HBsAg Seroconversion Research Articles

Effect of tenofovir-based HIV pre-exposure prophylaxis against HBV infection in men who have sex with men.

Men who have sex with men (MSM) are vulnerable to contracting HBV as a sexually transmitted infection. We evaluated the incidence of HBV infection (HBI) and the prophylactic effect of tenofovir-based pre-exposure prophylaxis (PrEP) on HBI in an MSM cohort. MSM who were older than 16 years were enrolled from January 2018 and followed up until June 2021 and tested for HIV, bacterial sexually transmitted infections, and HBsAg/ HBsAb and HBcAb every 3 months based on inclusion criteria, including HBsAg, HBcAb, HBsAb, and HIV negativity at enrollment. HBI was defined as seroconversion of HBsAg or HBcAb status. The log-rank test was used to evaluate the prophylactic effect of PrEP against HBI. As a substudy, individuals excluded from the main study due to HBs Ab positivity were evaluated for HBI incidence. Among 1577 MSM, 786 participants (546 PrEP nonusers, 131 daily PrEP users, and 109 event-driven PrEP users) met the criteria and were included. The annual incidence of HBV among PrEP nonusers (3.8%, 21 infections, with 559.5 person-years) was significantly higher ( p = 0.018, log-rank test) than that among daily PrEP users [0.77%, 1 infection (admitted nonadherence), with 129.3 person-years] and event-driven PrEP users (no infection with 93.8 person-years). Although the incidence of HBI and HIV infection decreased with PrEP use, the incidence of other sexually transmitted infections was higher in both daily and event-driven PrEP users. The annual incidence of HBV among HBsAb-positive and HBcAb-negative PrEP nonusers was 1.8% (3 infections, with 167.5 person-years). Tenofovir-based PrEP prevented HBI among MSM in a real-world setting.

Serum IL-5 levels predict HBsAg seroclearance in patients treated with Nucleos(t)ide analogues combined with pegylated interferon.

Knowing about cytokine profile contributes to clarify the underling immune mechanism of HBsAg seroclearance rate increase. This study aims to investigate cytokine changes during nucleos(t)ide analogues (NAs) and peginterferon-α (Peg-IFNα) therapy and their impact on the HBsAg serologic response. A total of 78 HBV DNA-negative chronic Hepatitis B (CHB) patients were studied after a lead-in phase of NAs with complete serum cytokines. Serum cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-17 and TNF-α) were quantified by flow cytometry (FCM) every 24 weeks, before, during and at the end of NAs and Peg-IFNα treatment. Clinical and laboratory data were also taken at the same time. Analysis was performed between cured and uncured groups characterized by HBsAg seroclearance. PBMCs samples from five patients (two in cured group and three in uncured group) were analyzed by FCM. HBsAg seroclearance was achieved in 30 (38,5%) patients defined as the cured group. In comparison to uncured individuals, cured patients showed similar expressions of serum IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17 and TNF-α during the treatment of NAs and Peg-IFNα. Compared with the uncured groups, IL-5 was remarkably increased in cured patients. IL-5 at weeks 24 and 48 were associated with HBsAg seroconversion (p=0.033 and 0.027, respectively). PBMCs sample analysis confirmed the predicted value of IL-5 in response to NAs and Peg-IFNα treatment. IL-5 at weeks 24 and 48 might be used as a biomarker for HBsAg seroclearance in NAs-experienced CHB patients treated with NAs combined with Peg-IFNα. More importantly, exploiting the expression of this cytokine may help to develop a better understanding of the immune pathogenesis of chronic HBV infection.

