Academic literature on the topic 'HBeAg Seroconversion'

ABSTRACTNucleos(t)ide analogues rarely result in a durable off-treatment response in chronic hepatitis B infection, whereas pegylated interferon (Peg-IFN) induces a long-lasting response only in a subset of patients. We assessed the effect of sequential combination therapy with Peg-IFN-α2a and entecavir in hepatitis B e antigen (HBeAg)-positive patients with prior long-term entecavir therapy and investigated the predictors of response to treatment. HBeAg-positive individuals who did not achieve HBeAg seroconversion during previous long-term entecavir therapy, receiving Peg-IFN-α2a added to ongoing entecavir therapy (sequential combination [S-C] therapy;n= 81) for 48 weeks or remaining on entecavir monotherapy (n= 116), were retrospectively included. A matched pair was created at a 1:1 ratio from each treatment group. The primary endpoint was HBeAg seroconversion at week 48. Subgroup analysis of response prediction was conducted for 81 patients with S-C therapy. More patients in the S-C therapy group achieved HBeAg seroconversion than those in the entecavir group (44% versus 6%;P< 0.0001). An HBeAg level of <200 signal-to-cutoff ratio (S/CO) at baseline was a strong predictor for higher HBeAg seroconversion than that achieved when HBeAg was ≥200 S/CO (64.2% versus 17.9%;P< 0.0001). Hepatitis B surface antigen (HBsAg) levels at baseline and the decrease in HBsAg levels predicted HBsAg loss in the S-C therapy group. The combination of baseline HBeAg of <200 S/CO and HBsAg of <1,000 IU/ml and an HBsAg decline at week 12 of ≥0.5 log10IU/ml provided the highest rate of HBeAg seroconversion (92.31%) and HBsAg loss (83.3%) at week 48. Patients receiving sequential combination therapy have a higher rate of HBeAg seroconversion and are more likely to experience HBsAg clearance than do those continuing entecavir monotherapy. Sequential combination therapy can be guided by baseline HBsAg/HBeAg levels and on-treatment HBsAg dynamics.

Abstract Objective To investigate the efficiency of pegylated interferon α therapy for patients with HBeAg-positive chronic hepatitis B (CHB) and explore whether liver histopathological features and other factors might influence HBeAg seroconversion. Methods Total of 80 HBeAg-positive CHB patients who received liver puncture were treated with pegylated interferon α once a week for 48 weeks. The rate of HBeAg seroconversion was determined after therapy, and the factors influencing HBeAg seroconversion were analyzed. Results The rate of HBeAg seroconversion was 30.00％ at the end of treatment. The rate of HBeAg seroconversion gradually increased with the elevation of liver inflammatory activity (χ2 = 9.170, P = 0.027). But liver fibrosis has little correlation with the rate of HBeAg seroconversion (χ2 = 5.917, P = 0.116). Except HBeAg, other baseline indexes including gender, age, serum ALT and serum HBV DNA 1evels had no statistical difference between the patients with HBeAg seroconversion and the patients without HBeAg seroconversion. By binary logistic regression analysis, liver inflammation and HBeAg were influencing factors for HBeAg seroconversion. Conclusions Pegylated interferon α therapy induces a higher rate of HBeAg seroconversion in HBeAg-positive chronic hepatitis B patients with severe liver inflammation, so the liver biopsies should be performed in time.

ABSTRACT The level of hepatitis B virus (HBV) DNA in serum reflects the replicative activity of HBV. To compare serum HBV DNA levels in different states of hepatitis B, 47 sera of patients with HBeAg-positive chronic hepatitis B, 4 sera of patients with HBeAg-negative chronic hepatitis B, 40 samples of patients after HBeAg seroconversion during alpha interferon treatment, 57 sera of inactive HBsAg carriers, and 42 sera of patients who had recovered from chronic hepatitis B more than 12 months prior to blood collection were checked for the presence of HBV DNA with the Amplicor HBV Monitor Test. In patients with HBeAg-positive chronic hepatitis B, the median of serum HBV DNA levels (8.3 × 108 copies/ml) was significantly higher than that for patients after HBeAg seroconversion (6.2 × 103 copies/ml) and than that for inactive HBsAg carriers (5.6 × 103 copies/ml). None of the patients who had recovered from hepatitis B had detectable HBV DNA in serum. Quantitative PCR proved to be a valuable tool for identification of different states of HBV infection. This technique was found to be a good method for determination of serum HBV DNA levels both for patients with HBeAg seroconversion and for inactive carriers who showed low viremia not detectable by conventional hybridization assays.

