Establishment and validation of a nomogram for predicting the risk of liver inflammation in chronic HBV infection

Objective:To establish a non-invasive quantitative and visual predictive model for assessing the occurrence of significant inflammation in chronic HBV infection,and to present nomogram to validate the efficacy.Methods:A total of 180 patients with chronic HBV infection that were admitted to the Department of Infectious Liver Diseases of the First Affiliated Hospital of Hainan Medical College from January 2019 to December 2021 with informed consent and underwent liver biopsy puncture were selected,and to prevent overfitting of the model,131 patients and 49 patients were randomly divided into a model group and a validation group according to randomization,to collect the clinic information,serological examination,liver elastography and liver histopathology results.The patients were divided into non-significant inflammation and significant inflammation groups in the modeling group.The R 4.1.1 package and the rms package were used to build the column line graph model,while the Bootstrap method was applied to repeat the sampling 1000 times for internal and external validation,and the H-L goodness of fit test and ROC curve were used to assess the calibration and discrimination of the column line graph model respectively.Results:A total of 180 patients with chronic HBV infection were included,and 92 patients(51.1%)had significant inflammation.In the modeling set,67 patients(51.1%)had significant inflammation.In the modeled group,comparison of HBV DNA,PLT,ALT,AST,ALP,GGT,PAB,H.A,PⅢP,CⅣ,L.N,IL-6,LSM and HBeAg for non-significant inflammation and significant inflammation showed statistically significant differences(P<0.05).Nomogram were obtained using stepwise regression analysis to establish a predictive model for the risk of significant inflammation following chronic HBV infection.The χ^(2) values of the H-L goodness-of-fit test for the modelling and validation groups were 0.279 and 2.098,respectively,corresponding to P values of 0.87 and 0.35,suggesting that the nomogram has good predictive accuracy;the area under the ROC curve of the column line plot predicting the occurrence of significant inflammation after HBV infection for the modelling and validation groups was 0.895[95%CI(0.843-0.948)]and 0.760[95%CI(0.622-0.897)],suggesting that the column line plot model has good discrimination.Conclusion:After stepwise regression analysis,it was established that PLT,Ln(HBV-DNA),AST,C桇and LSM were more closely associated with the occurrence of significant inflammation after HBV infection,and a visualization of the occurrence of significant inflammation nomogram was established by comprehensive assessment,and the effectiveness was good.

Numerical Procedure for Fractional HBV Infection with Impact of Antibody Immune

The current investigations are presented to solve the fractional order HBV differential infection system(FO-HBV-DIS)with the response of antibody immune using the optimization based stochastic schemes of the Levenberg-Marquardt backpropagation(LMB)neural networks(NNs),i.e.,LMBNNs.The FO-HBV-DIS with the response of antibody immune is categorized into five dynamics,healthy hepatocytes(H),capsids(D),infected hepatocytes(I),free virus(V)and antibodies(W).The investigations for three different FO variants have been tested numerically to solve the nonlinear FO-HBV-DIS.The data magnitudes are implemented 75%for training,10%for certification and 15%for testing to solve the FO-HBV-DIS with the response of antibody immune.The numerical observations are achieved using the stochastic LMBNNs procedures for soling the FO-HBV-DIS with the response of antibody immune and comparison of the results is presented through the database Adams-Bashforth-Moulton approach.To authenticate the validity,competence,consistency,capability and exactness of the LMBNNs,the numerical presentations using the mean square error(MSE),error histograms(EHs),state transitions(STs),correlation and regression are accomplished.

GLOBAL ASYMPTOTICAL PROPERTIES FOR A DIFFUSED HBV INFECTION MODEL WITH CTL IMMUNE RESPONSE AND NONLINEAR INCIDENCE

This article proposes a diffused hepatitis B virus （HBV） model with CTL immune response and nonlinear incidence for the control of viral infections. By means of different Lyapunov functions, the global asymptotical properties of the viral-free equilibrium and immune-free equilibrium of the model are obtained. Global stability of the positive equilibrium of the model is also considered. The results show that the free diffusion of the virus has no effect on the global stability of such HBV infection problem with Neumann homogeneous boundary conditions.

