Hepatitis B virus infection and the risk of gynecologic cancers: a systematic review and meta-analysis.

OBJECTIVES: The relationship between hepatitis B virus (HBV) infection and gynecologic cancers is controversial. We aimed to evaluate the risk of gynecologic cancers associated with HBV infection using a meta-analysis. METHODS: Two independent reviewers identified publications in the PubMed, Embase and Cochrane Library databases that reported an association between HBV and the risk of gynecologic malignancy from inception to December 31, 2022. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the included articles. Pooled odds ratios (ORs) and 95% corresponding confidence intervals (CIs) were calculated using a fixed effects model or random effects model. RESULTS: We collected data from 7 studies that met the inclusion criteria, including 2 cohort studies and 5 case-control studies. HBV was significantly associated with the risk of cervical cancer in the general population (OR 1.22, 95% CI 1.09-1.38, P = 0.001), although the same trend was not found in endometrial cancer (OR 1.30, 95% CI 0.95-1.77, P = 0.105) and ovarian cancer (OR 1.03, 95% CI 0.79-1.35, P = 0.813). Subgroup analysis showed that HBV infection was positively associated with the risk of cervical cancer (OR 1.27, 95% CI 1.13-1.44, P = 0.000) in case-control studies. Asian women infected with HBV have a significantly increased risk of cervical cancer (OR 1.24, 95% CI 1.10-1.40, P = 0.001) and endometrial cancer (OR 1.46, 95% CI 1.07-1.99, P = 0.018). Hospital-based studies were found to be associated with an increased risk of cervical cancer (OR 1.30, 95% CI 1.14-1.47, P = 0.000) and endometrial cancer (OR 1.61, 95% CI 1.04-2.49, P = 0.032). The results of Begg's and Egger's tests showed no publication bias. CONCLUSIONS: This meta-analysis shows a positive association between HBV infection and cervical cancer. HBV is positively correlated with the risk of cervical cancer and endometrial cancer in Asian women and hospital-based populations. More multicenter prospective studies are required to confirm the findings.

Infectivity of Hepatitis B Virus Surface Antigen-Positive Plasma With Undetectable HBV-DNA: Can HBsAg Screening Be Discontinued in Egyptian Blood Donors?

Hepatitis B Virus (HBV) infectivity data were reviewed and the 50% infectious dose (ID50) was reassessed in different HBsAg-positive infection stages enabling modelling of transfusion-transmitted (TT)-HBV infection risk if HBsAg donor screening was replaced by individual donation nucleic acid amplification technology (ID-NAT). Quantitative HBsAg and HBV-DNA assays were performed against international standards to compare the ratio between potential infectious HBV virions and subviral HBsAg particles in Egyptian HBsAg-positive blood donors as well as in Japanese chimpanzee samples of known infectivity. HBV-DNA load below the quantification limit of detection was estimated against a reference standard by replicate NAT testing (n = 25). Infectivity of chimpanzee samples collected during ramp-up and declining viremic phase were tested in a human liver chimeric mice (HLCM) model and compared with published infectivity data from different HBsAg-positive infection stages. Lowest estimates of ID50 in HBsAg-positive plasma were 3-6 HBV virions in chimpanzee studies. Infectivity decreased approximately 10-100-fold in the declining viremic phase using HLCM. In acute phase samples, HBV to HBsAg particle ratios varied between 1:102-104 but in HBsAg-positive blood donors this particle ratio reached 1:106-1012 when viral load was below 100 HBV-DNA copies/mL. Modelled TT-HBV risk of an HBsAg-positive/ID-NAT nonreactive blood transfusion was estimated at 5.5%-27% for components containing 20-200 mL of plasma when assuming an ID50 of 316 (point estimate between 100 and 1000) virions. It cannot be ensured that discontinuation of HBsAg donor screening and reliance on ID-NAT alone is safe.

Hepatic macrophage niche: a bridge between HBV-mediated metabolic changes with intrahepatic inflammation.