Tenofovir Induced Hepatitis B Surface Antigen Loss and Seroconversion in Two Patients with E-Antigen Negative Chronic Hepatitis B Infection: Case Series

Two cases of HBsAg seroconversion, following treatment with Tenofovir disoproxil fumarate, a nucleotide reverse transcriptase inhibitor, were reported amongst the patients with chronic hepatitis B infection attending gastrointestinal clinic in a tertiary hospital. The patients had liver biopsy done during their evaluation, following which they were commenced on the medication. Tenofovir was taken for four years and two years respectively before they lost the hepatitis B surface antigen and developed quantifiable antibodies to the surface antigen (Anti-HBs). Loss of HBsAg is a rare event, and seroconversion in patients with CHB is even less common. Studies have shown that HBsAg loss and seroconversion is less likely with patients on the oral antiviral agents compared with pegylated interferon. Although, both patients had very low pretreatment hepatitis B viral load which might indicate strong immune response to the virus, a factor that could have been partly responsible for the seroconversion. They however, had significant liver fibrosis on histology prior to their seroconversion and will require hepatocellular cancer surveillance until normalization of the liver histology can be ascertained

The effectiveness of combination therapy with interferon and nucleoside analogs in pediatric patients with chronic hepatitis B: a systematic review and meta-analysis.

It is a challenging issue regarding the optimal antiviral treatment of children with chronic hepatitis B (CHB). The efficacy comparison of interferon (IFN) or nucleos(t)ide analogs (NAs) monotherapy with their combination could better understand this issue. PubMed, EMBASE, Cochrane Library, Wanfang, CNKI, and abstracts of major international hepatology meetings were searched from inception to Feb 8, 2022. Randomized control trials and observational studies reporting the efficacy of combination therapy with IFN and NAs in children with CHB were eligible. A total of 17 studies were included. Compared with IFN monotherapy, combination therapy with IFN and NAs was significantly associated with increased rates of HBV DNA undetectable, HBeAg clearance, HBeAg seroconversion, alanine transaminase (ALT) normalization as well as the composite treatment response both at the end of treatment and during the follow-up period (RRs ranged from 1.23 to 1.75). A favorable trend for HBsAg seroconversion was found in IFN plus NAs-treated children, but not for the HBsAg clearance at the end of treatment. Although a similar trend towards the superiority of the combination therapy versus NAs monotherapy was observed (RRs ranged from 1.24 to 2.33) except for the HBV DNA undetectable rate at the end of treatment, the number of reported studies was limited. Combination therapy with IFN and NAs is more effective than IFN monotherapy in viral suppression and serological response for children with CHB. More studies were still needed to reveal the efficacy of this combination therapy compared with NAs monotherapy.

Comparison of the side effects of antivirals in chronic hepatitis B patients: a single-center experience.

Entecavir (ETV), Tenofovir Disoproxil Fumarate (TDF), and Tenofovir Alafenamide (TAF) have been approved for treating Chronic Hepatitis B (CHB) and recommended due to their high safety profile and high resistance barriers. This study aimed to evaluate the kidney functions, bone, and metabolic parameters in CHB patients receiving ETV, TDF, and TAF treatment. In this retrospective cohort study, a total of 469 CHB patients who were treated with TDF (n = 256), ETV (n = 184), or TAF (n = 129) for at least six months between March 2012 and March 2022, were enrolled. No significant difference was observed between three groups regarding ALT normalization, HBV DNA suppression, and HBs Ag seroconversion (p = 0.15, p = 0.26, p = 0.72). After the treatment, there was a significant decrease in GFR values in the TDF, ETV, and TAF groups (p<0.01, p = 0.01, p = 0.01, respectively). No significant improvement was observed in the GFR values after TAF treatment in 77 patients who had switched from TDF to TAF (p = 0.51). Moreover, no significant decrease in bone mineral densities was observed in the TDF, ETV, and TAF groups (p = 0.24, p = 0.41, p = 0.95, respectively). There was no significant difference between the three groups in metabolic parameters (serum glucose, lipid profile, calcium and phosphorus levels, etc.) when the data were adjusted for underlying comorbidities. ETV, TDF, and TAF are comparably safe and effective antiviral agents against CHB.