Objective: Published network meta-analyses of chronic hepatitis B (CHB) treatments are either out-of-date or excluded key treatments. Therefore, we aimed to comprehensively update the efficacy evidence for the following end points: Hepatitis B surface antigen (HBsAg) loss, hepatitis B early antigen (HBeAg) seroconversion and hepatitis B virus DNA (HBV DNA) suppression. Materials & methods: Approved treatments in CHB and their combinations were evaluated. A systematic literature review was conducted to identify all randomized controlled trials in treatment-naïve CHB patients. Included studies reported at least one of the end points of interest. A frequentist probability network meta-analysis was performed for each end point. The choice of fixed effect or random-effect model was based on the I-square statistic, a measure of variation in study outcomes between studies. The analyses were performed separately for HBeAg-positive and HBeAg-negative patients. For the primary analyses, end points measured 48 ± 4 weeks after treatment initiation were considered. Results: A total of 47 randomized controlled trials (13,826 patients), covering 23 unique treatment regimens, were included: a total of 29 reported HBsAg loss, 36 reported HBeAg seroconversion and 37 reported HBV DNA suppression. For both HBsAg loss and HBeAg seroconversion, pegylated interferon-based regimens were the most effective strategy in both HBeAg-positive and HBeAg-negative patients. On the other hand, for HBV DNA suppression, nucleosides-based regimens were the most effective strategy in both HBeAg-positive and HBeAg-negative patients. Conclusion: Our findings confirm available evidence around the comparative efficacy of available CHB treatments. Therefore, they can be used to update relevant cost–effectiveness analyses and clinical guidelines.

It is well appreciated that ethnicity influences the natural history and immune responses during a chronic hepatitis B infection. In this study, we explore the effect of ethnicity and treatment cessation on Hepatitis B surface Antigen (HBsAg) seroclearance in patients with Nucleos(t)ide Analogue (NA)-induced Hepatitis B e Antigen (HBeAg) seroconversion. We performed a multi-ethnic, multicentric observational cohort study. The analyzed cohort consisted of 178 mono-infected, predominantly male (75.3%) chronic hepatitis B patients of mixed ethnicity (44.4% Asians, 48.9% Caucasians) with nucleos(t)ide analogue-induced HBeAg seroconversion. Treatment was withdrawn in 105 patients and continued in 73, leading to HBsAg loss in 14 patients off- and 16 patients on-treatment, respectively. Overall, HBsAg loss rates were not affected by treatment cessation (hazard ratio 1.45, p = 0.372), regardless of consolidation treatment duration. Caucasian ethnicity was associated with an increased chance of HBsAg loss (hazard ratio 6.70, p = 0.001), but hepatitis B virus genotype was not (p = 0.812). In conclusion, ethnicity is the most important determinant for HBsAg loss after NA-induced HBeAg seroconversion, with up to six-fold higher HBsAg loss rates in Caucasians compared to Asians, irrespective of treatment cessation and consolidation treatment duration.