Hepatitis B Virus (HBV) is a stealthy and insidious pathogen capable of inducing chronic necro-inflammatory liver disease and hepatocellular carcinoma (HCC), resulting in over one million deaths worldwide per year. The traditional understanding of Chronic Hepatitis B (CHB) progression has focused on the complex interplay among ongoing virus replication, aberrant immune responses, and liver pathogenesis. However, the dynamic progression and crucial factors involved in the transition from HBV infection to immune activation and intrahepatic inflammation remain elusive. Recent insights have illuminated HBV's exploitation of the sodium taurocholate co-transporting polypeptide (NTCP) and manipulation of the cholesterol transport system shared between macrophages and hepatocytes for viral entry. These discoveries deepen our understanding of HBV as a virus that hijacks hepatocyte metabolism. Moreover, hepatic niche macrophages exhibit significant phenotypic and functional diversity, zonal characteristics, and play essential roles, either in maintaining liver homeostasis or contributing to the pathogenesis of chronic liver diseases. Therefore, we underscore recent revelations concerning the importance of hepatic niche macrophages in the context of viral hepatitis. This review particularly emphasizes the significant role of HBV-induced metabolic changes in hepatic macrophages as a key factor in the transition from viral infection to immune activation, ultimately culminating in liver inflammation. These metabolic alterations in hepatic macrophages offer promising targets for therapeutic interventions and serve as valuable early warning indicators, shedding light on the disease progression.

Outcomes of a 1-Year Pilot Study Implementing Universal Hepatitis Delta Virus Testing Among Veterans With Chronic Hepatitis B.

Current US guidelines recommend risk-based testing for hepatitis delta virus (HDV) in persons with chronic hepatitis B (CHB). While there is debate as to whether a risk-based or universal testing approach is most effective, limited data exist on universal HDV testing programs in the United States. We performed a 1-year pilot study evaluating the outcomes of a universal HDV testing approach among US veterans with CHB. All consecutive adults with CHB receiving care at hepatology clinics at a single-centre Veterans Affairs Health System from 1 October 2022 to 30 September 2023 were prospectively tested for anti-HDV antibody (anti-HDV). Patients who were anti-HDV Ab-positive were subsequently tested for HDV RNA. Comparison of HDV testing between groups utilised chi-square testing. A total of 91 consecutive CHB patients (90.0% male, mean age 60.9 ± 14.1 years, 73.9% Asian, 26.1% non-Asia, 16.5% cirrhosis and 17.1% with active or past history of drug use) had anti-HDV ordered. Overall, 76.9% (n = 70) completed anti-HDV testing; 4.3% (n = 3) were positive. HDV RNA testing was ordered in all three patients; two patients completed HDV RNA testing and one had detectable HDV RNA. No significant differences in completion of anti-HDV testing was observed by age, sex, race/ethnicity, cirrhosis status or drug use history. Among a single-centre prospective cohort study piloting a universal HDV testing approach, one patient with viremic HDV was identified. Implementing true reflex testing of all CHB patients with anti-HDV, followed by automated HDV RNA testing for anti-HDV-positive patients would improve the HDV testing cascade and timely diagnosis of HDV.

Seroprevalence of hepatitis B, C, and its associated risk factors among clinically suspected patients attending poly and Maraki Health Centers, Gondar City, North West Ethiopia.