Longitudinal monitoring of post-vaccination immunity against hepatitis B in children after standard immunization in the first year of life and optimization of vaccination strategy

A clinical and laboratory examination of 62 children aged 10—17 years vaccinated against hepatitis B according to the standard scheme (0—1—6 months) in the first year of life strictly according to the National Calendar of preventive vaccinations in a standard dose (10 micrograms of recombinant HBsAg) with a monocomponent vaccine was carried out.The majority of children (58%) had indicators of seroconversion of HBsAg — anti-HBs-antibodies. This indicates the fact of long-lasting Grund immunity — 10—17 years after timely 3-fold immunization against hepatitis B according to the standard scheme at a standard dose (10 mcg of recombinant HBsAg in the first year of life in the absence of Wooster immunization (revaccination) in subsequent age periods, including children with a burdened premorbid background (87.1% among those observed). Since among those observed were children with invasive medical interventions (50%), the established fact reflects the protective effect of standard Grund immunization even in children at risk — with a positive parenteral history. At the same time, the total assessment of serological and molecular biological results found that after triple immunization against hepatitis B according to the standard scheme in the first year of life, out of 62 children aged 10—17 years, the proportion of seronegative was 42%. Low levels of antibodies (10—100 IU/l) were detected in 43% of cases, high (100—1000 IU/l) — in 15% of cases. No child had an antibody level exceeding &gt;1000 IU/l. These results require the development of new approaches to immunization of children against hepatitis B with mandatory revaccination at an older age.

Interferon add-on therapy increased clinical cure significantly for interferon-experienced chronic hepatitis B patients with low HBsAg.

Currently, interferon add-on therapy brings hope for clinical cure of chronic hepatitis B patients with low HBsAg. However, in clinical practice patients with poor responses to their first interferon therapy were often switched to nucleos(t)ide analog therapy and then labeled as unsuitable patients for interferon therapy. Even if their HBsAg levels dropped to a low level, they were reluctant or not recommended to take interferon again, which caused them to miss out on interferon add-on therapy and clinical cure. Therefore, it is urgent to elucidate the effectiveness of interferon add-on therapy to get clinical cure for these interferon-experienced patients with low HBsAg. The purpose of this study was to investigate whether interferon-experienced patients could achieve the same HBsAg clearance and HBsAg seroconversion rates as interferon-naive patients. Also, the associated factor of HBsAg clearance and seroconversion were aimed to be clarified. 292 patients, including 85 interferon-experienced patients, were enrolled with HBsAg< 1500 IU/ml, HBeAg negative and HBV-DNA negative. And then, peg-interferon α-2b add-on therapy was performed. The results showed that the week 48 HBsAg clearance and seroconversion rates of all patients were 29.8% and 22.0%. There was no statistically significant difference between interferon-experienced and interferon-naive patients in week 48 HBsAg clearance and seroconversion rates, suggesting satisfactory clinical cure of the interferon add-on therapy for interferon-experienced patients. The age, baseline HBsAg, and week 12 HBsAg were negative correlated factors for week 48 HBsAg clearance and seroconversion. Furthermore, the age, baseline HBsAg and week 12 HBsAg for predicting the week 48 HBsAg clearance were cut off at 40.5 years, at 152.0 IU/ml and at 34.99 IU/ml, and for predicting seroconversion were cut off at 40.5 years, at 181.9 IU/ml and at 34.99 IU/ml, correspondingly. Significantly, interferon-experienced patients with low HBsAg were suggested with interferon add-on therapy to achieve clinical cure as soon as possible. This research provided evidences and cut-offs for the interferon add-on therapy against chronic hepatitis B.

335.2: Long-term Outcomes of Liver Transplantation Using Grafts From Donors With Active Hepatitis B virus Replication: A Multicenter Cohort Study

