Chronic HBV-infected Individuals Research Articles

Impact of IRGM gene promoter polymorphisms on susceptibility to chronic HBV infection.

The autophagy gene immunity-related GTPase M (IRGM) can affect the immune response against intracellular pathogens. The study was performed to determine any possible association between three IRGM single-nucleotide polymorphisms (SNPs) (rs4958842, rs4958843 and rs4958846) and chronic hepatitis B virus (HBV) infection. A total of 171 chronic HBV-infected individuals and 171 healthy controls were collected. Peripheral blood cells and Sanger sequencing were used to extract genomic DNA and determine the SNP genotypes, respectively. The C allele of rs4958843 is a risk factor for chronic HBV infection in various genetic models, including allelic, codominant and dominant models, with the following respective statistical data: allelic (T vs. C: OR=1.371, 95% CI=1.009-1.863, p=.043), codominant (TT vs. CC: OR=2.137, 95% CI=1.104-4.138, p=.024) and dominant (TT+TC vs. CC: OR=1.976, 95% CI=1.106-3.533, p=.021) models. The genotype and allele distributions of rs4958842 and rs4958846 showed no significant differences between chronic HBV infection patients and healthy controls. IRGM rs4958843 CC genotype carriers had significantly elevated values of alanine transaminase, aspartate transaminase alpha-fetoprotein and total bilirubin (OR=3.467, 95%CI=1.167-10.298), which was positively associated with the disease progression of HBV infection. Mutant allele C of IRGM rs4958843 polymorphism is associated with the risk of chronic HBV infection in the Han people in central China and contributes to the disease progression.

Impacts of optimal control strategies on the HBV and COVID-19 co-epidemic spreading dynamics

Different cross-sectional and clinical research studies investigated that chronic HBV infected individuals’ co-epidemic with COVID-19 infection will have more complicated liver infection than HBV infected individuals in the absence of COVID-19 infection. The main objective of this study is to investigate the optimal impacts of four time dependent control strategies on the HBV and COVID-19 co-epidemic transmission using compartmental modeling approach. The qualitative analyses of the model investigated the model solutions non-negativity and boundedness, calculated all the models effective reproduction numbers by applying the next generation operator approach, computed all the models disease-free equilibrium point (s) and endemic equilibrium point (s) and proved their local stability, shown the phenomenon of backward bifurcation by applying the Center Manifold criteria. By applied the Pontryagin’s Maximum principle, the study re-formulated and analyzed the co-epidemic model optimal control problem by incorporating four time dependent controlling variables. The study also carried out numerical simulations to verify the model qualitative results and to investigate the optimal impacts of the proposed optimal control strategies. The main finding of the study reveals that implementation of protections, COVID-19 vaccine, and treatment strategies simultaneously is the most effective optimal control strategy to tackle the HBV and COVID-19 co-epidemic spreading in the community.

The relationship between the distribution of HBcAg in liver cells and the pathological manifestations of the liver in 429 HBeAg-positive chronic HBV-infected individuals

The relationship between the distribution of HBcAg in liver cells and the pathological manifestations of the liver in 429 HBeAg-positive chronic HBV-infected individuals

Restoration of IL-11 and IL-15 cytokine production post calcium modulators and ROS treatment can assist viral clearance both in vitro and in vivo.

