Chronic Hepatitis B Virus Carriers Research Articles

HBsAg Seroclearance and Seroconversion: Incidence and Patient Profiles at the Centre Hospitalier Universitaire Yalgado Ouedraogo

Introduction: HBsAg seroclearance is a rare event in the natural history of chronic hepatitis B virus (HBV) infection. Data on HBsAg seroclearance and seroconversion are scarce in Burkina Faso. This study assessed the incidence and determined the profile of patients with HBsAg clearance and conversion at the Yalgado Ouédraogo University Hospital. Patients and Methods: This was a retrospective descriptive cross-sectional study conducted from 1 January 2006 to 31 July 2023, i.e. 17 years and 6 months, at the Yalgado Ouédraogo University Hospital. Patients were included who were chronic HBV carriers who had lost HBsAg spontaneously or after the introduction of nucleoside analogue therapy, had a viral load of HBV on admission and were negative for antibodies to hepatitis C virus (HCV), hepatitis D virus (HDV) and human immunodeficiency virus (HIV). HBsAg seroclearance was defined as serum HBsAg negativity, checked at least once, and seroconversion as the disappearance of serum HBsAg and the appearance of anti- Bs antibodies > 10 IU/ml. Results: Of the 1507 patients in our cohort, 27 lost their HBsAg during the study period. The overall incidence of HBsAg loss was 1.8% and 55.5% of patients seroconverted to HBsAg within 12 months of HBsAg loss. The mean age of patients on admission was 31.3 ± 8.9 years, with a sex ratio of 2. The mean age of patients at the time of HBsAg loss was 39.9 ± 10.2 years. The mean duration of HBsAg carriage was 9 ± 5 years. All patients were inactive carriers. Untreated patients represented 74.1% of the cohort. Quantitative HBsAg was less than 100 IU/mL in 81.8% of patients, and 88% of patients had undetectable DNA before loss of HBsAg. Conclusion: Although HBsAg seroclearance is associated with a good long-term prognosis, it remains a rare event. Patients at risk of developing hepatocellular carcinoma (HCC) after HBs seroclearance should be monitored at intervals that can be determined on the basis of further studies.

Prevalence, Profiling and Molecular Identification of Hepatitis B Virus Infection among the Tertiary Students within Birnin Kebbi Metropolis, Nigeria

A cross sectional study aim the prevalence, profiling and molecular identification of hepatitis B virus infection from the tertiary institutions students in Birnin kebbi metropolis. 329 blood samples were analyzed across the two (2) institutions for HBV using rapid diagnostic kits positive samples were taken for profiling using 5panel cassetes for serological markers and polymerase chain reaction to confirm. The social demographical factors of HBV infection were determine using a structured questionnaire. The prevalence rate of HBV markers at WUFPBK were HBsAg 25(41.25%), HBsAb 3(4.95%), HBeAg 5(8.25%), HBeAb 6(9.9%) HBcAb 15(24.75%) and FUBK: HBsAg 18(29.52%), HBsAb 0(0%), HBeAg 2(3.28%), HBeAb 1(1.64%) and HBcAb 6(9.8%). Seven (7) positives sample indicating HBeAg and HBeAb were used to detected HBV DNA, this indicates the virus replicating in chronic HBV carriers and spread through risks factors associated with HBV.

Three-dimensional liver organoids as a novel platform for studying hepatitis B virus infection

Hepatitis B virus (HBV) infection is a major global health problem that contributes to chronic liver diseases, such as cirrhosis and hepatocellular carcinoma. Despite advances in antiviral therapy and the availability of preventive vaccines, current treatments often do not completely eradicate the virus, particularly in chronic HBV carriers, and the incidence of liver cancer due to chronic HBV infection remains high. A major obstacle to HBV research is the lack of infection models that can accurately recapitulate the complex interactions between HBV and the host. Existing models, such as hepatoma cell lines and animal models, are limited by species-specific barriers and the lack of support for the complete viral life cycle. These limitations pose significant challenges to the study of HBV pathogenesis and the development of therapies aimed at complete eradication of HBV. In recent years, 3-dimensional (3D) liver organoids have emerged as promising in vitro model systems to study HBV infection and HBV-mediated liver disease. These organoids serve as a suitable physiologically relevant platform for investigating HBV pathogenesis, including the ability of HBV to promote liver tumorigenesis. Furthermore, liver organoids can be genetically modified, patient-derived, expanded, and biobanked, providing a powerful tool for studying HBV pathogenesis and personalized medicine, drug discovery, and screening. In this review, we explore the utilization of 3D liver organoids as a research model for studying HBV infection and HBV-associated liver cancer, highlighting their advantages over conventional models.