ABSTRACT The aim of the current study was to evaluate viral suppression following combined treatment with an S/pre-S1/pre-S2 vaccine and lamivudine in patients with chronic hepatitis B. We established a randomized, controlled clinical trial to compare the responses of three different treatment groups: those receiving vaccine monotherapy, lamivudine monotherapy, or combination treatment. Viral response was evaluated via hepatitis B virus (HBV) DNA suppression using different levels of classification. Seroconversion was evaluated via HBeAg loss, HBeAg seroconversion, HBsAg loss, and anti-HBs response. We found that the group receiving combination treatment demonstrated a significant increase in viral suppression over that for the lamivudine or vaccine monotherapy group, although the HBeAg seroconversion rate was not different. This enhanced suppression effect in the combination group was reversed after the discontinuation of vaccine treatment, suggesting that booster doses are required for a sustained viral response. Anti-HBs was detected in 55/120 vaccine recipients, but only 3 patients demonstrated HBsAg loss, indicating that the vaccine-induced anti-HBs was unable to completely neutralize HBsAg in the serum. At the study end point, anti-HBs responders showed significantly higher HBeAg seroconversion rates, greater suppression of HBV DNA levels, and a lower median reduction in HBV DNA levels than those of anti-HBs nonresponders. Our results suggest that combined treatment with the vaccine and lamivudine was significantly more effective than lamivudine monotherapy in the short term and was especially successful in producing viral suppression and an enhanced anti-HBs antibody response.

The aim of treatment of chronic hepatitis B with interferon is to induce a transition from the replicative phase of the disease to a nonreplicative state, with loss of hepatitis B virus (HBV)-DNA, seroconversion from hepatitis B e antigen (HBeAg)-positive to anti-HBe antibody-positive, and normalization of liver enzymes. The authors’ experience in 22 patients with chronic hepatitis B treated with recombinant human interferon alpha-2b (5 MU/m2 subcutaneously three times/week for 16 weeks) is reported. Before treatment all patients had been positive for hepatitis B surface antigen (HBsAg) and HBeAg for at least six months, had abnormal serum aminotransferases, had no evidence of hepatitis D or human immunodeficiency virus (HIV) infection and had compensated liver disease. Eleven of 22 patients (50%) responded to treatment with loss of HBeAg and appearance of anti-HBe antibodies, and normalization of serum aminotransferases within six months of interferon cessation. Patients were followed for 3.4±1.2 years after treatment. Ten of 11 responders remained negative for HBeAg and HBV-DNA; one patient relapsed and responded to a second course of interferon with loss of HBeAg and HBV-DNA. Seven of the 11 nonresponders underwent spontaneous (n=5) or retreatment-induced (n=2) seroconversion from HBeAg to anti-HBe and loss of HBV-DNA during follow-up. The other four nonresponders remained positive for HBeAg and HBV-DNA; three of the four progressed to decompensated liver disease. It is concluded that interferon is an effective treatment of chronic hepatitis B in 50% of patients with features similar to those used as selection criteria in the present study. These criteria probably also identify patients who have a high likelihood of spontaneous HBeAg to anti-HBe seroconversion, and it is possible that the benefit of interferon is its acceleration of this seroconversion.

Introductıon: HBV infection is a global public health problem. Tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) are nucleotide reverse transcriptase inhibitors (NRTIs) that are used for the treatment of CHB infection. The aim of this study was to evaluate the treatment response and efficacy of TDF, which was a new treatment regimen in Turkey Materials and Methods: This descriptive, retrospective study was conducted between January 2009 and January 2011 at Inonu University Faculty, Turgut Ozal Medicine Center, Department of Internal Medicine, Division of Hepatology Outpatient Clinic. We included hepatitis B positive patients who started to use Tenofovir (TDF). We retrospectively reviewed the electronic medical files of Hepatitis B patients. HBsAg, Hepatit B surface antibody (Anti-HBsAb), HBeAg, Hepatit B e antibody (Anti-HBeAb), HBV-DNA, aspartate aminotransferase (AST), alanine aminotransferase (ALT) values were evaluated in the 1, 3., 6., 9., and 12. months. Result: None of the patients under TDF treatment were “primary resistant”. ALT normalization at 12th month was seen in 80.4% of study population. HBsAg seroconversion were detected only in one patient (0.85%) at 9 months and HBeAg seroconversion were observed in 9 (8.3%) under TDF treatment. At the sixth month of TDF treatment, complete response were found in 77 (65.8%), partial response in 21 (18%) and inadequate response were in 19 (16.2%). Among HBeAg positive patients, 44 (80 %) patients had undetectable HBV DNA levels at the end of 12th month and among HBeAg negative patients, 52 (91.2%) patients had undetectable HBV DNA levels at the end of 12th month (p<0.01). Discussion and Conclusion: among patients with chronic HBV infection, Tenofovir had satisfying antiviral efficacy. There is no primary resistance in patients treated with Tenofovir. Patients had statistically significant improvement in AST, ALT, HBV DNA levels