Hepatitis B virus (HBV) infection alters the cytokines production to establish persistent infection. A reversion of cytokines back to their normal state can be a promising therapeutic approach to establish an optimal host immune response. We investigated the alteration in expression of IL-15 and IL-11 after HBV infection in vitro and in vivo in PBMCs of 63 individuals divided into various HBV-infected patient groups. The mRNA expression was evaluated post-anti-oxidant and calcium modulators treatment by Real-time qPCR. In vitro mRNA expression of both cytokines, post-infection was down-regulated considerably. Interestingly, in line with in vitro results, both cytokines' in vivo expression was intensively down-regulated in chronic HBV-infected individuals rather than healthy controls. Both cytokines' expression was up-regulated in cases of recovery compared with the inactive carriers and chronic HBV-infected individuals. IL-15 mRNA expression was significantly up-regulated in both cell lines post EGTA and Ru360 treatment while a significant increase was observed in the HepAD38 cell line with NAC and BAPTA treatment. IL-11 mRNA expression was significantly up-regulated in the HepG2 cell line after all modulator treatments, whereas in the HepAd38 cell line it was observed after BAPTA treatment. Our results thus indicate that viral infection tends to down-regulate the expression of cytokines and an in vivo up-regulation is an indication of recovery. Treatment of anti-oxidants and calcium modulators has resulted in the successful restoration of these cytokines thus pointing towards the use of calcium modulators to boost natural antiviral cytokine production.

HBsAg Seroconversion May Not be a Durable Event in the Course of Chronic HBV Infection in Adults

Background: HBsAg sero-clearance with or without appearance of anti-HBs is considered to be a functional cure in chronic HBV infected individuals. However data regarding durability of HBsAg sero-clearance is limited. Methods: We retrospectively analyzed chronic HBV infected patients who had cleared HBsAg during their follow up, either spontaneously or on antiviral treatment. Results: Of the 270 patients with chronic HBV infection, 15(5.5%) lost HBsAg after a median of 60 months(9-110) of follow up. The mean age of the cohort was 49.5(12.2) years ,12 (80%) were males and 4(26%)were HBeAg positive. The baseline Median ALT, HBV DNA load and liver stiffness was 41.5 (16-1134) IU/L, 140000 (622-100000000) IU/ml and 8.05(5.3-35.3) kPa respectively. 12 (80%) cleared HBsAg while being on NUCs( 10 entocavir, 1 TAF, 1 adefovir, none of our pt received peg interferon) and 3 achieved spontaneous HBsAg sero-clearance. Of all patients who cleared the virus, 33% were cirrhotic (13%compensated and 20 % decompensated). 7(46.6% achieved Anti-HBs antibodies > 10 mIU/ml, after a medain of 8 (0-166) months after clearance of HBsAg. HBsAg sero-reversion occurred in 5(33.3%). All patients who had seroreversion were on entecavir. The median time from HBsAg detection to HBsAg clearance was 60 months in both the groups, i.e those who had seroreversion and those who continued to have clearance. In 4(80%) sero-reversion occurred after stopping antivirals. 1 patient who had seroreversion had received steroids for autoimmune hemolytic anemia. On the other hand none of the spontaneously serocleared patients developed sero-reversion. The anti HBsAb titre was >10mIU/ml in 2(40%) of those who had seroreversion. Conclusion: HBsAg seroclearance is not durable in one third of adult patients with chronic hepatitis B infection, especially if it induced by Nucleos(t)ide analogue therapy.

Comparative expression of pro-inflammatory and apoptotic biosignatures in chronic HBV-infected patients with and without liver cirrhosis

The interplay of immune mediators is paramount to optimal host anti-viral immune responses, especially against chronic hepatitis B virus (HBV) infection. Here, we investigated the dynamic changes in host immune responses in chronic HBV-infected individuals with and without liver cirrhosis by examining the signatures of apoptosis and plasma levels of pro-inflammatory cytokines, chemokines, and cytotoxic proteins. A total of 40 chronic HBV patients with and without liver cirrhosis were studied for plasma levels of immune mediators, and signatures of apoptosis in peripheral blood mononuclear cells (PBMCs). The intracellular concentrations of reactive oxygen species (ROS) in patients with chronic HBV with liver cirrhosis was relatively higher as compared to chronic HBV patients. The onset of apoptosis was sustained due to ongoing liver inflammation in concert with plasma TNF-α and IL-6 levels. Plasma VEGF was upregulated among chronic HBV patients with liver cirrhosis, whereas CCL2, CCL5 and granzyme B levels were down-regulated. High levels of ROS, IL-6 and TNF-α correlated with ongoing inflammation among chronic HBV patients with liver cirrhosis, which likely attributed to the expression of biosignatures of apoptosis and activation in immune cells.