SMC5/6-Mediated Transcriptional Regulation of Hepatitis B Virus and Its Therapeutic Potential.

Cells have developed various mechanisms to counteract viral infections. In an evolutionary arms race, cells mobilize cellular restriction factors to fight off viruses, targeted by viral factors to facilitate their own replication. The hepatitis B virus (HBV) is a small dsDNA virus that causes acute and chronic infections of the liver. Its genome persists in the nuclei of infected hepatocytes as a covalently closed circular DNA (cccDNA) minichromosome, thus building up an episomal persistence reservoir. The chromosomal maintenance complex SMC5/6 acts as a restriction factor hindering cccDNA transcription, whereas the viral regulatory protein HBx targets SMC5/6 for proteasomal degradation, thus relieving transcriptional suppression of the HBV minichromosome. To date, no curative therapies are available for chronic HBV carriers. Knowledge of the factors regulating the cccDNA and the development of therapies involving silencing the minichromosome or specifically interfering with the HBx-SMC5/6 axis holds promise in achieving sustained viral control. Here, we summarize the current knowledge of the mechanism of SMC5/6-mediated HBV restriction. We also give an overview of SMC5/6 cellular functions and how this compares to the restriction of other DNA viruses. We further discuss the therapeutic potential of available and investigational drugs interfering with the HBx-SMC5/6 axis.

Interrelationships among MTHFR gene polymorphisms, MTRR gene polymorphisms, and HBV gene BCP 1762/1764 mutations with disease progression in Chronic hepatitis B virus infection patients

Objective Chronic hepatitis B virus (HBV) infection is a major disease that seriously affects the health of patients. In this paper, the relationship among MTHFR gene polymorphism, MTRR gene polymorphism and 1762/1764 mutation in the BCP region of HBV gene with disease progression in chronic HBV patients was studied. Methods A total of 144 chronic HBV infection patients from January 2021 to June 2022 in the Third People’s Hospital of Zigong City, were included as the study subjects. These patients were divided into hepatitis B primary liver cancer patients group (PLC) in 51 cases, Non-primary liver cancer patients group (Non-PLC) in 93 cases, Non-PLC is also divided into chronic hepatitis B virus carriers (CHC) in 49 cases, hepatitis B Live cirrhosis(LC) in 44 cases. MTHFR (C677T), MTRR (A66G) and MTHFR (A1298C) genes polymorphisms were detected by PCR-dissolution curve. The level of HBV-DNA was quantified by real-time PCR, and the 1762/1764 mutation site in the BCP region of the HBV gene were detected by ARMS-PCR. Data were statistically analyzed using the SPSS statistical software. Results The proportion of HBV mutations in BCP region 1762/1764 in PLC group was 82.4%, which was higher than that in LC group (63.6%) and CHC group (51.0%), and the differences were statistically significant (p < 0.05). There were no significant differences in the distribution of MTHFR C677T, MTHFR A1298C and MTRR A66G polymorphisms among CHC, LC and PLC (p > 0.05). The polymorphism distribution of MTHFR C677T, MTRR A66G and MTHFR A1298C genes in patients with chronic hepatitis B virus infection at different stages (CHC, LC and PLC) showed no gender or age differences between and within groups (p > 0.05). Among the patients with MTHFR 677CT + TT, MTRR 66AG + GG and MTHFR 1298AA genotype, the proportion of HBV mutation in BCP region 1762/1764 in PLC group was higher than that in CHC group and LC group, and the differences were statistically significant (p < 0.05). Folate levels in the PLC group were lower than those in the non-PLC group (CHC and LC patients), and the difference was statistically significant compared with the CHC group (p < 0.05). In different MTHFR C677T and MTRR A66G genotypes, the serum GGT activity were statistically significant between mutant PLC and mutant Non-PLC (p < 0.05). Conclusion MTHFR C677T, MTRR A66G and MTHFR A1298C gene polymorphisms distribution have no gender and age differences in chronic hepatitis B virus infection patients. The mutation of HBV gene BCP region 1762/1764 may be associated with the occurrence and development of liver cancer in patients with chronic HBV infection. Single difference of MTHFR C677T, MTHFR A1298C and MTRR A66G gene polymorphisms may have little effect on the disease progression in patients with chronic HBV infection. MTHFR 677CT + TT, MTRR 66AG + GG and MTHFR 1298AA genotype combined with HBV gene BCP region 1762/1764 mutation may be closely related to the occurrence and development of hepatitis B liver cancer.