Background: Hepatitis B and C viruses are major global health problems with a high mortality rate, mostly due to serious liver diseases such as liver cirrhosis, liver failure, and hepatocellular carcinoma. The objective of this study was to determine the prevalence of the hepatitis B and C viruses and associated risk factors among clinically suspected patients attending Poly and Maraki Health Centers in Gondar City. Methods: An institution-based cross-sectional study was conducted to recruit 422 clinically suspected patients attending Poly and Maraki Health Centers between June and August 2020. The blood sample was tested for hepatitis B surface antigen and anti-Hepatitis C virus antibodies using commercially available rapid test kits. We used logistic regression and chi-square analysis to assess factors associated with Hepatitis B virus and Hepatitis C virus infections. Results: The overall prevalence of hepatitis B surface antigen and anti-Hepatitis C virus antibodies was 29 (6.9%) and 5 (1.2%), respectively. The prevalence of Hepatitis B virus and Hepatitis C virus was found to be significantly higher at Maraki Health Center. Multiple sexual partners (adjusted odd ratio (AOR = 12.299; 95% CI = 2.515-60.142), history of delivery by traditional birth attendants (AOR = 6.284; 95% CI = 2.373-16.637), surgical history (AOR = 3.679; 95% CI = 1.009-13.417), previous hepatitis infections (AOR = 10.374; 95% CI = 1.128-95.444), and upper abdominal pain (AOR = 3.382; 95% CI = 1.215-9.414) were significantly associated with an increased risk of Hepatitis B virus infections. On the other hand, a history of blood transfusion (AOR = 43.132; 95% CI = 1.385-1343.176) and a history of kidney dialysis (AOR = 71.199; 95% CI = 2.074-2444.646) were significantly associated with Hepatitis C virus infection. Conclusions: According to the WHO endemicity classification, the prevalence of the hepatitis B virus was intermediate, while that of the hepatitis C virus was low. Therefore, it is necessary to strengthen the efforts to control and prevent Hepatitis B virus and Hepatitis C virus infections.

Anti-HBc mirrors the activation of HBV-specific CD8+ T cell immune response and exhibits a direct effect on HBV control.

BACKGROUND: Hepatitis B core antibody (anti-HBc) is commonly present in patients with chronic hepatitis B virus (HBV) infection and serves as a marker of humoral immunity. Herein, we aim to investigate the correlation between anti-HBc and antiviral immune response and its putative role in HBV control. METHODS: Quantitative anti-HBc and levels of anti-HBc subtypes were measured in chronic hepatitis B (CHB) patients. The effects of anti-HBc on immune cells and HBV replication were evaluated using the HBV mouse models and human hepatoma cell lines. RESULTS: Baseline levels of IgG1 and IgG3 anti-HBc were elevated in CHB patients with favorable treatment response, and correlated with the virological response observed at week 52. Additionally, increased levels of IgM and IgG1 anti-HBc were observed exclusively in CHB patients with liver inflammation. Notably, significant correlations were identified between quantitative levels of anti-HBc and the frequencies of HBcAg-specific CD8+ T cells. Intriguingly, HBcAg efficiently activates T cells aided by B cells in vitro experiments. Moreover, anti-HBc inhibits HBV replication either by a direct effect or through complement-mediated cytotoxicity in HBV-producing cell lines. CONCLUSIONS: Anti-HBc reflects the activation of an HBV-specific CD8+ T cell immune response and may have anti-HBV activity.

Novel genetic variants in the NLRP3 inflammasome-related PANX1 and APP genes predict survival of patients with hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND: The nod-like receptor protein 3 (NLRP3) is one of the most characterized inflammasomes involved in the pathogenesis of several cancers, including hepatocellular carcinoma (HCC). However, the effects of genetic variants in the NLRP3 inflammasome-related genes on survival of hepatitis B virus (HBV)-related HCC patients are unclear. METHODS: We performed multivariable Cox proportional hazards regression analysis to evaluate associations between 299 single-nucleotide polymorphisms (SNPs) in 16 NLRP3 inflammasome-related genes and overall survival (OS) of 866 patients with HBV-related HCC. We further performed expression quantitative trait loci (eQTL) analysis using the data from the GTEx project and 1000 Genomes projects, and performed differential expression analysis using the TCGA dataset to explore possible molecular mechanisms underlying the observed associations. RESULTS: We found that two functional SNPs (PANX1 rs3020013 A > G and APP rs9976425 C > T) were significantly associated with HBV-related HCC OS with the adjusted hazard ratio (HR) of 0.83 [95% confidence interval (CI) = 0.73-0.95, P = 0.008], and 1.26 (95% CI = 1.02-1.55, P = 0.033), respectively. Moreover, the eQTL analysis revealed that the rs3020013 G allele was correlated with decreased mRNA expression levels of PANX1 in both normal liver tissues (P = 0.044) and whole blood (P < 0.001) in the GTEx dataset, and PANX1 mRNA expression levels were significantly higher in HCC samples and associated with a poorer survival of HCC patients. However, we did not observe such correlations for APP rs9976425. CONCLUSIONS: These results indicated that SNPs in the NLRP3 inflammasome-related genes may serve as potential biomarkers for HBV-related HCC survival, once replicated by additional larger studies.

