The prevalence of hepatitis B virus infection among HIV-infected patients in the Ningxia Hui Autonomous Region, China, November 2002 to July 2023.

We tested HIV-infected people with HBV serological markers of Ningxia. Of 1008 HIV-positive individuals, 70 (6.9 %) tested positive for HBsAg, 570 (56.5 %) tested positive for anti-HBs, and 483 (47.9 %) tested positive for anti-HBc. Of 70 HBV-positive individuals, 13 (18.5 %) tested positive for HBeAg, 31 (44.3 %) tested positive for anti-HBe, 3 (4.2 %) exhibited acute infection.

Reactivation Risk of Latent Tuberculosis or Inactive Hepatitis B Virus Infection and Effectiveness of Ustekinumab in Chinese Plaque Psoriasis Patients: A 28-Week Retrospective, Observational Study.

Introduction: This study observed the effectiveness of ustekinumab and reactivation risk of concurrent latent tuberculosis infection (LTBI) and inactive hepatitis B virus (HBV) infection in Chinese mainland psoriasis patients on ustekinumab treatment. Methods: This retrospective, multicenter, observational study was conducted in three centers in China. Adult patients with moderate to severe plaque psoriasis were treated with ustekinumab for 28 weeks. The effectiveness endpoint included 75% and 90% improvement in Psoriasis Area Severity Index (PASI75/90) response rate, percentage of PASI improvement, change of absolute PASI score and body surface area involvement (BSA) score, absolute PASI ≤1/3 and Physicians' Global Assessment (PGA)=0/1, as well as Dermatology life quality index (DLQI)=0/1 response rate at week 4, 16 and 28. Screening of tuberculosis and hepatitis were performed at baseline and week 28. Results: A total of 82 patients were enrolled between March 2021 and May 2023 and the number of patients combined with LTBI and inactive HBV infection was 20 and 21 respectively. The PASI75 and PASI90 response rate at week 28 was 95.1% and 81.7% respectively. The mean PASI score decreased from 14.93 ± 12.07 at baseline to 0.78 ± 1.86 at week 28, and the mean BSA score decreased from 21% ± 18% at baseline to 1% ± 2% at week 28 (both P<0.001 compared with baseline). DLQI 0/1 response rate at week 28 was 73.2%. No reactivation of LTBI and inactive HBV infection and also no new-onset tuberculosis and hepatitis B occurred in patients without LTBI and inactive HBV infection at baseline. Conclusion: Ustekinumab demonstrated great effectiveness in Chinese plaque psoriasis patients and good safety in psoriasis concurrent with LTBI and inactive HBV infection under the real-world setting.

Hepatitis B Elimination Globally-The Answer May Not Be the Same for Everyone.

While progress has been made towards global elimination of hepatitis B virus, many countries lag behind. A one-size-fits-all approach is not practical to address HBV. Rather, the approach should be tailored to local prevalence, risk factors and available resources.

Exploration of 1-(indolin-1-yl)-2-(thiazol-2-yl)ethan-1-one derivatives as novel anti-HBV agent with potential TLR7-agonistic effect.

Hepatitis B virus (HBV) infection, as a serious global public health issue, is closely related to the immune dysfunction. Herein, thirty-seven 1-(indolin-1-yl)-2-(thiazol-4-yl)ethan-1-one derivatives were prepared as potential immunomodulatory anti-HBV agents. Anti-HBV activity evaluation confirmed compound 11a could significantly suppress the HBV DNA replication in both wild and resistant HBV stains, with IC50 values of 0.13 µM and 0.36 µM, respectively. Preliminary action mechanism studies showed that 11a had an inhibitory effect on cellular HBsAg secretion and could effectively activate TLR7, thereby inducing the secretion of TLR7-regulated cytokines IL-12, TNF-α and IFN-α in human PBMC cells. SPR analysis confirmed that 11a could bind to TLR7 protein with an affinity of 7.06 µM. MD simulation predicted that 11a could form tight interactions with residues in the binding pocket of TLR7. Physicochemical parameters perdition and pharmacokinetic analysis indicated that 11a displayed relatively favorable drug-like properties. Considering all the results, compound 11a might be a promising lead for developing novel immunomodulatory anti-HBV agents.