DYNAMICAL BEHAVIOR OF A STOCHASTIC HBV INFECTION MODEL WITH LOGISTIC HEPATOCYTE GROWTH

This paper is concerned with a stochastic HBV infection model with logistic growth. First, by constructing suitable stochastic Lyapunov functions, we establish sufficient conditions for the existence of ergodic stationary distribution of the solution to the HBV infection model. Then we obtain sufficient conditions for extinction of the disease. The stationary distribution shows that the disease can become persistent in vivo.

Establishment and Validation of a nomogram for Predicting the Risk of Liver Fibrosis in Chronic HBV Infection

Objective:To establish a non-invasive quantitative and visual predictive model for assessing the occurrence of significant fibrosis in chronic HBV infection,and to present nomogram to validate the efficacy.Methods:A total of 180 patients with chronic HBV infection that were admitted to the Department of Infectious Liver Diseases of the First Affiliated Hospital of Hainan Medical University from January 2019 to December 2021 with informed consent and underwent liver biopsy puncture were selected.131 patients and 49 patients were randomly divided into a model group and a validation group according to randomization.The patients were divided into non-significant fibrosis and significant fibrosis groups in the modeling group.To collect the clinic information,serological examination,liver elastography and liver histopathology results and to establish a rosette model to predict the risk of chronic HBV infection with significant fibrosis.Results:A total of 180 patients with chronic HBV infection were included,and 113 patients(62.7%)had significant fibrosis.In the modeling set,84 patients(64.1%)had significant fibrosis.In the modeled group,comparison of HBV DNA,PLT,ALT,AST,ALP,ALB,PAB,IL-6,HA,PⅢP,CIV,L.N and LSM for non-significant fibrosis and significant fibrosis showed statistically significant differences.The χ^(2) values of the H-L goodness-of-fit test for the modelling and validation groups were 4.988 and 0.527,respectively,corresponding to P values of 0.08 and 0.77,suggesting that the nomogram has good predictive accuracy;the area under the ROC curve of the column line plot predicting the occurrence of significant fibrosis after HBV infection for the modelling and validation groups was 0.843[95%CI(0.775-0.910)]and 0.776[95%CI(0.714-0.838)],suggesting that the column line plot model has good discrimination.Conclusion:After stepwise regression analysis,it was established that ALB,HA,PⅢP,LSM and IL-6 were more closely associated with the occurrence of significant fibrosis after HBV infection,and a visualization of the occurrence of significant fibrosis column line graph model was established by comprehensive assessment,and validation was given that all were superior to the traditional models FIB-4 and APRI.

IL-6 Plays a Crucial Role in HBV Infection

Interleukin-6(IL-6),a cytokine mainly produced by activated monocytes,has broad pleiotropic actions that affect the functions of a variety of lymphoid cells.The roles of IL-6 in regulating immunity to infections are currently being defined.Remarkably,IL-6-mediated cellular and humoral immune responses play a crucial role in determining the outcome of viral infection.This article reviews the current knowledge on the critical role of IL-6 in hepatitis B virus(HBV)infection.As a competent intermediary,IL-6 derived from activated monocytes plays an important role in promoting lymphocytes responses that are essential for effective viral control.However,as a mediator of inflammation,IL-6 is also involved in the development of HBV-induced liver cirrhosis and exacerbating liver injury.Overall,the current data point to IL-6 as an immunoregulatory cytokine in HBV infection.Immunotherapeutic strategies aimed at optimizing the beneficial effects of IL-6 in HBV infection may prove to be an ordeal in the future,as they should foster the strengths of IL-6 while circumventing potential drawbacks.

New perspective on the natural course of chronic HBV infection

Chronic hepatitis B virus （HBV） infection is a significant threat to public health and an enormous burden on society. Mechanisms responsible for chronic HBV infection remain poorly understood. A better understanding of the natural course of chronic HBV infection may shed new light on the mechanisms underlying this disease and help in designing new antiviral strategies. Natural course of chronic HBV infection is conventionally viewed as an uninterrupted process that is usually marked by HBV e antigen （HBeAg） seroconversion or characterized by different phases associated with assumed host responses to HBV infection. However, none of these descriptions captures or highlights the core events that determine the natural course of chronic HBV infection. In this review, we briefly present the current knowledge on this subject and explain the significance and implication of events that occur during infection. A pre-core mutant becomes predominant in the viral population following elimination of the wild-type virus in duck hepatitis B virus-chronically infected animals. The coupled events in which first there is viral clearance that clears wild-type virus and then there is the reinfection of wild-type virus cleared livers with mutant virus are highly relevant to understanding of the natural course of chronic HBV infection under both treated and untreated conditions. In our new perspective, a general natural course of chronic HBV infection comprises cycles of viral clearance and reinfection, and such cycles prolong the chronic HBV infection course. Reviewing published data on the natural course of chronic HBV infection can reduce the possibility of missing important points in the initial data interpretation.