ABSTRACTThe aims of this study were to investigate the efficacy of prolonged entecavir (ETV) therapy in treatment-naive chronic hepatitis B (CHB) patients and to determine whether continuous ETV therapy is feasible to achieve HBeAg seroconversion, particularly in patients with partial virological response (PVR). A total of 142 treatment-naive patients with CHB were enrolled. The mean duration of treatment was 65 (range, 26 to 90) months, and 86 patients (60.6%) were HBeAg positive. PVR was defined as detectable hepatitis B virus (HBV) DNA (>116 copies/ml) at year 1. The cumulative incidence of virological response (VR) increased from 54.9% at year 1 to 98.2% at year 7. HBeAg positivity (odds ratio [OR], 4.146;P= 0.001) and initial alanine aminotransferase (ALT) (OR, 0.997;P= 0.004) were independent risk factors for PVR. Among the 64 patients with PVR, 47 patients (73.4%) achieved VR within 4 years after prolonged ETV therapy without treatment adaptation. Three patients (2.1%) experienced virological breakthrough and HBV variants with genotypic resistance. The cumulative rate of HBeAg seroconversion was significantly higher in the patients with VR than in the patients with PVR (P= 0.018). None of the PVR patients with HBV DNA at ≥5,000 copies/ml at year 1 ever experienced HBeAg seroconversion. Multivariate analysis identified VR at year 1 as the only determinant of HBeAg seroconversion (hazard ratio [HR], 3.009;P= 0.010). In conclusion, although there were patients with PVR, prolonged ETV therapy showed excellent VR, with only 2.1% emergence of viral resistance during a 7-year follow-up. However, to achieve HBeAg seroconversion, drug modification is needed for HBeAg-positive patients with PVR (especially those with HBV DNA at ≥5,000 copies/ml at year 1).

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Introduction: The hepatitis B virus (HBV) present diversity of its genome, which is to be classified in different genotypes and subgenotypes (A-J). It has been demonstrated that different genotypes are related to the natural history of infection. The maintenance of viral replication could be one of the factors related to genotypes. Objectives: To identify the viral replication status of HBV carriers among the subgenótipos A1 and D4. Materials and methods: HBV carriers identified have been studied in two studies involving individuals from the state of Maranhão, northeast,Brazil, which had genotyping and subgenotypes, serology for HBeAg and anti-HBe and certain viral loads. Serological tests were performed by ELISA, HBV – DNA quantification real time PCR and genotyping performed by sequencing. Results: We identified 146 patients. Among these, 136 were subgenotype A1 or D4. It is 85 - A1 (62.5%) and 51 - D4 (37.5%). No difference was found between groups when age was evaluated (42 ± 12 vs 38 ± 17 p=0.11) or gender (male 48.5% vs 51.5% p=00.18). Among the D4 subgenotype carriers had more patients with HBeAg positive (23.5% vs 9.4%, p=0.02) and a higher proportion of patients with viral loads above 20.000 IU / ml (43.1% vs 12.9 % p <0.0001), even when only those with negative HBeAg (25.6% vs 6.5%, p=0.007) when compared with the A1 subgenotype. Conclusion: HBV carriers, subgenotype D4, compared to A1 subgenotype have delayed HBeAg seroconversion and higher levels of HBV – DNA, suggesting that this subgenotype is possibly related to
Introdução: O vírus da hepatite B (VHB) apresenta diversidade do seu genoma, o que o faz ser classificado em diferentes genótipos e subgenótipos (A-J). Tem sido demonstrado que os diversos genótipos estão relacionados com a história natural da infecção. A manutenção da replicação viral pode ser um dos fatores relacionado aos genótipos. Objetivos: Identificar o estado de replicação viral do VHB entre portadores dos subgenótipos A1 e D4. Materiais e métodos: Foram estudados portadores do VHB identificados em dois estudos que envolveram indivíduos provenientes do estado do Maranhão, nordeste do Brasil, que tinham determinação de genótipos e subgenótipos, sorologias para o HBeAg e anti-HBe e cargas virais determinadas. Sorologias foram realizadas por ELISA, VHB–DNA quantificado por PCR em tempo real e genotipagem realizada por sequenciamento. Resultados: Foram identificados 146 portadores. Dentre estes, 136 eram subgenótipo A1 ou D4. Sendo 85 - A1 (62,5%) e 51 - D4 (37,5%). Não houve diferença entre os grupos quando foi avaliado idade (42±12 vs 38±17 p=0,11) ou gênero (masculino 48,5% vs 51,5% p=0,18). Entre os portadores do subgenótipo D4 havia mais indivíduos com HBeAg positivo (23,5% vs 9,4%, p=0.02) e maior proporção de portadores de cargas virais acima de 20.000 UI/ml (43,1% vs 12,9% p<0,0001), mesmo quando avaliados apenas aqueles com HBeAg negativos (25,6% vs 6,5% p=0,007), quando comparados com os de subgenótipo A1. Conclusão: Portadores do VHB, subgenótipo D4, quando comparados com subgenótipo A1 apresentam soroconversão mais tardia do HBeAg e maiores níveis de VHB–DNA, sugerindo que esse subgenótipo possivelmente está relacionado com potencial para doença mais grave e maior facilidade de transmissão da infecção.