Statin Use and the Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B.

Statins have pleiotropic effects that may include chemoprevention. Several observational studies have suggested that statins may prevent hepatocellular carcinoma (HCC), but they have not yet been fully studied in patients with chronic hepatitis B virus (HBV) infections. A hospital-based retrospective cohort of 7,713 chronic HBV-infected individuals between January 2008 and December 2012 were analyzed. The primary outcome was the development of HCC. Patients who used statins for at least 28 cumulative defined daily doses during the follow-up period were defined as statin users (n=713). The association between the use of statin and the incidence of HCC was analyzed using the multivariable Cox regression model with time-dependent covariates. During a median follow-up of 7.2years (min-max: 0.5-9.9), HCC newly developed in 702 patients (9.1%). Statin use was associated with a lower risk of HCC (adjusted hazard ratio=0.36, 95% confidence interval: 0.19-0.68, adjusted for age, sex, cirrhosis, diabetes, hypertension, serum alanine aminotransferase, cholesterol, HBV DNA level, antiviral treatment, and antiplatelet therapy). The observed benefit of the statin use was dose-dependent (adjusted hazard ratio [95% confidence interval], 0.63 [0.31-1.29]; 0.51 [0.21-1.25]; 0.32 [0.07,1.36]; and 0.17 [0.06, 0.48] for patients with statin use of 28-365, 366-730, 731-1095, and more than 1,095 cumulative defined daily doses, respectively). In subgroup analysis, the association between statin use and reduced risk of HCC was observed in all prespecified subgroups analyzed. Statin use was associated with a reduced risk of HCC development in chronic HBV-infected patients, suggesting that statins may have a chemopreventive role in this population. These findings warrant a prospective evaluation.

Serum HBV RNA quantification: useful for monitoring natural history of chronic hepatitis B infection

BackgroundAs an alternative biomarker of intrahepatic covalently closed circular DNA (cccDNA) transcriptional activity, hepatitis B virus (HBV) RNA may evolve during long-lasting virus-host interactions during chronic hepatitis B viral infection. The distribution pattern of serum HBV RNA levels in the natural course of chronic HBV infection remains unclear. The aim of this study was to evaluate the levels of HBV RNA during the natural course of CHB and the role in distinguishing the natural history of HBV infection.MethodsA total of 291 treatment-naïve chronic HBV carriers were enrolled. Based on the clinical, biochemical, serological, and histological data as well as HBV DNA levels, patients were classified into the following four categories: the immune-tolerant phase (IT,n = 35), HBeAg-positive immune-active phase (EPIA,n = 121), inactive chronic hepatitis B(ICH,n = 77) and HBeAg-negative immune reactive hepatitis (ENH,n = 58). The parameters and distribution patterns of serum HBV RNA were evaluated in relation to viral replication status, immune phase, disease category and Child-Pugh class. The relationships between serum HBV RNA and other serum hepatitis B viral markers were also analyzed.ResultsSerum HBV RNA levels were significantly lower in the HBeAg-negative patients compared to those in the HBeAg-positive patients, with the lowest levels seen in inactive carriers. In HBeAg-negative patients, serum HBV RNA levels increased if there is reactivation to active hepatitis and showed obvious superiority for the combination of serum HBV DNA (cutoff>3.39 Log copies/mL) and HBsAg (cutoff>2.74 Log IU/mL) in discriminating between ‘HBeAg-negative immune reactive’ phase and inactive chronic hepatitis B phases of HBeAg-negative chronic HBV infection. Serum HBV RNA levels were positively correlated with serum HBV DNA and HBsAg levels in all chronic HBV-infected patients. A stratified analysis revealed that a correlation between serum HBV RNA and HBV DNA or HBsAg was present in HBeAg-positive patients; however, in HBeAg-negative patients, serum HBV RNA was positively correlated with HBV DNA only.ConclusionDuring the natural course of chronic HBV infection, serum HBV RNA levels vary. Serum HBV RNA can act as a biomarker to predict the natural history of disease in chronic hepatitis B patients. In treatment-naïve HBeAg-negative chronic HBV-infected individuals, serum HBV RNA shows superiority in differentiating the ‘HBeAg-negative reactive’ phase.