New Gene Variants Associated with the Risk of Chronic HBV Infection

Some patients with chronic hepatitis B virus(HBV)infection failed to clear HBV,even persistently continue to produce antibodies to HBV.Here we performed a two stage genome wide association study in a cohort of Chinese patients designed to discover single nucleotide variants that associate with HBV infection and clearance of HBV.The first stage involved genome wide exome sequencing of 101 cases(HBsAg plus anti-HBs positive)compared with 102 control patients(antiHBs positive,HBsAg negative).Over 80%of individual sequences displayed 209 sequence coverage.Adapters,uncertain bases[10%or low-quality base calls([50%)were filtered and compared to the human reference genome hg19.In the second stage,579 chronic HBV infected cases and 439 HBV clearance controls were sequenced with selected genes from the first stage.Although there were no significant associated gene variants in the first stage,two significant gene associations were discovered when the two stages were assessed in a combined analysis.One association showed rs506121-“T”allele[within the dedicator of cytokinesis 8(DOCK8)gene]was higher in chronic HBV infection group than that in clearance group(P=0.002,OR=0.77,95%CI[0.65,0.91]).The second association involved rs2071676—A allele within the Carbonic anhydrase(CA9)gene that was significantly elevated in chronic HBV infection group compared to the clearance group(P=0.0003,OR=1.35,95%CI[1.15,1.58]).Upon replication these gene associations would suggest the influence of DOCK8 and CA9 as potential risk genetic factors in the persistence of HBV infection.

The Expression of CD2 in Chronic HBV Infection

It was previously reported that several kinds of intercellular adhesion molecules are closely related to chronic HBV infection. The complex of CD2 and CD58 plays an important role in enhancing the adhesion of T lymphocytes to target cells, and promoting hyperplasia and activation of T lymphocytes. In this study, we detected the level of CD2 expressed on the surface of PBMC, the expression level of CD2 mRNA in PBMC and the percentage of CD2 positive cells in PBMC of patients with chronic HBV infection and compared them with the expression level of normal controls. We also determined the level of serum HBV DNA from patients with chronic HBV infection and from normal controls. The clinical characteristics of hepatic function were tested as well. The results showed that the expression of CD2 significantly increased with the severity of chronic HBV infection, which suggested that CD2 might contribute to the hepatocyte damage in chronic HBV infection. Cellular ＆ Molecular Immunology.

HBV and HCV infection and pancreatic ductal adenocarcinoma

Introduction Pancreatic ductal adenocarcinoma(PDAC)is a highly lethal malignancy,with a poor overall fiveyear survival.Its dismal prognosis,even after curative resection,depends on its advanced stage at diagnosis,early metastatic spread,aggressive biological behavior and inefficacy of available systemic therapies.[1]To date,epidemiological studies have identified some risk factors for this cancer,including cigarette smoking habit,family history as well as high dietary fat consumption,alcohol abuse,diabetes mellitus,metabolic syndrome and chronic pancreatitis history.[1]

Interest of Non-Invasive Markers (APRI, FIB-4) for Assessing Hepatic Fibrosis in Patients with Chronic Viral Hepatitis B without Cytolysis and with Low Viral Replication

Background and Objectives: The indication for treatment in HBsAg-positive patients with low viral load and normal transaminases requires an assessment of fibrosis. In resource-limited settings, free hepatic fibrosis evaluation tests can aid in therapeutic decision-making. Our study aims to demonstrate the utility of assessing hepatic fibrosis using non-invasive markers (APRI and FIB-4) in patients with chronic B viral hepatitis without cytolytic activity and low viral replication in our context. Patients and Methods: This is a retrospective cross-sectional study conducted between January 2018 and December 2021 at the University Hospital Center of Bouaké. Included were all patients aged ≥18 with normal transaminases (Results: Our study included 241 patients, with a mean age of 36.19 years (±10.52 years) and a male predominance of 52%. The mean FibroScan® value was 6.44 ± 2.3 kPa, and 68 patients (28.22%) had fibrosis >7 kPa. To exclude significant fibrosis (FS Conclusion: A significant proportion of HBV-infected patients with normal ALT and low viral load have active liver disease. Both FIB-4 and APRI biological scores are useful in identifying individuals without significant fibrosis with a good negative predictive value (>50%).