博士
國立臺灣大學
臨床醫學研究所
99
Background: Hepatitis B virus (HBV) is a global health hazard, which may cause acutehepatitis, fulminant hepatic failure, chronic hepatitis, liver cirrhosis, and even hepatocellular carcinoma. There are 350 million chronic HBV infected patients in the world, and annually 1 million patients died of complication associated with HBV. During the chronic course of HBV infection, HBeAg seroconversion generally indicates the decrease in viral replication and subsidence of disease activity. However, the role of host factors on the process of spontaneous HBeAg seroconversion is unclear. Thus, we aimed to elucidate the possible roles of hormone and cytokine on the complex immune process. Study Design and Methods: This is a long-term prospective cohort study. To confirm the impacts of hormone, we investigated the serum testosterone levels and HBV viral load at early (10years), middle (15 years), and late (20years) puberty. We also checked the SRD5A2 V89L polymorphism and the CAG repeat number of androgen receptor exon-1. About the roles of cytokines, we checked 11 single nucleotide polymorphism located at 5 Th1 and Th2 cytokine gene (IL-2, IL-4, IL-10, IL-12β, IFN-γ), and the serum cytokine levels and viral load at immune tolerance phase, inflammatory/clearance phase, and post HBeAg-seroconversion inactive phase. We further investigated the association between IL-10 and IL-12 in the liver with HBV infection and the relationship with IFN-γ and possible downstream signals. The impact of different host immune stress (IL-10 genotype) on the mutation pattern of HBV precore/core gene was also done. Results: Earlier onset of puberty and higher SRD5A2 enzyme activity were associated with more viral load decrement during the puberty period (10-20 years) and earlier spontaneous HBeAg seroconversion. IL-10 -1082 G/G genotype and IL-12β C/G genotype were associated with higher baseline IL-10 serum levels and HBcAg inducible IL-12 levels, and both predict earlier onset of spontaneous HBeAg seroconversion. Intrahepatic IL-10 and IL-12βmRNA levels were associated with IFN-γ expression, which associated with lower furin and higher PD-1/PD-L1 expression in subjects with chronic HBV infection at the inflammatory phase. G/G genotype of IL-10 -1082 also associated with higher C2189A mutation rate at the HBV precore/core gene, which is also associated with lower HBV viral load. Discussion: This study provided some new evidence of the impacts of hormone and cytokine on the natural course of chronic HBV infection. We also demonstrated that, different host immune stress may associate with different HBV mutation pattern and clinical outcomes.