Nature of Host Immunity during Hepatitis B Virus Infection and designing Immune Therapy.

Hepatitis B virus (HBV) infections represent one of the major public health problems in global context. More than 2 billion people in the world have been infected with this virus at some point of time in their life and millions are chronically infected, indicating that chronic HBV-infected subjects remain as a living source of HBV transmission. The public health impact of this is tremendous. Considerable numbers of chronic HBV-infected individuals would eventually develop progressive liver diseases and their complications like hepatic failure, liver cirrhosis (LC), and hepatocellular carcinoma (HCC). Epidemiological studies have suggested that about 0.6 to 1.2 million people die annually from HBV-related liver diseases. These figures about death due to HBV and sufferings from HBV-related diseases indicate a notion of medical emergencies about HBV. In addition to these, the impact of HBV on health care delivery system moves beyond these numbers of HBV-related patients and HB-related deaths. This is because significant insights have already been developed about epidemiology, virology, and pathogenesis of HBV. Also, an effective and widely used preventive vaccine is available against HBV. In addition to these, antiviral drugs against HBV have been developed from early 1980s and several such drugs are now available commercially in the open market around the worldwide. Unfortunately, the ongoing therapeutic regimens could not stand the test of time and new insights about HBV pathogenesis are required for the development of new, novel, and evidence-based therapies for chronic HBV infections.How to cite this article: Akbar SMF, Al-Mahtab M, Khan SI. Nature of Host Immunity during Hepatitis B Virus Infection and designing Immune Therapy. Euroasian J Hepato-Gastroenterol 2018;8(1):42-46.

Hyper-Expression of PD-1 Is Associated with the Levels of Exhausted and Dysfunctional Phenotypes of Circulating CD161++TCR iVα7.2+ Mucosal-Associated Invariant T Cells in Chronic Hepatitis B Virus Infection

Mucosal-associated invariant T (MAIT) cells, defined as CD161++TCR iVα7.2+ T cells, play an important role in the innate defense against bacterial infections, and their functionality is impaired in chronic viral infections. Here, we investigated the frequency and functional role of MAIT cells in chronic hepatitis B virus (HBV) infection. The peripheral CD3+CD161++TCR iVα7.2+ MAIT cells in chronic HBV-infected patients and healthy controls were phenotypically characterized based on CD57, PD-1, TIM-3, and CTLA-4, as well as HLA-DR and CD38 expression. The frequency of MAIT cells was significantly decreased among chronic HBV-infected individuals as compared to controls. Expression of CD57, PD-1, CTLA-4, as well as HLA-DR and CD38 on MAIT cells was significantly elevated in chronic HBV-infected individuals relative to controls. The percentage of T cell receptor (TCR) iVα7.2+ CD161+ MAIT cells did not correlate with HBV viral load but inversely with HLA-DR on CD4+ T cells and MAIT cells and with CD57 on CD8+ T cells suggesting that decrease of MAIT cells may not be attributed to direct infection by HBV but driven by HBV-induced chronic immune activation. The percentage and expression levels of PD-1 as well as CTLA-4 on MAIT cells inversely correlated with plasma HBV-DNA levels, which may suggest either a role for MAIT cells in the control of HBV infection or the effect of HBV replication in the liver on MAIT cell phenotype. We report that decrease of TCR iVα7.2+ MAIT cells in the peripheral blood and their functions were seemingly impaired in chronic HBV-infected patients likely because of the increased expression of PD-1.