Seroprevalence of Hepatitis B Virus (HBV) among Voluntary Healthy Blood Donors at Tellewonyan Memorial Hospital Voinjama, Lofa County, Liberia

Background: The prevalence of transfusion associated hepatitis B virus (HBV) infection differs across different population geographically. Ascertaining the seroprevalence of HBV infection is vital to informing the way of precautionary and control strategies. This study sought to establish the seroprevalence of hepatitis B surface antigen (HBVsAg) among blood donors in Yelewonyan Memorial Hospital Lofa, Liberia. Methods: This was a retrospective study which involved reviewing of blood donation records for the year 2020 at Telewonyan Memorial Hospital in Lofa County. The data obtained from the records were analyzed. Data analysis was done using SPSS version 12 for windows. Results: A total of 584 voluntary blood donors were screened for donation in 2020. Out of 584, 554 (95.9%) were males while the rest were females. Prevalence of 3.3% was observed among blood donors in Telewonyan Memorial Hospital. There is a significant difference between gender and age with HBV seropositivity among blood donors. Conclusion: The findings of this study suggest that the study site is of low endemicity with HBV infection. Usually, males are more probably to be HBVsAg seropositive than their female’s counterpart. Planning more extensive study and educational programs would help minimize the spread of HBV infection among the general population.

Baseline HBV Load Increases the Risk of Anti-tuberculous Drug-induced Hepatitis Flares in Patients with Tuberculosis

Hepatitis associated anti-tuberculous treatment（HATT） has been a main obstacle in managing patients co-infected with Mycobacterium tuberculosis and hepatitis B virus（HBV）. Therefore, we evaluated the factors related to the severity of adverse effects during HATT, especially those associated with liver failure. A retrospective study was carried out at Tongji Hospital from 2007 to 2012. Increases in serum transaminase levels of 〉3, 5, and 10 times the upper limit of normal（ULN） were used to define liver damage as mild, moderate, and severe, respectively. Patients with elevated total bilirubin（TBil） levels that were more than 10 times the ULN（〉171 μmol/L） with or without decreased（〈40%） prothrombin activity（PTA） were diagnosed with liver failure. A cohort of 87 patients was analyzed. The incidence of liver damage and liver failure was 59.8%（n=52） and 25.3%（n=22）, respectively. The following variables were correlated with the severity of hepatotoxicity： albumin（ALB） levels, PTA, platelet counts（PLT）, and the use of antiretroviral therapies（P〈0.05）. Hypo-proteinemia and antiretroviral therapy were significantly associated with liver failure, and high viral loads were a significant risk factor with an odds ratio（OR） of 2.066. Judicious follow-up of clinical conditions, liver function tests, and coagulation function, especially in patients with high HBV loads and hypoalbuminemia is recommended. It may be advisable to reconsider the use of antiviral drugs failure during the course of anti-tuberculous treatment of HBV infection patients to avoid the occurrence of furious liver failure.

Perilipin2 inhibits the replication of hepatitis B virus deoxyribonucleic acid by regulating autophagy under high-fat conditions