Background: Liver grafts from donors with hepatitis B infection contributed to expanding the donor pool under the Hepatitis B immunoglobulin (HBIG) and antiviral agents (NA: Nucleos(t)ide analogs) in the hepatitis B virus (HBV) endemic area. The purpose of this study is to describe the long-term outcome of liver transplantation (LT) using grafts from donors with active and chronic hepatitis B virus infection. Methods: Between January 2000 and April 2019, 2260 liver transplants (LTs) were performed at Seoul National University (SNU) Hospital, SNU Bundang Hospital (SNUBH), and Seoul Metropolitan Government-SNU Boramae Hospital. Twenty-six (1.2%) grafts from donors with HBsAg (+), HBeAb (+), or HBV DNA (+) were classified as active and chronic HBV hepatitis grafts and retrospectively reviewed. The demographics of donors and recipients, as well as the outcomes of transplantation, were analyzed. HBV reactivation has been defined as an increase in viral DNA in HBsAg (+) grafts and seroconversion to HBsAg positive grafts in chronic hepatitis grafts. Additionally, we used the chronic HBV infection stage to evaluate and manage recipients who received HBV-infected grafts. Results: Sixteen LT were performed on deceased donors using active HBsAg (+) grafts. Ten living donor LT were performed using inactive HBV grafts; eight patients with inactive hepatitis; HBsAg (-), HBcAb (+), and HBV DNA (+), and two patients with chronic HBV hepatitis with seroconversion; HBsAg (-), HBsAb (+), and HBeAg (+) (Figure 1). The recipients were aged 59.0 ± 10.3 years and had a MELD score of 19.9 ± 8.4. The mean duration of follow-up was 82.6 ± 60.1 months. Depending on the donor and recipient’s serology, NA and HBIG were administered during the perioperative period. Deaths (n=8) occurred between 2.0 and 47.3 months following LT. All deaths were reported in DDLT. When compared with LT using grafts without HBV, LT using HBV infected grafts did not show any significant difference in patient survival (30.8% vs. 18.6%, p=0.247) (Figure 2). The most common causes of death were infection (n=4) and HCC recurrence (n=3). All recurred HCC patients died of cancer. HBV reactivation was identified in 1 patient but resolved spontaneously without additional management. All 10 LDLT recipients survived and were in good condition during follow-up. Survivors were in inactive or resolved status for HBV infection under the HBIG and NA. No graft failure was observed. Fourteen patients followed-up more than 5 years were stable and no increase in HCC recurrence rate was observed 5 years after transplantation. Conclusion: Considering their long-term outcomes, liver grafts with active and chronic HBV infection can be safely used for LT in HBV endemic area.

Hepatitis B–Related Hepatic Flare During Immune Reconstitution Syndrome After Antiretroviral Treatment Initiation in an HBV Surface Antigen–Positive Patient With HIV: Viroimmunological and Histological Characterization

HIV and hepatitis B virus (HBV) coinfection is relatively common. Initiation of antiretroviral therapy (ART) in people with HIV (PWH) causes a progressive restoration of cell-mediated immune functions. In the presence of overt or occult coinfections, immune restoration might lead to immune reconstitution inflammatory syndrome (IRIS). Here, we describe the clinical, immunological, virological, and histological characterization of a case of HBV-related IRIS hepatitis in a PWH after ART initiation. A liver biopsy was performed during HBV-related IRIS hepatic flare, and liver samples were analyzed through immunohistochemistry and molecular techniques, with the assessment of intrahepatic HBV-DNA, covalently closed circular DNA, and HBV pregenomic RNA through a droplet digital polymerase chain reaction system. Immune activation and senescence were also longitudinally assessed. In this clinical case, the hepatic flare occurred 6 weeks after ART initiation with a therapeutic regimen including tenofovir alafenamide (TAF) and emtricitabine (FTC). The episode was self-limiting, characterized by hyperactivation of peripheral blood CD4+ and CD8+ T-lymphocytes, and resolved without ART discontinuation, leading to the achievement of HBsAg seroconversion (HBsAg-/HBsAb+) and HBV-DNA plasma undetectability. Notably, hyperactivation of the immune system plays a pivotal role in promoting the control of HBV replication, thus triggering the achievement of HBsAg seroconversion during treatment with TAF/FTC.