Serum HBV DNA plus RNA shows superiority in reflecting the activity of intrahepatic cccDNA in treatment-naïve HBV-infected individuals

BackgroundBoth serum hepatitis B virus (HBV) DNA and RNA can reflect intrahepatic covalently closed circular DNA (cccDNA) activity. However, correlations among viral markers haven’t been fully explored. ObjectivesHere we investigated the correlations between serum HBV RNA and other viral markers in acute hepatitis B patients and treatment-naïve chronic HBV-infected individuals. Study designThe serum viral markers of 19 acute hepatitis B patients and 84 treatment-naïve chronic HBV-infected individuals at different infection stages were quantified. Correlations among viral markers were analyzed by Pearson’s or Spearman’s correlation analysis. ResultsSerum viral markers and intrahepatic cccDNA levels were lower in acute hepatitis B patients than in treatment-naïve chronic HBV-infected individuals. Serum HBV RNA levels were positively correlated with serum HBV DNA, HBsAg and intrahepatic cccDNA levels in HBeAg-positive chronic HBV-infected individuals. Total serum HBV nucleic acids (HBV DNA plus RNA) showed superiority in reflecting intrahepatic cccDNA activity. Stratified analysis revealed that such correlations were only found in HBeAg-positive chronic hepatitis B phase. Moreover, high-frequency R193M and P196A mutations were found in the RT region of HBV polymerase leading to lower serum HBV DNA and higher serum HBV RNA levels in HBeAg-negative chronic HBV infection phase. ConclusionsHBV replication capability was lower in acute hepatitis B patients than in chronic HBV-infected individuals. In treatment-naïve HBeAg-positive chronic HBV-infected individuals, serum HBV DNA plus RNA showed superiority in reflecting intrahepatic cccDNA activity than each alone. Moreover, mutated RT region of HBV polymerase might lead to the attenuated reverse transcriptional activity of HBV polymerase in HBeAg-negative chronic HBV infection phase.

Spontaneous relapse in patients with inactive chronic hepatitis B virus infection.

Background:Chronic hepatitis B virus infection (HBV) may reactivate during the course of the disease and is called spontaneous relapse. The purpose of this study was to evaluate the incidence of relapse of hepatitis in subjects with inactive HBV carriers.Methods:This follow-up study was performed on 785 patients with inactive HBV carriers that were followed-up at six month intervals. The presence of serum HBsAg and anti-HBe, without HBeAg, HBV DNA levels <2000 IU/ml with normal alanine aminotransferase (ALT) levels was defined as inactive carriers. Patients who developed ALT ≥80 IU/L with HBV DNA levels ≥2000 IU/ml were considered as spontaneous relapse.Results:Seven hundred- eighty five cases (441 males, 344 females) of chronic HBV infected individuals were followed-up. The mean age at the entrance of the study was 30.5±11.8 years. The mean follow-up duration was 5.9±5 years. Relapse was seen in 35 (4.5%) cases, in 27 out of 441 (6.1%) males and in 8 out of 344 (2.3%) females and in 4.2% subjects ≥30 years versus in 4.7% cases of under 30 years (p>0.05). The development of relapse in males was higher than females (hazard ratio 2.53, 95% CI 1.2-5.6, p=0.021), but age ≥30 or <30 years did not have effect (hazard ratio1.21, 95% CI 0.62-2.36, p=0.58).Conclusions:The results show that spontaneous relapse of hepatitis may develop during the course of chronic HBV infection. We suggest that all patients with chronic hepatitis B, regardless of their age, be examined for the possibility of relapse.