BACKGROUND Chronic hepatitis B virus(HBV)infection is often associated with increased lipid deposition in hepatocytes.However,when combined with non-alcoholic fatty liver disease or hyperlipidemia,it tends to have a lower HBV deoxyribonucleic acid(DNA)load.The relationship between lipid metabolism and HBV DNA replication and its underlying mechanisms are not well understood.AIM To investigate the relationship between lipid metabolism and HBV DNA replication and its underlying mechanisms.METHODS 1603 HBsAg-seropositive patients were included in the study.We first explored the relationship between patients'lipid levels,hepatic steatosis,and HBV DNA load.Also,we constructed an HBV infection combined with a hepatic steatosis cell model in vitro by fatty acid stimulation of HepG2.2.15 cells to validate the effect of lipid metabolism on HBV DNA replication in vitro.By knocking down and overexpressing Plin2,we observed whether Plin2 regulates autophagy and HBV replication.By inhibiting both Plin2 and cellular autophagy under high lipid stimulation,we examined whether the Plin2-autophagy pathway regulates HBV replication.RESULTS The results revealed that serum triglyceride levels,high-density lipoprotein levels,and hepatic steatosis ratio were significantly lower in the HBV-DNA high load group.Logistic regression analysis indicated that hepatic steatosis and serum triglyceride levels were negatively correlated with HBV-DNA load.Stratified analysis by HBeAg showed significant negative correlations between HBV-DNA load and hepatic steatosis ratio in both HBeAgpositive and HBeAg-negative groups.An in vitro cell model was developed by stimulating HepG2.2.15 cells with palmitic acid and oleic acid to study the relationship between HBV-DNA load and lipid metabolism.The results of the in vitro experiments suggested that fatty acid treatment increased lipid droplet deposition and decreased the expression of cell supernatant HBsAg,HBeAg,and HBV DNA load.Western blot and polymerase chain reaction analysis showed that fatty acid stimulation significantly induced Plin2 protein expression and inhibited the expression of hepatocyte autophagy proteins.Inhibition of Plin2 protein expression under fatty acid stimulation reversed the reduction in HBsAg and HBeAg expression and HBV DNA load induced by fatty acid stimulation and the inhibition of cellular autophagy.Knocking down Plin2 and blocking autophagy with 3-methyladenine(3-MA)inhibited HBV DNA replication.CONCLUSION In conclusion,lipid metabolism is a significant factor affecting HBV load in patients with HBV infection.The in vitro experiments established that fatty acid stimulation inhibits HBV replication via the Plin2-autophagy pathway.

the Study of Hepatitis B Virus Reactivation

Hepatitis B virus(HBV) reactivation after chemotherapy or immunosuppressive therapy is a cause of liver-related morbidity and mortality. Not all chronic hepatitis B patients will lead to HBV reactivation. The incidence is 0.3%-30.2% according to the reports. The mechanism of HBV reactivation is still unclear, but it is believed that the viral load is increasing due to the suppression of immune response. No uniform diagnostic criteria are available. HBV reactivation can be confirmed by an increase of serum HBV DNA level. Recently, awareness of reactivation of occult HBV has been improved, especially in HBV endemic area. Preemptive antiviral therapy was the best approach to prevent the HBV reactivation. HBV reactivation can lead to acute hepatitis, severe hepatitis and acute liver failure. Therefore, it is worthy of great attention and further study. Antiviral therapy is safe and effective to prevent HBV reactivation.

Antibiotic-induced gut bacteria depletion has no effect on HBV replication in HBV immune tolerance mouse model

Commensal microbiota is closely related to Hepatitis B virus(HBV)infection.Gut bacteria maturation accelerates HBV immune clearance in hydrodynamic injection(HDI)HBV mouse model.However,the effect of gut bacteria on HBV replication in recombinant adeno-associated virus(AAV)-HBV mouse model with immune tolerance remains obscure.We aim to investigate its role on HBV replication in AAV-HBV mouse model.C57BL/6 mice were administrated with broad-spectrum antibiotic mixtures(ABX)to deplete gut bacteria and intravenously injected with AAV-HBV to establish persistent HBV replication.Gut microbiota community was analyzed by fecal qPCR assay and 16S ribosomal RNA(rRNA)gene sequencing.HBV replication markers in blood and liver were determined by ELISA,qPCR assay and Western blot at indicated time points.Immune response in AAV-HBV mouse model was activated through HDI of HBV plasmid or poly(I:C)and then detected by quantifying the percentage of IFN-γ^(+)/CD8^(+)T cells in the spleen via flow cytometry as well as the splenic IFN-γmRNA level via qPCR assay.We found that antibiotic exposure remarkably decreased gut bacteria abundance and diversity.Antibiotic treatment failed to alter the levels of serological HBV antigens,intrahepatic HBV RNA transcripts and HBc protein in AAV-HBV mouse model,but contributed to HBsAg increase after breaking of immune tolerance.Overall,our data uncovered that antibiotic-induced gut bacteria depletion has no effect on HBV replication in immune tolerant AAV-HBV mouse model,providing new thoughts for elucidating the correlation between gut bacteria dysbiosis by antibiotic abuse and clinical chronic HBV infection.