Sociodemographic and clinical features related to hepatitis B virus infection among rejected blood donors in Luanda, Angola.

Background: Hepatitis B virus (HBV) remains a public health concern. Blood donors screened for HBV surface antigen (HBsAg) along with aspartate transaminase (AST)/alanine aminotransferase (ALT) could play a key in providing safe blood products. We investigated the features related to HBV infection among rejected blood donors in Luanda, Angola. Methods: This was a cross-sectional study conducted with 164 rejected donors. Donors were screened for HBsAg from March to May 2022. Overall, 63.4% tested positive for HBV. Results: The mean age of the HBV-positive (29.2 ± 8.02) was lower than the HBV-negative (33.9 ± 10.0) (p < 0.001). Donors between 20 and 40 years (odds ratio [OR]: 2.34, p = 0.045), females (OR: 1.40, p = 0.516), residents in urbanized areas (OR: 1.23, p = 0.530), low educational (OR: 1.54, p = 0.458), unemployed (OR: 1.65, p = 0.271), and unmarried (OR:1.41, p = 0.616) might be likely to contract HBV. AST/ALT ratio was higher in HBV-infected (2.07 ± 1.42) than in HBV-uninfected (1.90 ± 1.14). About 20% of HBV-positive were classified as having acute liver disease, while 80% with chronic liver disease, based on AST/ALT ratio. Age ranged from 20 to 40 years (OR: 1.97, p = 0.305), females (OR: 1.61, p = 0.557), donors from non-urbanized (OR: 1.69, p = 0.557), a low educational (OR: 1.64, p = 0.571), and unemployed donors (OR: 1.81, p = 0.289) were likely to develop chronic liver disease. Conclusions: Our findings indicated the failure of viral hepatitis control measures. Authorities should consider including HBV nucleic acid testing to ensure early identification of HBV in Angola.

Successful Treatment of Hepatitis B Virus Reactivation With a Combination of Entecavir and Short-Term Administration of Interferon-ß Twice per Day.

Hepatitis B virus (HBV) reactivation-related hepatitis is likely to progress to acute liver failure, with high morbidity and mortality, even when nucleoside analogs are administered after the onset of hepatitis. We report a case of adult T-cell leukemia/lymphoma (ATLL) with the development of HBV reactivation-related hepatitis during chemotherapy and successful treatment by a combination of entecavir and short-term intravenous administration of interferon (IFN)-ß 3 MIU twice per day. This outcome suggests that this combination therapy has a potent effect in rapidly suppressing HBV replication in the early phase of hepatitis and may be effective and safe for the treatment of HBV reactivation-related hepatitis.

Lipid nanoparticle-encapsulated DOCK11-siRNA efficiently reduces hepatitis B virus cccDNA level in infected mice.

The hepatitis B virus (HBV) infects many people worldwide. As HBV infection frequently leads to liver fibrosis and carcinogenesis, developing anti-HBV therapeutic drugs is urgent. Therapeutic drugs for preventing covalently closed circular DNA (cccDNA) production, which can eliminate HBV infection, are unavailable. The host factor dedicator of cytokinesis 11 (DOCK11) is involved in the synthesis and maintenance of HBV cccDNA in vitro. However, the effectiveness of DOCK11 as a target for the in vivo elimination of HBV cccDNA remains unclear. In this study, we assess whether DOCK11 inhibitors suppress HBV cccDNA production in mouse models of HBV infection. The tocopherol-conjugate hetero- gapmer, a DNA/RNA duplex of gapmer/complementary RNA targeting the DOCK11 sequence, partially reduces the expression of DOCK11, but not that of HBV cccDNA, in the livers of HBV-infected human hepatocyte chimeric mice, along with weight loss and decreased serum human albumin levels. Lipid nanoparticle-encapsulated chemically modified siRNAs specific for DOCK11 suppress DOCK11 expression and decrease HBV cccDNA levels without adverse effects in the mice. Therefore, nucleic acid-based drugs targeting DOCK11 in hepatocytes are potentially effective anti-HBV therapeutics that can reduce HBV cccDNA levels in vivo.

