Different Phases Of Chronic Hepatitis B Research Articles

The Characteristics of Natural Killer Cells and T Cells Vary With the Natural History of Chronic Hepatitis B in Children

Background and Aims: The immune status of children with chronic hepatitis B (CHB) in different phases is still unclear. The aim of this study was to investigate the phenotype and cytokine-producing ability of natural killer (NK) and T cells and to better understand the immune characteristics of children with different phases of CHB.Methods: Treatment-naive children with CHB were divided into groups with different clinical phases of CHB. Fresh peripheral blood drawn from hepatitis B virus (HBV)-infected and healthy children was processed to perform flow cytometric analysis.Results: A total of 112 treatment-naive children with CHB and 16 comparable healthy controls were included in this study. The expression of HLA-DR on NK cells and CD38 on T cells were upregulated, especially in the IA phase, in children with CHB compared with healthy controls. The ability of circulating NK cells instead of CD8+ T cells to produce IFN-γ in children with CHB was slightly increased, but TNF-α production seemed to be decreased compared with that in healthy controls. The expression of some activation markers varied among children with different phases of CHB, especially the higher CD38 expression found on T cells in the IA phase. Regression analysis revealed that IFN-γ and TNF-α production by NK cells and CD8+ T cells seemed to have positive correlations with ALT elevation and an activated status of NK cells or T cells.Conclusion: NK cells and T cells tended to be phenotypically activated (especially in the IA phase) in children with CHB compared with healthy controls. However, their cytokine-producing function was not obviously elevated, especially IFN-γ production by CD8+ T cells. More studies investigating the mechanism and observing the longitudinal changes in the immune status in children with CHB are needed.

P-119 GENETIC VARIABILITY OF HEPATITIS B VIRUS AMONG DIFFERENT PHASES OF CHRONIC INFECTION AND HIV COINFECTION IN BRAZIL

Molecular studies regarding hepatitis B virus (HBV) infection are essential as the disease severity depends on these specifications. This study aims to determine HBV genotypes and subgenotypes, nucleos(t)ide analogs (NA) resistance, and HBsAg escape mutations in HBV patients according to different phases of chronic hepatitis B (CHB) and HIV status. A total of 93 HBsAg+ patients over 18 years of age were included. Four different phases of CHB have included: 10 immune tolerant phases (IT), 5 immune reactive HBeAg positive phase (IR), 46 low replicative (LR) state, 23 HBeAg-negative CHB (ENH), and also 9 HIV/ HBV coinfected individuals. Samples were submitted to PCR for detecting an overlapping poI/ S gene region and direct sequenced. Phylogenetic analyses were performed using Mega-X software, identification of vaccine escape and NA resistance was made using the Geno2Pheno HBV website. Mean age was 44.5± 13.3 years and most of HBV subjects were males (56.9%). Most of the individuals presented genotype A (75.3%) irrespective of group, subgenotype A1 (61 3%), followed by genotypes D (17.3%), F (6.4%), E (1.1%). Genotypes D and F were prevalent in LR group (75% and 66.6%, respectively) and genotype E was found only in IT group (1/1). It was not found NA resistance described to common antiviral treatment. However, high frequency of some specific mutations was found in all groups, such as, M129L (72.0%); W1 53RW (36 5%); V1 63I (64.5%); I253V (55.9%); V278IV (30.1%). Seven subjects (7.5%) presented HBsAg escape mutation of whom the majority had genotype A (85.7%) and belongs to LR group (57.1%); 1 had genotype D (14.3%), 2 were HIV/ HBV coinfected (28.6%) and 1 was ENH (14.3%). It was found a high prevalence of genotype A1 irrespective of CHB phase or HIV coinfection and HBsAg escape mutations could impact antiviral treatment and diagnosis.

An Immuno-Clinic score model for evaluating T cell immunity and predicting early antiviral therapy effectiveness in chronic hepatitis B.