Antiviral Therapy of Liver Cirrhosis Related to Hepatitis B Virus Infection

Hepatitis B virus (HBV) infection is a leading cause of liver disease worldwide,with 75% of those affected distributed in the Asia-Pacific region.Approximately one million HBV-infected patients die of liver cirrhosis and hepatocellular carcinoma (HCC) each year.If left untreated,6-20% of chronic hepatitis B (CrHB) patients will develop cirrhosis over five years.The cumulative incidence of HBV-related cirrhosis,disease progression,and prognosis are closely associated with serum HBV DNA levels.Antiviral therapy in HBV-related cirrhosis has been documented by several long-term cohort studies to decrease disease progression to hepatic decompensation and HCC.The approval and availability of oral antiviral agents with better safety profiles has greatly improved the prognosis for HBV-related cirrhosis.Here,we discuss the significance of antiviral therapy for HBV-related cirrhosis and the management of HBV-related diseases in the future.

Macrophage Phenotypes and Hepatitis B Virus Infection

Globally, hepatitis B virus (HBV) infection and its related liver diseases account for 780,000 deaths every year. Outcomes of HBV infection depend on the interaction between the virus and host immune system. It is becoming increasingly apparent that Kupffer cells (KCs), the largest population of resident and monocyte-derived macrophages in the liver, contribute to HBV infection in various aspects. These cells play an important role not only in the anti-HBV immunity including virus recognition, cytokine production to directly inhibit viral replication and recruitment and activation of other immune cells involved in virus clearance but also in HBV outcome and progression, such as persistent infection and development of end-stage liver diseases. Since liver macrophages play multiple roles in HBV infection, they are directly targeted by HBV to benefit its life cycle. In the present review, we briefly outline the current advances of research of macrophages, especially the studies of their phenotypes, in chronic HBV infection.

Discovery of a novel sodium taurocholate cotransporting polypeptide(NTCP) inhibitor: Design, synthesis, and anti-proliferative activities

Sodium taurocholate cotransporting polypeptide(NTCP)is identified as the functional receptor for HBV entry,which is responsible for upregulated HBV transcription in the HBV life cycle.Besides,NTCP is also implicated in the progression of HBV-induced hepatocellular carcinoma(HCC).Thereby,NTCP-targeting entry inhibitors are proposed to suppress HBV infection and replication in HBV-induced hepatoma therapy.Herein,we integrated in silico screening and chemical synthesis to obtain a small-molecule NTCP inhibitor B7,which exhibited moderate anti-proliferative activities against HepG2 cells and anti-HBV activity in vitro.Additionally,CETSA assay,molecular docking,and MD simulation validated that B7 could bind to NTCP.Furthermore,western blot analysis demonstrated that B7 induced apoptosis with an increased expression of Bax and caspase 3 cleaving as well as a decreasing expression of Bcl-2 in HepG2 cells.Taken together,our study identified B7 as a novel NTCP inhibitor with anti-proliferation activities which might provide a new opportunity for HCC therapy.

Fitting logistic regression models to assess vitamin D deficiency with clinical parameters in chronic hepatitis B patients

Statistical models provide a quantitative structure with which clinicians can evaluate their hypotheses to explain patterns in observed data and generate forecasts.In contrast,vitamin D is an important immune modulator that plays an emerging role in liver diseases such as chronic hepatitis B(CHB).Therefore,we quantified 25(OH)D_(3) serum levels in 292 CHB patients tested for their association with clinical parameters.Of 292 patients,69(63%),95(47%),and 39(19%)had severe vitamin D deficiency(25(OH)D_(3)<10 ng/mL),vitamin D insufficiency(25(OH)D_(3)10 and<20 ng/mL),or adequate vitamin D serum levels(25(OH)D_(3)20 ng/mL),respectively.In both univariate and multivariate analyses,zinc serum level was a strong predictor of low 25(OH)D_(3) serum levels(P<0.001).Results of fitted models showed that lower vitamin D levels were significantly associated with:younger age,lower uric acid levels,HBeAg-positive status,lower calcium levels(p<0.05).Vitamin D deficiency(<20 ng/ml)or severe deficiency(<10 ng/ml)was observed more frequently among HBV patients(52%).Vitamin D deficiency was observed in most CHB patients.Generally,our results recommend that substitution of vitamin D can be a substitution method in the treatment of patients with HBV-associated disorders.