Discovery of hepatitis B virus subviral particle biogenesis inhibitors from a bioactive compound library

High levels of hepatitis B virus (HBV) surface antigen (HBsAg) in the blood of chronic HBV carriers are considered to drive the exhaustion of antigen-specific T and B lymphocytes and thus responsible for the persistence of infection. Accordingly, therapeutic elimination of HBsAg may facilitate the activation of adaptive antiviral immune responses against HBV and achieve a functional cure of chronic hepatitis B. We discovered recently that an amphipathic alpha helix spanning W156 to R169 of HBV small envelope (S) protein plays an essential role in the morphogenesis of subviral particles (SVPs) and metabolism of S protein. We thus hypothesized that pharmacological disruption of SVP morphogenesis may induce intracellular degradation of S protein and reduce HBsAg secretion. To identify inhibitors of SVP biogenesis, we screened 4417 bioactive compounds with a HepG2-derived cell line expressing HBV S protein and efficiently secreting small spherical SVPs. The screen identified 24 compounds that reduced intracellular SVPs and secreted HBsAg in a concentration-dependent manner. However, 18 of those compounds inhibited the secretion of HBsAg and HBeAg in HBV replicon transfected HepG2 cells at similar efficiency, suggesting each of those compounds may disrupt a common cellular function required for the synthesis and/or secretion of these viral proteins. Interestingly, lycorine more efficiently inhibited the secretion of HBsAg in HepG2 cells transfected with HBV replicons, HepG2.2.15 cells and HBV infected - HepG2 cells expressing sodium taurocholate cotransporting polypeptide (NTCP). The structure activity relationship and antiviral mechanism of lycorine against HBV have been determined.

Burden, Outcome, and Comorbidities of Extrahepatic Manifestations in Hepatitis B Virus Infections.

Hepatitis B virus (HBV) infections affect approximately 296 million people around the world, and the prevalence of any past or present HBV infection during the years 2015-2018 was as high as 4.3%. Acute HBV infection often presents with nonspecific symptoms and is usually self-limited, but 5% of patients can have persistent infections leading to chronic HBV infection and the risk of turning into chronic HBV infection is significantly higher in babies with vertical transmission (95%). Patients with chronic HBV infection are usually asymptomatic, but 15 to 40% of chronic HBV carriers develop cirrhosis and/or hepatocellular carcinoma. In addition to liver-related disorders, HBV is also associated with several extrahepatic complications, including glomerulonephritis, cryoglobulinemia, neurologic disorders, psychological manifestations, polyarthritis, and dermatologic disorders. Making the diagnosis of HBV can be challenging since patients with chronic infections can remain symptom-free for decades before developing cirrhosis or hepatocellular carcinoma, and patients with acute HBV infection may have only mild, nonspecific symptoms. Therefore, understanding how this virus causes extrahepatic complications can help clinicians consider this possibility in patients with diverse symptom presentations. The pathophysiology of these extrahepatic disorders likely involves immune-related tissue injury following immune complex formation and inflammatory cascades. In some cases, direct viral infection of extrahepatic tissue may cause a clinical syndrome. Currently, the American Association for the Study of Liver Diseases recommends treatment of chronic HBV infections with interferon therapy and/or nucleos(t)ide analogs, and this treatment has been reported to improve some extrahepatic disorders in some patients with chronic HBV infection. These extrahepatic complications have a significant role in disease outcomes and increase medical costs, morbidity, and mortality. Therefore, understanding the frequency and pathogenesis of these extrahepatic complications provides important information for both specialists and nonspecialists and may help clinicians identify patients at an earlier stage of their infection.