We generated an Immuno-Clinic score (ICS) model to evaluate T cell immunity based on the clustering of antiviral cytokines and inhibitory molecules in 229 naïve chronic hepatitis B (CHB) patients. 126 patients receiving antiviral therapy were used to validate the model for predicting antiviral therapy effectiveness. Through receiver-operator characteristic curve analysis, the area under the curve, sensitivity, and specificity of the ICS model were 0.801 (95%CI 0.703-0.900), 0.727, and 0.722, respectively. The cut-off value was 0.442. Re-evaluation of T cell immunity in different phases of CHB showed that patients in the immune tolerant phase had the lowest percentage of ICS-high (15%), while patients in the inactive carrier phase had the highest percentage of ICS-high (92%). Patients in the immune active and gray zone phases had 17% and 56% ICS-high, respectively. Elevation of ICS as early as four weeks after treatment could predict the effectiveness of hepatitis B virus (HBV) DNA loss and normalization of alanine aminotransferase, while eight weeks after treatment could predict HBV surface antigen decline. Thus, this ICS model helps clinicians choose an optimal time for initiating antiviral therapy and predicting its efficacy.

Transition to HBeAg-negative chronic hepatitis B virus infection is associated with reduced cccDNA transcriptional activity

HBeAg seroconversion during the natural history of chronic hepatitis B (CHB) is associated with a strong drop in serum HBV DNA levels and a reduction of intrahepatic covalently closed circular DNA (cccDNA) content. Of particular interest is the transition to HBeAg-negative chronic infection (ENCI). ENCI, previously known as inactive carrier state, is characterized by very low or negative viremia and the absence of liver disease. The molecular mechanisms responsible for the transition to ENCI and for the control of viral replication in ENCI are still poorly understood. To identify which step(s) in the viral life cycle are controlled during the transition to ENCI, we quantified cccDNA, pre-genomic RNA (pgRNA), total HBV RNA and DNA replicative intermediates in 68 biopsies from patients in different phases of CHB. HBeAg seroconversion is associated with a reduction of cccDNA amounts as well as transcriptional activity. Silencing of cccDNA is particularly pronounced in ENCI, where there was ~46 times less pgRNA per cccDNA compared to HBeAg-negative CHB. Furthermore, a subgroup of patients with HBeAg-negative CHB can be characterized by reduced replication efficiency downstream of pgRNA. The reduction in serum viral load during the transition to ENCI seems to primarily result from strong inhibition of the transcriptional activity of cccDNA which can be maintained in the absence of liver disease. During the natural course of chronic hepatitis B virus infections, the immune response can gain control of viral replication. Quantification of viral DNA and RNA in liver biopsies of patients in different stages of chronic hepatitis B allowed us to identify the steps in the viral life cycle that are affected during the transition from active to inactive disease. Therapeutic targeting of these steps might induce sustained inhibition of viral transcription.

Integrated Analysis of Gene Expression Profiles Reveals Deregulation of the Immune Response Genes during Different Phases of Chronic Hepatitis B Infection

Background: The natural history of chronic hepatitis B (CHB) infection is divided into different phases including immune tolerance (IT), immune clearance (or immune active [IA]), inactive carrier (IC), and reactivation. Despite utilizing high-throughput data, the distinct immunological mechanisms of these phases have been insufficiently investigated. Objectives: The aim of the present study was to determine candidate disease-associated genes and significantly altered biological processes for each phase of CHB infection. Methods: The gene expression profiles of 83 CHB patients (22 IT, 50 IA, and 11 IC phases) were obtained from gene expression omnibus (GEO dataset: GSE65359) and analyzed by bioinformatics tools. Several plugins of Cytoscape software were used to construct protein-protein interaction (PPI) networks and measure their topological properties. Subsequently, functional annotation and signaling pathway enrichment were carried out using the database for annotation, visualization and integrated discovery (DAVID) and Kyoto encyclopedia of genes and genomes (KEGG). Results: 449 and 452 deregulated genes were identified in IT-IA and IA-IC patients, respectively. Gene ontology and KEGG pathway analyses showed that several immune response-associated genes and signaling pathways (i.e. cytokine-cytokine receptor interaction, chemokine signaling pathway and T cell receptor signalling pathway) were upregulated in the IA phase, but downregulated in the IC phase. The LCK (encoding a tyrosine kinase) was determined as the most important hub gene of both constructed PPI networks. Furthermore, other immune response-associated genes such as CXCR3, VCAN, MYC, and STAT1 were found to be the important hub genes in clinical phases of CHB. Conclusions: The immune response-related pathways were found to be up and downregulated in the immune clearance phase and inactive carrier phase of CHB, respectively. The LCK hub gene might help the pathogenesis of different phases of CHB and serve as a therapeutic target for the treatment of hepatitis B virus.