Hepatitis B virus infection during pregnancy and the risk of postpartum hemorrhage: a protocol for systematic review and meta-analysis.

Background: Hepatitis B virus (HBV) infection is a significant public health issue worldwide, with a hepatitis B surface antigen (HBsAg) seroprevalence of 3.5%. Maternal HBV infection during pregnancy, a common comorbidity, is associated with an increase in the risk of adverse obstetric and perinatal outcomes. However, the relationship between maternal HBV infection and postpartum hemorrhage (PPH), a leading contributor to maternal morbidity and mortality, is currently uncertain. The aim of this study is to comprehensively clarify the potential impact of maternal HBV on PPH risk. Methods and Analysis: The authors initially searched five English databases and three Chinese databases from their inception to 26th June 2023. Two reviewers will independently conduct study selection, data extraction, and quality assessment. Cohort and case-control studies investigating the effect of maternal HBV infection on PPH will be included, with study quality assessed using the Newcastle-Ottawa Scale (NOS). Meta-analyses will be performed using a fixed-effects model for I 2≤50% or a random-effects model otherwise. Several categories of subgroup analyses (e.g. sample size more than 1000 vs. less than 1000) and sensitivity analyses (e.g. omit NOS scores less than 7) will be conducted, and publication bias will be assessed through funnel plots, Begg's and Egger's tests using STATA 18.0. Ethics and Dissemination: This systematic review and meta-analysis do not require ethics approval and the results will be published in peer-reviewed journals. The findings of this systematic review will provide evidence on the impact of maternal HBV infection on PPH, which will contribute to better prevention and management of PPH in clinical practice and a better understanding of the disease burden of HBV infection. PROSPERO registration number: CRD42023442626.

Investigating linkage to care following community-based screening for hepatitis B virus in rural Senegal: A mixed methods study.

This paper investigates linkage to care following community-based screening for hepatitis B virus (HBV) in rural Senegal. HBV-positive participants who completed a biological and clinical examination to assess liver disease and treatment eligibility were referred to a regional hospital (if eligible for treatment), invited to join the Sen-B research cohort study (adults with detectable viral load) or referred to their local health centre (all others). Logistic regressions were conducted to investigate factors associated with (i) uptake of the scheduled post-screening examination, and (ii) HBV management initiation. Obstacles to HBV management were identified using thematic analysis of in-depth patient interviews. Of the 206 HBV-positive participants, 163 (79.1%) underwent the examination; 47 of the 163 (28.8%) initiated HBV management. Women, people not migrating for >6 months/year, individuals living in households with more agricultural and monetary resources, with other HBV-positive participants, and beneficiaries of the national cash transfer program, were all more likely to undergo the examination. The likelihood of joining the Sen-B cohort increased with household monetary resources, but decreased with agricultural resources. Initiation of HBV management in local health centre was higher among participants with a non-agricultural economic activity. Individuals reported wariness and confusion about HBV management content and rationale at various stages of the care continuum, in particular with respect to venous blood sampling and management without treatment. In conclusion, HBV community-based test-and-treat strategies are feasible, but early loss to follow-up must be addressed through simplified, affordable management and community support and sensitization.

Risk Factors and Comorbidities Associated With Hepatocellular Carcinoma in Patients With Chronic Hepatitis B Virus Infection.

INTRODUCTION/OBJECTIVES: Chronic hepatitis B virus infection (CHBVI) is a major public health problem affecting about 296 million people worldwide. HBV infects the liver, and when it becomes chronic, may cause cirrhosis and hepatocellular carcinoma (HCC). The aim of our study was to identify the risk factors and comorbid medical conditions that were associated with HCC in patients who had CHBVI. METHODS: We performed a retrospective electronic medical record review of adult patients diagnosed with CHBVI, who presented to our primary care office between October 1, 2017 and October 21, 2022. Selected variables in patients with CHBVI with HCC (HCC group) were compared to those without HCC (NoHCC group). RESULTS: Among 125 patients with CHBVI, 24% had HCC and 76% did not have HCC. There were higher frequencies of association of certain comorbidities in the HCC group compared to NoHCC group, such as anemia (63.3% vs 26.3%; P < .001), ascites (53.3% vs 1.1%; P < .001), portal hypertension (43.3% vs 0.0%; P < .001), chronic kidney disease (40.0% vs 13.7%; P = .002), and HCV coinfection (13.3% vs 7.4%; P < .001). The logistic regression model showed increased odds of HCC for each year of increase in age (OR = 1.06, 95% CI = 1.01-1.11; P = .014), and increased odds in men (OR = 5.96, 95% CI = 1.71-20.73; P = .005). Although Asians represented the racial majority in both the groups, there was no significant difference in the race distribution between the two groups. CONCLUSION: In patients with CHBVI, increasing age and male sex are factors associated with increased odds of having HCC. Patients with CHBVI and HCC have higher frequencies of association of tobacco use, recreational drug use, anemia, ascites, portal hypertension, chronic kidney disease, and co-infection with HCV.

