HBeAg-negative Chronic HBV Infection Research Articles

Histological Findings in Antigen E Positive and Negative in Chronic Hepatitis B.

To determine the histopathological findings in patients with HBeAg-positive chronic HBV infection (immunotolerant phase in old terminology) and HBeAg-negative chronic HBV infection (inactive carrier phase in old terminology). Observational study. Place and Duration of the Study: Department of Gastroenterology, University of Health Sciences, Diyarbakir Gazi Yasargil Education and Research Hospital, Diyarbakir, Turkiye and Diyarbakir and Mersin University School of Medicine, Diyarbakir, Turkiye, from May 2014 to August 2022. The difference between fibrosis and histological activity indices of 289 patients in the immunotolerant and inactive carrier phase who had liver biopsy was examined statistically. Additionally, the relationship of these data with age and gender was investigated. While 236 (81.7%) of the patients were in the inactive carrier phase, 53 (18.3%) patients were in the immunotolerant phase. The mean fibrosis score of patients in the immunotolerant stage was 2.0 ± 1.2, while it was 2.0 ± 1.0 in inactive carriers (p = 0.753). The number of patients with a fibrosis score of two and above was 21 (39.6%) in immunotolerant patients and 52 (22.0%) in inactive carrier patients (p = 0.004). In patients under 30 years of age, the mean fibrosis score was 1.7 ± 1.0. It was 2.0 ± 1.1 in those over 30 years of age (p = 0.016). Biochemical parameters or viral load cannot clearly reflect cellular damage in the liver. In the future, HBV DNA positivity alone may be the only criterion for the treatment. Chronic viral hepatitis B, Fibrosis, Immune tolerance phase, Inactive carrier phase.

Can quantitative surface antigen levels and systemic immune-inflammation index be predictive as a new indicator for the initiation of treatment in chronic hepatitis b?

The natural history of chronic HBV infection (CHB) is generally divided into four phases: HBeAg-positive chronic HBV infection (EPCI) and -hepatitis (EPCH), HBeAg-negative chronic HBV infection (ENCI) and -hepatitis (ENCH). This study aimed to investigate changes in serum quantitative surface antigen (qHBsAg), systemic immune-inflammation index (SII) and systemic inflammatory response index (SIRI) in a large number of CHB patients. Three hundred seventy-two CHB patients who underwent liver biopsy between January 2015 and February 2020 were evaluated. The SII-values were strongly significant between EPCI-EPCH ( P = 0.002), however, there was significant difference between ENCI-ENCH ( P = 0.025). Considering the SIRI results, there was a significant difference between both EPCI-EPCH ( P = 0.009) and ENCI-ENCH ( P = 0.118). In HBeAg-positive patients HBV-DNA, qHBsAg, and SII were found to be predictive ( P = 0.029, P = 0.039, P = 0.027, respectively) while in HBeAg-negative patients, age, AST, HBV-DNA, qHBsAg, SII, and SIRI were found to be predictive ( P = 0.047, P = 0.084, P = <0.001, P = 0.001, P = 0.012, P = 0.002, respectively). In EPCH phase, whereby accuracy rate results of HBV-DNA, qHBsAg, and SII were 75.3%, 73.4%, and 60.4%, respectively, while in the ENCH phase the accuracy rates of age, AST, HBV-DNA, qHBsAg, SII, and SIRI values were 57.8%, 65.6%, 68.3%, 63.8%, 57.3% and 53.2%, respectively. HBV-DNA, qHBsAg, and SII are predictive in EPCH patients. Age, AST, HBV-DNA, qHBsAg, SII and SIRI are all predictive in ENCH patients. In patients with CHB, we recommend using SII to distinguish between EPCI-EPCH and ENCI-ENCH. Based on its sensitivity and features, we believe that qHBsAg and SII are suitable measuring instruments in discrimination both of EPCI-EPCH and ENCI-ENCH.

Rapid monophasic HBsAg decline during nucleic-acid polymer-based therapy predicts functional cure.