Longterm Outcome of Therapeutic Vaccination with a Third Generation Pre-S/S HBV Vaccine (PreHevbrioR) of Chronically HBV Infected Patients.

Several antiviral treatment regimens for chronic hepatitis B (CHB) virus infection have been shown to be effective in suppressing viral load and reducing the risk of hepatocellular injury and its complications. It has been hypothesized that high levels of circulating HBV surface antigen(s) may lead to immune tolerance against HBV and contribute to chronic carriership. Conversely, low-level HBsAg may create a window for the reconstitution of an HBV-specific immune response through vaccination and control of infection. Previous studies in non-responders to yeast-derived HBV vaccines, using a third-generation pre-S/S vaccine, have led to up to 95% anti-HBs seroconversion. This report evaluates the long-term outcome after experimental vaccination with a pre-S/S HBV vaccine intended as a therapeutic intervention in chronic HBV carriers. Four low-level HBsAg carriers (<500 IU/mL) were vaccinated three to seven times with 20 μg PreHevbrioR. Three out of four carriers eliminated HBsAg completely and seroconverted to anti-HBs. One patient seroconverted to anti-HBs but remained with a borderline HBsAg titer (10 IU/mL). Serum anti-HBs levels following repeated vaccination varied between 27 and >1000 IU/L, respectively. Long-term observation (>6 years) showed that after discontinuing NUC treatment for at least two years, HBsAg and HBV DNA remained negative with anti-HBs positive titers ranging between 80 and >1000 IU/L. Based on our preliminary observations, there is a rationale to further evaluate the role of this vaccine as a therapeutic agent.

Prospects for Controlling Hepatitis B Globally.

Infection with the hepatitis B virus (HBV) is highly prevalent globally. Over 250 million people suffer from chronic hepatitis B, and more than 800,000 patients die each year due to hepatitis B complications, including liver cancer. Although protective HBV vaccines are recommended for all newborns, global coverage is suboptimal. In adults, sexual transmission is by far the most frequent route of contagion. The WHO estimates that 1.5 million new HBV infections occur annually. Oral nucleos(t)ide analogues entecavir and tenofovir are the most frequent antivirals prescribed as HBV therapy. Almost all patients adherent to the medication achieve undetectable plasma viremia beyond 6 months of monotherapy. However, less than 5% achieve anti-HBs seroconversion, and viral rebound occurs following drug discontinuation. Therefore, nucleos(t)ide analogues need to be lifelong. New long-acting formulations of tenofovir and entecavir are being developed that will maximize treatment benefit and overcome adherence barriers. Furthermore, new antiviral agents are in development, including entry inhibitors, capside assembly modulators, and RNA interference molecules. The use of combination therapy pursues a functional HBV cure, meaning it is negative for both circulating HBV-DNA and HBsAg. Even when this goal is achieved, the cccDNA reservoir within infected hepatocytes remains a signal of past infection, and HBV can reactivate under immune suppression. Therefore, new gene therapies, including gene editing, are eagerly being pursued to silence or definitively disrupt HBV genomes within infected hepatocytes and, in this way, ultimately cure hepatitis B. At this time, three actions can be taken to push HBV eradication globally: (1) expand universal newborn HBV vaccination; (2) perform once-in-life testing of all adults to identify susceptible HBV persons that could be vaccinated (or re-vaccinated) and unveil asymptomatic carriers that could benefit from treatment; and (3) provide earlier antiviral therapy to chronic HBV carriers, as being aviremic reduces the risk of both clinical progression and transmission.

Stat3 activation-triggered transcriptional networks govern the early stage of HBV-induced hepatic inflammation.

Until now, it remains a mystery that chronic hepatitis B virus (HBV)-infected patients in the "immune tolerance phase" will transition to the "immune activation phase" as they age. In this study, we reveal that Stat3 activation-triggered hepatic transcriptional alterations are distinctive characteristics of the early stage of immune/inflammation activation in chronic HBV infection. For the first time, we discover a mechanism that might trigger the transition from immune tolerance to immune activation in chronic HBV carriers.