Implementation of Guideline-Based HBV Reactivation Management in Patients with Chronic HBV Infections of HBsAg or Resolved HBV Infection Undergoing Immunosuppressive Therapy.

INTRODUCTION: Although patients with HBV have a risk of reactivation after immunosuppressive therapy (IST), the status of their risk management is unclear in Japan. This study aims to describe the proportion of patients who received preventive management of HBV reactivation during ISTs in patients with chronic HBV infection of HBsAg or resolved HBV infection. METHOD: A retrospective cohort study was conducted using the JMDC Japanese claims database from April 2011 to June 2021. Patients with HBV infections of HbsAg who received ISTs or patients who had resolved HBV infections who received ISTs were identified from the database and evaluated for appropriate management to prevent HBV reactivation. RESULTS: In total, 6242 eligible patients were identified. The proportions of patients with appropriate HBV reactivation management, stratified by the HBV reactivation risk level of IST, was 43.1% (276/641) for high-risk, 40.2% (223/555) for intermediate-risk and 14.9% (741/4965) for low-risk patients. When the evaluation period for the outcome calculation was shortened from 360 to 180 days, the proportion for high risk increased to 52.7%. The odds ratios of large hospitals for receiving appropriate management were 2.16 (95% CI 1.12-4.44) in the high-risk, 4.63 (95% CI 2.34-10.25) in the intermediate-risk and 3.60 (95% CI 3.07-4.24) in the low-risk patients. CONCLUSION: HBV reactivation management was tailored according to the reactivation risk associated with IST. However, adherence to HBV reactivation management guidelines was sub-optimal, even among high-risk patients. This is especially the case for ensuring smaller-sized medical institutions, highlighting the need for further educational activities.

The study assesses the implementation of guideline-based management of hepatitis B virus reactivation during immunosuppressive therapy in Japan. The appropriate management of hepatitis B virus treatment involves prophylactic nucleos(t)ide analog (NUC) therapy and regular monitoring of hepatitis B virus DNA. This study aims to assess the extent to which these management practices are implemented in a clinical setting in Japan using a retrospective cohort study using the Japanese Medical Claims Database. The analysis identified 6242 eligible patients and identified whether they received appropriate management to prevent hepatitis B virus reactivation based on the level of risk associated with their immunosuppressive therapy. Based on the guidelines, the proportions of patients receiving appropriate reactivation management were 43.1% for high-risk, 40.2% for intermediate-risk and 14.9% for low-risk immunosuppressive therapy patients. Shortening the evaluation period from 360 to 180 days showed an increase in the proportion of high-risk patients to 52.7%, which indicated the potential challenge for continued monitoring after immunosuppressive therapy administration. The study shows that large hospitals present higher odds of patients receiving appropriate management. Overall, adherence to hepatitis B virus reactivation management guidelines was suboptimal, especially in smaller medical institutions, emphasizing the need for additional educational activities.

A Systematic Review of the Advances in the Study of T Lymphocyte Suppressor Receptors in HBV Infection: Potential Therapeutic Targets.