Design, synthesis and anti-HBV activity study of novel HBV capsid assembly modulators.

Capsid assembly modulators (CAMs) have the potential to cure chronic hepatitis B, as demonstrated in clinical trials. Lead compounds NVR3-778 and 5a were found to exist in normal and flipped conformations through induced fit docking. Therefore, we designed and synthesized series I and II compounds by interchanging the amide and sulfonamide bonds of 5a to modify both the tolerance region and solvent-opening region. Among them, compound 4a (EC50 = 0.24 ±â€¯0.10 µM, CC50 > 100 µM) exhibited potent anti-HBV activity with low toxicity, surpassing the lead compounds NVR3-778 (EC50 = 0.29 ±â€¯0.03 µM, CC50 = 20.78 ±â€¯2.29 µM) and 5a (EC50 = 0.50 ±â€¯0.07 µM, CC50 = 48.16 ±â€¯9.15 µM) in HepAD38 cells. Additionally, compared with the lead compound, 4a displayed a stronger inhibitory effect on HBV capsid protein assembly. Molecular dynamics (MD) simulations confirmed that the normal conformation of 4a had relatively stable conformation at different frames of binding modes. Furthermore, 4a showed better metabolic stability in human plasma than positive control drugs. Therefore, compound 4a could be further structurally modified as a potent lead compound.

Hypermethylation of the glutathione peroxidase 4 promoter predicts poor prognosis in patients with hepatitis B virus-associated acute-on-chronic liver failure.

Background: Hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) is a syn-drome with a high short-term mortality rate, and its prognosis is critical in clinical management. This study aimed to investigate the clinical significance of glutathione peroxidase 4 (GPX4) in the occurrence and development of HBV-ACLF and its prognostic value for 90-day mortality. Methods: The expression levels of GPX4, oxidative stress-related molecules and inflammatory cytokines in serum or peripheral blood mononuclear cells (PBMCs) of 289 participants were determined by RT-qPCR or ELISA, and the methylation level of GPX4 promoter in PBMCs was determined by MethyLight. Results: The expression levels of GPX4 in the PBMCs and serum of HBV-ACLF patients were lower than those in non-HBV-associated acute-on-chronic liver failure (non-HBV ACLF) patients, patients with chronic hepatitis B (CHB) and healthy control (HC) individuals, while the methylation level of the GPX4 promoter was greater. In HBV-ACLF patients, the methylation level of the GPX4 promoter is correlated with oxidative stress, inflammation-related molecules, and some clinicopathological indicators. The methylation level of the GPX4 promoter was identified as an independent risk factor for 90-day mortality in HBV-ACLF patients and yielded a larger area under the receiver operating characteristic curve (AUROC) than the model for end-stage liver disease (MELD) score in predicting 90-day mortality. Conclusion: The GPX4 promoter methylation level has promising potential as a predictor of 90-day mortality in patients with HBV-ACLF.

Interleukin-8 in HepG2 cells: Enhancing antiviral proteins in uninfected cells but promoting HBV replication in infected cells.

In vitro studies have revealed that hepatitis B virus (HBV) infection upregulates interleukin-8 (IL-8), which enhances HBV replication. Clinically, elevated IL-8 levels in chronic HBV patients are associated with diminished therapeutic efficacy of interferon-α (IFN-α). Our study advances these findings by demonstrating that IL-8 promotes the expression of myxovirus resistance A (MxA) and protein kinase R (PKR) in HepG2 cells via the PI3K-AKT pathway. However, HBV-infected cells fail to exhibit IL-8-induced upregulation of MxA and PKR, likely due to HBV's upregulation of PP2A that inhibits the PI3K-AKT pathway. Notably, IL-8 targets the C/EBPα transcription factor, increasing HBV promoter activity and viral replication, which in turn partially suppresses the expression of MxA and PKR induced by IFN-α. Our findings uncover a mechanism by which HBV may evade immune responses, suggesting potential new strategies for immunotherapy against chronic HBV infection.