Prevalence of Hepatitis D virus infection among Hepatitis B virus surface antigen positive children attending two selected Hospitals in Jos, Nigeria

Hepatitis B virus is a member of Hepadnaviridae family that cause liver infections in humans. These viral infections are characteristically linked with cirrhosis, chronic hepatitis, and hepatocellular carcinoma that are the leading cause of morbidity and mortality in the population of developing countries including Nigeria. Young children and newborns are more likely to have liver damage early in life and become chronic HBV carriers. This study identified the frequency of hepatitis B and D co-infection in children visiting the emergency pediatric units of Plateau State Specialist Hospital and Bingham University Teaching Hospital in Jos, Plateau State, Nigeria. The virus was screened using immunochromatographic Skytec® HBsAg test strips and Alere chase buffer for the qualitative detection of HBsAg in serum. HBsAg positive samples were confirmed using HBsAg Monolisa ELISA kit. Using an Italian HDV ELISA kit, samples that tested positive for HBsAg were further examined to evaluate the presence of HDV co-infection. The finding of this study revealed that 4.4% of children had HBsAg markers on their bodies. None of the children with HBV infection were co-infected with HDV. The HBV prevalence was found to be highest in children aged 6 to 10 years. Females had higher levels of HBV seropositivity (5.5%). Risk factors in children included birthplace (native households), failure to check children's HBV status after immunization, and history of jaundice. To properly manage and prevent this infection, it is advised that children should be promptly immunized at birth, their HBV status should be confirmed following immunization and they should be revaccinated if necessary.

Protective effect of N-acetylcysteine against hepatocellular carcinoma in hepatitis B virus carriers.

Hepatitis B virus (HBV) infection is a leading risk factor for hepatocellular carcinoma (HCC), contributing to cancer development through direct genomic integration and chronic inflammation. N-acetylcysteine (NAC), known for its antioxidant properties, is widely utilized in cancer prevention. However, clinical evidence regarding its protective effect against HCC in HBV carriers remains sparse. In this retrospective cohort study spanning 2008 to 2018, we utilized Taiwan's National Health Insurance Research Database (NHIRD) to include 1,061,174 chronic HBV carriers. Participants were stratified into NAC users and non-users using Propensity Score Matching. We assessed the incidence of HCC in both cohorts, examining the relationship between NAC usage duration and HCC incidence, and evaluating the dose-response effect. NAC users exhibited a significantly lower risk of developing HCC (adjusted hazard ratio [aHR]: 0.38; 95% confidence interval [CI]: 0.36-0.40; P < 0.0001). A dose-response relationship was evident, with higher cumulative defined daily doses (cDDDs) of NAC correlating with reduced HCC risk, revealing a significant trend (P < 0.0001). Notably, a daily NAC intensity of > 1.4 DDDs was associated with a decreased risk of HCC in HBV patients. Our results demonstrate that the use of NAC, in a dose-dependent manner, is intricately linked with a diminished incidence of HCC in individuals chronically infected with the HBV.

Prevalence of hepatitis B virus infection and its associated factors among students in N'Djamena, Chad.

Infection by hepatitis B virus (HBV) is a major issue in public health. The prevalence of HBV in Chad is 12.4%, all age groups considered. Here, we aimed to determine the prevalence of HBV and its associated factors among university students in N'Djamena, the country's capital. A cross-sectional survey of students at either the University of N'djamena or Emi Koussi University was conducted from 3 to 23 July 2021. All participating students provided signed, informed consent and were included in the study consecutively. Blood samples were collected, and serum tested for hepatitis B surface antigen (HBsAg) using the Determine HBsAg rapid test kit, with confirmation of positive tests on an Abbott Architect i1000SR analyzer. Descriptive analysis and logistic regression were used to determine associations between the outcome variable and independent/covariate variables. A total of 457 students with a median age of 24 years were included across different faculties. The prevalence of HBV infection was 14.87% (68/457). Most students (75%) were aged 25 years or less. Unprotected sex was reported by 64.9% of the students and multiple sexual partners by 53.6%. Furthermore, 45.7% of them reported having no knowledge of hepatitis B. Having an HBsAg-positive mother (AOR: 2.11), having a history of transcutaneous medical procedures (AOR: 2.97) and living with a family (AOR: 4.63) were significantly associated with HBV status. Age ≥26 years appeared as a protective factor (AOR = 0.41). Our study detected a high, 14.87% prevalence of HBV infection among students in N'djamena, Chad, and shed light on its associated factors. HBV prevention strategies should include raising awareness among students, making full hepatitis vaccination mandatory before children begin school, promoting mass screening to identify and treat chronic HBV carriers and reduce transmission, and reducing the cost of vaccination.