Effects of total nocturnal sleep time and siesta on hepatocellular carcinoma risks in individuals with chronic HBV infection

The aim of this study was to investigate the effects of total nocturnal sleep time and siesta on hepatocellular carcinoma (HCC) risks in chronic HBV infected individuals. This research was retrospective. A case–control study with 226 HCC patients and 375 controls enrolled was conducted. All subjects were chronic HBV infected. The total nocturnal sleep time and siesta or not were recorded by interview. We found that the total nocturnal sleep time and siesta were associated with the incidence of HCC (p < 0.001). The adjusted OR of HCC for the subjects with the shortest total nocturnal sleep time (≤ 6 hs) was 2.557 (p = 0.032), relative to those who slept between 6 and 8 h. The patients who slept ≥ 8 h experienced much lower risk. The adjusted OR of HCC for subjects with total nocturnal sleep time ≥ 8 h were 0.507 (p = 0.005) relative to those who slept 6–8 h. The subjects without siesta habit experienced a higher risk of HCC compared to those who with the siesta habit (adjusted OR 2.157, p = 0.001). These findings indicate that lack of nocturnal sleep is a potential risk factor for HCC in chronic HBV infected individuals whereas the siesta is a protective factor.

Restoration of Microrna-126 Expression Reduces Apoptosis in Hepatitis B Virus Infected Hepatocellular Carcinoma Cells

Background and Aim: Hepatocellular carcinoma (HCC) is third leading cause of cancer related mortality worldwide. Chronic hepatitis B (CHB) is one of the reasons for HCC development. India has over 40 million chronic HBV infected individuals, but estimation of HCC is grim. The reasons of the under report may be due to its asymptomatic appearance, late detection in the advanced stages and poor awareness. Extrapolating our previous findings of miR-126 as biomarker for HBV related HCC, here we have elucidated the pathophysiological role of overexpressed miR-126 in hepatocarcinogenesis. Methods: Targets of miR-126 were identified using TargetScan, microRNA.org and miRecords. premiR-126 was cloned, overexpressed in HepG2 cell line and expression of miR-126 and its targets were verified by qRT-PCR and western blot analysis. Trancriptional regulation of miR-126 was decided using ENCODE Chip seq database and verified by ChIP analysis. Cellular apoptosis was determined by Annexin V/PI method. Results: To validate our previous oveservation, miR-126 expression was verified in HBV transfected cell line along with two transactivator proteins HBx and HBc independently. Similar to the data in HCC samples, miR-126 was overexpressed in HBV-DNA transfected cells, but no effect of HBc and HBx was noted. Considering Bioinformatics analysis and ENCODE ChIP-seq data, binding of MYC as major transcription factor for miR-126 was validated by ChIP analysis with anti-MYC antibody and also verified after overexpression of Myc-cDNA. This data correlated with MYC overexpression in HCC samples compared to liver cirrhosis. In silico analysis showed that miR-126 could target several proteins involved in apoptosis and inflammosome pathways (CASP1/CASP3/APAF1/CARD16). Furthermore, apoptosis assay and western blot analysis also showed that miR-126 reduces apoptotic cell death by reducing CASP3 expression. Conclusion: Thus, our data highlights that miR-126 may induce uncontrolled proliferation of cancer cells and inhibition of mir-126 may be an important therapeutic strategy for HBV-related HCC. The authors have none to declare.

Association between metabolic factors and chronic hepatitis B virus infection.

There are limited data regarding the relationship between chronic hepatitis B virus (HBV) infection and metabolic factors. This article aims to highlight the link of metabolic factors with hepatitis B surface antigen (HBsAg) serostatus, HBV load, and HBV-related hepatocellular carcinoma (HCC). Although HBsAg-positive serostatus was positively correlated with a high risk of metabolic syndrome in students, chronic HBV-infected individuals have high serum adiponectin levels. The androgen pathway in HBV carriers with a low body mass index is more triggered which leads to enhanced HBV replication. High HBV load was inversely associated with obesity in hepatitis B e antigen (HBeAg)-seropositive HBV carriers; while in HBeAg-seronegative HBV carriers, high HBV load was inversely related to hypertriglyceridemia rather than obesity. For overweight and obese HBV-infected patients, high HBV load was positively associated with serum adiponectin levels. Several large cohort studies have revealed a positive link of diabetes with incidence of HBV-related HCC. However, the association between incidence of HCC and metabolic factors other than diabetes is still inconclusive. More long-term prospective studies should elucidate the association of chronic HBV infection and its outcomes with metabolic factors in clinical practice.