Analyzing the interplay among serum HBV DNA, HBsAg, anti-HBs, and alanine aminotransferase (ALT) during nucleic-acid polymer (NAP)-based therapy for chronic hepatitis B provides a unique opportunity to identify kinetic patterns associated with functional cure. All participants with HBeAg-negative chronic HBV infection in the REP 401 study (NCT02565719) first received 24 weeks of tenofovir-disoproxil-fumarate (TDF) monotherapy. The early triple therapy group (n = 20) next received 48 weeks of TDF+pegylated interferon-α2a (pegIFN)+NAPs. In contrast, the delayed triple therapy group (n = 20) next received 24 weeks of TDF+pegIFN before 48 weeks of triple therapy. Three participants discontinued treatment and were excluded. Functional cure (HBsAg and HBV DNA not detectable with normal ALT) was assessed at 48 weeks post-treatment. Different kinetic phases were defined by at least a 2-fold change in slope. A single-phase decline was categorized as monophasic, and 2-phase declines were categorized as biphasic. Fourteen (35%) participants achieved a functional cure. HBV DNA remained below or near undetectable for all participants by the end of TDF monotherapy and during subsequent combination therapies. Three HBsAg kinetic patterns were found in both the early and delayed groups, nonresponders (n = 4 and n = 4), monophasic (n = 11 and n = 11), and biphasic (n = 4 and n = 3), respectively. All participants who achieved a functional cure had a monophasic HBsAg kinetic pattern during triple therapy. Among participants with a monophasic HBsAg decline, those who had a functional cure had a shorter median time to HBsAg loss of 21 (interquartile range=11) weeks compared with those who did not achieve functional cure [median: 27 (7) weeks] (p = 0.012). Functional cure was associated with a rapid monophasic HBsAg decline during NAP-based therapy. A nonmonophasic HBsAg kinetic pattern had a 100% negative predictive value (NPV) for a functional cure.

Can Hepatitis B Virus (HBV) Reactivation Result from a Mild COVID-19 Infection?

Hepatitis B virus reactivation (HBVr) is a well-described result of immunosuppressive therapy initiation in various diseases, with the dose and duration of treatment being the main factors determining the probability for reactivation. Such cases have also been described in COVID-19 patients treated with immunosuppressive therapies. Nevertheless, cases of COVID-19 infection that led to HBVr with no concurrent immunosuppressive treatment or any other related cause have also been reported. By that observation, we present a patient followed for a period spanning 20 years with HBeAg negative chronic HBV infection and non-detectable HBV DNA who, after a mild COVID-19 infection treated only with low-dose and short-duration-inhaled corticosteroids (ICS), developed elevated AST and ALT as well as elevated HBV DNA levels. Other etiologies of abnormal liver biochemistries during the diagnostic workout were excluded; thus, the diagnosis of HBV reactivation was established. Treatment with entecavir was initiated, leading to the normalization of AST and ALT levels and a decreasing trend of HBV DNA levels. Since other causes of reactivation were excluded, and the ICS dose and duration were found baring only a very low risk (&lt;1%) for HBVr, COVID-19 infection could be considered the most probable cause of reactivation, hence underlining the need for the close monitoring of those patients.

Assessment of Viral and Clinical Characteristics Among Patients With Chronic Hepatitis B Virus Infection in Georgia

Hepatitis B virus infection (HBV) is one of the major healthcare problems in Georgia. To achieve viral hepatitis elimination, gaps in diagnosis and management of chronic HBV infection need to be addressed. The aim of our study was to collect data on clinical and viral characteristics of patients with chronic HBV infection to estimate the proportion of patients who may need antiviral treatment. All relevant deidentified data about demographic, clinical, and viral characteristics were extracted from patients' medical records. Descriptive statistical analyses were done for univariate assessment of demographic, virologic, and clinical characteristics. Chi-square test was used to assess the associations between HBV-DNA level, HBeAg, alanine aminotransferase (ALT), and liver fibrosis. In total, 96% (124/129) of patients with chronic HBV infection are HBeAg-negative; 84% (145/173) had no or mild fibrosis, and 3% (6/162) had advanced liver fibrosis/cirrhosis. Sixty-five out of 126 (51%) patients were classified as HBeAg-positive or HBeAg-negative chronic HBV infection (without hepatitis); 11 (9%) as chronic hepatitis B; 46 (37%) had not classified in any of the known HBV phases, while 30 of them (24% out of total) had high viral load and normal ALT. Statistically significant association was seen between high HBV-DNA and HBeAg-positivity (P= .043). High ALT level was also associated with liver fibrosis (P= .015). Significant positive correlation between age and the presence of moderate or advanced liver fibrosis was observed (P= .002). This is the first study about the clinical and viral characteristics of patients with chronic HBV infection in Georgia. The vast majority were HBeAg-negative, only 3% had advanced liver diseases; about half of patients had inactive diseases. However, one out of four patients had a high viral load but normal ALT. By the evaluation of HBV phases, we estimated that 12%-36% of patients with chronic HBV monoinfection require antiviral treatment.