Background: HBV-specific T lymphocytes are pivotal in eliminating the hepatitis B virus (HBV) and regulating intrahepatic inflammatory reactions. Effective T cell responses curtail HBV infection; however, compromised immunity can result in persistent infection. Beyond the acute phase, the continued presence of antigens and inflammation leads to the increased expression of various inhibitory receptors, such as PD-1, CTLA-4, Tim-3, LAG3, 2B4, CD160, BTLA, and TIGIT. This escalates the dysfunction of and diminishes the immune and proliferative abilities of T cells. Methods: In this study, we reviewed English-language literature from PubMed, Web of Science, and Scopus up to 9 July 2023. This paper aims to elucidate the inhibitory effects of these receptors on HBV-specific T lymphocytes and how immune function can be rejuvenated by obstructing the inhibitory receptor signaling pathway in chronic HBV patients. We also summarize the latest insights into related anti-HBV immunotherapy. Result: From 66 reviewed reports, we deduced that immunotherapy targeting inhibitory receptors on T cells is a reliable method to rejuvenate T cell immune responses in chronic HBV patients. However, comprehensive combination therapy strategies are essential for a functional cure. Conclusions: Targeting T cell suppressor receptors and combining immunotherapy with antiviral treatments may offer a promising approach towards achieving a functional cure, urging future research to prioritize effective combination therapeutic strategies for chronic HBV infection.

Diagnostic precision of Truenat® technique and co-relation of ALT levels with HBV-DNA viral load among HBsAg positive patients at a tertiary care hospital in Eastern Uttar Pradesh.

Background and Objectives: In India, it is estimated that there are 40 million people suffering from Hepatitis B virus (HBV). Quantification of the viral burden is an important laboratory tool in the management. However, widespread use of different HBV-DNA assays is still affected by the high cost and variable diagnostic precision. The present study was conducted to evaluate the diagnostic precision and co-relation of ALT levels with HBV-DNA by Truenat®-PCR. Materials and Methods: In this prospective cross-sectional study a total of 567 serums were collected from patients by rapid HBsAg, and processed for liver function tests (LFT). The viral HBV-DNA amplification detection was carried out through by Truenat®-PCR test. Results: Out of 567 samples, 452 samples were found to be positive by both rapid and Truenat®-PCR and 106 were negative for HBV-DNA followed by 9 invalid. High ALT level found in 73% of positive patients who had HBV-DNA level (>100000 copies/ml) which is significantly higher in 447 patients as compared to those have below ≤100000 copies/ml. Conclusion: Truenat®-PCR technique is a highly sensitive and can be performed with low resources for effective control of HBV infection. Evaluation of HBV-DNA levels and serum ALT levels showed a significant proportion of patient harbored ongoing viral replication and disease progression.

Effect of S-region mutations on HBsAg in HBsAg-negative HBV-infected patients.

BACKGROUND: Occult HBV infection (OBI) is a special form of hepatitis B virus (HBV) infection that may cause Liver cirrhosis and hepatocellular carcinoma, causing significant harm to patients. Given the insidious nature of OBI, it is usually not easy to be detected. Most of the samples currently studied are concentrated on blood donors, however, patients in this special state have not been fully studied. This project aimed to study the effect of HBV S region mutations on HBsAg in patients with clinical OBI. METHODS: Collect 107 HBsAg-/HBV DNA + blood samples from Beijing Youan Hospital, Capital Medical University from August 2022 to April 2023. Next, the successfully extracted and amplified HBV DNA S regions were sequenced. Construct mutant plasmids to verify the cell function of the high-frequency mutation sites and explore the possible molecular mechanism. RESULTS: Sixty-eight HBsAg-negative samples were sequenced, revealing high-frequency amino acid substitution sites in the HBV S protein, including immune escape mutations (i.e., sY100C、sK122R、sI126T、sT131P、and sS114T) and TMD (Transmembrane domain) region substitutions (i.e., sT5A、sG10D、sF20S、and sS3N). We constructed a portion of the mutant plasmids and found that sT5A, sF20S, sG10D, sS3N, sI68T, and sI126T single point mutations or combined mutations may decrease HBsAg expression or change the antigenicity of HBsAg leading to detection failure. CONCLUSIONS: HBsAg-negative patients may show various mutations and amino acid replacement sites at high frequency in the HBV S-region, and these mutations may lead to undetectable Hepatitis B surface antigen (HBsAg), HBsAg antigenic changes or secretion inhibition.

Potential role of Vitamin D in immune response in patients with viral hepatitis.