碩士
國立臺南大學
資訊教育研究所
93
The genetic programming (GP) can evolve programs automatically by simulating the evolutionary mechanism on computers. The study is major to derive functions by using GP that has the ability to classify and predict patients’ HBeAg seroconversion. Four functions ''classifying whether HBeAg is seroconversion or not now'', ''predicting whether HBeAg will be seroconversed or not within the several months of future'', ''looking for the regulation of HBeAg before seroconversion'', and ''predicting whether HbeAg will seroconverse or not after the particular month'' . According to the results by analysing the real clinical data, the analysis approach proposed in the study can be applied to other similar researchs and prediction.

碩士
國立臺南大學
資訊教育研究所碩士班
94
The infection of Hepatitis B Virus (HBV) has always been one of the most significant studies of public health in Taiwan. Thus, this research has taken the clinical information of HBV patients provided by College of Medicine National Cheng Kung University as experimental specimen. Also, a slightly modified model of Artificial Neural Network, which regularly is applied to time series, has been chosen for predicting HBeAg seroconversion of HBV patients, mutation rate of HBV DNA sequence of the next month, and even for making it possible to predict for a longer period of time through referencing Artificial Neural Network based on the patients’ specimen of the past months. The predicted result indicates that the sensitivity, specificity and average prediction ability of HBeAg seroconversion are 74.44%, 82.81% and 81.73%. Besides, if mutation rate of HBV DNA sequence of the next month is taken as a predicted goal, the predicted result shows that the minimum Root Mean Squared Error is 0.00175 and the maximum is only 0.00277; while the minimum Mean Relative Error is 0.08449 and the maximum is 0.32982. Finally, if mutation rate of HBV DNA sequence of the sixth month is taken as a predicted goal, only one out of the four patients is at 0.00381 in terms of Root Mean Squared Error, which is slightly higher, and the patients are below 0.002. The minimum Mean Relative Error is 0.245442 and the maximum is 0.781983. The above result shows that the model of Artificial Neural Network based on the concept of time series has verified its positive effect on predicting HBeAg seroconversion of HBV patients and mutation rate of HBV DNA sequence.