Intrahepatic transcriptomics reveals gene signatures in chronic hepatitis B patients responded to interferon therapy

ABSTRACT Chronic hepatitis B virus (HBV) infection remains a substantial public health burden worldwide. Alpha-interferon (IFNα) is one of the two currently approved therapies for chronic hepatitis B (CHB), to explore the mechanisms underlying IFNα treatment response, we investigated baseline and 24-week on-treatment intrahepatic gene expression profiles in 21 CHB patients by mRNA-seq. The data analyses demonstrated that PegIFNα treatment significantly induced antiviral responses. Responders who achieved HBV DNA loss and HBeAg or HBsAg seroconversion displayed higher fold change and larger number of up-regulated interferon-stimulated genes (ISGs). Interestingly, lower expression levels of certain ISGs were observed in responders in their baseline biopsy samples. In HBeAg+ patients, non-responders had relative higher baseline HBeAg levels than responders. More importantly, HBeAg− patients showed higher HBsAg loss rate than HBeAg+ patients. Although a greater fold change of ISGs was observed in HBeAg− patients than HBeAg+ patients, upregulation of ISGs in HBeAg+ responders exceeded HBeAg− responders. Notably, PegIFNα treatment increased monocyte and mast cell infiltration, but decreased CD8 T cell and M1 macrophage infiltration in both responders and non-responders, while B cell infiltration was increased only in responders. Moreover, co-expression analysis identified ribosomal proteins as critical players in antiviral response. The data also indicate that IFNα may influence the production of viral antigens associated with endoplasmic reticulum. Collectively, the intrahepatic transcriptome analyses in this study enriched our understanding of IFN-mediated antiviral effects in CHB patients and provided novel insights into the development of potential strategies to improve IFNα therapy.

OS091 - ALT flares were linked to HBsAg reduction, seroclearance and seroconversion: interim results from a phase IIb study in chronic hepatitis B patients with 24-week treatment of subcutaneous PD-L1 Ab ASC22 (Envafolimab) plus nucleos (t)ide analogs

OS091 - ALT flares were linked to HBsAg reduction, seroclearance and seroconversion: interim results from a phase IIb study in chronic hepatitis B patients with 24-week treatment of subcutaneous PD-L1 Ab ASC22 (Envafolimab) plus nucleos (t)ide analogs

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

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

Prediction for HBsAg seroconversion in children with chronic hepatitis B

BackgroundTo establish a prediction of HBsAg seroconversion in children with chronic hepatitis B (CHB), so as to help clinicians to choose therapeutic strategy.MethodsA total of 63 children with HBeAg-positive CHB aged 1 to 17 years, who admitted to the fifth medical center of Chinese PLA general hospital and treated with interferon α (IFNα) 48 weeks were enrolled, the clinical data were measured. Based on the results of HBsAg seroconversion (HBsAg < 0.05 IU/mL and anti-HBsAg > 10 IU/L) at week 48, the patients were divided into HBsAg seroconversion (S) group and non-HBsAg seroconversion (NS) group. Multivariate COX regression was used to identify the impact factors associated with HBsAg seroconversion. A novel prediction index was established and the area under the receiver operating characteristic curve (AUROC) was used to assess the prediction for HBsAg seroconversion.ResultsThe 63 patients were divided into S group (20.6%, 13/63) and NS group (79.4%, 50/63). Univariate and multivariate analysis identified age, baseline intrahepatic cccDNA and serum HBsAg levels were independent impact factors for HBsAg seroconversion. Intrahepatic cccDNA was positively correlated with serum HBsAg (r = 0.464, p = 0.000). AUROC of HBV cccDNA was 0.83 (95% CI 0.71 to 0.95) and AUROC of baseline HBsAg was 0.77 (95% CI 0.61 to 0.92). Intrahepatic cccDNA ≤ 0.08 log10 copies/106 cell is regarded as cutoff value, the positive predictive value(PPV) and negative predictive value(NPV) for HBsAg seroconversion were 86.8% and 60.0%, respectively, with a sensitivity of 92.0% and specificity of 56.2%. HBsAg ≤ 3.68 log10 IU/mL is used as cut off value, the PPV and NPV for HBsAg seroconversion were 91.2% and 56.3%, respectively; the sensitivity and specificity was 86.0% of 69.2%, respectively. There was no statistical difference between them for predicting HBsAg seroconversion (p = 0.146).ConclusionsHBsAg seroconversion can be predicted by the baseline serum HBsAg or intrahepatic cccDNA in children with CHB. Using the index, clinicians can choose more reasonable therapeutic strategy and reduce the waste of medical resources.