Genetic diversity of hepatitis B virus quasispecies in different biological compartments reveals distinct genotypes

The selection pressure imposed by the host immune system impacts hepatitis B virus (HBV) quasispecies variability. This study evaluates HBV genetic diversity in different biological fluids. Twenty paired serum, oral fluid, and DBS samples from chronic HBV carriers were analyzed using both Sanger and next generation sequencing (NGS). The mean HBV viral load in serum was 5.19 ± 4.3 log IU/mL (median 5.29, IQR 3.01–7.93). Genotype distribution was: HBV/A1 55% (11/20), A2 15% (3/20), D3 10% (2/20), F2 15% (3/20), and F4 5% (1/20). Genotype agreement between serum and oral fluid was 100% (genetic distances 0.0–0.006), while that between serum and DBS was 80% (genetic distances 0.0–0.115). Two individuals presented discordant genotypes in serum and DBS. Minor population analysis revealed a mixed population. All samples displayed mutations in polymerase and/or surface genes. Major population analysis of the polymerase pointed to positions H122 and M129 as the most polymorphic (≥ 75% variability), followed by V163 (55%) and I253 (50%). Neither Sanger nor NGS detected any antiviral primary resistance mutations in the major populations. Minor population analysis, however, demonstrated the rtM204I resistance mutation in all individuals, ranging from 2.8 to 7.5% in serum, 2.5 to 6.3% in oral fluid, and 3.6 to 7.2% in DBS. This study demonstrated that different fluids can be used to assess HBV diversity, nonetheless, genotypic differences according to biological compartments can be observed.

Apulian infectious diseases network: survey on the prevalence of delta infection among chronic HBV carriers in Apulia.

The current prevalence and clinical burden of Hepatitis Delta Virus (HDV) infection in Apulia are unknown. This study aimed to define the current epidemiological scenario of delta infection and to detect difficulties in the diagnosis and clinical management of HDV patients in Apulia. From May to September 2022, a fact-finding survey was conducted at eight Infectious Diseases Units of the Apulian region; each Unit was asked to complete a questionnaire on screening and diagnosis of HDV infection and demographic, virological, and clinical characteristics of HDV patients. A total of 1,461 HBsAg-positive subjects were followed up on an outpatient basis. Screening for HDV ranged from 30 to 90% of HBsAg + carriers in a single center. Overall, 952 HBsAg ± subjects (65%) were tested for HDV, and 80/952 (8.4%) were anti-HDV positive. Serum HDV RNA was detected only in 15/80 (19%) anti-HDV-positive subjects, and 12/15 patients (80%) were viremic. Sixty-five anti-HDV-positive subjects (81%) were from Italy; risk factors for HDV acquisition included the presence of HDV infection in the family (29/80 = 36%), drug addiction (12/80 = 15%), and co-infection with HCV or HIV (7/80 = 9%). Liver cirrhosis and hepatocellular carcinoma were diagnosed in 41 (51%) and 4 (5%) patients, respectively. Fifty-seven patients (71%) received nucleos(t)ide analog treatment. The results of this survey show that HDV screening is variable and insufficient, thus real prevalence data on delta infection are lacking in Apulia. Moreover, the HDV RNA test is not available in most laboratories and is not provided by the national health system. These results underline the need for an organizational model to optimize the management of HDV patients throughout the Apulian region.

