolism influenced both by HBV infection and associated gut microbiome modulations, and may lead to novel strategy for clinical management for chronic HBV infection.
| S-EPMC8520922 | biostudies-literature
Project description:Alzheimer's disease (AD) is the most common form of dementia. However, the etiopathogenesis of this devastating disease is not fully understood. Recent studies in rodents suggest that alterations in the gut microbiome may contribute to amyloid deposition, yet the microbial communities associated with AD have not been characterized in humans. Towards this end, we characterized the bacterial taxonomic composition of fecal samples from participants with and without a diagnosis of dementia due to AD. Our analyses revealed that the gut microbiome of AD participants has decreased microbial diversity and is compositionally distinct from control age- and sex-matched individuals. We identified phylum- through genus-wide differences in bacterial abundance including decreased Firmicutes, increased Bacteroidetes, and decreased Bifidobacterium in the microbiome of AD participants. Furthermore, we observed correlations between levels of differentially abundant genera and cerebrospinal fluid (CSF) biomarkers of AD. These findings add AD to the growing list of diseases associated with gut microbial alterations, as well as suggest that gut bacterial communities may be a target for therapeutic intervention.
| S-EPMC5648830 | biostudies-other