Role of hepatosteatosis in HBsAg seroconversion in HBeAg-negative chronic hepatitis B patients.

In chronic Hepatitis B virus (HBV) infection, certain individual and viral characteristics such as advanced age, presence of hepatic steatosis (HS), normal ALT levels, initially negative HBeAg and HBV DNA, and genotype of the virus are associated with HBsAg seroclearance and seroconversion. Herein, we report the results of our study evaluating the association between hepatosteatosis and HbsAg seroconversion. The clinical and biochemical data of patients with CHB and hepatosteatosis (HS) (HBsAg seroconversion, n:52, and non-HbsAg seroconversion, n:352), and the rate of development of HBsAg seroconversion were evaluated. We collected data from 404 patients with HBeAg negative CBH (mean age ± SD: 36.2±11years; 223 [55.2%] men, 181 [44.8%] women). The mean age at diagnosis of disease was 36.2±11years. The mean duration of the disease was 10.6±7years. Seroconversion developed in 52 patients (12.8%) with serum HBsAg positive (mean ± SD: 12.7±5.8). Elderly age and the duration of disease time were significantly associated with seroconversion (P<.001). The presence of serum HBsAg seroconversion was significantly associated with hepatosteatosis (OR: 3.06, 95% CI 1.64-5.71, P<.01). Serum HBsAg seroconversion was more frequent in patients with mild HS than patients with moderate-severe HS (P=.04). In multivariate regression analysis, the presence of HS was found to be an independent factor predicting the development of HBsAg seroconversion (OR: 2.07 95% GA:1.07-4.0 P=.03). The presence of mild HS in HBeAg negative chronic hepatitis B patients contributes to HBsAg seroconversion. Further studies are required to better understand the relationship between steatosis and HBsAg seroconversion.

Clinical follow-up of children with immune-tolerant chronic hepatitis B receiving antiviral therapy

Objective To investigate the long-term clinical benefits of antiviral therapy in children with immune-tolerant chronic hepatitis B. Methods Long-term follow-up was performed for 46 children with immune-tolerant chronic hepatitis B who were enrolled in the treatment group of the previous randomized controlled trial, and clinical evaluation was performed at weeks 108, 120, 132, 144, 168, and 192 after the trial started. Results All 46 patients completed the follow-up. From week 96 (after the clinical trial started) to week 192 (when the follow-up ended), another 3 patients achieved serum HBV DNA clearance, another 7 patients achieved serum HBeAg clearance, another 6 patients achieved HBeAg seroconversion, and another 3 patients achieved HBsAg seroconversion, while there was no change in the number of patients who achieved serum HBsAg clearance, with a total number of 37 (80.4%), 22 (47.8%), 21 (45.7%), 10(21.7%), and 10(21.7%), respectively. Among these patients, 9(19.6%) did not achieve HBV DNA clearance and they all had virologic breakthrough after drug withdrawal. Conclusion Further large-sample clinical trials are needed to investigate antiviral therapy for children with immune-tolerant chronic hepatitis B.

Changes in the Hepatitis B Surface Antigen Level According to the HBeAg Status and Drug Used in Long-term Nucleos(t)ide Analog-treated Chronic Hepatitis B Patients.