Importance of CHB's grey zone: analysis of patients with HBeAg negative chronic hepatitis B virus infection.

HBeAg-negative chronic HBV infection is defined by viremia < 2,000 IU/ml (or < 20,000 IU/ml), normal ALT activity and minimal liver fibrosis. Some patients do not meet all the criteria and belong to the so-called grey zone. The aim of the work was to analyse a group of patients with asymptomatic chronic HBV infection, divide them according to the levels of HBV DNA during follow-up and to compare the clinical and laboratory parameters of the patients within the groups. We retrospectively analysed patients with HBeAg-negative chronic HBV infection examined in the Centre for Viral Hepatitis of the Department of Infectology in Košice, Slovakia, from September 2018 to December 2021. Patients were divided into three groups based on HBV DNA levels ​​during long-term follow-up ( 2,000 IU/ ml). We evaluated selected demographic, anamnestic and laboratory data (HBV DNA, ALT, fibrosis stage). Of the 280 enrolled patients, 160 were men (57.1 %), the average age was 48.0 years, and the mean length of follow-up was 4.7 years. HBV DNA levels ​​were consistently 2,000 IU/ml in 62 patients. 165 patients had normal ALT activity, 74 had fluctuating ALT activity, and permanently increased ALT in 41 patients. 139 patients underwent transient elastography examination, 16 of them had stage F2 fibrosis, two stage F3 and 1 had cirrhosis. When comparing the three groups divided according to HBV DNA, patients with fluctuating HBV DNA had the longest follow-up, but patients with HBV DNA permanently over 2,000 IU/ml were the youngest and the highest proportion of them had elevated ALT activity. 165 patients (58.9%) met the extended criteria of asymptomatic carriers, 115 were in the grey zone. Patients with HBeAg-negative chronic HBV infection often have fluctuating HBV DNA and ALT values ​​during follow-ups. Statistically significantly higher proportion of abnormal ALT activity in patients with HBV DNA > 2,000 IU/ml may suggest higher risk of adverse outcomes. Initiation of treatment in such patients is not always necessary unless they also meet the other indication criteria for treatment. The exact definition of the grey zone is currently absent (Tab. 2, Fig. 2, Ref. 16).

QHBsAg for the Identification of Liver Histological Abnormalities in HBeAg-Negative Chronic Hepatitis B Patients with Normal and Mildly Elevated ALT Levels.

Backgrounds Noninvasive detection of histological abnormalities remains challenging in patients with HBeAg-negative chronic HBV infection with normal or mildly elevated levels of alanine aminotransferase (ALT). This study aimed to assess the utility of serum quantitative hepatitis B surface antigen (qHBsAg) in identifying significant histological lesions in this population. Methods This is a single-center study with retrospective analysis of 392 treatment-naive patients of HBeAg-negative chronic HBV infection with normal or mildly elevated levels of ALT. Results In this cohort, significant necroinflammation and fibrosis were found in 69.4% and 61.5% of patients, respectively. Patients with qHBsAg >1000 IU/mL (N = 236) had more hepatic inflammation of ≥G2 (75.4% vs. 60.9%, P < 0.01) or fibrosis ≥ S2 (66.1% vs. 54.5%, P < 0.05) compared to those without (N = 156). Serum HBsAg (cutoff point = 1000 IU/mL), aspartate aminotransferase (AST) level (cutoff point = 25 IU/L), age (cutoff point = 40 years), and HBV family history were identified as independent predictors of significant histological abnormalities in multivariate logistic analysis. Conclusions A significantly higher proportion of patients with histological abnormalities were found in patients with qHBsAg >1000 IU/mL than those without. The qHBsAg level together with age, AST, and family history of HBV infection could be used as an algorithm to help noninvasive patient selection for antiviral therapy.