The impact of DNA tumor viruses in low-to-middle income countries (LMICS): A literature review.

DNA viruses are common in the human population and act as aetiological agents of cancer on a large scale globally. They include the human papillomaviruses (HPV), Epstein-Barr virus (EBV), Kaposi sarcoma-associated herpesvirus (KSHV), hepatitis viruses, and human polyomaviruses. Oncogenic viruses employ different mechanisms to induce cancer. Notably, cancer only develops in a minority of individuals who are infected, usually following protracted years of chronic infection. The human papillomaviruses (HPVs) are associated with the highest number of cancer cases, including cervical cancer and other epithelial malignancies. Hepatitis B virus (HBV) and the RNA virus hepatitis C (HCV) are significant contributors to hepatocellular cancer (HCC). Other oncoviruses include Epstein-Barr virus (EBV), Kaposi sarcoma-associated herpes virus (KSHV), human T-cell leukemia virus (HTLV-I), and Merkel cell polyomavirus (MCPyV). The identification of these infectious agents as aetiological agents for cancer has led to reductions in cancer incidence through preventive interventions such as HBV and HPV vaccination, HPV-DNA based cervical cancer screening, antiviral treatments for chronic HBV and HCV infections, and screening of blood for transfusion for HBV and HCV. Successful efforts to identify additional oncogenic viruses in human cancer may provide further understanding of the aetiology and development of cancer, and novel approaches for prevention and treatment. Cervical cancer, caused by HPV, is the leading gynaecological malignancy in LMICs, with high age-standardised incidence and mortality rates, HCC due to HBV is an important cause of cancer deaths, and the burden of other cancer attributable to infections continues to rise globally. Hence, cancers attributable to DNA viruses have become a significant global health challenge. These viruses hence warrant continued attention and interrogation as efforts to understand them further and device further preventive interventions are critical.

Evaluation of hepatic injury in chronic hepatitis B and C using APRI and FIB-4 indices compared to fibroscan results.

Background: Hepatitis B (HBV) and hepatitis C viruses (HCV) are significant causes of liver disease worldwide. Liver fibrosis (LF) is a complication of chronic liver damage caused by HBV and HCV due to our limited knowledge comparing the diagnostic performance of platelet to aspartate aminotransferase ratio index (APRI) and fibrosis-4 (FIB-4) index with fibroscan. Methods: This study evaluated liver damage in HBV and HCV using APRI, FIB-4, and fibroscan indices. This retrospective cohort descriptive-analytical study was conducted on patients with HBV and HCV. This study uses laboratory results and imaging to investigate liver damage in chronic HBV and HCV patients. APRI and FIB-4 were computed based on laboratory results. Results: A total of 185 patients (82 hepatitis B and 103 hepatitis C) were included in the study. Thirteen patients had liver cirrhosis. There was no statistically significant difference between the fibroscan results in the two groups (P=0.99). The HBV group's mean APRI and FIB-4 were lower than HCV, but no significant difference was observed (P>0.05). Our results in HBV and HCV patients showed that APRI and FIB-4 accomplished well anticipating cirrhosis with an area under the receiver operating characteristic curve (AUC) of 0.771-0.845 and 0.871-0.910, respectively. Conclusion: Fibroscan is a powerful tool superior to APRI and FIB-4 in predicting LF and cirrhosis. Nevertheless, APRI and FIB-4 are inexpensive and non-invasive indicators with acceptable efficacy in predicting advanced fibrosis or cirrhosis. However, these two measures are not reliable in low-grade fibrosis.

Cross-sectional study of hepatitis B virus infection in female breast cancer patients in China for the first time diagnosed.