The HBsAg levels have been used to monitor the chronic hepatitis B (CHB) treatment response to antiviral therapy. On the other hand, it is unclear if the HBsAg quantification levels at each treatment point differ according to the HBeAg status and drug in CHB patients. This study compared the changes in HBsAg in CHB patients according to the HBeAg status and treatment drugs. CHB patients with at least 1 year of follow-up treatment with one drug, either entecavir (ETV) or tenofovir (TDF), were enrolled in this study. The mean HBsAg levels were measured annually for up to 6 years. A linear mixed model was used to compare the HBsAg quantification levels during the follow-up period. An independent samples t-test was used to analyze the differences in the HBsAg quantification levels at each treatment time point. Ninety-seven patients were enrolled in this study; 59 among them were HBeAg-positive. Two patients in the TDF group achieved HBsAg seroconversion. The HBsAg level decreased during the follow-up in the ETV and TDF groups. The HBsAg level was lower in the TDF group than the ETV group during the follow-up. On the other hand, subgroup analysis showed that this trend was the same only in the HBeAg-negative patients, not in the HBeAg-positive patients. In the HBeAg-negative patients, HBsAg level in the TDF group was significantly lower than that in the ETV group at 36, 48, and 72 months. The change in HBsAg level from the baseline increased at a decreasing rate during the follow-up in both groups. Furthermore, the change in the HBsAg level in the TDF group was significantly larger than that of the ETV group at 36 months in the HBeAg-negative patients. Although TDF might be more efficient than ETV in reducing the HBsAg level in HBeAg-negative patients in a few years, HBsAg seroconversion occurred very rarely. A further large-scale, long-term study will be needed to confirm the antiviral effects on the HBsAg level.

ВОЗМОЖНОСТИ ЭТИОТРОПНОЙ ТЕРАПИИ ПРИ ОСТРОЙ И ХРОНИЧЕСКОЙ ФОРМАХ ГЕПАТИТА В

Background. Currently, etiotropic therapy of hepatitis B in most cases is carried out using nucleot(s)ide analogues. The ultimate goal of the therapy depends on the period of its administration – in acute or chronic hepatitis. The influence of the molecular genetic profile of the hepatitis B virus on the effectiveness of therapy in both acute and chronic forms of the disease has not yet been established, which requires further research. Objective. To assess the possibilities of modern etiotropic therapy in acute and chronic forms of hepatitis B. Material and methods. The article analyzes the indicators of clinical, laboratory and instrumental data of patients who received etiotropic therapy with nucleot(s)ide analogues. Results. Etiotropic therapy resulted in a viral load decrease to an undetectable level in all patients regardless of the course of hepatitis B and infection with either a "mutant" or "wild" virus strain. In acute hepatitis B, HBV DNA was not detected in 100% of cases after 24 weeks of therapy, in HBsAg seroconversion - after 36 weeks; in chronic hepatitis B - after 36 weeks without HBsAg seroconversion. Six months after the completion of the treatment, the patients with chronic hepatitis B developed relapse in 89.7% of cases, but the viral load was less than 2000 IU / ml, and the severity of liver fibrosis was insignificant. In the rest of the cases, resumption of therapy was required. Conclusions. It was found that mutations of the hepatitis B virus do not affect the effectiveness of etiotropic therapy. The rate of viral load decrease correlates with the form of hepatitis B and is significantly higher in acute disease.

STUDY OF PREVALENCE OF HEPATITIS B SURFACE ANTIGEN (HBSAG) IN BLOOD DONOR POPULATION BORN PRIOR TO AND AFTER IMPLEMENTATION OF HBV VACCINATION IN KERALA, SOUTH INDIA

BACKGROUND: Since 1995 Hepatitis B vaccination became a part of Extended immunization Program (EIP) in India, neonates started getting immunoprophylaxis against Hepatitis B virus. Since vaccination started recently, exact prevalence of immunized persons were not available, but anyway vaccinated blood donors over 18 years old are progressively increasing MATERIALS AND METHODS: In this study 2400 blood donors were screened for HBsAg by enzyme linked immunosorbent assays, among the donor blood samples which are positive for HBsAg were noted. Various demographic patterns of blood donor were analyzed. To know about impact of vaccination on prevalence HBV infection among donors who born after the implementation of mandatory HBV vaccination schedule was compared with blood donors those who are born before HBV vaccination schedule RESULTS: Among the blood donors overall prevalence of HBV infection was 0.75% HBsAg. HBV vaccinated blood donor were protected from getting disease ,showing P value of 18 years (0.07), 19 years(0.01), 20 years(0.02) CONCLUSION: Young blood donors born after implementation of universal HBV vaccination in lndia presented higher prevalence of HBsAg but lower incidence of HBsAg seroconversion than older. HBV vaccine boosting for adolescents at 15–17 years old prior to reaching blood donor age may improve blood safety.