BACKGROUND: To study the relationship of Vitamin D with innate and adaptive immune response parameters in chronic hepatitis B and C patients. METHODS: The laboratory data between January 1, 2013 and February 1, 2023, for patients with chronic hepatitis B (CHB), and chronic hepatitis C (CHC) were extracted. Serum 25-hydroxyl vitamin D, hepatitis B virus serological markers, complements, and subsets of T lymphocytes were determined. Study cohorts were divided into groups based on serum 25-hydroxyl vitamin D levels with further evaluation of laboratory data. RESULTS: In CHB and CHC patients the percentage of CD4+ T lymphocytes and the CD4+/CD8+ ratio significantly decreased (P < 0.05), but the percentage of CD8+ increased (P < 0.05) compared to the control group. In CHB patients Vitamin D decrease was significant (P < 0.001) but not in CHC patients. Vitamin D showed a moderate negative influence on the CD8 cell count in CHB patients. The positive ratio of HBV DNA and HBsAg decreased with increasing serum vitamin D levels. The vitamin D deficient group showed significantly lower antibody production compared to the normal group, and exhibited significantly decreased CD4 numbers and increased CD8 numbers (P < 0.05 and P < 0.001, respectively), while the CD4/CD8 ratio was also significantly decreased in the insufficiency group (P < 0.001). Complement C3 levels were not associated with CD4 and CD8, but had an inverse relation with Vitamin D. Vitamin D levels were significantly associated with complement C3, CD8+, CD4+, CD19+ cells, and HBV DNA levels. CONCLUSIONS: Vitamin D may be a modulator of immune function not only via CD8+ and CD4+ cells but also via CD19+ cells in the course of chronic HBV infection. The negative relationship between vitamin D and complement C3 needs elucidation. Moreover, the increased proportion of B cells and decreased CD4+ cells in Vitamin D deficiency disrupt the immune response against HBV since the expected antibody response was not obtained despite the increase in B cell ratio. This indicates an influence of CD4+ cells for B cell functionality. In summary, sufficient levels of Vitamin D may lead to a sustained virological response that is debatable by artificially correcting the deficiency.

Unveiling NUSAP1 as a common gene signature linking chronic HBV infection and HBV-related HCC.

BACKGROUND: Hepatitis B virus (HBV) is a significant contributor to the development of hepatocellular carcinoma (HCC). Chronic HBV infection (CHB) facilitates disease progression through various mechanisms. However, the specific factor responsible for the progression of HBV infection to HCC remains unresolved. This study aims to identify the hub gene linking CHB and HBV-related HCC through bioinformatic analysis and experimental verification. METHODS: Differentially expressed genes (DEGs) were identified in datasets encompassing CHB and HBV-HCC patients from the GEO database. Enriched pathways were derived from GO and KEGG analysis. Hub genes were screened by protein-protein interaction (PPI) analysis and different modules in Cytoscape software. The significance of the selected hub gene in prognosis was further assessed in validated datasets. The effects of hub genes on cell growth and apoptosis were further determined in functional experiments. RESULTS: The study revealed upregulation of NUSAP1 in CHBs and HBV-HCCs. High expression of NUSAP1 served as an independent predictor for poor prognosis of liver cancers. Functional experiments demonstrated that NUSAP1 promotes cell growth, influences cell cycle process, and protects cells from apoptosis in HepG2.2.15 cells. CONCLUSION: NUSAP1 serves as a poor prognostic indicator for liver cancers, and potentially plays a crucial role in HBV-HCC progression by promoting proliferation and inhibiting apoptosis.

Assessment of prevalence and risk factors associated with Hepatitis B virus infection among blood donors in Mogadishu Somalia.