Kinetics of quantitative hepatitis B surface antigen in patients with rheumatic disease and chronic hepatitis B receiving biologic agents.

The effect of biologic treatment on quantitative Hepatitis B surface Antigen (qHBsAg) levels and HBsAg clearance in rheumatic patients with chronic HBV infection has not been well studied. We prospectively followed rheumatic patients with HBeAg-negative chronic HBV infection (n=28) treated with biologics and oral antivirals, categorized into patients with chronic hepatitis B (CHB, group A n=13) and chronic HBV infection (group B n=15) and matched them to appropriate non-rheumatic controls. qHBsAg kinetics were serially measured and compared between groups. No HBV reactivation (HBVr) was recorded during the 108.25 patient-year follow-up. Among patients with CHB, the annual rapid qHBsAg decline (i.e. decline >0.5log10 IU/mL/year) as well as HBsAg clearance did not differ between rheumatic patients [n=4 (32.7%), n=1 (7.7%)] and controls [n=6 (28.4%), p=.726 and n=2 (7.7%), p=.818, respectively]. In contrast, there was a slower annual qHBsAg decline in rheumatic patients with chronic HBV compared to non-rheumatic controls (-0.04 vs -0.13log10 IU/mL at year 1, p=.019) with no cases of rapid qHBsAg decline or HBsAg clearance in rheumatic patients (0%) compared to a cumulative incidence of 24% and a rate of 20%, respectively in controls. In biologic-treated rheumatic patients with HBeAg-negative HBV receiving antiviral prophylaxis, there was slower qHBsAg decline, lower cumulative rates of rapid qHBsAg decline and HBsAg clearance compared to non-rheumatic controls.

P.848Functionality in patients with newly diagnosed schizophrenia treated with paliperidone palmitate 3-month formulation in real-world clinical practice study (TIME study)

Recent studies have shown that antiviral treatment discontinuation is safe and associated with virologic remission in HBeAg-negative patients. However, the period of viral suppression and follow-up in these studies was relatively short.To investigate whether continuous viral suppression with tenofovir disoproxil fumarate for more than 7 years is associated with HBsAg loss and sustained response after treatment discontinuation and receiving a full course of hepatitis B vaccination.Patients with HBeAg-negative chronic HBV infection and more than 7 years of persistent viral suppression with tenofovir therapy were selected for treatment discontinuation and HBV vaccination. Follow-up with monthly ALT, HBV–DNA, and HBsAg determinations lasted 72 weeks. In patients with viral relapse, the viral quasispecies in the overlapping reverse transcriptase and small surface protein regions was analysed by ultra-deep pyrosequencing.Eight of 17 HBeAg-negative patients accepted tenofovir discontinuation: 5 patients achieved sustained response (persistent HBV–DNA levels <2000 IU/mL and normal ALT) despite an initial virologic relapse, one lost HBsAg, and two needed re-treatment. All patients with an on-treatment HBsAg level decline >5000 IU/mL achieved sustained response. Patients with HBsAg level <100 IU/mL during an ALT flare after antiviral discontinuation achieved sustained response. Significant changes were seen in the composition of the HBV quasispecies, and half the patients showed changes in HBV genotype.Even though the majority of patients presented an initial relapse with selection of HBV variants, most achieved sustained response. Changes in HBsAg levels on and off treatment may be useful for predicting the likelihood of virologic remission.