Serological profile of chronic hepatitis B carriers – A tertiary care experience

Background: Hepatitis B virus (HBV) infection in India has prevalence of around 40 million chronic HBV (CHB) carriers; 1 to 2 lakhs reported deaths annually due to its complications, such as cirrhosis and hepatocellular carcinoma. Most are asymptomatic, serving as the source of this highly transmissible infection. These patients must be evaluated and monitored regularly, for prediction of their prognosis to reduce their morbidity and mortality. Aims and Objectives: In this study, asymptomatic CHB carriers are evaluated, to assess the risk factors, and to determine replication markers of HBV and coinfection with hepatitis D virus. Materials and Methods: In this cross-sectional study, 123 asymptomatic CHB carriers were subjected to hepatitis B serological assays such as hepatitis B surface antigen, hepatitis B “e” antigen, anti-hepatitis B “e” antibody, and anti-HDV antibody by enzyme-linked immunosorbent assay. Results: Majority (70%) belonged to the age group of 21–50 years. Replicative carriers (HBeAg+) belonging to the age group below 40 years constituted 75% (P=0.04). The most common risk factor in the study group was frequent therapeutic injections (36.6%) followed by family contacts (33.3%). Significant part of family contacts was replicative carrier (P=0.025). Serological profile showed that 83.3% were HBe-seroconverted, with only16.2% showing HBeAg positivity. No patient showed co/super-infection with HDV. Conclusion: Preponderance of hepatitis B carrier status in young adult males and four fold increased incidence in family contacts than general population necessitates stringent screening of young adults and family contacts. Furthermore, this study mandates regular evaluation of chronic hepatitis B carriers by serological assays for better therapeutic management.

Triple motif proteins 19 and 38 correlated with treatment responses and HBsAg clearance in HBeAg-negative chronic hepatitis B patients during peg-IFN-α therapy

ObjectiveTo investigate whether the expression of triple motif protein 19/38 (TRIM19/38) mRNA in peripheral blood mononuclear cells (PBMCs) of HBeAg-negative chronic hepatitis B virus (HBV) carriers is associated with the response to pegylated interferon alpha (peg-IFN-α) treatment and HBsAg clearance.MethodsIn this prospective study, HBeAg-negative chronic HBV carriers treated with peg-IFN-α completed 48 weeks of follow-up. After treatment with peg-IFN-α, the patients were divided into responders (R group) and nonresponders (NR group) according to the changes in HBV DNA and HBsAg levels at week 48 of treatment. According to whether serum HBsAg loss or seroconversion occurred, the patients were divided into a serological response group (SR group) and a nonserological response group (NSR group). The level of TRIM19/38 mRNA in PBMCs was detected by real-time fluorescence quantitative PCR. The diagnostic performance of TRIM19/38 was analysed by calculating the receiver operating characteristic (ROC) curve and area under the ROC curve (AUC).Results43 HBeAg-negative chronic HBV carriers, 35 untreated CHB patients and 19 healthy controls were enrolled in this study. We found that TRIM19/38 mRNA levels were significantly lower in untreated CHB patients than in healthy controls. In HBeAg-negative chronic HBV carriers who underwent prospective follow-up, TRIM19/38 mRNA levels were negatively correlated with HBV DNA and ALT at baseline. Among the patients treated with peg-IFN-α, 16 patients achieved a treatment response (R group) and 27 patients did not achieve a treatment response (NR group). Compared with baseline, HBsAg levels in the R group decreased significantly at 12 and 24 weeks of treatment; at the early stage of peg-IFN-α treatment, the dynamic changes in TRIM19/38 mRNA levels in the R and NR groups were different, and the TRIM19/38 mRNA levels in the R group were significantly higher than those in the NR group, especially at 24 weeks of treatment. ROC curve analysis showed that the changes in mRNA levels of TRIM19 and TRIM38 predicted the treatment response, with AUCs of 0.694 and 0.757, respectively. Among the patients treated with peg-IFN-α, 11 patients achieved a serological response (SR group) and 32 patients did not achieve a serological response (NSR group). Compared with baseline, HBsAg levels in the SR group decreased significantly at 12 and 24 weeks of treatment; TRIM19/38 mRNA levels were significantly higher in the SR group than in the NSR group at week 24.ConclusionThe higher level of TRIM19/38 mRNA in PBMCs of HBeAg-negative chronic HBV carriers may be related to the early treatment effect of peg-IFN-α and HBsAg clearance. TRIM19 and TRIM38 have clinical significance in predicting virological response and guiding treatment regimens.