Correlation of Quantitative HbsAg with Quantitative HBV DNA in Different Phases of Chronic Hepatitis B (CHB) Patients

Background: Quantitative HBsAg (qHBsAg) level is increasingly recognized as an important marker in the course of HBV infection; however, its role in natural history of disease is still unclear. Aim: To study the baseline serum qHBsAg level and its association with quantitative HBV DNA levels in different phases of Indian chronic hepatitis B (CHB) patients. Materials: We conducted cross-sectional study of consecutive 120 CHB patients (mean age 37 [SD 13] years, 67% males). HBV DNA was measured by RT PCR and serum qHBsAg levels by Abott Architect Assay. Results: 90.8% were HBe-negative patients. Median serum qHBsAg of study cohort was 3.74 log10 IU/mL. Overall correlation between qHBsAg levels and HBV DNA levels was weak (spearmen r= 0.298) and also in HBe-negative patients (r= 0.179). Patient having qHBsAg/HBV DNA ratio > 49.09 have shown good correlation between qHBsAg levels and HBV DNA levels. Conclusion: Quantitative HBsAg level was widely distributed among the different phases of CHB. Serum qHBsAg may not replace serum HBV DNA test in majority of adult CHB population which are mainly in HBe-negative low replicate stage.

Hepatitis B Surface Antigen Quantification across Different Phases of Chronic Hepatitis B Virus Infection Using an Immunoradiometric Assay

Background/AimsQuantification of hepatitis B surface antigen (HBsAg) is an emerging serologic test and may be useful for identifying treatment strategies for chronic hepatitis B (CHB). This study aimed to evaluate HBsAg titers during the natural course of CHB and identify correlations between HBsAg titers and hepatitis B virus (HBV) DNA concentrations across different CHB phases measured using an immunoradiometric assay (IRMA).MethodsCHB phases were defined on the basis of HBV DNA concentrations, the presence of hepatitis B e antigen/antibody (HBeAg/Ab) and serum alanine aminotransferase levels. Serum HBsAg titers and paired HBV DNA concentrations in the different phases of CHB were compared using 627 serum samples.ResultsMean HBsAg titers were significantly higher in the immunotolerant (IT) phase and immunoreactive (IR) HBeAg-positive phase than in the low-replicative (LR) and HBeAg-negative CHB (ENH) states. The correlation between HBsAg titers and HBV DNA concentrations was modest in the IT (n=36, r=0.804, p<0.001) and IR (n=48, r=0.773, p<0.001) phases, and it was poor in the LR state (n=116, r=0.289, p=0.002); however, no significant correlation was observed in the ENH state (n=67, r=0.146, p=0.237) or in the oral nucleos(t)ide analogue-treated group (n=267).ConclusionsHBsAg quantification using IRMA might be useful for discriminating different CHB phases and different stages of chronic liver disease.

Antibody to hepatitis B core antigen levels in the natural history of chronic hepatitis B: a prospective observational study.