BACKGROUND: The Hepatitis B virus (HBV) is transmitted through contaminated blood or bodily fluids. Globally, over 81 million blood units are donated annually, a crucial therapeutic procedure without alternatives. However, blood-borne infections, including HBV, pose a significant hurdle to safe transfusions, especially in HBV-endemic regions like Somalia with limited screening. Therefore, this study aims to estimate the prevalence of Hepatitis B virus infection and identify risk factors associated with it among blood donors in Mogadishu, Somalia. METHOD: A hospital-based cross-sectional study was conducted between February and April 2023. Research tools included a 5-ml blood sample and a structured questionnaire. The presence or absence of HB markers was determined using a multi-HB rapid test and CDC's HB marker interpretation guideline. Logistic regression was used in univariate and multivariate models to identify risk factors associated with HBV infection, with significance set at a p-value < 0.05 in the final model. RESULT: A total of 494 blood donors were recruited for this study; 93.9% were male, with a mean age of 31.5 (SD = 8.11). The prevalence of Hepatitis B virus (HBV) infection among blood donors was 9.7%, with a 95% CI of 7.1-12.3. In multivariable logistic regression, those with a monthly income of less than 200 USD (AOR = 5.20, 95% CI = 1.61-16.79), those with an income between 200 and 400 (AOR = 3.59, 95% CI = 1.38-9.34), Jobless blood donors (AOR = 3.78, 95% CI = 1.17-12.20), those in business occupations (AOR = 3.35, 95% CI = 1.24-9.08), those with a history of STDs (AOR = 4.83, 95% CI = 2.03-11.50), those without a history of HB vaccine (AOR = 13.81, 95% CI = 2.46-77.41), those with a history of tooth extraction (AOR = 6.90, 95% CI = 2.66-17.88), and those who shared sharp equipment (AOR = 2.90, 95% CI = 1.07-7.82) were more likely to become infected with the Hepatitis B virus (HBV) compared to their counterparts. CONCLUSION: This study highlights a high prevalence of Hepatitis B virus (HBV) infection. Implementation efforts against HBV infection should specifically focus on low-income individuals, the jobless, and donors with a history of STD to mitigate the burden of HBV infection and promote safer blood donation. In addition, discouraging the sharing of sharp equipment, improving infection control practices during tooth extraction procedures, and enhancing HB vaccination uptake, particularly among individuals lacking a history of HB vaccine, is highly recommended.

[A real-world study on the features of postpartum hepatitis flares in pregnant women with chronic HBV infection].

Objective: To analyze the clinical features of postpartum hepatitis flares in pregnant women with hepatitis B virus (HBV) infection. Methods: A retrospective study was conducted. Patients who met the enrollment criteria were included. Liver function and HBV virology tests were collected from pregnant women with chronic HBV infection at delivery, 6, 24, 36, and 48 weeks after delivery through the hospital information and test system. Additionally, antiviral therapy types and drug withdrawal times were collected. Statistical analysis was performed on all the resulting data. Results: A total of 533 pregnant women who met the inclusion criteria were included, with all patients aged (29.5±3.7) years old. A total of 408 cases received antiviral drugs during pregnancy to interrupt mother-to-child transmission. There was no significant difference in the levels of alanine aminotransferase (ALT, z = -1.981, P = 0.048), aspartate aminotransferase (AST, z = -3.956, P < 0.001), HBV load (z = -15.292, P < 0.001), and HBeAg (z = -4.77, P < 0.001) at delivery in patients who received medication and those who did not. All patients ALT, AST, total bilirubin, direct bilirubin, and albumin showed an upward trend within six weeks after delivery. A total of 231 cases developed hepatitis within 48 weeks after delivery. Among them, 173 cases first showed ALT abnormalities within six weeks postpartum. Conclusion: Hepatitis flare incidence peaked six weeks after delivery or six weeks after drug withdrawal in pregnant women with chronic HBV infection.

The prevalence of occult hepatitis B infection among the blood donors in a donation center in Beijing.

Occult HBV infection (OBI) remains a potential threat for blood safety. The prevalence of OBI was investigated in a blood donation center of Chinese PLA General Hospital to improve HBV blood safety. 229446 samples from blood donors were screened by two different enzyme-linked immunosorbent assay (ELISA) kits. 78 samples were HBV DNA positive among 212134 ELISA nonreactive donor samples. The prevalence of OBI was 0.04% (76/212134). Ten samples of OBI were permitted by the donors' content for further research, and all of these were below 200IU/mL, and six of these were below 20IU/mL(6/10,60%). Genotype B and genotype C was 20% (2/10) and 80% (8/10), respectively. 16 amino acid mutations were detected in the S region of OBI, included three mutations in MHR region of S. The prevalence of OBI is rare in this donation center. These mutations we found may contribute to the multifactorial occurrence of OBI.