BACKGROUND: The correlation between breast cancer and hepatitis B virus (HBV) remains inconclusive. This study aims to explore the serological status of HBV infection and past infection in different age groups of female breast cancer patients, patients with benign breast diseases, and individuals undergoing routine physical examinations. METHODS: Serum data on HBV serological markers were collected and analyzed from 6072 female breast cancer patients first diagnosed from September 2012 to July 2020 at the First Affiliated Hospital of Chongqing Medical University, along with 4019 women with benign breast diseases and 54,740 healthy females undergoing routine physical examinations in the same period. The data were stratified by age for comparison between groups. RESULTS: The prevalence of HBV infection and past infection in the breast cancer group (7.9%, 55.1%) was higher than that in the benign breast disease group (6.5%, 39.1%) and the healthy females group(5.0%, 17.6%);the rate of only HBV surface antibody positivity (HBsAb ( +)) in the breast cancer group (10.3%) was lower than that in the benign breast disease group (26.9%) and the healthy females group (49.2%), with significant differences between the three groups (p < 0.05). Stratified by age, the prevalence of HBV infection in the breast cancer group (8%, 8.9%) and benign breast disease group (7.75%, 8.1%)was higher than that in the healthy females group (4.5%, 6.3%) in the 30-39 and 40-49 age group, respectively. The past infection rate of HBV in the breast cancer group (24.8%, 45.0%) was higher than that in the benign breast disease group (16.1%, 35.4%) in the ≤ 29 and 30-39 age group, respectively.. The past infection rate of HBV in the breast cancer group was higher than that in the healthy females group in all age groups, while the rate of only HBsAb ( +) in the breast cancer group was lower than that in the benign breast disease group and the routine physical examination group in all age groups. CONCLUSIONS: Breast cancer women and women with benign breast diseases have higher rates of hepatitis B virus infection and previous infections, with more significant differences among middle-aged women. Breast cancer women and women with benign breast diseases have lower rates of only HBsAb ( +) for HBV.

The Potential of the lncRNAs ADAMTSL4-AS1, AC067931 and SOCS2-AS1 in Peripheral Blood Mononuclear Cells as Novel Diagnostic Biomarkers for Hepatitis B Virus-Associated Hepatocellular Carcinoma.

Purpose: Long noncoding RNAs (lncRNAs) might be closely associated with hepatocellular carcinoma (HCC) progression and could serve as diagnostic and prognostic markers. This study aimed to investigate lncRNA-based diagnostic biomarkers for hepatitis B virus (HBV)-associated HCC. Materials and Methods: High-throughput transcriptome sequencing was conducted on the liver tissues of 15 patients with HBV-associated liver diseases (5 with chronic hepatitis B [CHB], 5 with liver cirrhosis [LC], and 5 with HCC). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze lncRNA expressions. Potential diagnostic performance for HBV-associated HCC screening was evaluated. Results: Through trend analysis and functional analysis, we found that 8 lncRNAs were gradually upregulated and 1 lncRNA was progressively downregulated by regulation of target mRNAs and downstream HCC-associated signaling pathways. The validation of dysregulated lncRNAs in peripheral blood mononuclear cells (PBMCs) and HCC tissues by qRT-PCR revealed that ADAMTSL4-AS1, SOCS2-AS1, and AC067931 were significantly increased in HCC compared with CHB and cirrhosis. Moreover, differentially expressed lncRNAs were aberrantly elevated in Huh7, Hep3B, HepG2, and HepG2.215 cells compared with LX2 cells. Furthermore, ADAMTSL4-AS1, SOCS2-AS1, and AC067931 were identified as novel biomarkers for HBV-associated HCC. For distinguishing HCC from CHB, ADAMTSL4-AS1, AC067931, and SOCS2-AS1 combined with alpha-fetoprotein (AFP) had an area under the curve (AUC) of 0.945 (sensitivity, 83.9%; specificity, 89.8%). Similarly, for distinguishing HCC from LC, this combination had an AUC of 0.871 (sensitivity, 91.1%; specificity, 68.2%). Furthermore, this combination showed the highest diagnostic ability to distinguish HCC from CHB and LC (AUC, 0.905; sensitivity, 91.1%; specificity, 75.3%). In particular, this combination identified AFP-negative (AFP < 20 ng/mL) (AUC = 0.814), small (AUC = 0.909), and early stage (AUC = 0.863) tumors. Conclusion: ADAMTSL4-AS1, SOCS2-AS1, and AC067931 combined with AFP in PBMCs may serve as a noninvasive diagnostic biomarker for HBV-associated HCC, especially AFP-negative, small, and early stage HCC.