Ten-year changes in clinical characteristics and antiviral treatment patterns of chronic hepatitis B in China: a CR-HepB-based real-world study

Objective: To understand ten-year changes in clinical characteristics and antiviral treatment patterns of chronic hepatitis B in China. Methods: Patients with chronic HBV infection:demographic, virologic, hematologic, blood biochemistry, and antiviral treatment data were extracted from the China Registry of Hepatitis B (CR-HepB) database between 2012 and 2022 for descriptive statistics and change trend analysis. Multiple group comparisons were conducted using the Kruskal Wallis H test, while counting data was compared between groups using χ (2) test. Results: A total of 180 012 patients with chronic HBV infection were included, with a median age of 40 years old, and a male proportion accounting for 60.2%. The HBeAg positive rate was 43.3%. Over time, the median age of new patients each year increased from 39 to 47 years, while the HBeAg positive rate decreased from 51.3% to 32.8%. The initial diagnosis of patients was mainly CHB (71.4%), followed by hepatitis B cirrhosis (11.8%), inactive HBsAg carrier status (10.6%), and chronic HBV carrier status (6.2%). Among the newly registered patients every year from 2012 to 2022, the proportion of hepatitis B cirrhosis remained stable, but after 2019, the proportion of CHB increased and the proportion of other diagnoses decreased. The proportion of patients with cirrhosis increased with age in different age groups, with 3.5%, 19.3%, and 30.4% in the < 40, 40-69, and≥70 age groups, respectively. The proportion of women in patients with cirrhosis also increased with age, from 16.1% in those < 30 years old to 44.3% in those≥80 years old. From 2012 to 2022, the proportion of patients receiving first-line nucleos(t)ide analog antiviral treatment increased year by year, from 51.0% in 2012-2013 to 99.8% in 2022. Conclusion: The CR-HepB registration data reflect the changes in clinical characteristics and antiviral treatment patterns in patients with chronic HBV infection in China over the past ten years and can thus provide a reference to promote hepatitis B diagnosis and treatment practice, as well as scientific research.

In Shortly About Hepatitis B

Hepatitis B is an infectious liver disease caused by the hepatitis B virus, which can be mild and last for several weeks, but also a serious lifelong infection (chronic hepatitis B). Acute hepatitis B lasts up to 6 months and is usually of a milder form, but it can also be more severe and require hospitalization. If the organism fails to overcome the viruses, the disease turns into a chronic form that can cause major consequences. Hepatitis B is one of the most common infectious diseases, and it is estimated that there are around 300 million chronic HBV carriers worldwide. The most common route of transmission is after a puncture or cut on an infected needle or other sharp object and the sexual route

Common Genetic Variants of Response to Hepatitis B Vaccines Correlate with Risks of Chronic Infection of Hepatitis B Virus: A Community-Based Case-Control Study.

Hepatitis B (HB) vaccination effectively reduces the risks of chronic infection with the hepatitis B virus (HBV). It is unknown whether there is a common genetic determinant for response to the HB vaccine and susceptibility to chronic HBV infection. This case-control study, which included 193 chronic HBV carriers and 495 non-carriers, aimed to explore the effects of the most significant single nucleotide polymorphisms (SNPs) in response to the HB vaccine on the risks of chronic HBV infection. Out of 13 tested SNPs, the genotype distributions of four SNPs at the human leukocyte antigen (HLA) class II region, including rs34039593, rs614348, rs7770370, and rs9277535, were significantly different between HBV carriers and non-carriers. The age-sex-adjusted odds ratios (OR) of chronic HBV infection for rs34039593 TG, rs614348 TC, rs7770370 AA, and rs9277535 AA genotypes were 0.51 (95% confidence interval [CI], 0.33-0.79; p = 0.0028), 0.49 (95% CI, 0.32-0.75; p = 6.5 × 10-4), 0.33 (95% CI, 0.18-0.63; p = 7.4 × 10-4), and 0.31 (95% CI, 0.14-0.70; p = 0.0043), respectively. Multivariable analyses showed that rs614348 TC and rs7770370 AA genotypes were significantly independent protectors against chronic HBV infection. The multivariable-adjusted ORs for subjects with none, either one, or both of the protective genotypes were 1.00 (referent), 0.47 (95% CI: 0.32-0.71; p = 3.0 × 10-4), and 0.16 (95% CI: 0.05-0.54; p = 0.0032), respectively. Among eight HBeAg-positive carriers, only one of them carried a protective genotype. This study shows that response to the HB vaccine and susceptibility to chronic HBV infection share common genetic determinants and indicates that HLA class II members are the main responsible host genetic factors.