碩士
國立臺灣大學
臨床醫學研究所
94
Background：Hepatitis B virus (HBV) infection is a major cause of acute and chronic liver disease worldwide, persistent hepatitis B virus infection is closely associated with the development of cirrhosis and hepatocellular carcinoma in Taiwan. Learning from nature history of hepatitis B infection, seroconvesion from HBeAg to anti-HBe usually indicates lower viral loads, resolved hepatitis activity and improved long-term outcome. Lamivudine is the first nucleoside analogue for the treatment of chronic hepatitis B, which has been shown to increase hepatitis B e antigen（HBeAg） seroconversion and reduce progression of hepatic fibrosis. Nevertheless, the relapse rate is high after cessation of lamivudine therapy unless HBeAg seroconversion occurs. Most of the published studies have shown that full HBeAg seroconversion response was durable in Western patients. However, it was not durable in Oriental countries, such as Korea and Taiwan. Hepatitis B e antigen (HBeAg) and an antibody（anti-HBe）are closely related to the level of hepatitis B virus replication and thus frequently used in assessing the activity of liver disease and monitoring the response to antiviral therapy.Therefore, it is important to identify factors associated with the development of HBeAg seroconversion in patients with HBeAg-positive chronic hepatitis B. The molecular basis of HBeAg is only partly clarified. From the viral replication’s point of view, when the precore region and core gene in HBV DNA are transcribed and translated, HBeAg is produced and secreted into the circulation. A point mutation from G to A at nucleotide (nt) 1896（A1896）converts codon 28 in the precore region from TGG for tryptophan to TAG for a stop codon and aborts the synthesis of HBeAg at the translation level. Likewise, a double mutation in the basal core promoter（BCP）changing nt 1762 and 1764 from A to T and G to A（T1762/A1764）,respectively, reduces the production of HBeAg by down-regulating the transcription of precore mRNAs. Convincing lines of evidence have indicated a close association of HBeAg seroconversion with the appearance of precore and BCP mutations as well as a decrease in the serum viral load. Another study revealed that precore 1896 wild vs. mutant strains ratio also played a role in the seroconversion of HBeAg and severity of disease activity. Liu et al reported that non-sustained HBeAg seroconversion might be due to the lack of sustained precore and BCP mutations after seroconversion. Lin et al reported that lamivudine therapy might result in the rapid selection of basal core promoter mutation of hepatitis B, but this mutation might revert to wild type gradually after cessation of therapy. The results of the present study have shown the genotype, age, and additional lamivudine therapy after HBeAg seroconversion are independent factors of sustained response to lamivudine therapy. However, the role of precore and BCP mutations in the development of sustained HBeAg seroconversion, either spontaneous or after lamivudine therapy remained unknown. Aim：Are the precore and/or BCP mutations of hepatitis B virus,either spontaneous or after lamivudine therapy associated with sustained HBeAg seroconversion？Hypothesis one is that the precore and/or BCP mutations of hepatitis B virus could determine the appearance of anti-HBe in the spontaneous HBeAg seroconversion. Hypothesis two is that the precore and/or BCP mutations of hepatitis B at the time of HBeAg loss or end of therapy in patient serum could determine the sustained e seroconversion after lamivudine treatment. Methods：We studied the factors in 25 patients with sustained HBeAg seroconversion as well as appearance of anti-HBe and 7 patients with sustained loss of HBeAg in the first part. We determined viral factors and status of precore and BCP mutations in the serum obtained 1 year before, 6 months before, 3 months before, at the time of , 6 months after and 1 year after HBeAg seroconversion or HBeAg loss. Secondly, both of host and viral factors as well as the drug factors were compared between 34 patients with sustained HBeAg seroconversion and 11 patients whose response was no sustained. All of patients with HBeAg positive and ALT level more than 5 times of normal upper limit without hepatitis C; hepatitis D and HIV were enrolled before therapy. All of them received a mean period 15 months（range, 6-35months）lamivudine therapy and had achieved complete responses（HBeAg seroconversion plus HBV DNA seroclearance by hybrid capture assay and normal alanine aminotransferase）and were followed-up for 6 months after end point of therapy. Stepwise logistic regression model was used to estimate the sustained response on the presence of the following variables: age; gender; genotype; pretherapy maximal ALT; the status of cirrhosis; time to HBeAg seroconversion; additional lamivudine treatment after HBeAg seroconversion; total duration of treatment; as well as HBV DNA level and status of precore mutation; basal core promoter mutation at the different time points which are of pretherapy, e antigen loss and end of therapy. The precore and basal core promoter regions were amplified and directly sequenced by polymerase chain reaction（PCR）-based assays. Besides, viral titer was checked by LightCycler real time PCR amplification machine. Results：We found that decline of serum viral load, frequently accompanied by hepatitis exacerbation, occurred since 1 year before HBeAg seroconversion. The proportions of precore and BCP mutations also increased gradually throughout the process of HBeAg seroconversion. The virologic features and proportions of precore and BCP mutations were similar between HBeAg seroconversion with anti-HBe group and HBeAg loss group. Before HBeAg seroconversion or loss, genotype B patients had higher serum viral loads（p=0.03~0.61）and lower proportions of BCP mutation（p=0.004~0.03）compared with genotype C patients. Secondly, no significant determinant was noted by step logistic regression analysis before lamivudine therapy between sustained and non-sustained HBeAg seroconversion groups. The mixed type and mutant type of precore region were replaced by wild type at the end of therapy and HBeAg seroconversion. The wild type（G1896）became dominant strain after lamivudine therapy, that was different from status of spontaneous HBeAg seroconversion. Conclusion: our data showed that to clarify the role of the sustained precore mutant strain in the sustained HBeAg seroconversion, it was possible to increase case number for improving the statistic power in the future. Besides, there is little PCR product amplified from the BCP region due to lower viral load after lamivudine therapy. We need a more sensitive method to detect the BCP mutation in the future.

The recombinant Hepatitis B surface antigen vaccine inadequately protects those living with HIV from Hepatitis B virus infection. This study utilized saved serum samples from a retrospective cohort of persons with HIV and documented vaccine-induced HBsAb seroconversion to determine factors associated with persistence of protective levels of HBsAb (≥10mIU/ml). HBsAb levels fell below 10mIU/ml in 27% of the cohort after a median follow-up of 43 months. HIV viral load suppression (<50copies/ml) at the time of vaccination was the major factor associated with persistence of protective levels of HBsAb (OR 3.83, p <0.01). Among individuals who lost protective levels of HBsAb, booster doses of vaccine re-instated the development of protective levels of HBsAb. Delaying or repeating HBV vaccination until after suppression of HIV viral load is achieved should be considered HBV antibody levels should be followed over time and boosters given with loss of protective levels of HBsAb.