Albumin-bilirubin score is associated with response to pegylated interferon and nucleos(t)ide analogues in chronic hepatitis B patients

Background and aimRecently, the role of albumin-bilirubin (ALBI) score in chronic hepatitis B (CHB) has not been well-understood. We aimed to investigate the association of ALBI score with natural history of chronic HBV infection and treatment response of CHB patients. MethodsThe ALBI score in a cohort of 849 individuals including 721 chronic HBV-infected patients naïve to anti-HBV treatment in different phases and 128 healthy controls were estimated. Additionally, the dynamic changes of ALBI score of 243 hepatitis B e antigen (HBeAg)-positive CHB patients treated with pegylated interferon-alpha (PEG-IFN-α) or nucleos(t)ide analogues (NAs) were tested for 72 weeks. ResultsALBI score differed among phases, with the highest score in HBeAg-positive CHB patients, followed by HBeAg-negative CHB patients, HBeAg-positive chronic HBV infection, and HBeAg-negative chronic HBV infection. Besides, CHB patients harbouring high baseline ALBI score exhibited a relatively stronger therapeutic response to PEG-IFN-α or NAs. Moreover, the rate of HBeAg and HBsAg loss in patients with ALBI grade 2 was persistently higher than that in patients with ALBI grade 1 throughout the course of treatment. Furthermore, ALBI score was an independent predictor of sustained response achievement. The combined use of ALBI score, HBeAg and ALT could enhance the predictive value of treatment response. ConclusionsALBI score differed significantly across the natural course of chronic HBV infection and was correlated with PEG-IFN-α and NAs treatment response in HBeAg-positive CHB patients, which suggested that ALBI score could be useful as an auxiliary clinical factor to determine the initiation of therapy and predict stronger antiviral treatment response.

FRI-210-Establishment of high rates of functional cure of HBeAg negative chronic HBV infection with REP 2139-Mg based combination therapy: Ongoing follow-up results from the REP 401 study

FRI-210-Establishment of high rates of functional cure of HBeAg negative chronic HBV infection with REP 2139-Mg based combination therapy: Ongoing follow-up results from the REP 401 study

FRI-211-Evaluation of the safety and tolerability of transaminase flares during antiviral therapy in patients with HBeAg negative chronic HBV infection or HBV/HDV co-infection

FRI-211-Evaluation of the safety and tolerability of transaminase flares during antiviral therapy in patients with HBeAg negative chronic HBV infection or HBV/HDV co-infection

THU-211-Evaluation of point shearwave elastography using acoustic radiation force impulse imaging for non-invasive assessment of liver fibrosis in HBeAg-negative chronic HBV infection: A prospective longitudinal study

THU-211-Evaluation of point shearwave elastography using acoustic radiation force impulse imaging for non-invasive assessment of liver fibrosis in HBeAg-negative chronic HBV infection: A prospective longitudinal study

Clinical Significance of Quantitative HBs Antigen in the Prediction of Liver Fibrosis in Patients with Chronic Hepatitis B.

Abstract The assessment of liver fibrosis in patients with chronic hepatitis B (CHB) is of great importance in evaluating the phases of chronic hepatitis B viral infection, prompt administration of antiviral therapy, prevention of disease progression and late complications of CHB infection. Aim: to investigate the clinical significance of quantitative HBs antigen as a predictor for liver fibrosis in patients with HBe antigen negative chronic hepatitis B and inactive carriers. Material and Methods: the study included 44 treatment naïve patients with chronic hepatitis B, divided into two groups, HBeAg negative chronic HBV infection or inactive carriers (IC) and HBeAg negative chronic hepatitis B patients. All patients underwent laboratory, serologic testing, ultrasound and transient elastography (TE). In both patient groups, quantitative HBs antigen (HBsQ), alanine aminotransferase (ALT), hepatitis B virus deoxyribonucleic acid (HBV DNA) and liver fibrosis were analyzed. Results: The value of HBsQ is significantly higher in patients with HBeAg negative CHB 2477.02±4535.44 IU/ml than in the IC group 8791±11891 IU/ml; Z=3.32, p&lt;0.001 (p=0.0009). In IC patients, 1 (4.76%) had fibrosis and 20 (95.24%)) did not have fibrosis. Out of 23 patients with HBeAg negative chronic hepatitis B, 8 (34.78%) had fibrosis and 15 (65.22%) did not have fibrosis. Patients with HBeAg negative hepatitis B had significantly higher liver fibrosis than IC; Fisher Exact Test p&lt;0.05 (p=0.02). The increase of HBsQ for one single unit (IU/ml) does not have predictive value for fibrosis (Ext (B) =1.00), 95% C.I. for EXP (B): 1.00-1.00 / p&gt;0.05. Conclusion: Quantitative hepatitis B surface antigen has intermediate weak statistically insignificant prediction for liver fibrosis R=0.25 (p&lt;0.10).