Changes of cytokine levels and T cell surface molecules in patients with chronic hepatitis B and the association with functional cure.

This study aimed to examine changes in levels of cytokine and T cell surface molecules in chronic hepatitis B (CHB) patients receiving sequential interferon therapy following 1-year nucleos(t)ide analogs (NAs) treatment. Cytokine levels were measured in 30 patients, and T cell surface molecule expression was measured in 48 patients receiving sequential interferon therapy and 24 patients only receiving NA mono-therapy. An HBsAg titer of <0.05 IU/ml was defined as a "functional cure." In the cured group (HBsAg < 0.05 IU/ml), a decreasing probability was observed in IFN-γ (after Week 0), and IL-22 and IP-10 (after Week 12). In the non-cured group (HBsAg ≥ 0.05 IU/ml), a probability of slightly decreasing was observed for IFN-γ (after Week 12), and a probability of increasing IP-10 concentration (after Week 0) was observed. Generalized estimating equation (GEE) analyses showed significant differences in the levels of IL-10, IL-23, CCL-3, IL-1β, IL-2, and IL-12P70 between the two groups. In GEE analysis, there were significant differences in expressions of CD45RO+ between the cured group and the non-cured group. The frequencies of T cells expressing Tim-3, CD62L, and CD152 were significantly lower in the sequential interferon therapy group than in the NA mono-therapy group. Changes in cytokine levels (IFN-γ, IP-10, IL-10, IL-23, CCL-3, IL-1β, IL-2, and IL-12P70) and T cell surface molecules (CD45RO+ ) may predict HBsAg seroconversion in CHB patients receiving sequential interferon therapy. The period from Weeks 12 to 24 during sequential interferon therapy may be a critical time of immune status change.

Switching to or Add-on Peginterferon in Patients on Nucleos(t)ide Analogues for Chronic Hepatitis B: The SWAP RCT

The optimal therapeutic strategy in nucleoside analogue (NA) experienced chronic hepatitis B (CHB) using peginterferon is still unclear; hence we explored a switch to or add-on peginterferon strategy versus continued NA. We conducted a randomized controlled trial of CHB patients on NA >12 months with HBV DNA(-) randomized to switch or add-on peginterferon-alpha2b (1.5 μg/kg/weekly) for 48 weeks versus continuing NA (controls) (allocation 2:2:1; Clinicaltrial.gov: NCT01928511) in tertiary Singapore hospitals. The primary composite endpoint at week 72 was hepatitis B e antigen (HBeAg) loss or quantitative HBsAg (qHBsAg) >1 log IU/mL reduction, and secondary endpoints were HBsAg loss, HBsAg seroconversion, qHBsAg <200 IU/mL, qHBsAg <100 IU/mL, HBV DNA(-), viral relapse, and safety. Analysis was by intention-to-treat (ITT). A total of 253 patients (controls 51, switch 103, add-on 99) were randomized. The primary ITT endpoint was achieved in 3.9% of controls, 33.3% of switch, and 26.7% of add-on (P < .0001, switch/add-on versus controls). HBsAg loss occurred in 0% of controls, 7.8% of switch, and 10.1% of add-on (ITT, P < .001, switch/add-on versus controls). HBeAg(+) patients on peginterferon had higher HBeAg loss than controls but poor HBsAg responses, whereas HBeAg(-) patients on peginterferon achieved better HBsAg responses than controls. Reduction in qHBsAg in HBeAg(+) was 0.14 log IU/mL versus 0.51 log IU/mL in HBeAg(-) (P < .0001) in peginterferon-treated patients. Clinical relapse was higher in switch (13.6% overall, 27% in HBeAg(+)) versus 1% add-on and 0% controls. Adverse events were typically interferon-related symptoms, with one death (myocardial infarction unrelated to therapy). ITT analysis showed that either peginterferon strategies were superior to NA for the primary endpoint and HBsAg loss, but add-on peginterferon is preferred to switch due to improved safety and similar efficacy. ClincialTrials.gov number: NCT01928511.