Was antiviral prophylaxis necessary after kidney transplantation utilizing HBcAb+ donors? A systematic review and meta-analysis.

BACKGROUND: Current guidelines lack consensus on whether antiviral prophylaxes should be administered after kidney transplantation from HBcAb+ donors. This systematic review and meta-analysis aimed to evaluate the incidence and risk factors of de novo HBV (DNH) infection, as well as graft and patient survival. METHODS: We searched PubMed, Embase, and the Cochrane Library up to December 31, 2023. We included relevant studies that assessed clinical outcomes following transplantation utilizing HBcAb+ kidneys. Summary measures of effect and 95% confidence intervals (CI) for prevalence, risk factors, as well as graft and patient survival were estimated using random-effects meta-analysis. RESULTS: Thirteen studies were included for the final analysis. The DNH incidence was at 0.36% (9/2516) with low heterogeneity (I2 = 6%). HBsAb+ recipients (OR: 0.78, 95%CI: 0.25-2.38), HBcAb+ recipients (OR: 3.11, 95%CI: 0.91-10.66, P = 0.071), and recipients not receiving any antiviral prophylaxis (OR: 1.26, 95%CI: 0.15-10.58) were not associated with higher DNH risk. Specifically, HBsAb-/HBcAb+ recipients had the highest DNH incidence (4.65%), followed by HBsAb-/HBcAb- (0.49%), HBsAb+/HBcAb- recipients (0.45%), and HBsAb+/HBcAb+ (0%). Furthermore, recipients receiving HBcAb+ kidneys had comparable graft survival (HR: 1.06, 95%CI: 0.94-1.19, P = 0.55) and patient survival (HR:1.16, 95%CI: 0.98-1.38, P = 0.090) compared with recipients receiving HBcAb- kidneys. CONCLUSION: Kidney transplantation utilizing HBcAb+ kidneys contributed to comparable graft and patient survival with an extremely low risk of HBV transmission. Antiviral prophylaxes may only be administered in HBsAb-/HBcAb+ recipients.

Predictors of HBsAg seroclearance in patients with chronic HBV infection treated with pegylated interferon-α: a systematic review and meta-analysis.

BACKGROUND AND AIMS: The identification of reliable predictors for hepatitis B surface antigen (HBsAg) seroclearance remains controversial. We aimed to summarize potential predictors for HBsAg seroclearance by pegylated interferon-α (PegIFNα) in patients with chronic HBV infection. METHODS: A systematic search of the Cochrane Library, Embase, PubMed, and Web of Science databases was conducted from their inception to 28 September 2022. Meta-analyses were performed following the PRISMA statement. Predictors of HBsAg seroclearance were evaluated based on baseline characteristics and on-treatment indicators. RESULTS: This meta-analysis encompasses 27 studies, including a total of 7913 patients. The findings reveal several factors independently associated with HBsAg seroclearance induced by PegIFNα-based regimens. These factors include age (OR = 0.961), gender (male vs. female, OR = 0.537), genotype (A vs. B/D; OR = 7.472, OR = 10.738), treatment strategy (combination vs. monotherapy, OR = 2.126), baseline HBV DNA (OR = 0.414), baseline HBsAg (OR = 0.373), HBsAg levels at week 12 and 24 (OR = 0.384, OR = 0.294), HBsAg decline from baseline to week 12 and 24 (OR = 6.689, OR = 6.513), HBsAg decline from baseline ≥ 1 log10 IU/ml and ≥ 0.5 log10 IU/ml at week 12 (OR = 18.277; OR = 4.530), and ALT elevation at week 12 (OR = 3.622). Notably, subgroup analysis suggests no statistical association between HBsAg levels at week 12 and HBsAg seroclearance for treatment duration exceeding 48 weeks. The remaining results were consistent with the overall analysis. CONCLUSIONS: This is the first meta-analysis to identify predictors of HBsAg seroclearance with PegIFNα-based regimens, including baseline and on-treatment factors, which is valuable in developing a better integrated predictive model for HBsAg seroclearance to guide individualized treatment and achieve the highest cost-effectiveness of PegIFNα.

Hepatitis B surface antigen positivity is associated with poor short- and long-term outcomes in patients with diffuse large B-cell lymphoma who received CHOP or R-CHOP.