Previous studies have revealed antibody to hepatitis B core antigen (anti-HBc) levels as a predictor of treatment response in hepatitis B early antigen (HBeAg)-positive chronic hepatitis B (CHB) patients in both interferon and nucleos(t)ide analog therapy cohorts. However, there is no information about anti-HBc levels in the natural history of CHB. This study aimed to define anti-HBc levels of different phases in the natural history of CHB. Two hundred eleven treatment-naive CHB patients were included in the study. They were classified into 4 phases: immune tolerance (IT) phase (n = 39), immune clearance (IC) phase (n = 48), low or no-replicative (LR) phase (n = 55), and HBeAg-negative hepatitis (ENH, n = 69). Fifty patients who were HBsAg negative and anti-HBc positive were also recruited as past HBV infection (PBI) control group. Anti-HBc levels were measured by a newly developed double-sandwich immunoassay. Correlation of anti-HBc levels with alanine aminotransferase (ALT) and other HBV-related markers within each phase was performed. Serum anti-HBc levels were statistically significant between patients in different phases of CHB (P < 0.001). The median anti-HBc levels were: IT (3.17 log 10 IU/mL), IC (4.39 log 10 IU/mL), LR (3.29 log 10 IU/mL), ENH (4.12 log 10 IU/mL), and PBI (0.61 log 10 IU/mL). There existed a strong correlation in IC (r = 0.489, P < 0.001), a poor correlation in ENH (r = 0.275, P = 0.042), and no correlation in patients with ALT reached 5 times upper limit of normal (r = 0.120, P = 0.616). Anti-HBc levels show significant differences during the natural course of CHB. These results may provide some potentially useful insights into hepatitis B pathogenesis and immune activation against hepatitis B virus.

Outcomes of Patients With Chronic Hepatitis B Who Do Not Meet Criteria for Antiviral Treatment at Presentation

The availability of potent, well-tolerated, oral antivirals with low rates of resistance has led many experts to recommend liberalizing indications for the treatment of chronic hepatitis B (CHB). This study sought to determine the rate of transitions to an active phase of infection, the frequency of treatment initiation, and the clinical outcomes of patients with CHB who did not meet treatment criteria at presentation. We reviewed medical records of patients with CHB, seen in the liver clinics at the University of Michigan Health System from 1999 through 2010, who did not receive antiviral treatment within 6 months of presentation. We collected data on transitions between different phases of CHB, hepatitis B e antigen (HBeAg) seroconversion, loss of hepatitis B surface antigen (HBsAg), and the development of hepatocellular carcinoma (HCC). Data analyses were censored or truncated at the time of treatment initiation or development of an outcome. Of the 234 patients analyzed, 52.1% were men (median age, 35 y), 72.2% were Asian, and 81.2% were HBeAg-negative. During a median follow-up period of 51 months, 19.2% of patients transitioned to a more active disease phase and 18.8% started antiviral therapy. Of the 44 HBeAg-positive patients, 4 patients (9%) had spontaneous HBeAg seroconversion. Nine HBeAg-negative patients but none of the HBeAg-positive patients lost HBsAg. The cumulative probability of HBsAg loss among HBeAg-negative patients was 1% at year 5 and 21% by year 10. No patients had flares of icteric hepatitis or hepatic decompensation. None of the HBeAg-positive patients developed HCC, whereas 2 HBeAg-negative patients developed HCC. Careful monitoring of patients with CHB who did not meet treatment criteria at presentation permits timely initiation of treatment, with a low risk of adverse clinical outcomes, based on a retrospective study with a median follow-up period of 4.3 years. These findings indicate that current guidelines for initiating treatment are appropriate.