A pilot integrated model nurse clinic increases the uptake of antiviral treatment for the prevention of mother-to-child transmission of HBV.

BACKGROUND AND AIMS: Mother-to-child-transmission (MTCT) of hepatitis B virus (HBV) may still occur despite birth-dose HBV vaccinations when pregnant women are positive for hepatitis B surface antigen (HBsAg) with high viral loads (HBV DNA ≥ 200 000 IU/mL). A pilot integrated model nurse clinic (IMNC) was started in 2020 to implement the pre-emptive antiviral therapy with tenofovir disoproxil fumarate (TDF). We aimed to evaluate the performance of IMNC on uptake of TDF. METHODS: This was a territory-wide retrospective cohort of all consecutive HBsAg-positive women of child-bearing age with pregnancy records in public hospitals 2019-2022. Demographic characteristics, liver biochemistries and virologic parameters, and TDF use were collected. Concurrently, data from a prospective audit in Union Hospital, the private hospital with the highest number of deliveries in Hong Kong, from June 2022 to May 2023 were compared. RESULTS: The prevalence rate of HBV DNA ≥ 200 000 IU/mL in pregnant women with available HBV DNA records was 29.2% (66/226) in 2019, 27.3% (99/363) in 2020, 15.9% (125/784) in 2021 and 17.2% (117/679) in 2022 (p < .001), out of 2052 pregnant women who had their HBV DNA checked within 1 year prior to delivery. An increasing uptake rate of TDF by highly viraemic pregnant women (i.e. ≥ 200 000 IU/mL) was noted after the commencement of IMNC in public hospitals, with 67% (45/67) in 2019, 83% (88/106) in 2020, 91% (117/128) in 2021 and 89% (149/167) in 2022. Moreover, all highly viraemic pregnant women from Union Hospital received TDF. Continuous use of TDF was associated with a reduced risk of postpartum biochemical flare. CONCLUSIONS: IMNC increases the uptake of antiviral treatment in pregnant women at risk of MTCT of HBV. IMNC contributes to hepatitis elimination through a structured care plan to prevent MTCT of HBV.

Construction of a novel prognostic scoring model for HBV-ACLF liver failure based on dynamic data.

Early prognostic assessment of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is important for guiding clinical management and reducing mortality. The aim of this study was to dynamically monitor the clinical characteristics of HBV-ACLF patients, thereby allowing the construction of a novel prognostic scoring model to predict the outcome of HBV-ACLF patients. Clinical data was prospectively collected for 518 patients with HBV-ACLF and randomly divided into training and validation sets. We constructed day-1, day-2, and day-(1 + 3) prognostic score models based on dynamic time points. The prognostic risk score constructed for day-3 was found to have the best predictive ability. The factors included in this scoring system, referred to as DSM-ACLF-D3, were age, hepatic encephalopathy, alkaline phosphatase, total bilirubin, triglycerides, very low-density lipoprotein, blood glucose, neutrophil count, fibrin, and INR. ROC analysis revealed the area under the curve predicted by DSM-ACLF-D3 for 28-day and 90-day mortality (0.901 and 0.889, respectively) was significantly better than those of five other scoring systems: COSSH-ACLF IIs (0.882 and 0.836), COSSH-ACLFs (0.863 and 0.832), CLIF-C ACLF (0.838 and 0.766), MELD (0.782 and 0.762) and MELD-Na (0.756 and 0.731). Dynamic monitoring of the changes in clinical factors can therefore significantly improve the accuracy of scoring models. Evaluation of the probability density function and risk stratification by DSM-ACLF-D3 also resulted in the best predictive values for mortality. The novel DSM-ACLF-D3 prognostic scoring model based on dynamic data can improve early warning, prediction and clinical management of HBV-ACLF patients.