O‐018: Updated Follow‐up Analysis in the REP 401 Protocol: Treatment of HBeAg Negative Chronic HBV Infection with REP 2139 or REP 2165, Tenofovir Disoproxil Fumarate and Pegylated Interferon α‐2a

O‐018: Updated Follow‐up Analysis in the REP 401 Protocol: Treatment of HBeAg Negative Chronic HBV Infection with REP 2139 or REP 2165, Tenofovir Disoproxil Fumarate and Pegylated Interferon α‐2a

Quantification of large and middle proteins of hepatitis B virus surface antigen (HBsAg) as a novel tool for the identification of inactive HBV carriers

ObjectiveAmong individuals with chronic hepatitis B, those with hepatitis B e-antigen (HBeAg)-negative chronic hepatitis (CHB) can be difficult to distinguish from those with HBeAg-negative chronic HBV infection, also referred to...

In HBeAg-negative chronic HBV infection, HBsAg levels profoundly differ among HBV-genotypes and can be affected by the extent of HBsAg variability: Can quantitative HBsAg truly reflect intra-hepatic HBV reservoir?

In HBeAg-negative chronic HBV infection, HBsAg levels profoundly differ among HBV-genotypes and can be affected by the extent of HBsAg variability: Can quantitative HBsAg truly reflect intra-hepatic HBV reservoir?

FRI-133 - In HBeAg-negative chronic HBV infection, HBsAg levels profoundly vary among different HBV-genotypes and can be influenced by the degree of HBsAg variability: can quantitative HBsAg truly reflect intra-hepatic HBV reservoir?

FRI-133 - In HBeAg-negative chronic HBV infection, HBsAg levels profoundly vary among different HBV-genotypes and can be influenced by the degree of HBsAg variability: can quantitative HBsAg truly reflect intra-hepatic HBV reservoir?

Tenofovir discontinuation after long-term viral suppression in HBeAg negative chronic hepatitis B. Can HBsAg levels be useful?

BackgroundRecent studies have shown that antiviral treatment discontinuation is safe and associated with virologic remission in HBeAg-negative patients. However, the period of viral suppression and follow-up in these studies was relatively short. ObjectivesTo investigate whether continuous viral suppression with tenofovir disoproxil fumarate for more than 7 years is associated with HBsAg loss and sustained response after treatment discontinuation and receiving a full course of hepatitis B vaccination. Study designPatients with HBeAg-negative chronic HBV infection and more than 7 years of persistent viral suppression with tenofovir therapy were selected for treatment discontinuation and HBV vaccination. Follow-up with monthly ALT, HBV–DNA, and HBsAg determinations lasted 72 weeks. In patients with viral relapse, the viral quasispecies in the overlapping reverse transcriptase and small surface protein regions was analysed by ultra-deep pyrosequencing. ResultsEight of 17 HBeAg-negative patients accepted tenofovir discontinuation: 5 patients achieved sustained response (persistent HBV–DNA levels <2000IU/mL and normal ALT) despite an initial virologic relapse, one lost HBsAg, and two needed re-treatment. All patients with an on-treatment HBsAg level decline >5000IU/mL achieved sustained response. Patients with HBsAg level <100IU/mL during an ALT flare after antiviral discontinuation achieved sustained response. Significant changes were seen in the composition of the HBV quasispecies, and half the patients showed changes in HBV genotype. ConclusionsEven though the majority of patients presented an initial relapse with selection of HBV variants, most achieved sustained response. Changes in HBsAg levels on and off treatment may be useful for predicting the likelihood of virologic remission.

Management of Decompensated Cirrhosis due to HbeAg-negative chronic HBV infection with Lamivudine monotherapy

Management of Decompensated Cirrhosis due to HbeAg-negative chronic HBV infection with Lamivudine monotherapy