IL28B Polymorphism Correlates with Active Hepatitis in Patients with HBeAg-Negative Chronic Hepatitis B

Background & AimsThe clinical relevance of single nucleotide polymorphisms (SNPs) near the IL28B gene is controversial in patients with hepatitis B virus (HBV) infection. This study aimed to investigate the role of viral and host factors, including IL28B genotypes, in the natural course of chronic hepatitis B (CHB).MethodsThe study enrolled consecutive 115 treatment-naive CHB patients. HBV viral loads, genotypes, precore and basal core promotor mutations, serum hepatitis B surface antigen (HBsAg) and interferon-gamma inducible protein 10 (IP-10) levels as well as four SNPs of IL28B were determined. Serial alanine transaminase (ALT) levels in the previous one year before enrollment at an interval of three months were recorded. Factors associated with active hepatitis, defined as persistent ALT >2× upper limit of normal (ULN) or a peak ALT level >5× ULN, were evaluated.ResultsThe prevalence of rs8105790 TT, rs12979860 CC, rs8099917 TT, and rs10853728 CC genotypes were 88.3%, 87.4%, 88.4% and 70.9%, respectively. In HBeAg-positive patients (n = 48), HBV viral load correlated with active hepatitis, while in HBeAg-negative patients (n = 67), rs10853728 CC genotype (p = 0.032) and a trend of higher IP-10 levels (p = 0.092) were associated with active hepatitis. In multivariate analysis, high viral load (HBV DNA >108 IU/mL, p = 0.042, odds ratio = 3.946) was significantly associated with HBeAg-positive hepatitis, whereas rs10853728 CC genotype (p = 0.019, odds ratio = 3.927) was the only independent factor associated with active hepatitis in HBeAg-negative population.ConclusionsHBV viral load and IL28B rs10853728 CC genotype correlated with hepatitis activity in HBeAg-positive and HBeAg-negative CHB, respectively. Both viral and host factors play roles in disease activity during different phases of CHB.

Antiviral drug-associated potential vaccine-escape hepatitis B virus mutants in Turkish patients with chronic hepatitis B

Background: The hepatitis B virus (HBV) polymerase (pol) gene completely overlaps with the envelope (S) gene. Mutations in the pol gene of HBV, either from selection of primary or secondary resistance mutations, typically result in changes in the overlapping hepatitis B surface antigen (HBsAg). Recent studies have conferred a new acronym to these HBV pol/ S gene overlap mutants: ADAPVEMs, for antiviral drug-associated potential vaccine-escape mutants. The present study aimed to assess the prevalence and pattern of ADAPVEMs in Turkish patients with chronic hepatitis B (CHB). Methods: The investigation was conducted between March 2007 and July 2010 and involved a total of 442 patients. These patients were in the following phases of HBV infection: immune tolerant (n = 50), immune reactive (n = 37), inactive carrier (n = 90), HBeAg-negative CHB (n = 217), and HBsAg-negative (n = 12), or were hemodialysis patients (n = 36). One hundred eighty-six patients were receiving nucleos(t)ide analogue (NUC) therapy and 256 patients had treatment-naıve CHB. Results: Seven types of ADAPVEM were detected in the total CHB patients: rtM204 V/sI195 M, rtM204I/sW196S, rtM204I/sW196L, rtV173L/sE164D, rtA181T/sW172*, rtA181T/sW172L, and rtA181 V/sL173F. The ADAPVEMs were associated with lamivudine, telbivudine, and adefovir. The prevalence of ADAPVEMs in all CHB patients was found to be 10% (46/442). The difference in the prevalence of ADAPVEMs across the different CHB clinical phases was not significant (Pearson Chi-square, p = 0.112). The prevalence of ADAPVEMs was 24% (44/186) in those undergoing NUC therapy and 0.7% (2/256) in the treatment-naıve group; this difference was significant (Pearson Chi-square, p = 0.00). Conclusion: We determined the prevalence and pattern of ADAPVEMs in Turkish patients in the different phases of CHB. Preferred drugs in Turkey, such as lamivudine, have the potential to cause the emergence of ADAPVEMs, with the possibility that these will spread to both individuals immunized with the hepatitis B vaccine and nonimmunized individuals. ADAPVEMs should be monitored in infected and treated patients and their public health risks assessed.