Hepatitis B virus (HBV) has been causally linked to a variety of renal diseases, the most common being glomerular diseases and systemic autoimmune disease. Membranous nephropathy (MN) is the commonest HBV-associated glomerulonephritis (HBV-GN), followed by membranoproliferative glomerulonephritis (MPGN), mesangial proliferative glomerulonephritis, immunoglobulin (Ig)-A nephropathy, and focal segmental glomerulosclerosis (FSGS). Polyarteritis nodosa is a rare manifestation. The incidence of HBV-associated renal diseases seems to be decreasing with the introduction of vaccination programmes.HBV-MN is the most frequent cause of nephrotic syndrome in children in countries with high endemicity of HBV infection. The clinical course is usually benign in children with high rates of spontaneous remission rates and low risk of progression to renal failure. The prognosis is worse in adults. Of the systemic autoimmune disorders associated with HBV infection that involve the kidneys, the strongest link has been found with polyarteritis nodosa (PAN), a lesion that causes arteritis of medium-sized renal vessels. HBV-associated PAN (HBV-PAN) usually manifests in the first year after infection, and is clinically indistinguishable from classic PAN.Diagnosis of HBV-GN or -PAN is based on the clinical picture, histological findings, evidence of viral replication in serum and/or liver and detection of HBV antigens or DNA in the tissue. Besides deposition of immune complexes, other mechanisms such as virus-induced cytopathic damage have been proposed to explain the pathogenesis.HBV-GN and HBV-PAN appear to respond to antiviral treatment. Both show remission after HBeAg seroconversion. The available studies predominantly employed first-generation agents like interferon alpha and lamivudine, which showed suppression of viral replication and clinical remission of HBV-associated renal disease. Immunosuppressive therapy appears to be inevitable for the control of severe HBV-PAN and could be helpful in addition to antiviral treatment for cases of HBV-GN not responding clinically to antiviral treatment.

Infection may be a primary cause of renal disease (e.g. postinfectious glomerulonephritis) or affect the kidneys on a background of debilitating illnesses and previous medical interventions. Renal disease may arise as a consequence of immune responses to a pathogen, direct invasion by the microorganism, or the effects of infection on the systemic or local circulations. Glomerulonephritis—associated with chronic and acute bacterial infections. Shunt nephritis follows colonization of a ventriculoatrial shunt, most commonly with Staphylococcus epidermidis, leading to constitutional symptoms, an acute inflammatory response, and (most characteristically) a type 1 mesangiocapillary glomerulonephritis. Infective endocarditis and other deep-seated bacterial infections may produce a similar renal picture, but they can mimic vasculitic syndromes and outcome is dependent on the response of the infection to treatment. Interstitial nephritis—bacteria that can cause this include leptospira (Weil’s disease), Rickettsia rickettsii (Rocky Mountain spotted fever), legionella, and mycobacteria. Viral infections include hantaviruses (haemorrhagic fever with renal syndrome and nephropathia epidemica) and, almost exclusively following renal transplantation, cytomegalovirus and polyomavirus hominis type 1 (BK) virus. HIV-associated renal disorders—these include HIV nephropathy, which is a focal segmental glomerulosclerosis of ‘collapsing’ form, occurring almost exclusively in black patients. Other morphologies are more common in other races, but interstitial disease is also common as a manifestation of infection or of drug toxicity. Hepatitis B virus—chronic infection is strongly associated with membranous nephropathy; affected individuals are HBeAg and HBsAg positive, usually with coexistent hepatitis; seroconversion from HBeAg positive to HBeAb positive (naturally or induced by treatment) is associated with remission of the renal lesion. Hepatitis C virus—chronic infection is the commonest cause of mixed essential (type II) cryoglobulinaemia in most populations.