Serum adiponectin levels are associated with hepatitis B viral load in overweight to obese hepatitis B virus carriers

This study aimed to investigate the association between serum adiponectin and chronic hepatitis B virus (HBV) infection. We conducted a campus-based cross-sectional study in Northern Taiwan, an HBV-endemic country. A total of 506 participants, including 147 chronic HBV-infected individuals and 359 healthy controls, were assessed for anthropometric indices, serum adiponectin levels, serum HBV viral load and markers, serum alanine aminotransferase levels and metabolic factors. Older age, male gender, higher alanine aminotransferase, higher body mass index, greater waist circumference, lower fasting glucose, higher triglycerides, and higher adiponectin were associated with chronic HBV infection in univariate analyses. In multivariate analysis, the presence of chronic HBV infection was positively associated with serum adiponectin levels (P < 0.0001) and high adiponectin levels over the 75th percentile (odds ratio, 4.25; 95% confidence interval, 2.36-7.66; P < 0.0001) after adjusting for age, gender, body mass index, and insulin resistance index. Furthermore, serum adiponectin levels were positively associated with HBV viral load in overweight to obese HBV-infected subjects (P = 0.018). Although chronic HBV-infected individuals were heavier than healthy controls, they had significantly higher serum adiponectin levels than healthy counterparts. Additionally, adiponectin levels were positively associated with HBV viral load in overweight to obese HBV-infected subjects. Future research should focus on elucidating adiponectin pathways, which may contribute to the development of adjuvant treatments for chronic HBV infection.

Variation in liver histopathology in chronic HBV-infected individuals with normal liver function tests correlates with HBV replication

Variation in liver histopathology in chronic HBV-infected individuals with normal liver function tests correlates with HBV replication

The relationship between HBV precore region mutation and the variation of T-lymphocyte subpopulations in chronic HBV-infected individuals with normal liver function tests

The relationship between HBV precore region mutation and the variation of T-lymphocyte subpopulations in chronic HBV-infected individuals with normal liver function tests

Real-time PCR quantification of serum and intracellular HBV DNA and HDV RNA in different subsets of chronic HBV infected individuals

Real-time PCR quantification of serum and intracellular HBV DNA and HDV RNA in different subsets of chronic HBV infected individuals

Hepatitis B virus DNA is more powerful than HBeAg in predicting peripheral T-lymphocyte subpopulations in chronic HBV-infected individuals with normal liver function tests

To investigate the peripheral T-lymphocyte subpopulation profile, and its correlations with hepatitis B virus (HBV) replication level in chronic HBV-infected (CHI) individuals with normal liver function tests (LFTs). Frequencies of T-lymphocyte subpopulations in peripheral blood were measured by flow cytometry in 216 CHI individuals. HBV markers were detected with ELISA. Serum HBV DNA load was assessed with quantitative real-time PCR. Information of age at HBV infection, and maternal HBV infection status was collected. ANOVA linear trend test and linear regression were used in statistical analysis. CHI individuals had significantly decreased relative frequencies of CD3(+), CD4(+) subpopulations and CD4(+)/CD8(+) ratio, and increased CD8(+) subset percentage compared with uninfected individuals (all P < 0.001). There was a significant linear relationship between the load of HBV DNA and the parameters of T-lymphocyte subpopulations (ANOVA linear trend test P < 0.01). The parameters were also significantly worse among individuals whose mothers were known to be HBV carriers, and those having gained infection before the age of 8 years. In multiple regressions, after adjustment for age at HBV infection and status of maternal HBV infection, log copies of HBV DNA maintained its highly significant predictive coefficient on T-lymphocyte subpopulations, whereas the effect of HBeAg was not significant. HBV DNA correlates with modification in the relative T-lymphocyte subpopulation frequencies. High viral load is more powerful than HBeAg in predicting the impaired balance of T-cell subsets.