Antiviral drug-associated potential vaccine-escape hepatitis B virus mutants in Turkish patients with chronic hepatitis B

The hepatitis B virus (HBV) polymerase (pol) gene completely overlaps with the envelope (S) gene. Mutations in the pol gene of HBV, either from selection of primary or secondary resistance mutations, typically result in changes in the overlapping hepatitis B surface antigen (HBsAg). Recent studies have conferred a new acronym to these HBV pol/S gene overlap mutants: ADAPVEMs, for antiviral drug-associated potential vaccine-escape mutants. The present study aimed to assess the prevalence and pattern of ADAPVEMs in Turkish patients with chronic hepatitis B (CHB). The investigation was conducted between March 2007 and July 2010 and involved a total of 442 patients. These patients were in the following phases of HBV infection: immune tolerant (n=50), immune reactive (n=37), inactive carrier (n=90), HBeAg-negative CHB (n=217), and HBsAg-negative (n=12), or were hemodialysis patients (n=36). One hundred eighty-six patients were receiving nucleos(t)ide analogue (NUC) therapy and 256 patients had treatment-naïve CHB. Seven types of ADAPVEM were detected in the total CHB patients: rtM204V/sI195M, rtM204I/sW196S, rtM204I/sW196L, rtV173L/sE164D, rtA181T/sW172*, rtA181T/sW172L, and rtA181V/sL173F. The ADAPVEMs were associated with lamivudine, telbivudine, and adefovir. The prevalence of ADAPVEMs in all CHB patients was found to be 10% (46/442). The difference in the prevalence of ADAPVEMs across the different CHB clinical phases was not significant (Pearson Chi-square, p=0.112). The prevalence of ADAPVEMs was 24% (44/186) in those undergoing NUC therapy and 0.7% (2/256) in the treatment-naïve group; this difference was significant (Pearson Chi-square, p=0.00). We determined the prevalence and pattern of ADAPVEMs in Turkish patients in the different phases of CHB. Preferred drugs in Turkey, such as lamivudine, have the potential to cause the emergence of ADAPVEMs, with the possibility that these will spread to both individuals immunized with the hepatitis B vaccine and nonimmunized individuals. ADAPVEMs should be monitored in infected and treated patients and their public health risks assessed.

The change of the quantitative HBsAg level during the natural course of chronic hepatitis B

There is insufficient information about HBsAg levels and their correlation with serum hepatitis B virus (HBV) DNA in chronic hepatitis B (CHB). We aimed to describe HBsAg levels during various phases of CHB and to investigate the correlation with serum HBV DNA levels. A total of 645 treatment-naïve Korean CHB patients were included in this retrospective cross-sectional study. They were categorized into immune tolerance (IT, n=56), HBeAg-positive hepatitis (EPH, n=150), inactive carrier (IC, n=274) and HBeAg-negative hepatitis (ENH, n=165). The baseline HBsAg and HBV DNA levels were measured. The mean HBsAg titres (log IU/ml) differed (P<0.001): IT 4.29, EPH 3.64, IC 2.05 and ENH 3.23. In 645 patients, HBsAg and HBV DNA showed a significant correlation (r=0.693, P<0.001), and this was also observed in the IT, EPH and IC groups (r=0.664, r=0.541, r=0.505, respectively, all P<0.001), but not in the ENH group (r=0.093, P=0.321). Age had a negative correlation with HBsAg (r=-0.451, P<0.001). The cirrhotic patients had a significantly lower HBsAg level than the non-cirrhotic patients (2.41 ± 1.36 vs. 3.02 ± 1.21 log IU/ml, P<0.001). The HBsAg level varied significantly in different phases of CHB and was correlated with HBV DNA during the IT, EPH and IC phases. These findings can provide additional information to understand the natural course and pathogenesis of CHB.