Objective: The development of diffuse large B-cell lymphoma (DLBCL) is closely related to the host infection status. China is a highly endemic area for hepatitis B virus (HBV) infection. It is not clear whether HBV infection has a consistent effect on the prognostic implications of patients with DLBCL in different treatment settings. Materials and methods: We conducted a cohort study of 692 patients with DLBCL receiving three or more cycles of treatment with a CHOP or R-CHOP regimen from the First Hospital of Jilin University between July 2011 and July 2022. The patients were divided into two groups based on their hepatitis B surface antigen (HBsAg) status: HBsAg-positive (n = 84, 12.1%) and HBsAg-negative (n = 608, 87.9%) groups. Tumor specimens from 180 patients with primary DLBCL were collected for next-generation sequencing (NGS). Results: The HBsAg-positive group had more frequent abnormal liver function (P = 0.003), hypoalbuminemia (P < 0.001), incidence of > 2 extranodal organs (P = 0.011), and spleen involvement (P < 0.001) than the HBsAg-negative group. HBsAg-positive patients had lower complete response (CR) and overall response rates (ORR) rates (all the p values < 0.05), in either the CHOP group or R-CHOP group. Among patients receiving R-CHOP, the rates of disease progression within 12 and 24 months were higher in the HBsAg-positive group than in the HBsAg-negative group (P=0.018, P=0.029). However, no significant difference in disease progression was observed between HBsAg-positive and HBsAg-negative patients in the CHOP group(P > 0.05). HBsAg positivity (OS: HR [95% CI] = 2.511 [1.214-5.192], P = 0.013) was only associated with poorer OS in the CHOP group. Whereas in the R-CHOP group, HBsAg positivity was associated with both poorer OS and PFS (OS: HR [95% CI] = 1.672 [1.050-2.665], P = 0.030; PFS: HR [95% CI] = 1.536 [1.013-2.331], P = 0.043). Additionally, HBsAg-positive patients with DLBCL also had a higher prevalence of mutations in MYC, ATM, PTPN6, and epigenetically regulated genes. Conclusion: These findings suggest that HBsAg-positive DLBCL patients may represent a distinct subgroup with a poorer prognosis. The standard therapies may be insufficient and new therapeutic strategies should be developed based on a better understanding of the underlying mechanisms of chemoresistance.

Risk of Tuberculosis and Hepatitis B Reactivation in Patients With Crohn's Disease on Ustekinumab: A Nationwide Real-World Study.

BACKGROUND: Ustekinumab (UST) was approved in China for moderate-to-severe Crohn's disease (CD) in 2020. The prevalence rates of tuberculosis and hepatitis B virus (HBV) infection are high in China, and no guideline clearly states that tuberculosis chemoprophylaxis or prophylactic anti-HBV therapy should be prescribed before UST administration. This study aimed to assess the risk of tuberculosis and HBV reactivation in CD patients with latent tuberculosis infection (LTBI) and previous HBV infection receiving UST. METHODS: A multicenter retrospective cohort study was carried out at 68 hospitals in China to assess 721 adult CD cases administered UST between May 1, 2020, and December 31, 2021. CD and concurrent LTBI or HBV carrier were included. Hepatitis B serology, T-SPOT.TB, and tuberculin skin tests were performed at baseline. The primary outcome was tuberculosis or HBV reactivation. RESULTS: Patients with CD-concomitant LTBI or who were HBV carriers receiving UST therapy were retrospectively enrolled from 15 hospitals in China. A total of 53 CD with LTBI patients and 17 CD with HBV carrier patients receiving UST were included. Treatment and follow-up durations were 50 ± 20 weeks and 50 ± 15 weeks in the LTBI and HBV carrier groups, respectively. A total of 25 CD patients with LTBI underwent chemoprophylaxis and 28 did not. A total of 11 HBV carriers had antiviral prophylaxis and 6 did not. No patient experienced tuberculosis or HBV reactivation or liver dysfunction during follow-up. CONCLUSIONS: UST was safe for treatment of CD because no patient developed tuberculosis, persistent hepatitis, or acute liver failure during therapy, whether with a prophylactic regimen or not, based on our sample size and limited follow-up time.