Hepatitis B surface antigen levels during the natural history of chronic hepatitis B: A perspective on Asia

Data from clinical trials suggest a potential role for on-treatment monitoring of serum HBsAg titres during interferon-alpha (pegIFN) therapy in predicting virological responses. However, baseline HBsAg titres during the natural history of chronic hepatitis B (CHB) have not been well-characterized. We aimed to define the serum HBsAg titres during the different phases of CHB in a cohort of Asian patients infected with either genotype B or C HBV. Two-hundred and twenty patients were classified into immune-tolerant (IT), immune-clearance (IC), non/low-replicative (LR) or hepatitis B e antigen negative hepatitis (ENH) phases. Serum HBsAg was quantified using the ARCHITECT platform (Abbott Laboratories, Chicago, USA). Correlation of HBsAg titre with HBV DNA and serum ALT within each phase of infection was performed. Median HBsAg titres were different between each phase of CHB (p=0.001): IT (4.53 log(10)IU/ml), IC (4.03 log(10)IU/ml), LR (2.86 log(10)IU/ml), and ENH (3.35 log(10)IU/ml). HBsAg titres were highest in the IT phase, and lowest in the LR phase. In general, median HBsAg titres were similar between genotypes B and C HBV. Serum HBsAg titres only correlated with HBV viral load in the IC phase. No correlation between the serum HBsAg level and ALT was observed. This study demonstrated significant differences in median baseline serum HBsAg titres across the different phases of CHB. These results provide further insight into the HBV viral life cycle in the setting of the various phases of CHB. Baseline HBsAg quantification may help refine future treatment algorithms for both immune-modulator therapy and oral nucleos(t)ide analogue therapy.

Economic Implications of Entecavir Treatment in Suppressing Viral Replication in Chronic Hepatitis B (CHB) Patients in China from a Perspective of the Chinese Social Security Program

Objectives Of estimated 112 million persons infected with chronic hepatitis B (CHB) in China, 15% to 40% will eventually develop liver complications. Most patients do not actively seek antiviral agents for treatment due in part to lack of good understanding of the disease. Entecavir is a new therapeutic option for CHB patients and the purpose of this study was to evaluate the cost-effectiveness of entecavir treatment in China, based on projected clinical benefits from its superior viral suppression efficacy. Methods The analysis was based on the perspective of the Chinese Social Security program. Adjusted relative risks on the association between viral load (VL) and clinical end points (liver cirrhosis/hepatocellular carcinoma) were derived from a publication of a Taiwan CHB prospective cohort with 42,115 person-years of follow-up, and applied to patients enrolled in a randomized phase III trial in China. In this trial, hepatitis B virus (HBV) DNA (by polymerase chain reaction assay) was the key efficacy end point after 48 weeks of treatment with either entecavir or lamivudine monotherapy. Entecavir and lamivudine daily prices were assumed to be Renminbi Yuan (RMB) 40 and 16.71, respectively. Life expectancy tables were based on China vital statistics. Direct medical cost and utility scores for different phases of CHB were estimated from published China specific data, and costs were adjusted to 2006 values using the Chinese Consumer Price Index. Probabilistic sensitivity analyses were conducted to evaluate parameter uncertainty on event distribution and treatment failure rates beyond the trial period. Results A total of 519 subjects were enrolled in the study, comprising of 82% males, 87% HBeAg+, and a mean age of 30 years. Based on the efficacy measurement of the percentage of patients achieving HBV DNA <300 copies/ml at week 48, entecavir was superior to lamivudine (78.7% vs. 46.7%, respectively [ P < 0.05]). In the base case, compared with lamivudine, 1 year of entecavir therapy gained 0.305 quality-adjusted life year (QALY) at an incremental cost of 5368 RMB, with a 3% annual discount. Compared with lamivudine, using entecavir cost an incremental 17,590 RMB per QALY gained (95% CI 6333–56,407). Conclusions Based on the results of this study, entecavir is likely to be cost-effective in treating hepatitis B patients in China based on the World Health Organization's recommended maximum willingness to pay threshold.

Serum hyaluronic acid: A promising marker of hepatic fibrosis in chronic hepatitis B

Serum hyaluronic acid: A promising marker of hepatic fibrosis in chronic hepatitis B